Sunday Poster Sessions, November 4, 2007

Topic: Liver Transplantation

520. Evaluation of Week 12 Response on SVR in HCV Post Transplant Patients Undergoing PEG/RBV Therapy

 

Background:

Current guidelines for treatment of chronic HCV utilize EVR to indicate which patients are likely to achieve an SVR. Reports show a 72% SVR rate in patients with an EVR. The purpose of this study was to evaluate the week 12 viral response on SVR rate in chronic HCV post liver transplant patients.

 

Methods:

This is a secondary analysis of a multi-center randomized clinical trial of post OLT patients with recurrent HCV treated with 2 dosages of PEG IFN alfa-2b plus ribavirin 800 mg/day. PEG IFN dosage began at 0.5 mcg/kg/wk and increased in the high dose group to 1.5 mcg/kg/wk over 6 weeks.

 

Results:

The total sample contained 59 patients (27 low dose and 32 on high dose treatment). There were 39 males and 20 females ranging from 37 to 67 years of age (mean 51.4 ± 6.0). Race distribution was White 45 (76%), Black 3 (5%), Hispanic 10 (17%) and Asian 1 (2%). At treatment week 12, 32 (54%) patients achieved undetectable HCV RNA, 4 (7%) patients had ≥2 log decrease with positive virus, and 23 (39%) patients had <2 log decrease (Table 1). There was higher SVR rate in the undetectable virus group at week 12 (23/32, 72%) compared to patients with positive virus and ≥2 log decrease (1/4, 25%) or <2 log decrease (0/23, 0%). SVR rate was notably higher in genotype 1 patients with week 12 undetectable virus vs. those with detectable virus, 13/19 (68%) vs. 0/25 respectively (p=0.001). In genotype 2/3 patients, SVR was achieved by 10/13 (77%) with week 12 undetectable virus vs. 1/2 (50%) with detectable virus (p=0.2). 1 patient, a male with genotype 3, stage 1 fibrosis on high dose therapy with detectable virus at week 12, achieved an SVR.

 

Conclusions:

·        Slow viral responders in the post-transplant population, within a ≥ 2 log decrease but positive virus a week 12, have a significantly reduced chance of SVR with the standard 48 weeks of treatment than those with undetectable virus at week 12.

·        Further investigation is needed to improve SVR rates for slow viral responding patients.

Number of Patients with Undetectable HCV RNA

PEG IFN Group

Week 12 Viral Response

n

Week 24

Week 48

SVR

p Value

Low Dose

<2 log decrease

19

1 (5%)

1 (100%)

0 (0%)

0.001

≥2 log decrease but positive

2

0 (0%)

0 (0%)

0 (0%)

Virus undetectable

6

6 (100%)*

5 (83%)

5 (83%)

High Dose

<2 log decrease

1

0 (0%)

0 (0%)

0 (0%)

 

≥2 log decrease but positive

5

1 (20%)

1(20%)

1 (20%)

Virus undetectable

26

26 (100%*

21 (81%)**

19 (73%)

*1 genotype 2/3 patient in each PEG dosing group discontinued at week 24 and subsequently relapsed **5 patients discontinued prior to week 48 with side effects

 


521. Chronic hepatitis E : a new entity in organ transplant patients

N. Kamar; J. Péron; L. Ouezzani; J. Mansuy; J. Selves; C. Bureau; J. Guittard; J. Izopet; D. Durand; J. Vinel; L. Rostaing 

 

Introduction:

Hepatitis E virus (HEV) is a RNA virus that causes acute hepatitis in developing countries, but also sporadic cases in industrialized countries (non travel associated or autochthonous hepatitis E). Non travel associated hepatitis E have a predilection for middle aged and elderly males, are caused by genotype 3 and can carry significant morbidity especially when seen in the context of chronic liver disease. We describe for the first time a chronic evolution in organ transplant patients.

 

Patients:

We identified 14 cases of hepatitis E infection in France that occurred in 13 organ-transplant patients who presented with unexplained elevation of liver enzymes levels. There were 3 liver-transplant patients, 8 kidney-transplant patients and 2 kidney-pancreas transplant patients. The median time since transplantation was 57 (6-168) months. Seven were asymptomatic while the 7 remaining patients presented with fatigue. Two patients had been in contact with animals and none had travelled abroad recently. At diagnosis, there was a significant increase in liver enzymes level, from 23 (12-95) to 115 (37-436) IU/L for AST (p=0.0015), from 26 (10-102) to 245 (66-874) IU/L for ALT (p=0.0015), from 32 (8-1164) to 132 (40-3482) IU/L for gGT (p=0.0015), and from 105 (26-226) to 249 (107-822) for alkaline phosphate (p=0.0015). Cytomegalovirus and hepatitis C virus Abs, as well as HBs antigen virus and IgM anti-hepatitis A virus were negative and remained negative until last follow-up. HEV serology was negative in all patients but one. HEV RNA was positive in the sera of all patients, and in the stool (n=3) when looked for. Nine patients underwent a liver biopsy at diagnosis which revealed signs of non specific modest inflammation. HEV RNA became negative within three months in 8 patients (group I), while it remained positive in the 6 other patients (group II), respectively 9, 12, 13, 15, 16, and 27 months after diagnosis. The time between the transplantation and the diagnosis was significantly shorter in patients who developped chronic hepatitis, i.e. 82 ± 17 months in group I vs. 31.6 ± 10 in group II (p=0.02). Two patients who had chronic hepatitis E infection underwent a second liver biopsy, respectively 12 and 18 months after diagnosis. Both biopsies revealed signs of chronic active hepatitis associated to liver fibrosis.

 

Conclusion:

  • In organ-transplant patients, HEV should be considered an etiological agent for hepatitis E (HCV RNA in serum and the stools).
  • For the first time, we have shown that HEV infection can involve to chronic hepatitis at least in organ-transplant patients.
  • A longer follow-up is required to assess the outcome of HEV infection in the setting of organ-transplant receipents.

 


522. Post-Liver Transplant Survival in Hepatitis C Patients is Improving, Not Declining.

J. G. O'Leary; L. M. Grant; H. Randall; N. Onaca; L. Jennings; G. Klintmalm; G. L. Davis 

 

Introduction:

Outcomes after orthotopic liver transplant (OLT) for chronic hepatitis C (HCV) have been reported to be worsening over the last 2 decades. We analyzed our center’s experience over 15 years to identify trends in post-OLT survival in patients with and without HCV.

 

Methods:

Patient and graft survival of adult primary OLT recipients from January 1991 to June 2006 at Baylor Regional Transplant Institute (n=2051) were evaluated by Kaplan-Meyer analysis.

 

Those with or without HCV were analyzed by era:

·        Era 1:1991-1994 (n=509),

·        Era 2:1995-1998 (n=459),

·        Era 3:1999-2002 (n=532), and

·        4:2003-6/2006 (n=551).

Differences in eras with disparate survivals were assessed by univariate and multivariate analysis.

 

Results:

Overall, patient and graft survival were significantly lower among HCV recipients than in others (p<0.0001). This difference was dependent on the era of transplantation with improvement in HCV patient (p=0.0015) and graft (p<0.0001) survival in sequential eras: 5-year patient survival of 61.5%, 62.6%, and 75.6% for eras 1, 2, and 3, respectively (era 4 not evaluable yet). The change is largely related to changes in listing criteria for hepatocellular carcinoma (HCC) beginning in era 3. Survival in those transplanted for HCV with HCC has improved dramatically over time (p<0.0001). In fact, there was no change in post-OLT patient survival over time (p=0.19) when those with HCC were excluded from the HCV cohort, while graft survival still improved in successive eras (p=0.007). There was no change in survival of non-HCV recipients between eras (p = 0.14), although graft survival improved after 1994 and has remained stable since (p=0.02). The impact of potentially detrimental changes in recipient demographics over the eras including older patients, older donors, and a higher proportion with HCC have likely been ameliorated by positive trends including shorter cold ischemia time, fewer retransplants, greater use of tacrolimus and mycophenolate, and less steroid-resistant rejection.

 

Conclusion:

1.     Post-transplant survival after OLT for chronic hepatitis C has improved significantly over the last 15 years despite demographic changes in patients and grafts that have been previously shown to impair survival.

2.     A major reason for this improvement is better selection of patients with concurrent hepatocellular carcinoma.

3.     Risk factors for death in patients with HCV post-liver transplant are:

a.      CMV>3 months post-transplant

b.     Recepient age > 60 years

c.     Donor age > 50 years

d.     Re-operation < 3 months

No donor organs were obtained from executed prisoners or other institutionalized persons. The authors have no conflicts of interest.

 


526. Sustained virological response in patients successfully treated for recurrent hepatitis C following liver transplantation is highly durable.

L. Lilly; N. Girgrah; G. Therapondos 

 

Introduction/Aim:

Successful treatment of chronic hepatitis C virus (HCV) infection is defined by undetectable serum HCVRNA six months following cessation of antiviral therapy (sustained virological response; SVR). This response seems highly durable in immunocompetent HCV patients, with rates >96% reported after several years of follow-up. However, it is unclear whether an immunosuppressed patient population will enjoy the same long term success. We therefore examined our liver transplant patient population with SVR to assess the durability of their response.

 

Patients:

Over 150 patients in the liver transplant program at our institution have been treated for recurrent HCV; to date, 75 have achieved an SVR. Qualitative HCVRNA determinations were made q3m for one year from cessation of treatment, and annually thereafter, as well as during any rise in liver enzymes.

 

Results:

39/75 patients (52%) were Genotype 1 (G1), and 24 (32%) were G2 or G3, the remainder were other genotypes or unknown. Two patients were transplanted for HCV/hepatitis B coinfection, and had undetectable HBVDNA prior to treating HCV. All patients who had undetecteable HCVRNA 3m following treatment achieved an SVR. Follow-up from SVR ranged from 3m to 84m. Two patients died during the follow-up period, one 8m and the other 22m from end of treatment; both were HCVRNA negative 2m prior to death. Only one patient relapsed during the observation period. This patient had received an HCV positive graft, and become HCVRNA negative on combination therapy, remaining so for 18m after end of treatment. Retransplantation with combined liver/kidney then took place and, 3m later, serum HCVRNA became detectable.

 

Conclusions:

An SVR achieved in liver transplant patients appears to be as durable as that seen in a non-transplant population, with the only relapse in a patient who underwent retransplantation and had marked augmentation of immunosuppression. Further, HCVRNA determination 3m after end of treatment may suffice to define SVR in this difficult-to-treat population.

 


527. Comparison between hepatic elasticity measurements (Fibroscan®) and liver biopsy in patients transplanted for HCV cirrhosis.

F. Feitosa; S. Radenne; T. Bizollon; A. dOliveira; P. Pradat; R. Parana; C. Trepo 

 

Context and objectives:

Liver biopsy is considered the gold standard to evaluate outcome post liver transplantation. Because of its non invasiveness, hepatic elasticity measurement (Fibroscan®) has increasingly gained attention for the evaluation of fibrosis in transplanted patients. Our purpose was therefore to compare Fibroscan® values with those of liver biopsy in patients transplanted for HCV cirrhosis.

 

Patients and methods:

All consecutive patients transplanted for HCV cirrhosis who underwent a medical visit at Hôtel-Dieu Hospital between april and november 2006 and who had a recent liver biopsy or with indication for it were invited to participate in this study. 38 patients (27 men, mean age 58,3 years), between 44 and 75 years were included. We evaluated ALT values, viral load and genotype, treatment for chronic hepatitis, time between the biopsy and transplantation and between biopsy and Fibroscan® and possibility of any other hepatic comorbidity. The results of Fibroscan® were converted in Metavir Score values (using the values already validated for) and those were compared with the results of his biopsy.

 

Results:

15 patients (39%) had fibrosis lower than F2 at liver biopsy and 3 (8%) were F4. For Fibroscan®, these results were 16 (42%) and 9 (24%), respectively. The mean duration between the transplantation and the biopsy was 76,8 months (3-172) and 3,2 months between the transplantation and the Fibroscan® (0-9). 17 patients (45%) had cleared HCV following therapy. At the time of transplantation, 8 patients (21%) presented already hepatocellular carcinoma on the explanted liver. The observed concordance between the methods was 0,71 (27 patients) and the expected concordance was 0,51. The sensibility of Fibroscan® was 0,76 (IC 0,58-0,94) and its specificity, 0,65 (IC 0,53-0,76) with predictive positive and negative values of 0,72 and 0,65, respectively. The prevalence and the corrected prevalence was 0,55 and 0,57. The positive likelihood ratio was calculated at 2,2 and the negative as 0,37. Intermethods reliability shows a Kappa index at 0,41 (IC 0,09-0,73; statistical significance> 0,5). The comparison of all epidemiological and laboratory parameters between the two groups (concordants and non-concordants) did not show any statistically significant difference.

 

Conclusions:

·        Our data failed to show a close correlation between Fibroscan® and the liver biopsy in these patients.

·        This discordance may be in part due to the high proportion of cases with mild fibrosis that all the more it emphasizes the need for specific validation of the Metavir Scores with Fibroscan® measurements in the context of transplantation which warrant further studies.

 


530. Metabolic Syndrome is an Independent Predictor of Fibrosis Progression in Patients with Recurrent Hepatitis C (HCV) After Liver Transplantation (LT) Using Serial Biopsy Specimens

I. A. Hanouneh; C. M. Miller; A. J. McCullough; R. Lopez; F. Aucejo; A. E. Feldstein; N. N. Zein 

 

While hyperinsulinemia and its associated metabolic syndrome (MS) have been implicated in the progression of hepatic fibrosis in HCV patients, little is known about consequences of MS after LT.

 

Aim:

Assess the interaction between MS and fibrosis progression in patients with recurrent HCV after LT using serial liver biopsies.

 

Methods:

Using electronic pathology database, we identified all LT/HCV patients with at least two post-transplant liver biopsies (1998–2006). MS was defined using ATP III criteria at 1 year post LT. Ludwig-Batts scoring system was used to stage all biopsies (408 biopsies from 95 patients). The first biopsy that showed progression post LT was used for the time-to-progression analysis. Univariable and multivariable logistic regression analysis was performed to identify factors associated with fibrosis progression.

 

Results:

MS was present in 50% of patients. Median follow-up was 22 (Q25, Q75: 12.0, 31.2) months during which 71% of subjects had fibrosis progression. Overall median rate of fibrosis progression was 0.08 unites per month (Q25, Q75: 0.0, 0.17). By unvariate analysis, high HCV RNA at 4 months post-LT (p<0.001), diabetes (p=0.046), CMV infection (p=0.006) and MS (p=0.049) were associated with progression of fibrosis. In multivariate analysis, MS was not associated with fibrosis progression during the first year post-LT [OR=1.06, 95% CI: 0.49-2.26] but was independently associated with progression of fibrosis beyond 1 year after LT (OR=6.3, p=0.017). High viral load at 4 months post-LT (OR=1.1, p=0.004), steroid therapy for acute rejection (OR=1.9, p = 0.05), and CMV infection (OR=1.9, p=0.01) were independently associated with fibrosis progression. A Kaplan-Meier plot below outlines the association between MS and fibrosis progression.

 

Conclusion:

MS, a potentially modifiable factor, is common and appears to be strongly associated with long-term fibrosis progression in the setting of recurrent HCV after LT.

 

 


531. Multicenter randomized trial in HCV-infected patients treated with peginterferon alfa-2a and ribavirin followed by ribavirin alone after liver transplantation: Final report

Y. Calmus; C. Duvoux; G. Pageaux; M. Messner; P. Wolf; L. Rostaing; C. Vanlemmens; D. Botta-Fridlund; S. Dharancy; J. Gugenheim; F. Durand; M. Neau-Cransac; O. Boillot; O. Chazouillères; I. Lonjon-Domanec; L. Samelson; D. Samuel 

 

Aim:

The aim of this randomized, double-blind study was to determine the effect of placebo or maintenance therapy with ribavirin (RBV) monotherapy, after a year of combination therapy with peginterferon-alfa 2a (PEG-IFNα-2a) and RBV, on continued eradication of HCV after liver transplantation (LT).

 

Methods:

The study enrolled 100 patients (age 53.2 ± 8.3; male 73.3%; time since transplant 1.2 ± 118.0; Geno 1, 73.4%, Geno 2, 2.1%, Geno 3 5.9%, Geno 4 2.0%) with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring) on a liver biopsy obtained 1–5 years after LT. At inclusion, the activity and fibrosis scores (METAVIR) were 1.67 ± 0.76 and 1.47 ± 0.70, respectively. PEG-IFNα-2a and RBV were initiated at 90 µg/wk and 600 mg/d, respectively, and increased to 180 µg/wk and 1000 mg/d or adjusted as a function of hematological tolerance. At week 52, combination therapy was discontinued and patients were randomized to RBV alone or placebo for a further 48 weeks (blinded). 75% of patients received tacrolimus and 25% cyclosporine. Growth factor use was permitted.

 

Results:

After one year of combined therapy, 63 patients were negative by PCR and randomized between RBV alone or placebo. At 78 weeks (6 months after combined therapy), a sustained virological response (SVR) was obtained in 40% of ITT patients (40/100). At 30 months (M30) (6 months after the end of the maintenance period), 47% of the patients randomized to RBV (16/34) and 55% of those randomized to placebo (16/29) had undetectable HCV-RNA (NS). At M30, the histological activity score was 1.52 ± 1.08 (vs 1.63 ± 0.74 at M12) in the RBV group and 1.72 ± 0.84 (vs 1.51 ± 0.88 at M12) in the placebo group (NS). At M30, the fibrosis score was 1.52 ± 1.08 (vs 1.63 ± 0.91 at M12) in the RBV group and 1.72 ± 1.07 (vs 1.51 ±1.09 at M12) in the placebo group (NS).

 

The fibrosis score marginally improved in the RBV group between M12 and M30 (-0.14 [CI : -0.5;-0.22]), whereas it worsened in the placebo group (+0.26 [CI : -0.02;+0.54])(p=0.07).

 

Conclusion:

·        After 1 year’s combination therapy with peginterferon alfa-2a plus ribavirin, a SVR was achieved in 40% of patients following liver transplantation in ITT analysis.

·        A maintenance therapy with one year of ribavirin does not improve long-term virological response, but may lead to an improvement in fibrosis score.

 


532. Hepatitis C Virus (HCV) Infection is a Protective Factor for Hepatitis B Virus Reactivation (HBVr) After Receiving Hepatitis B Core Positive (HBcAb+) Donors for Liver Transplantation (LT).

M. Orrego; R. Restrepo; B. Aguilar; V. Araya; K. D. Rothstein; C. Manzarbeitia; D. J. Reich; S. Munoz 

 

Introduction:

Hepatitis B reinfection (HBVr) occurs with a variable frequency after receiving a HBcAb+ liver donor. However, there is little data on clinical, serological and virological factors associated with HBVr after LT.

 

Aim:

To determine the incidence of HBVr in LT recipients and to identify clinical, serological and virological factors associated with HBVr.

 

Methods:

Retrospective analysis of our LT population from June 1995 to May 2007. Non-HBV infected recipients with complete laboratory data post LT were studied. HBVr was defined as a positive HBsAg or HBV DNA >20,000 IU/ml post LT. Fisher’s exact test was used for group comparisons.

 

Results:

60 of 550 LT recipients (10.9%) received HBcAb+ donors. 42 of 60 patients met inclusion criteria. 6 of 42 (14%) LT recipients had HBVr. Lamivudine prophylaxis was used post LT in 6% of the recipients. 74% of the recipients had HCV infection. Median time for HBVr was 20.7 (5.8 to 110) months. 76% were male. Mean age was 54.3 years.

 

We identified three different groups for HBV (table1). Of the 26 patients in the MG, one (4%) patient had HBVr. In the UG, 4 of 12 (33%) patients developed HBVr. The UG had 8.7 (95%CI, 1.1 to 69) times the risk of HBVr compared to the MG after LT (p=0.03). The remaining 4 patients were vaccinated and one (25%) patient had HBVr.

 

There was no difference in HBVr in the vaccinated group compared to the MG and the UG. To investigate HBVr by LT recipient diagnosis, we compared HCV infected recipients (74%) to non-HCV recipients (26%). Of the 31 HCV infected recipients, 2 (6.4%, 95% CI, 0% to 21%) developed HBVr. In contrast, 4 (36%, 95% CI, 10% to 69%) of the non-HCV recipients had HBVr. The non-HCV recipients had 5.6 (95% CI, 1.2 to 27) times the risk for HBVr in comparison with HCV infected recipients (p=0.03). Since both HCV infected recipients and MG recipients appeared to be protected against HBVr, we tested if the combination was also protective. 3 (60%) of the 5 recipients in the UG with non-HCV diagnosis had HBVr compared to 0 of 22 recipients in the MG with HCV infection (p=0.003).

 

Conclusions.

·        Serological and virological characteristics have important implications to allocate HBcAb + livers. Recipients in the matched group with HCV infection appear to be protected from HBV reactivation after LT.

·        The unmatched group and non-HCV recipients have higher risk of HBV reactivation and therefore, HBV antiviral prophylaxis should be strongly considered.

·        HBVr in the vaccinated group may have been explained for low HBsAb titers in the recipient.

Table 1

Groups

Matched group (MG)

Unmatched group(UG)

Vaccinated group

Donor

HBcAb+ / HBsAb+ or -

HBcAb+ / HBsAb+ or -

HBcAb+ / HBsAb+ or -

Recipient

HBcAb+ / HBsAb+ or -

 

HBcAb- / HBsAb -

 

HBcAb– / HBsAb +

 


533. High Prevalence of Glomerulonephritis in Patients with End-stage HCV-induced Cirrhosis

B. McGuire; B. A. Julian; J. Novak; S. Bynon; W. J. Cook; S. Eddleman; D. E. Eckhoff 

 

Introduction:

Patients undergoing liver transplantation for cirrhosis due to hepatitis C virus (HCV) infection have a greater frequency of renal insufficiency after liver transplantation compared to patients without HCV. It is speculated that there is a greater prevalence of glomerulonephritis (GN) at the time of liver transplantation, but there are no data to support this postulate. The aims of this study were to determine the prevalence and type of renal pathology with HCV-induced and nonviral-induced cirrhosis and to correlate renal pathology with serum and urinary markers of renal disease.

 

Methods:

Forty adult patients undergoing liver transplantation for cirrhosis (including 30 patients with HCV-induced cirrhosis previously reported) were evaluated prior to liver transplantation for renal dysfunction (serum creatinine), hematuria (dipstick > trace blood), and proteinuria (urinary protein/creatinine ratio >0.3). At the end of transplantation, a needle biopsy of the right kidney was done.

 

Results:

The clinical data for the six patients with nonviral-induced cirrhosis included: mean age 55 yr (44-68), 5 men, and cause of liver disease was 2 non-alcoholic steatohepatitis, 2 alcohol, 1 primary sclerosing cholangitis and 1 cryptogenic. Hepatoma was present in 1 patient, diabetes in 3 and hypertension in 4. The mean calculated MELD score was 23. Preoperatively, 5 patients had one or more abnormal noninvasive study (3 elevated serum creatinine, 2 hematuria, and 2 proteinuria); 1 patient had normal studies. Kidney biopsy showed 3 patients with IgA nephropathy (IgAN) and 3 without GN. The clinical data for the 34 patients with HCV-induced cirrhosis included: mean age 52 yr (41-73), 23 men, 13 hypertensive, 8 diabetic, and 2 had hepatorenal syndrome at engraftment requiring hemodialysis. Mean calculated MELD score was 24.

 

Preoperatively, 19 patients had at least one abnormal noninvasive study (13 elevated serum creatinine, 12 hematuria, and 7 proteinuria); 15 patients had normal studies. Kidney biopsy showed 29 patients with an immune-complex GN (14 membranoproliferative GN, 9 IgAN, and 6 mesangial GN). No patient in either group had cryoglobulins by electronmicroscopy or serum measurement. At liver engraftment, histologically recognizable glomerular disease affected 29/34 (85%) of patients with end-stage HCV cirrhosis versus 3/6 (50%) of patients with nonviral-induced cirrhosis (p = 0.05).

 

Conclusion:

·        Patients with HCV-induced cirrhosis have a higher prevalence of immune-complex GN compared to patients with nonviral-induced cirrhosis at the time of engraftment.

·        These findings may explain the decline in renal function that commonly occurs after liver engraftment for HCV.

 


535. Anti-HCV Immune Responses modulate recurrence of HCV infection and severity of liver histology after liver transplantation in HIV/HCV co-infected patients

A. Samri; A. Roque-Afonso; O. Beran; C. Feray; E. Dussaix; D. Samuel; B. Autran; J. Duclos-Vallée 

 

Background:

Liver transplantation (LT) in HIV/HCV co-infected patients is successful. Hepatitis C reinfection is the major cause of recipient mortality. The aim of this work was to evaluate the immune responses against HCV before and after LT in HIV/HCV co-infected patients.

 

Methods:

14 patients with HIV viral load (VL)<50 copies/mL and CD4 counts>200/mm3 receiving a graft for HCV-cirrhosis were included. Patients were monitored for HCV and HIV VL, liver histology and immune responses in pre- and post-transplantation course (2 years). T cell responses were evaluated in blood by IFN-γ-ELISpot assays using recombinant (r) proteins: core, NS3, and NS4 (HCV), HIV-1-p24 and CMV, PPD and candida, and 16 pools of HCV-peptides (core, NS3, and NS5) and 1 pool of HIV-1-p24-peptides.

 

Results:

Before LT and 2 years after, median CD4 counts and HCV-VL were 276 and 238/mm3 and 5.73 and 6.40 log IU/mL. During the follow-up, T-cell responses against opportunistic antigens were detected in 13/14 patients with median frequency of 245 SFC/106 PBMC (range: 50 to 1677). 11/16 patients had responses against rHIV-1-p24 protein with a median frequency of 110 SFC/106 PBMC (range: 50 to 930). HCV-specific CD4 T cell responses were detected in 4 patients and directed against core in 3 patients (from 67 to 187 SFC/106 PBMC) and NS3 and NS4 in the fourth patient (87 and 50 SFC/106 PBMC). Ex vivo CD8 responses against HIV-1-p24 pool were observed in 7/11 patients with a median frequency of 195 SFC/106 PBMC (range: 60 to 875) whereas responses against HCV-peptides were detected in 1 patient and directed against core and NS5 (153 and 220 SFC/106 PBMC respectively). In 3 patients without ex vivo CD8 response, in vitro HCV-peptide stimulation lead to generate responses directed against core in 1 patient (2340 SFC/106 PBMC) and NS3 in 3 patients (from 203, 280 and 1460 SFC/106 PBMC). Interestingly, 6/7 patients with anti-HCV responses had also anti-candida responses vs 1/7 patients without anti-HCV responses. The seven patients with anti-HCV responses had F0(n=3) or F1(n=2) or F2(n=2) (METAVIR) score at 2 years. 3/7 had undetectable HCV-VL. In patients with no anti-HCV response, the scores observed were: F1(n=1), F2(n=1), F3(n=2) and F4(n=3).

 

Conclusions:

Overall, higher levels of IFNγ secretion to HCV and candida are associated with less severe fibrosis. Our results demonstrate that immune responses against HCV modulate recurrence of HCV infection and severity of liver histology after LT in HIV/HCV co-infected patients.

 


536. Serum Levels Of Fibrosis Progression Biomarkers Measured Early After LT Are Associated To Severe HCV Recurrence

D. Micheloud; M. Salcedo; S. Resino; D. Rincon; E. Alvarez; G. Clemente; M. Catalina; J. Gomez-Camarero; R. Lorente; M. Muñoz-Fernandez; R. Bañares 

 

Background:

Severe hepatitis C (HCV) recurrence is the most important influencing factor of survival after liver transplantation (LT). Portal hypertension (PH) and fibrosis stage (FS) at 12th month after LT have been associated to severe recurrence and poor survival. Several serum biological markers have been proposed as predictors of fibrosis progression in non-transplanted HCV infected patients.

 

Aims:

To analyze the relationship between the early expression (3 mo) of a serum panel of biological markers related to progression of liver damage (TNF-alpha, IP-10, MCP-1, sICAM-1, sVCAM-1, VEGF, HGF, Ang2, MMP9, TIMP-1 and hyaluronic acid) and severity of HCV recurrence after LT.

 

Patients and Methods:

Thirty-seven consecutive LT recipients due to HCV (n=19) or alcoholic (n=18) cirrhosis were included. All patients received tacrolimus or cyclosporine based immunosuppression with steroids. In all cases rejection and technical complications were excluded at the time of evaluation. Serum samples were collected at 3 mo after LT. Severe HCV recurrence was defined as fibrosis stage ≥F1 (Metavir score) in the one-year protocol biopsy and/or the existence of a HVPG value ≥6mmHg. Values are expressed as median (IQR).

 

Results:

At one year, 12 out 19 patients had severe HCV recurrence. No liver fibrosis was found in the biopsies performed in non-HCV patients. Patients with severe HCV recurrence compared to non-severe HCV recurrence and to non-HCV alcoholic patients presented at 3 mo significantly higher level of IP10 [(820 (2409), 348 (280), 180 (240) pg/ml], sVCAM-1 [2466 (839), 1266 (916), 1354 (1330) ng/ml] and hyaluronic acid [624 (246), 434 (351), 326 (207) pg/ml]. ROC curves were able to identify significant value to predict severe recurrence in HCV positive patients: IP10>590: 0.74 (0.5-0.9); sVCAM-1>1481: 0.89 (0.7-1); hyaluronic acid>461: 0.70 (0.5-0.9).

 

Conclusions:

·        Serum levels of IP10, sVCAM-1 and hyaluronic acid measured early after LT are associated to severe HCV recurrence.

·        Evaluation of these biomarkers may be useful for early identification of patients with bad prognosis in which a more aggressive therapeutic approach could be necessary.

 


538. Transient elastography (TE) is an accurate tool in monitoring liver transplanted (LT) patients with recurrent hepatitis C

C. Rigamonti; M. Donato; F. Agnelli; M. Fraquelli; G. Casazza; G. Rossi; M. Colombo 

 

Background and aims:

We previously demonstrated that TE reliably predicts severity of graft damage in LT patients. However, to what extent TE helps monitoring patients with recurrent hepatitis C under protocol liver biopsies (LB) needs to be assessed.

 

Methods:

34 patients (28 males, median age 57 years) with recurrent hepatitis C, who underwent sequential protocol LB and TE examinations twice, during a follow-up period of 18 months (first examinations at 6-96 months, median 6, from LT). Grading and staging were assessed according to Ishak score (grading 0-18; staging 0-6). TE examination was considered adequate if at least ten valid measurements for each patient were obtained with a >65% success rate. Changes in liver fibrosis and TE values were assessed as follows: worsening fibrosis (wF) or improvement fibrosis (iF) was ≥1 point staging increase or decrease, respectively; worsening TE (wTE) or improvement (iTE) was defined as ≥30% increase or decrease of TE baseline value. Four groups were identified: wF/wTE=group 1; iF/iTE or stable F/stable TE=group 2; wF/stable TE=group 3; iF/wTE=group 4.

 

Results:

Median length of LB was 30 mm (range 15-60). At first examination median grading was 7 (range 1-11), staging 1 (0-5), TE 6.9 kPa (4.0-20.2). At second examination median grading 7 (range 1-13), staging 2 (1-6), TE 8.5 kPa (4.1-27.1). Changes in histological grading and staging positively correlated with changes in TE values (r=0.47, p=0.005 and r=0.68, p<0.0001, respectively). 11/34 (32%) patients were in group 1, 17/34 (50%) were in group 2, 3/34 (9%) were in group 3, and 3/34 (9%) were in group 4. In particular, in the group 3 staging worsened in one patient from 0 to 1, in the other two from 1 to 2; only one had grading decreased from 9 to 5. In the group 4: one with stable staging had grading increased from 8 to 13; the second developed de novo autoimmune hepatitis during follow-up, and the third had severe intrahepatic siderosis. Overall, sensitivity and specificity of TE in predicting wF were 79% and 85%, respectively.

 

Conclusions:

In patients with recurrent hepatitis C TE accurately predicted wF. TE could spare the need for protocol LB in patients with iTE or stable TE.

 


539. Patients with HCV-Induced Cirrhosis with Immune-complex Glomerulonephritis Have Progressive Proteinuria After Liver Transplantation

B. McGuire; B. A. Julian; J. Novak; S. Bynon; W. J. Cook; J. M. Vincent; D. E. Eckhoff 

 

Patients undergoing liver transplantation for cirrhosis due to hepatitis C virus (HCV) infection have a high frequency of renal failure after liver transplantation. We have previously shown that immune-complex glomerulonephritis (GN) is common and often subclinical in patients with end-stage HCV-induced cirrhosis.

 

Aim:

The aim of this study was to determine the development of clinical renal injury after liver transplantation of these patients.

 

Methods:

Twenty-seven patients with HCV-induced cirrhosis undergoing liver transplantation were evaluated prior to surgery for renal dysfunction (serum creatinine), hematuria (dipstick > trace blood), and proteinuria (urinary protein/creatinine ratio > 0.3). At engraftment, a needle biopsy of the right kidney was done. Clinical features included mean age 53 years (41-73), 20 men, 22 Caucasians, hypertension in 10, diabetes in 6, and hepatoma in 10. Mean MELD score was 25. Preoperatively, 12 patients had elevated serum creatinine and 12 had 1 or more urinary abnormality (5 isolated proteinuria); 10 patients had normal noninvasive studies. Renal biopsy showed 12 patients with membranoproliferative GN (MPGN), 6 with IgA nephropathy (IgAN), 6 with mesangial GN (MesGN), and 3 with minor glomerular abnormalities. At last follow-up, the noninvasive renal markers were repeated.

 

Results:

At last visit (1 or 2 years after transplantation), 11 patients had proteinuria (6 with MPGN, 3 with IgAN and 2 with MesGN). Of these 11 patients, 8 had no proteinuria at liver engraftment. Two of these 8 patients underwent a second renal biopsy about 1 year after liver transplantation to evaluate proteinuria. Histology showed worsening immune-complex-associated glomerular injury without calcineurin inhibitor toxicity. Of the 7 patients who were proteinuric at 1 year post-transplant, the Modified Diet in Renal Disease (MDRD) estimated glomerular filtration rate was 48 ml/min/1.73 m2, compared to 69 ml/min/1.73 m2 for the nonproteinuric patients (p = 0.07).

 

Conclusions:

Proteinuria within two years after liver transplantation for HCV-induced cirrhosis is common, even when the urinalysis was normal at the time of engraftment. Patients with HCV-induced cirrhosis who develop proteinuria after liver transplantation may have an underlying GN rather than calcineurin nephrotoxicity and are likely to be at increased risk of progressive renal dysfunction.

 


540. Fibrosis Progression on Protocol Liver Biopsies In Patients With Recurrent HCV Following Liver Transplantation

E. De Martin; S. Boninsegna; M. Senzolo; M. Guido; M. Gambato; G. Germani; A. Masier; G. Zanus; U. Cillo; P. Burra 

 

Background and Aim

The recurrence of hepatitis C following liver transplantation (LT) is universal and it frequently leads to progressive fibrosis and cirrhosis with poor outcome. The aim was to evaluate the progression of fibrosis on protocol liver biopsies in patients transplanted for HCV cirrhosis.

 

Materials and Methods

A cohort of patients transplanted (1999-2005) for HCV cirrhosis who underwent protocol liver biopsies consecutively performed at our Gastroenterology Unit at 6, 12 and 24 months after LT were included in the study. Histological stage of fibrosis was evaluated according to Scheuer (score 0-4). The fibrosis progression rate (FPR) was expressed as fibrosis unit per month (FU/mo) and compared over 2 periods (6-12 mo; 12-24 mo after LT). When indicated, patients underwent PEG-IFN/Ribavirin antiviral therapy. Statistical analysis: Wilcoxon rank, Friedman and Kruskal Wallis tests.

 

Results

54 patients underwent 3 serial and consecutive liver biopsies, M/F 20/34, age 55±7yrs, follow-up 24-95mo. Overall, at 6, 12 and 24 months after LT the stage of fibrosis 3 or 4 was reported in 3.7%, 7.4% and 13% of patients respectively, stage of fibrosis (mean value) was 1.17, 1.20, 1.70 respectively, FPR was 0.005 FU/mo (6-12 mo) and 0.0416 FU/mo (12-24 mo). 9/54 (16,7%) underwent antiviral therapy, SVR was seen in 4/9 (44,4%) patients. At 6, 12 and 24 months after LT the stage of fibrosis 3 or 4 was reported in 0%, 11,1% and 22,2% of treated and in 4,4%, 6,7% and 11,1% of non-treated patients, the stage of fibrosis was 1.44, 1.61, 2.11 in treated (p=ns) and 1.12, 1.12, 1.61 (p=.003) in non treated patients, FPR was 0.0283 and 0.0416 in treated and 0 and 0.0416 in non treated patients at 6-12 and 12-24 mo respectively. According to SVR, at 6, 12 and 24 mo after LT, stage of fibrosis 3 or 4 was 0%, 0%, 0% in SVR+ and 0%, 20% and 40% in SVR- patients, stage of fibrosis was 1.25, 1.25 and 1.5 in SVR+ and 1.6, 1.9 and 2.6 in SVR- patients, FPR was 0.00 and 0.02 for SVR+ and 0.05 and 0.06 for no SVR at 6-12 and 12-24 mo after LT respectively (p=ns).

 

Conclusion

·        The fibrosis progression due to HCV recurrence is accelerated between the 1st and 2nd year compared to the early period after LT, with a lower stage and slower FPR seen in patients who were not selected for antiviral therapy.

·        In patients without SVR, pre-cirrhosis or cirrhosis is seen in 40% of cases at 2 years after LT.

 


541. Consensus Interferon Therapy for Hepatitis C Recurrence After Pegylated Interferon Failure Post Liver Transplant

M. Ghabril; R. C. Dickson; J. Lucas; J. Aranda-Michel; A. Keaveny; B. Rosser; D. M. Harnois; H. Bonatti; R. Satyanarayana; W. R. Hewitt; J. H. Nguyen 

 

Background:

Treatment of Hepatitis C (HCV) after liver transplantation (LT) with pegylated interferon/ribavirin (PEG) is associated with limited sustained viral response (SVR). Consensus interferon/ribavirin therapy (CIFN) may be effective after PEG non-response or relapse, but data is limited post LT.

Aim: To evaluate outcomes of CIFN in HCV LT recipients not achieving SVR with PEG.

 

Methods:

572 HCV patients received LT between 2/98 & 9/06 and 233 underwent antiviral treatment with PEG. Charts of patients without SVR to PEG who were then treated with CIFN were retrospectively reviewed. Data up to 6/2007 were collected. Target dose interferon in PEG was defined as peg interferon alpha-2a 180mcg or alpha -2b 1.5mcg/kg weekly and CIFN ≥ 9mcg daily. Target dose ribavirin was ≥800 mg daily. Virologic endpoints were SVR, relapse and virologic response (VR) defined as ≥ 2 log drop in HCV RNA. Advanced fibrosis was defined as Batts Ludwig score ≥ 3.

 

Results:

34 patients who failed PEG (32 nonresponders/2 relapse) were treated with CIFN and 16 remained on CFIN at last follow up. Mean age 51±7, 65% males, 85% caucasian, 97% genotype 1. PEG & CIFN treatments were compared in the same 34 patients (table). Patients achieving target dose PEG and CIFN had similar VR (37% & 42%). Of the 21 patients with no VR to PEG, 6(30%) had a VR to CIFN, while 4(22%) with no VR to CIFN had a previous VR to PEG. A mean follow-up of 49 months post LT, 35% had advanced fibrosis on last liver biopsy and 1 patient underwent re-LT for HCV related graft failure.

 

Summary:

In patients without SVR to PEG after LT treated with CIFN, treatment with either PEG or CIFN was limited by tolerance. Virologic endpoints were similar between treatments though more than 20% with no VR to one interferon had a VR response to another. SVR, the most critical treatment endpoint was rare.

 

Conclusion:

CIFN for HCV recurrence after PEG treatment failure post LT has limited efficacy. There remains a need for additional therapeutic strategies in this difficult to treat group.

 

 

PEG

CIFN

Time from LT (months)

*14±12

*37±22

Full dose interferon

56%

56%

Full dose ribavirin

44%

50%

Growth factors used

79%

84%

Advanced fibrosis

18%

31%

VR

33%

44%

Relapse

6%

3%

SVR

0

3%

Discontinuation due to intolerance

24%

32%

*P if <0.05

 


543. What is the risk of HBV transmission in recipients of liver graft from HBc Positive Antibody, HBs Negative Antigen donors? A single center experience over 10 years.

B. Roche; A. Roque-Afonso; T. Antonini; M. Gigou; D. Castaing; D. Samuel 

 

Background :

Liver graft from HBc positive antibody (HBcAb), HBs antigen negative (HBsAg) donors are used to expand the pool of graft despite a known risk of HBV transmission. Various prophylaxis strategies were used in small series to prevent the risk of HBV transmission. The aim of the present study was to report our experience over 10 years using a prophylaxis with HBs antibody immunoglobulins (HBIG).

 

Methods :

From 1997 to 2006, 80 HBcAb + liver grafts out of 947 grafts (8.4%) were used. These grafts were used for 21 HBsAg positive recipients and 59 HBsAg negative recipients (HCV cirrhosis n=22, alcoholic cirrhosis n=14, amyloid neuropathy n=11, miscellaneous n=12). Among the 59 HBsAg negative recipients, 30 were HBsAb and HBcAb negative, 13 were HBsAb positive and HBcAb negative and 16 HBcAb positive +/- HBsAb positive. HBsAg positive recipients received a prophylaxis regimen using HBIG +/- antivirals according to pre-transplant HBV vital load. Among HBsAg negative recipients, 44 received HBIG prophylaxis using 10000 IU IV during anhepatic phase and reinjection of 5000 IU IV when HBsAb was below 100 IU/L.

 

Results :

Mean follow-up was 47.8 months (1-115.8). HBV infection occurred in 13 recipients (16.2%) during follow-up at a mean delay of 15 months (6-45) after transplantation. HBV DNA became positive in 13 patients and HBsAg in 12. No HBV infection occurred in HBsAg positive recipients. HBV infection occurred in 12 out of 30 HBsAb and HBcAb negative recipients (40%) and 1 out of 13 HBsAb positive recipients (7.7%). Among the 30 HBsAb and HBcAb negative recipients, HBV infection occurred in 7 out of 20 who received HBIG prophylaxis (35%) and 5 out of 9 who received no prophylaxis (55%). HBV infection of the graft was treated with lamivudine in 13 recipients and adefovir was add-on in 6 lamivudine-resistant patients. A HBsAg / HBsAb seroconversion was observed in 3 recipients during follow-up.

 

Conclusions :

The use of liver grafts from HBcAb positive, HBsAg negative donors is relevant to expand the liver graft pool. These grafts should be used in priority for HBsAg positive or HBV immune recipients (past infection or HBV vaccination). This study confirms a high risk of HBV transmission for HBsAb and HBcAb negative recipients despite HBIG prophylaxis. Future studies should evaluate a combined prophylaxis with HBIG and antivirals in this group of recipients.

 


544. Response of fibrosing cholestatic recurrent hepatitis C following liver transplantation to combination interferon/ribavirin therapy.

L. Lilly; M. Deschenes; P. J. Marotta 

 

Introduction/Aim:

Fibrosing cholestatic hepatitis C (FCHC) is an uncommon (<5%) presentation of recurrent HCV following liver transplantation. It is characterized by very high bilirubin and alkaline phosphatase and modestly elevated transaminases, with a biopsy demonstrating marked cholestasis, minimal necroinflammation, bridging fibrosis, and numerous apoptotic bodies. Outcome is uniformly poor, and retransplantation generally unsuccessful. We examined the response of FCHC to interferon/ribavirin therapy, using data collected from three Canadian liver transplant programs.

 

Patients:

15 patients from the University of Toronto, University of Western Ontario and McGill University Liver Transplant Programs who developed FCHC following liver transplantation from 2000-2005 and received combination therapy with interferon or PEG-interferon and ribavirin were included. All cases were biopsy-proven, and antiviral treatment was commenced at 50-75% of standard doses; growth factors were administered as required.

 

Results:

9/15 patients were male; mean age at transplant was 54y [range 39-69y]. Nine received deceased donor, and five living donor, grafts. Ten patients had genotype 1;  2 had genotype 2, 3 had genotype 4.  Four patients received standard IFN and 11 patients received PEG IFN, in addition to ribavirin. 5/15 (genotype 1 = 3, genotype 2 = 2) patients (33%) achieved an SVR, and 10/15 had no response. Eight of these patients succumbed to liver failure 2-22m following FCHC diagnosis; one patient is alive 6.5 yrs after transplant with decompensated graft cirrhosis. Two of the five SVR patients have since died, one from systemic sepsis 22m post transplant, and the other 17m post transplant from biliary tract complications.

 

Conclusions:

Combination therapy with interferon and ribavirin offers some hope in the management of fibrosing cholestatic hepatitis (FCHC), although the overall prognosis remains poor.

 


545. Predicting Cardiovascular Events After Liver Transplantation

M. Herman; S. Pungpapong; J. Aranda-Michel; B. Rosser; D. M. Harnois; R. C. Dickson; R. Satyanarayana; D. Yip; A. Keaveny 

 

Introduction:

Cardiovascular disease (CVD) is a leading cause of late death post-liver transplantation (LT). CVD risk factors are common in LT patients. The optimal method and timing of risk stratification for CVD post-LT are not established. The Framingham risk score (FRS) estimates the risk of death or developing symptomatic coronary heart disease (CHD) in non-LT patients. In European cohorts, FRS increased post-LT, but had limited discriminatory capability. In our LT patients at a U.S. center, we evaluated changes in CV risk factors over time and subsequent CV events (CVE), defined as the need for intervention (surgical/medical) in CHD or peripheral vascular disease, transient ischemic attack, or cerebrovascular accident.

 

Methods:

This retrospective review of 120 consecutive first LT recipients (65% male, mean age of 55 ± 10 yrs) followed subjects for a mean of 1601 days (range 233-1907) post-LT. Fasting total, HDL and LDL-cholesterol (TC, HDL-C, LDL-C), glucose, weight and blood pressure (BP) were measured and FRS calculated at pre-LT and regular intervals post-LT (at 4 and 12 months, then annually). Diabetes mellitus (DM) was defined as plasma glucose >126 mg/dL and/or the continuing requirement for DM therapy. Hypertension (HTN) was defined as a systolic BP >140, diastolic BP >90 or the use of anti-hypertensive agents. The change over time (slope) for risk factors was calculated and the association between risk factor trajectory and CV events were examined with logistic regression models.

 

Results:

9 non-fatal CVE's occurred in our cohort over the follow-up period. CV risk factor data are shown (see Table) for selected visits. Increasing body mass index (BMI) increased the odds of developing DM {OR 1.07 (95% CI 1-1.13), p<0.01}. The FRS slope correlated with CVE, {OR 1.4 (95% CI 1-1.9), p=0.04}.

 

Conclusions:

CV risk factors are prevalent and clinically useful over time in U.S. LT patients. Changes in FRS over time identify patients at risk for CVE post-LT, with the odds of CVE increasing by 40% for each 1-unit increase in slope. Risk factor modification studies in this population appear warranted.

CV Risk Factors Pre and Selected Visits Post-LT

 

Pre-LT

(n=120)

4-month visit post-LT

(n=120

Year 4 visit Post-LT

(n=69)

Mean time post-LT (days) ± SD

-

 

152 ± 66

 

1601 ± 164

BMI >30 (%)

35%

36%

43%

BMI >35 (%)

14%

11%

15%

Mean TC (mg/dL) ± SD

151.5±49.5

174.1 ± 50

181.8 ± 46.9

Mean HDL-C(mg/dL)± SD

40.2± 19.7

40.8 ± 14.3

48.8 ± 14.2

Mean LDL-C (mg/dL) ± SD

92.1 ± 37

97.8 ± 42.4

96.8 ± 34.8

Prevalence of HTN(%)

-

59%

72%

Prevalence of DM (%)

24%

38%

36%

FRS ± SD

5 ± 5.2

7.5 ± 7.2

7.7 ± 6.7

 


546. Transplantation Trends in Recipients Over the age of 65

N. Kemmer; K. Safdar; T. E. Kaiser; V. Zacharias; M. Atiq; K. Ahmed; N. Malik; G. W. Neff 

 

Introduction:

Liver transplantation (LT) provides long-term survival for adults with end-stage liver disease. As a result of improved survival and an aging United States population the demand for LT in older patients is expected to increase.

 

Aim:

The aim of this study is to describe the transplantation trends in the older recipient (65 yrs and older).

 

Method:

Using the UNOS database, we identified all LT recipients between 1990 and 2006. The data collected included demographics, diagnosis, LT year, survival information and UNOS region. We used Kaplan Meier method to calculate overall survival (1, 3, 5 and 10 yr) and Cox regression modeling techniques for predictors of survival.

 

Results:

During the study period 5630 (7.6%) LT recipients were > 65 years. Of these, there were 3030 (56.5%) males with a median age of 67 (range 65 – 87). There were 4256 (79.4%) Caucasians, Hispanic (10.3%), African Americans (3.6%) and rest (6.7%). Hepatitis C (21%) was the most common indication followed by cryptogenic (15.1%), alcohol liver (13%), Hepatocellular Carcinoma (10.4%), Primary biliary cirrhosis 9.2%, Primary sclerosing cholangitis 5.1% and others 26.2%. There was an increase in LT for older patients from 4.1% in 1990 to 10.2% in 2006 (p=0.002), as well as a regional variation (p<0.001). The 10-yr patient and graft survival was 60% and 57% for <65 yrs vs. 42% and 40% for >65 yrs (p <0.0001).With age stratification (65 – 75 yrs vs. >75yrs), there was no difference in overall survival but when adjusted for race there was a significant difference in graft survival with a 10 yr (Caucasian 40%, Hisp 44% and African Americans 19%) (p=0.04). No other predictors of survival were identified.

 

Conclusion:

·        The demand for LT in recipients older than 65 years is increasing; there is regional variability and a change in LT indication (cryptogenic 2nd most common).

·        Although their survival is reduced when compared to recipients <65 yrs, there appears to be no difference in unadjusted survival with age stratification above 65 years.

·        Among ethnic minorities, African Americans have a disproportionately lower % LT and a decreased survival

 

 


547. The effect of disease recurrence on graft survival following orthotopic liver transplantation

I. A. Rowe; K. Webb; B. K. Gunson; N. Mehta; S. Haque; J. M. Neuberger 

 

Introduction:

Disease recurrence following transplantation is well recognised but since the impact of recurrence on graft survival is less clear we undertook a retrospective analysis to determine both the frequency and impact of disease recurrence on graft survival.

 

Methods:

All 1840 adult patients who underwent liver transplantation between 1982 and 2004 were included. Disease recurrence was diagnosed on clinical, serological, histological or radiological grounds as appropriate. Where graft loss was due to factors associated with the indication (such as a return to alcohol consumption), the graft loss was attributed to disease recurrence. The most common disease indication was primary biliary cirrhosis (PBC) so these patients were used as the comparison group. To eliminate those grafts lost where recurrence was unlikely only those 1499 patients surviving more than 90 days after transplantation were included in the analysis. The risk of graft loss from disease recurrence for first grafts was calculated using the Cox regression model.

 

Results:

The risk of graft loss from recurrent disease was greatest, when compared to PBC, in those transplanted for hepatitis C virus (HCV) (hazard ratio (HR) 11.6; 95% confidence interval (CI) 5.1-26.6), primary sclerosing cholangitis (PSC) (HR 6.0; 95% CI 2.5-14.2) and autoimmune hepatitis (AIH) (HR 4.1; 95% CI 1.3-12.6). The overall risk of graft loss was also significantly greater in HCV (HR 2.1 vs. PBC; 95% CI 1.5-3.0), PSC (HR 1.6 vs. PBC; 95% CI 1.2-2.3) and AIH (HR 1.6; 95% CI 1.0-2.4) although when recurrent disease was excluded as a cause of graft loss there was no difference in the overall risk of graft loss (HCV: HR 1.4; 95% CI 0.9-2.1, PSC: HR 1.4; 95% CI 0.9-2.0, AIH: 1.4; 0.9-2.2 all vs. PBC).

 

When the rate of disease recurrence and the rate of graft loss from disease recurrence were compared, proportionally more grafts were lost in HCV (14.3% of grafts lost to recurrent disease vs. 77% of grafts affected), PSC (8.4% vs. 37%), and AIH (6.2% vs. 28%) than in PBC (1.3% vs. 24%). There was no statistically significant difference in the risk of graft loss due to recurrent disease, when compared with PBC, for patients transplanted for alcohol related liver disease (ALD) (HR 1.0;95% CI 0.2-4.9), non-alcoholic steatohepatitis (HR 2.2;95% CI 0.6-8.4) and fulminant hepatic failure (HR 1.7;95% CI 0.4-6.6).

 

Conclusion:

Disease recurrence is a significant cause of graft loss particularly in HCV, PSC and AIH. Graft loss from disease recurrence in part explains the increased overall rate of graft loss in these groups.

 


552. MELD-Na is superior to other organ allocation systems

M. R. Foxton; P. Muiesan; N. Heaton; J. G. O'Grady; M. A. Heneghan 

 

Introduction

There is ongoing analysis of the optimal method of organ allocation. The MELD system is inaccurate for up to 20% of the population on the liver transplant waiting list.This is most likely due to significant clinical variables such as ascites not being accounted for. We analyzed several scoring systems for end-stage liver disease to assess which predicted survival on the waiting list.

 

Methods

All patients listed with UK Transplant (UKT) at our centre, between January 2000 and December 2003, were included in the study. Patients were excluded if they were super-urgently listed, listed for multiple organ transplants, non-NHS entitled for liver transplant or their indication for transplant was amyloidosis. The scoring systems examined were the Child-Pugh score, MELD score, MELD-Na score and three variants of the Child Pugh score incorporating creatinine at the time of listing with UKT. A positive outcome was surviving to transplantation or being delisted due to improvement obviating the need for transplant. A negative outcome was death on the transplant list or being delisted due to the developments of contraindications for transplant. Receiver-operating characteristic (ROC) curves were generated for each scoring system based on these outcome measures and the areas under the curve (AUC) were compared using the Hanley-McNeil method.

 

Results

Seven hundred and eighty seven patients were listed. After exclusions, 490 patients were analysed in the study. The median age of the patients was 55 years and the predominant aetiologies were alcoholic liver disease and hepatitis C. The median Child-Pugh score was 9 and the median MELD score was 15. There were 416 patients with a positive outcome including 402 transplants. The remaining 74 patients with a negative outcome had significantly higher CPS (11 vs 9), MELD (18 vs 14), MELD-Na (38 vs 16) and modified CP scores (All p values <0.0001). There was no difference in time on the waiting list (64 vs 68 days; p=0.18). The AUC for all scoring systems was >0.705 (p<0.001) indicating that they performed well and were clinically applicable. However, MELD-Na was significantly better than the other scoring systems with an AUC of 0.828 (p<0.001).

 

Conclusion

·        All scoring systems analysed performed adequately in predicting a negative outcome on the transplant waiting list with no difference between CP score and MELD score.

·        However, MELD-Na was significantly better than all the other scoring systems at predicting waiting list mortality and thus any changes in organ allocation warrant comparison with this scoring system.

 


553. Long term results of a randomized trial of tacrolimus monotherapy versus triple therapy in HCV cirrhosis liver transplant recipients.

P. Manousou; D. Samonakis; A. Corbani; E. Cholongitas; A. Sigalas; E. Xirouchakis; V. Calvaruso; F. Grillo; D. Patch; J. O'Beirne; A. P. Dhillon; K. Rolles; B. Davidson; A. K. Burroughs 

 

Introduction

Less potent immunosuppression has been considered to be beneficial in reducing severity of HCV recurrence. However some reports suggest benefit with low dose steroid maintenance. Optimal immunosuppression regimen is unknown.

 

Aim of the study

To evaluate benefit of tacrolimus monotherapy versus triple therapy in a randomized trial.

 

Patients and methods

88 consecutive patients with first transplant for HCV cirrhosis with/without HCC were randomized to tacrolimus (MT) 0.1 mg/kg/day in 2 divided doses, or the same tacrolimus dose with 1mg/kg azathioprine and 20mg prednisolone daily (TT) the latter was tailed off to zero at 3-6 months.

Patients had scheduled biopsies with Hepatic Venous Pressure Gradient (HVPG) measurement yearly. Fibrosis was staged using Ishak score and stage 4(F4) was the predetermined end-point. Cox regression was used to evaluate factors associated with F4: age and gender of recipient and donor, histological acute hepatitis, rejection episodes, HCC before LT, addition of MMF, and allocated treatment.

 

Results

Randomization resulted in no significant differences in pre, peri or post operative variables (median follow up 48 months). Mortality was not significantly different: 8 of 43 in MT at 1m, 1m, 1m, 2m, 3m, 4m, 4m, 6m and 5 of 45 in TT at 5m, 7m, 11m, 37m, and 66m). Retransplantation in 3 MT and 3 TT; frequency of scheduled biopsies was similar. During follow up (re-transplants censored), 13 MT and 6 TT reached F4. Cox regression revealed that randomization to therapy and episodes of acute hepatitis were two factors independently associated with F4 (p=0.036). Kaplan Meier analysis showed TT patients had significantly slower progression (p=0.048) than MT patients. HVPG gradient was available in 33 MT and 30 TT patients. Kaplan Meier analysis showed a significantly shorter time to reach HVPG≥10mmHg in MT group compared to TT group (p=0.038).

 

Conclusion

·        The use of low dose azathioprine long term and short term low dose prednisolone in addition to tacrolimus in HCV cirrhosis recipients resulted in a slower onset of histological severe fibrosis and portal hypertension compared to tacrolimus alone, independent of other factors known to affect fibrosis.

·        This randomized trial supports observational reports of the benefit of low dose steroids, as well as azathioprine, used as maintenance immunosuppression after liver transplantation for HCV positive recipients.

 


554. Graft Survival after Living Donor or Cadaveric Liver transplantation: An Analysis Stratified by Donor Risk

S. Patel; I. Lent; A. Bozorgzadeh; M. Orloff; G. Tsoulfas; R. Kashyap; A. Jain; P. Abt 

 

Introduction:

Living donor liver transplantation (LDLT) has become an accepted alternative to transplantation with a cadaveric organ. Recently, cadaveric donor characteristics as codified by the Donor Risk Index (DRI) have illuminated the requirement to balance donor qualities and recipient risk of death on the wait list as a means to optimize the survival benefit of transplantation. Within this framework, the role of the living donor graft remains unclear.

 

Methods:

Utilizing United Network for Organ Sharing data from 2002 to 2006, we analyzed graft survival comparing 4 different graft types stratified by donor risk characteristics: low-risk living donor (LRLD – Relative Risk [RR] of graft loss <1.7), high-risk living donor (HRLD, RR >1.7), low-risk deceased donor (LRDD, <1.7) and high-risk deceased donor (HRDD, RR >1.7). Graft survival was modeled using Cox regression while controlling for recipient characteristics, which included age, race, diagnosis, dialysis, medical condition, life support and Model for End-Stage Liver Disease (MELD) score.

 

Results:

98% of LDLT transplants were performed in recipients with a MELD score of 25 or less. Overall 3 year graft survival for LRLD, HRLD, LRDD, and HRDD was 77%, 65%, 80%, and 67%, respectively (p-value < 0.001) (Fig. 1). The relative risk of graft loss, in reference to the LRLD group, was 1.7 for HRLD (95% CI 1.05-2.75), 0.9 for LRDD (95% CI 0.72-1.12), and 1.4 for HRDD (95% CI 1.18-1.86).

 

Conclusions:

·        Survival with high risk living donor grafts is similar to high DRI cadaveric organs in patients with low to moderate MELD scores.

·        Consideration of donor characteristics relative to recipient risk of wait list death should be considered in LDLT.

 

 


558. Smoking related morbidity and mortality post liver transplantation

J. A. Leithead; J. W. Ferguson; P. C. Hayes 

 

Introduction:

The negative health implications of cigarette smoking in the non-transplant setting are well recognised. However, the morbidity and mortality associated with tobacco use amongst liver transplant recipients specifically remains unclear. The aim of this study was therefore to assess the influence of smoking on both short and long term outcomes post liver transplantation.

 

Methods:

A single-centre retrospective case-note study of 136 consecutive patients transplanted between 01/01/96 and 12/31/2000. Smoking status was based on documentation during liver transplant assessment. Patients who did not have smoking status recorded or who were described as ex-smokers were excluded from further analysis. Mean follow-up time was 8.8 (range 6.4-11.3 years).   

 

Results:

Of the remaining 108 patients, 23% were smokers, 18% were ex-smokers and 58% were non-smokers. No difference was observed between the two groups with regards age, gender, prevalence of HCC, Child Pugh score, listing renal function, and the presence of pre-transplant diabetes, hypertension and cardiovascular disease. Post transplant a similar proportion of patients in each group received cyclosporin, and were treated for diabetes, hypertension and hypercholesterolaemia.

 

All cause mortality

·        Smoking at the time of assessment was associated with increased all-cause mortality, the estimated 1, 5, and 10 year survival was 94% ,68% and 54% respectively for active smokers and 94%, 83%, and 77% for life-long non-smokers (p=0.04).

·        This increased risk of death was not maintained in ex-smokers (p=ns).

·        On multivariate analysis only smoking (HR2.23, 95% CI 1.08-4.61, p=0.03) and peri-operative renal replacement therapy (HR 2.78, 95% CI 1.35-6.74 p<0.01) were independent predictors of death.

 

Conclusions:

·        Smokers are 2 times more likely than non-smokers to die post liver transplantation during a follow-up period of 10 years.

·        This increased mortality rate is non-graft related and appears to be a result of increased cardiovascular-related and sepsis-related death.

·        Prospective studies are required to assess the impact of smoking cessation on long term outcome.

 


561. Combined liver heart transplantation in the United States

H. S. Te; S. R. Mohanty; N. Reau; K. G. Reddy; R. Satoskar; D. M. Jensen 

 

Introduction:

Combined liver-heart transplantation has been increasingly performed in the United States, but published data on the overall patient and graft outcomes has been limited. AIM: To review the indications, management, complications and outcomes of combined liver-heart transplantation in the United States.

 

Methods:

Patients who received combined liver-heart and liver-heart-kidney transplants were identified from the UNOS Database. Demographic characteristics such as age and gender, and clinical data such as indication for transplantation, duration of follow-up, current immunosuppressive agents, complications, patient and graft survival times, and cause of death were obtained.

 

Results:  

From October, 1987 to February, 2007, a total of 47 cases of combined liver-heart (n=41) and liver-heart-kidney transplantation (n=6) were performed in the United States at 15 transplant centers. One pediatric case was excluded from the analysis. The mean age of the recipients was 46 years (range, 22-65), with 31 (67%) being males. The most common indication for both the heart and the liver transplantation was amyloidosis (30%). Patients were followed for a mean duration of 1362 days or 3.7 years (range, 1-4598 days or 0-12.6 years). Patient and graft survival rates, as well as the comparative OPTN/SRTR patient survival rates, are shown in the Table. The most common causes of death were cardiac, sepsis, and multiorgan failure. At the latest follow-up of patients who survived at least six months after transplantation (n=39), 71.8% of patients were on at least two immunosuppressive agents, most commonly consisting of a calcineurin inhibitor and corticosteroids. There were seven episodes of liver graft rejection in six (13%) patients and five episodes of heart graft rejection in five (10.9%) patients. Five patients developed malignancy involving the skin, the larynx, and unknown sites (n=2) at year 2 to 8 of follow-up. Only

 

Conclusion:  

Combined liver-heart and liver-heart-kidney transplantation is a viable option for candidates who need the combined organ transplantation, with outcomes comparable to those of single organ recipients.

 


564. Implementation of a liver allocation system based on MELD score in three transplant centers of the same city. Can the score differences be solved?

X. Xiol; P. Gines; L. Castells; A. Ribalta; J. Twose; C. Ventura; J. Reverter; X. Fuentes; R. Deulofeu 

 

MELD score is considered an objective and reproducible measure of liver disease severity. However, MELD score can be influenced by specific laboratory methodologies. In order to implement an organ allocation system based on MELD score in the three Hospitals of Barcelona with liver transplant program, all patients in the waiting list at the three centers were studied simultaneously: blood samples were obtained from each patient and divided in three aliquots, which were processed in the three laboratories. Two laboratories (A, C) expressed creatinine and bilirubin in mg/dl and one (B) in µmol/l. Therefore, a conversion factor was used in laboratory B (creatinine x 0.0113 and bilirubin x 0.0588). MELD was calculated according to the reported mathematical formula.

 

Results:

74 patients, 51 from hospital A, 15 from B and 8 from C, were studied; 4 cases had a missing value and were excluded. Overall, there were significant differences in the three laboratory parameters, the greatest difference being in INR. Mean values and 95% CI for each variable are shown in the table.

MELD score was identical in the three centers in only 6 out of the 70 patients (9%). Scores from laboratories A and C differed considerably: 22 cases had a difference of 1 point, 21 cases of 2 points, 10 cases of 3 points and in 7 cases the difference was greater than 3 points.

 

Conclusions:

·        There were significant differences in the three laboratory variables and in the calculation of MELD score among the three centers.

·        In two of them, MELD score differed in two points or more in 38 out of the 70 the cases (54%). In order to guarantee an equitable organ allocation based on MELD score, similar laboratory methodologies should be implemented in centers that belong to the same organ procurement area, so that relevant differences in calculated MELD scores are avoided.

·        Alternatively, the existence of a central laboratory in each organ procurement area should be considered.

 

 

Laboratory A

Laboratory B

Laboratory C

p

Creatinine mg/dl

1.23 (1.05-1.42)

1,20 (1-1.40)

1,21 (1.03-1.41)

0.001

Bilirubin mg/dl

2.96 (2.29-3.64)

3.28 (2.47-4.09)

3.11 (2.38-3.84)

0.001

INR

1.40 (1.32-1.48)

1.52 (1.42-1.61)

1.67 (1.51-1.83)

0.001

MELD

14.3 (13.8-16.3)

15.1 (13,1-15.4)

15.9 (14.6-17.3)

0.001

MELD range

6-29

6-31

6-40

 

 


566. Outcomes of Transplantation with previously Refused Donor Livers in Region 8

S. L. Eswaran; E. R. Lyden; T. M. McCashland 

 

Intro:

There is a 10-20% mortality for patients awaiting liver transplantation (LT). There are various refusal reasons (RR) for donor livers (DLs). After refusal, DLs may be offered to another patient or center.

 

Aim:

Evaluate the frequency of RR and outcomes of LT with previously refused DLs. Methods: We requested data from UNOS-OPTN between July 2004-June 2006 in Region 8 regarding donors and recipients who received living and deceased livers on the first offer (Group A) and who received previously refused livers (Group B). We determined graft survival (GS) and patient survival (PS). Split livers were excluded.

 

Results:

Eleven centers were offered 764 DLs (Group A=315;41% and Group B=437;59%). The mean number of DL refusals was 12.64 (range 1-221). The most common RRs were donor age/quality (37%), donor size/weight (35%) and transplant center personnel limitations (10%), including heavy work load, operational, or surgeon unavailable. Group B had more male recipients (59% vs 72%; p=0.0003), older donor age (35 vs 38 yrs;p = 0.013), longer cold ischemic times (CIT) (6.23 vs. 7.42 hrs; p<0.0001), shorter warm ischemic times (WIT) (47.18 vs 42.8 hrs; p=0.003) and shorter length of hospitalization post LT (19 vs 14 days;p=0.003). There was no difference in 1 month (92% vs 94%) and 1 year (83% vs 85%) GS (p=0.20, 95% CI).(Figure) Group B had a longer PS (86% vs 91%) at one year (p=0.0069, 95% CI); however, when adjusted for gender, donor age, CIT, WIT and length hospitalization post LT, a previously refused status was no longer associated with a longer PS.

 

Conclusion:

·        There were differences between recipients who received first offer donor livers (DLs) and recipients who received refused DLs with respect to recipient gender, donor age, CIT, WIT and length of hospitalization post LT; however, there was no difference in PS of the two groups after adjusting for these LT variables.

·        GS is equivalent in LT with previously refused DLs compared with first offer DLs.

 

 


576. Sexual dysfunction before and after liver transplantation (LT).

L. Grellet; P. Perney; H. Rigole; Y. Duny; D. Larrey; F. Blanc; G. Pageaux 

 

Sexual disorders are frequently described in patients with cirrhosis, often related to the endocrine consequences of advanced liver disease. It is assumed that LT will help to recover from these symptoms.

 

Aim :

To report on the prevalence of sexual dysfunction in liver transplant patients before and after LT, emphasizing the potential recovery of pre-LT disorders and the occurrence of de novo post-LT disorders.

 

Methods :

During a direct interview, a sexual history was taken by a sexology medicine specialist in all liver transplant recipients seen at the out-patient clinic between may and december 2006. Exclusion criteria were : age < 18 or > 70, LT < 6 months, evolutive cancer, interferon treatment for HCV reinfection, severe renal or cardiac dysfunction. The following domains were assessed : hypoactive sexual desire in men and women, erectile dysfunction in men and inadequate vaginal lubrication in women, premature or delayed or absent ejaculation in men, orgasmic disorder in women, pain with intercourse in men, dyspareunia or vagisnismus in women.

 

Results :

93 pts fulfilled the inclusion criteria and 89 accepted to complete the study. There were 64 males, mean age 54 ± 9 yrs and 25 females, mean age 51 ± 10 yrs. Indication for LT were : alcoholic liver disease in 52, virus in 15, alcohol plus virus in 9, others in 13. The mean delay form LT was 55 months (6-225).

 

Evolution of sexual disorders before and after LT : hypoactive sexual desire was present in 29 % of male and 40 % of female, and improved in 73.6 % of male and 0 % of female. Erectile dysfunction was present in 39 % of male and improved in 68 % of them. Inadequate lubrication was present in 24 % of female and improved in none. Premature ejaculation was present in 21 % of male and improved in 7 % of them. Orgasmic disorder was present in 14 % of male and 36 % of female and improved in 66 % of male and 11 % of female. Pain was absent in male and present in 1 female before and after LT.

 

De novo sexual disorders after LT : hypoactive sexual desire was present in 6.2 % of male and 12 % of female. Erectile dysfunction was present in 14 % of male. Premature ejaculation was present in 3 % of male. Orgasmic disorder was present in 3 % of male.

 

Conclusion :

Sexual disorders were frequent in liver transplant patients before LT. They frequently improved after LT in male, but almost never in female. This point emphasizes the unclear impact of advanced liver disease in women’s sexual dysfunction. De novo sexual disorders after LT were unusual. Overall, 34.8 % of liver transplant recipients experienced sexual disorder. This will need further attention.

 


585. Trends in Liver Transplantation for Hepatocellular Carcinoma in the United States.

B. H. Leach; J. Prather; D. Scott; D. Norman; J. M. Schwartz 

 

Background:

Liver transplantation (LT) is an effective treatment for select patients with hepatocellular carcinoma (HCC). HCC patients who meet criteria are prioritized for liver allocation in 11 US geographic regions. It is unclear if the priority allocated for HCC accurately reflects risk of death or withdrawal from the waiting list. Furthermore, details regarding regional differences in transplantation rates, deaths on the waiting list or waiting list removal for HCC are unknown.

 

Aims:

1) To evaluate transplantation rates and waiting list mortality for HCC patients and non-HCC patients listed for LT, and 2) To compare regional rates of LT, waiting list mortality and waiting list removal in patients with HCC.

 

Methods:

Data regarding 71,428 adult deceased donor LT candidates who were on the list between February 2001 and January 2007 were obtained from the United Network of Organ Sharing. Patients with a primary or secondary diagnosis of HCC or those with an HCC exception were identified. Rates of transplantation, waiting list removal and death on the waiting list were expressed as the number of events/patient year according to the pre-MELD period and four periods of MELD priority assigned to HCC patients. Rates of transplantation, regional rates of transplantation for HCC, waiting list removal and waiting list mortality were compared using unadjusted crude rate analysis.

 

Results:

LT rates for HCC increased from 0.2/patient year prior to the MELD era to 1.5/patient year in MELD era 4 (p<0.05). HCC LT rates increased during the 4 MELD eras (1.1/patient year-1.5/patient year, (p<0.05). LT rates for HCC varied according to UNOS region (range 0.77/patient year in region 5 to 3.68/patient year in region 3, p<0.05). LT rates were higher for HCC patients compared to non-HCC patients (1.25/patient year vs. 0.28/patient year respectively, (p<0.05), and death rates on the waiting list were lower in HCC patients (0.08/patient year vs. 0.11/patient year, p <0.05). Waiting list removals were similar for HCC patients and non-HCC patients (0.27/patient year vs. 0.26/patient year respectively, p=NS).

 

Conclusions:

1) Rates of LT for HCC have increased, however, rates vary substantially according to geographic region; 2) Unadjusted waiting list mortality is lower in HCC patients than non-HCC patients despite equivalent drop out rates. Appraisal of the long term impact of allocation policies for HCC is therefore necessary to provide equitable access to LT.

 


589. Pre-transplant variables predict qualify of life in liver transplant recipients

S. Saab; B. Surti; A. Ibrahim; F. A. Durazo; S. B. Han; H. Yersiz; D. Farmer; R. M. Ghobrial; L. Goldstein; M. J. Tong; R. Busuttil 

 

Introduction:

With an increasing number of liver transplant recipients living, understanding quality of life issues is essential. Our goal is to specifically identify the pre-transplant predictors of post-transplant quality of life in liver transplant recipients. Understanding how these variables will affect quality of life can help determine if specific interventions will further improve quality of life post-transplant.

 

Methods:

Three hundred and eight adult liver transplant recipients seen at UCLA were administered the Short Form 36 and a questionnaire regarding work history and insurance coverage. Variables associated with post-transplant quality of life were studied in a multivariate analysis. Interaction terms were used to examine effect modification.

 

Results:

The mean age of participants (± standard deviation [SD]) was 51 (± 13.99) years. Most patients (50%) were transplanted for viral hepatitis. Post-transplant quality of life domains were associated with a number of pre-transplant factors: Physical Functioning (work hours, gender, ethnicity), Role-Physical (work hours, body mass index, renal failure, ascites, and pay change post transplant), Bodily Pain (ascites, pay change), General Health (encephalopathy, ascites), Vitality (ascites), Social Functioning (disease etiology, ascites), Role-Emotional (ascites), and Mental Health Factors (work hours).

 

Conclusions:

Our results demonstrate that pre-transplant factors such as work hours, body mass index, renal failure, and disease etiology predicted impaired quality of life in liver transplant recipients. In addition, pre-transplant manifestations of portal hypertension such as ascites and encephalopathy continue to affect patients even after transplantation. Interventions to modify these pre-transplant variables may further improve quality of life in liver transplant recipients.

 

Pre-transplant Variables

Quality of Life Domain that is Impaired

Coefficient

p-value

Ascites

Role-Physical

-11.73

0.01

Bodily Pain

-14.17

0.02

Social Functioning

99.58

0.04

Role-Emotional

-33.01

0.02

Encephalopathy

General Health

-16.70

0.02

Renal Failure

Role-Physical

-1.80

<0.01

Disease Etiology

Social Functioning

28.47

0.01

Work Hours

Role-Physical

0.32

<0.01

Mental Health Factors

0.54

0.05

Pay change

Role-Physical

-2.10

<0.01

Bodily Pain

-0.69

<0.01

General Health

-1.10

<0.01

Body Mass Index

Role-Physical

0.02

0.04

Gender

Physical Functioning

8.83

<0.01

Ethnicity

Physical Functioning

1.51

0.03

 


593. GB Virus-C Infection is Associated with Better 10-Year-Survival of Liver Transplant Recipients

K. Rifai; S. Pischke; S. Heringlake; H. Wedemeyer; J. Klempnauer; C. P. Strassburg; M. P. Manns; H. L. Tillmann 

 

Background & Aims:

We earlier demonstrated a beneficial influence of the GB virus C (GBV-C, or hepatitis G virus) on the long-term course of HIV infection. An influence of GBV-C on the short-term survival of liver transplant recipients was not observed. Here we describe the long-term outcome of patients with GBV-C after liver transplantation (OLT).

 

Methods:

We studied overall survival rates of 200 patients transplanted at our center between 1992 and 1996. GBV-C envelope antibodies (anti-E2) and RNA were tested directly before transplantation. 63/200 patients had anti-E2, 17 patients were viremic and in 8 patients both GBV-C antibodies and RNA were found. There were no differences regarding diagnosis, age or sex between the different groups. Survival rates were assessed in 2006, thus 10 years after OLT, by using Kaplan-Meier and Cox's regression analysis.

 

Results:

Overall 1-, 3- and 10-year patient survival rates were 75%, 69% and 56%. Mean patient and graft survival was 7,8±5,5 and 7,1±5,5 years, respectively. A worse outcome was found for patients requiring retransplantation (p<0.0001) and those with tumor disease (p<0.0001). If patients surviving at least 3 years were analysed, those who were GBV-C RNA positive had a significantly longer survival than RNA-negative patients. In Cox’s regression including patient age and sex, need of retransplantation and presence of tumor disease, GBV-C viremia (p<0.03) and absence of retransplantation (p<0.04) were independently associated with patient survival.

 

Conclusions:

·        Patients with active GBV-C infection showed longer survival after liver transplantation, once they survived the first 3 years.  This actually is in line with data from renal transplant recipients.

 

Discussion:

·        We would speculate that GBV-C might ameliorate immune activation status, explaining both improved outcome in HIV and organ transplantation. 

 


598. Hepatocellular Carcinoma (HCC) in Patients with HCV versus non-HCV Cirrhosis: Graft and Patient Survival after Liver Transplantation (LT) in Pre-MELD and MELD Era

P. J. Thuluvath; D. L. Segev 

 

HCC in the presence of HCV may have a worse outcome after LT because of the confounding effects of recurrent HCV and higher HCC recurrence. Our objective was to assess the survival of patients with HCC in those with HCV and non-HCV cirrhosis using UNOS database from 1994-2006.

 

Methods:

Patients with HCC were stratified into HCV (HCC-HCV) and non-HCV (HCC-non HCV)and also into MELD and pre-MELD era because of the potential impact of MELD on outcomes. In the pre-MELD era, there were 1,886 HCC patients (639 HCV, 1,079 non-HCV, HCV status unknown in 168) and during MELD era, there were 798 patients (283 HCV, 431 non-HCV and 84 unknown). For the purpose of this study, we analyzed patients with unknown HCV status separately (not shown). Comparative analysis was made of HCV (HCV) and non-HCV (non-HCV) patients without HCC after stratification as discussed above. We calculated unadjusted graft and patient survival rates (%) at 1, 3 and 5 years for pre-MELD and 1 and 3 years for MELD patients.

 

Results:

Pre-MELD era – graft survival rates for HCC-non HCV was higher than HCC-HCV patients at 1-yr (77.7 vs. 73.8), 3-yr (63.3 vs. 58.2) and 5 years (56.8 vs. 48.7); pre-MELD era patient survival was similar at 1-yr (80.7 vs. 79.4) and 3-yr (66.2 vs.64.5), and higher at 5-yr (59.9 vs.55.2) for HCC-non HCV. Pre-MELD era graft survival rates for patients without HCC in non-HCV at 1-yr (80.6 vs.79.7), 3-yr (74.4 vs. 69.3) and 5-yr (69.2 vs. 61.8) was also higher than HCV patients as expected; similar trend was also seen for patient survival at 1-yr (85.2 vs. 84.1), 3-yr (79.7 vs. 74.5) and 5-yrs (74.8 vs. 67.3).

 

MELD era – graft survival rates were similar for HCC-non HCV and HCC-HCV patients at 1-yr (83.7 vs. 82.7), but was higher at 3-yr (72.2 vs. 65.7); MELD era patient survival was similar at 1-yr (87.1 vs. 86.6) and was higher at 3-yr (77.3vs. 71.9). MELD era graft survival rates for patients without HCC in non-HCV at 1-yr (82.1 vs. 82.7) and 3-yr (74.5 vs. 69.7), and patient survival 1-yr (86.7 vs. 5.4) and 3-yr (81.3 vs. 76.5) showed similar trend. Survival differences showed similar trends as shown in the table.

 

Conclusions:

·        There has been an improvement in 3-year graft (8.9% for non-HCV, 7.5% for HCV) and patient (14.8% for non-HCV, 13.1% for HCV) survival in MELD era compared to pre-MELD era for HCC patients with similar trends in survival rates in HCV and non-HCV patients with and without HCC suggesting that lower survival in patients with HCV and HCC is mainly due to the confounding effect of HCV.

 

Graft Survival Difference (%)

Patient Survival Difference (%)

Year

1-yr

3-yr

5-yr

1-yr

3-yr

5-yr

Pre-MELD

Non-HCV vs. HCV (no HCC)

Non-HCV vs. HCV (HCC)

 

MELD

Non-HCV vs. HCV (no HCC)

Non-HCV vs. HCV (HCC)

 

+0.9

+3.9

 

+0.8

+1.0

 

+5.1

+5.1

 

+4.8

+6.5

 

+7.4

+8.1

 

NA

NA

 

+1.1

+1.3

 

+1.3

+0.5

 

+5.2

+1.7

 

+4.8

+5.4

 

+7.5

+4.7

 

NA

NA

 


601. Assessment of liver transplant candidates by an addiction medicine specialist : a prospective study.

H. Rigole; P. Perney; M. Bismuth; F. Navarro; D. Larrey; F. Blanc; G. Pageaux 

 

It is important, but not always performed, to ascertain an alcohol history in all patients undergoing liver transplantation (LT). However, the points of view of addiction specialists and LT specialists differ about their consideration of alcoholic disease.

 

Aim :

Assessment of alcohol behavior in LT candidates by an addiction specialist in order to appreciate this specific approach.

 

Methods :

All patients were seen during the pre-transplant evaluation by an addiction specialist. The diagnostic systems used to assess alcohol disorders were WHO classification, DSM-IV and Babor’s classification. The following characteristics were considered as predictive of severe alcohol relapse after LT : alcohol dependence, young age, number of withdrawals, family history of alcohol abuse, associated drugs addictions. During the evaluation, a brief intervention about alcohol disorders was performed, and a specific management of alcohol abuse was proposed, not imposed, to all patients with predictive factors of severe relapse after LT.

 

Results :

80 patients have been studied. The primary indication for LT was alcoholic liver disease (ALD) in 39 patients, HCV in 20 patients, HBV in 11 patients, others in 10 patients. Abnormal alcohol behavior was present in 57 of the 80 patients : the 39 ALD patients, 13 of 20 HCV patients, 5 of 11 HBV patients. Among these 57 alcohol abusers, 28 were excessive drinkers without dependence and 29 were alcohol-dependant : 19 of 39 ALD patients, 6 of 13 HCV patients, 4 of 5 HBV patients. Predictive factors of severe alcohol relapse after LT were found in 19 patients, 17 of alcohol-dependant patients and 2 of excessive drinkers. Only one of these 19 patients had accepted a pre-LT management of alcohol disorder. During the follow-up, 3 patients died, 1 was withdrawn from the waiting list, 41 are still on the waiting list and 35 have been transplanted : 20 ALD, 8 HCV, 7 others. With a mean follow-up of 6 months (3-16), no severe relapse was observed.

 

Conclusion :

A specific assessment of LT candidates by an addiction specialist has detected 71 % of alcohol abusers and 36 % of alcohol dependant patients. Moreover, among patients with viral liver disease, 58 % were alcohol abusers and 32 % were alcohol-dependant. Predictive factors of severe alcohol relapse after LT were found in 23,7 % of patients. Among these, the majority did not adhere to a rehabilitation program. The impact of the pre-LT brief intervention is under evaluation. These preliminary results are in favour of the intervention of an addiction specialist during the evaluation of LT candidates.

 


602. The Readability of Health Education Materials for Liver Transplant Patients

N. M. Lee; A. Muir; C. Brady 

 

The listing process for liver transplantation (LT) is complex and requires patients to comprehend their disease and aspects of LT care. However, millions of adult Americans are illiterate and may not benefit from printed LT educational tools. Laws require many public documents to be written at an eighth-grade level or lower to ensure readability.

 

Aims:

(1) To determine the readability of printed LT educational brochures,

(2) to quantify educational levels of patients listed for LT, and

(3) to determine if demographic factors are associated with patient educational level.

 

Methods:

We used the United Network for Organ Sharing database to identify U.S. citizens listed for LT from 1987 to 2005. Chi-squared analysis and t-tests determined the relationship between patient demographic factors and educational level. Readability of brochures was determined by using computer software that measured Flesch Reading Ease scores and Flesch-Kincaid grade levels. Reading ease scores range from 0 to 100, with lower scores indicating increased difficulty in readability.

 

Results:

Of 60,222 patients, 22,533 (37.42%) were female and 37,689 (62.58%) were male; 3043 (5.05%) had less than high school education; 57,179 (94.95%) had a high school education or above. Patients with less than high school education were more likely to be female, of older age, have Medicare or Medicaid, and be of Hispanic, Asian, or other race (table). Calculated Flesch-Kincaid grade levels and Reading Ease scores for brochures were: American Society of Transplantation: Getting a New Liver (6.2, 74.7), American Liver Foundation (ALF) Liver Transplant (6.6, 71.9), National Institutes of Health: What I Need to Know About Liver Transplantation (7.2, 67.5), American Liver Society LT brochure (7.3, 67.3), and ALF Facts on Liver Transplantation (11.4, 42.1).

 

Conclusions:

·        Most LT patients have completed at least the eighth grade and are likely to understand LT educational brochures.

·        However, the LT evaluation process may exclude many patients with poor literacy skills, and current brochures may be too advanced for those who are beginning to consider LT.

·        Future strategies for educating patients who are considering liver transplantation will need to involve efforts to effectively provide information to patients with poor literacy skills.

 

 

Less than high school

High school or above

p-value

 

Gender (%)

Male

Female

 

1702 (4.52)

1341 (5.95)

 

35,987 (95.48)

21,192 (94.05)

< 0.0001

 

Age (mean ± SD)

53.03 ± 9.88

49.79 ± 10.16

< 0.0001

 

Race (%)

White

Black

Hispanic

Asian

Other

 

1436 (3.15)

151 (3.26)

127 (19.60)

179 (9.22)

1150 (15.57)

 

44,176 (96.85)

4483 (96.74)

521 (80.40)

1762 (90.78)

6237 (84.43)

< 0.0001

 

Primary Pay (%)

Private

Medicaid

Medicare

Other government

Self

Other

 

1269 (3.15)

913 (10.83)

689 (8.29)

118 (5.41)

20 (4.21)

34 (5.96)

 

38,983 (96.85)

7521 (89.71)

7621 (91.71)

2063 (94.59)

455 (95.79)

536 (94.04)

< 0.0001

 


603. Long Term Outcomes Of Liver Transplantation In A High-MELD Cohort

J. Lee; M. Lee; L. Shapiro; A. L. Yang; A. S. Lapasaran; S. Parvez; A. Kamal; E. B. Keeffe; C. O. Esquivel; A. Ahmed 

 

BACKGROUND:

MELD scores predict both pre-transplant and post-transplant mortality. Diabetes mellitus has also been shown to predict post-transplant mortality, but the relative importance of these two factors remains unknown.

 

METHODS:

We reviewed all adult liver transplants performed at our institution between February 1995 and June 2006. Of 530 transplants performed, information regarding MELD score and the presence or absence of diabetes was available for 431. Patients with acute liver failure (n=17), those undergoing kidney-liver transplant (n=28), and those who died prior to discharge (n=51) were excluded. The remaining 370 patients were divided into four groups, based on MELD score (<30 or ≥30) and the presence or absence of diabetes.

 

RESULTS:

As expected, survival was poorer in the high MELD group (Log-rank statistic 23.2, p<0.001). However, patients with a MELD score ≥30 and without diabetes had a similar outcome as patients with a MELD score less than 30 and with diabetes (Log-rank statistic 0.51, p =0.47). The outcome was poor in patients with diabetes and MELD ≥30, but the observation in this group was limited by a small sample size and needs to be studied further.

 

CONCLUSIONS:

Our results suggest that patients with MELD score ≥30 in the absence of diabetes have a favorable post-transplant outcome. The presence or absence of diabetes appears to limit the reliability of MELD score as an allocation system for liver transplantation and its ability to predict post-transplant survival outcomes. Further validation studies are needed to assess the impact of diabetes on MELD score.

 

 

MELD < 30

MELD ≥ 30

-DM

+DM

-DM

+DM

Number of Patients

254

55

54

7

Mean Age (yr)

50.1

54.4

47.8

51.3

Mean BMI (kg/m2)

27.1

28.2

26.9

27.9

Hepatitis C (%)

48

53

31

86

Overall Survival (%)

95

82

89

71

Mean Follow-up (yr)

4.99

3.88

3.38

1.49

 


611. Development of a UK Score for Patients with End-stage Liver Disease

K. M. Barber; S. E. Pioli; J. E. Blackwell; D. Collett; J. M. Neuberger; A. E. Gimson 

 

Background:

Although the MELD score is widely used to predict mortality on the liver transplant list, it has not been validated for use in the UK. A score for UK patients with end-stage liver disease has therefore been developed.

 

Methods:

The study cohort comprised adult elective patients registered for their first liver transplant at the 7 UK centres between 1 April 2003 and 31 March 2006. Patients were followed-up until death, liver transplantation or last known follow-up. Patients with any type of cancer recorded as their primary liver disease were excluded. The resulting cohort comprised 1,103 patients. Cox proportional hazards models were used in modelling the hazard of death on the list. The clinical components considered for inclusion in the UK specific score, termed UKELD, were INR, serum creatinine, bilirubin and sodium, and the UKELD score was expressed as a linear combination of the logarithms of the clinical components. The UKELD score was compared to MELD and MELD-Na by computing the change in the log likelihood (-2logL) statistic on adding each of the three scores to a Cox model that included relevant patient-specific factors. The UKELD score was validated using data from the 7 UK centres on adult elective patients registered for their first liver transplant between 1 April 2006 and 31 March 2007. The resulting cohort comprised 452 patients. The patients in the validation cohort were divided into 3 groups based on their risk score, with patients having a high, medium and low score. The Kaplan-Meier estimate of the survivor function for each group was then compared to the model based estimates of the survivor function, adjusted for patient specific-factors.

 

Results:

The UKELD score is calculated using the following formula:

UKELD=[(5.395xln(INR))+(1.485xln(creatinine))+(3.13xln(bilirubin))–(81.565xln(sodium))]+435

 

The results from the validation confirmed this score is an appropriate measure of disease severity for UK patients. As UKELD increases the risk of death on the transplant list also increases. UKELD was found to be a superior predictor of mortality on the transplant list compared to MELD and MELD-Na.

 

Conclusion:

The UKELD score is deemed appropriate to use to predict mortality on the transplant list for UK patients with end-stage liver disease. Patients with cancer and those with other variant diseases may need to be awarded additional UKELD points to avoid disadvantaging them.

 


612. Proposal of New Selection Criteria for Living Donor Liver Transplantation Candidates for Hepatocellular Carcinoma.

A. Taketomi; K. Sanefuji; T. Iguchi; H. Kayashima; N. Harada; K. Sugimachi; Y. Yamashita; T. Ikegami; T. Yoshizumi; Y. Soejima; Y. Maehara 

 

Introduction:

The Milan criteria have been accepted as the selection criteria for hepatocellular carcinoma (HCC) patients. However, many patients who did not meet the Milan criteria have survived after undergoing living donor liver transplantation (LDLT). As a result, different patient selection criteria are thus considered to be necessary in LDLT in order to save as many individuals as possible with advanced HCC.

 

Patients and Methods:

Of 214 adult-to-adult LDLT patients, 90 with concurrent HCC were included in the study. The mean age of the patients was 56.8 years old (range: 21 to 70). Sixty-five patients (72.2%) suffered from a hepatitis C virus infection. The overall survival rates according to various factors were compared to identify the risk factors for survival and to establish new selection criteria for LDLT candidates for HCC.

 

Results:

Fifty-three patients (58.9%) preoperatively exceeded the Milan criteria. The 1-, 3- and 5-year overall survival rates of the patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those for patients who exceeded the criteria were 85.5%, 68.2%, and 68.2%, respectively. In a multivariate analysis, both the tumor diameter (p=0.0187) and the des-gamma-carboxy prothrombin value (DCP; p=0.026) were found to be favorable independent factors of survival after LDLT. Therefore, the authors devised new selection criteria for HCC patients (which are named the KU criteria; a tumor diameter of less than 5 cm or a DCP of less than 300 mAU/ml). The 1-, 3- and 5-year overall or recurrence-free survival rates of the 85 patients who met the KU criteria were 92.1 / 85.2 / 85.2% or 90.6 / 87.1 / 87.1%, respectively, which were significantly different from those of the 5 patients who did not meet the KU criteria (80 / 20 / - % or 20 / 0 / 0 %; p< 0.0001).

 

Conclusions:

A combination of two factors, namely the tumor size and the DCP level, was found to be useful for predicting survival after LDLT. These new selection criteria (the KU criteria) might therefore be useful for expanding the selection of LDLT candidates for HCC.

 

 


616. Transplant costs of adult living donor liver transplantation at an experienced transplant center are similar to deceased donor liver transplantation despite increased surgical costs

J. C. Lai; J. C. Emond; R. S. Brown 

 

BACKGROUND:

The growing deficit of organs available for transplantation warrants continued evaluation of the application of adult living donor liver transplantation (LDLT). Several studies have reported the costs of deceased donor liver transplantation (DDLT), but data regarding the costs of LDLT are limited by including early experience, which is associated with increased complication rates, and small sample sizes.

 

AIM:

To provide a comparison of transplant hospitalization costs of LDLT vs DDLT after the initial experience. METHODS: This was a retrospective cohort of consecutive patients who received liver transplants at our institution from 1/1/00–12/31/06 for whom financial data were available. Our primary outcome was cost, estimated from total charges of the transplant hospitalization (converted into relative cost units), including donor charges for LDLT. All charges were classified into cost categories, including: floor services, diagnostics, laboratory, surgical, pharmacy, and other services. Our independent variable was type of transplant (LDLT/DDLT). Covariates included age, sex, race, insurance status, MELD, and length of stay (LOS). Any variable associated with total costs (p<.2) in bivariate analysis was included in multivariate analysis (MVA) with and without LOS as a covariate.

 

RESULTS:

This study included 469 patients (n=84 LDLT vs n=385 DDLT). Baseline characteristics differed substantially between LDLT and DDLT, including age (50 vs 54 yrs, respectively), %male (51% vs 74%), pre-transplant MELD (20.6 vs 23), %white (62% vs 48%), %black (1% vs 12%), %Hispanic-white (30% vs 18%), and %other (7% vs 22%). LOS and insurance status were similar. Total charges for LDLT were 5% lower than for DDLT, but this was not statistically significant (Table). Cost category analysis revealed increased surgical charges for LDLT, but decreased charges for labs and pharmacy (Table). In MVA, LDLT was similar in cost to DDLT after adjustment for age, black race, private insurance, and MELD score, both with (p=0.53) and without (p=0.31) adjustment for LOS. Age, MELD, and black race did predict higher cost.

 

CONCLUSION:

In a comparison of the financial costs of LDLT vs DDLT at an experienced transplant center, overall transplant costs of LDLT were similar to DDLT, despite increased surgical costs.

 

Table: Comparison of total and select cost category charges, in relative cost units

Description

LDLT(n=84)

DDLT(n=385)

p value

Total

 

160,253

168,081

0.58

 

Surgical

35,117

20,992

<0.01

Laboratory

20,054

28,159

<0.01

Pharmacy

12,594

23,272

<0.01

 


617. Successful Algorithm for Selective Liver Biopsy in the Right Lobe Liver Donor (RLD)

M. Simpson; J. E. Verbesey; U. Khettry; F. Gordon; J. J. Pomposelli; R. L. Jenkins; E. A. Pomfret 

 

Background.

Routine vs. selective pre-donation liver biopsy (LBx) remains controversial for assuring the safety of RLD. We report the results of our selective algorithm for LBx in RLD.

 

Methods.

Between 12/99 and 3/07, 380 potential RLD were evaluated and 131 donated. Indications for selective LBx were: abnormal liver function tests, abnormalities noted on imaging studies, BMI>28, and a genetic relation to a recipient with immune mediated liver disease. All donors had a LBx at the time of surgery. The same pathologist reviewed all LBx.

 

Results.

Of the 380 potential RLD evaluated (53.9% male, mean age 37.6), 139(36.6%) were accepted as donors, 140(36.8%) were rejected for either donor or recipient reasons, 68(17.9%) withdrew from the process, 23(6.1%) had their recipient receive a deceased donor graft, and 10(2.6%) are currently completing evaluation. 81(21.3%) met criteria and had a selective LBx. 7 results are still pending. 58(78.4%) had either normal (n=21) or mild macrosteatosis of 0-5%(n=37) and 40 of these went on to LD right hepatectomy (LDRH). 12 RLD were eliminated as donors as a result of abnormal LBx. Of the 89 who did not have LBx, none had abnormal liver histology at LDRH. 3/81 (3.7%) had complications from the LBx resulting in overnight admission (2 for pain, 1 for bleeding, transfusion not required).

 

Conclusions:

Use of this algorithm for selective pre-donation LBx in the RLD resulted in 78.7% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for LBx. Routine pre-donation LBx is unnecessary in potential RLD.

 


618. High MELD scores do not predict one-year survival rate of patients with a small-for-size graft in adult living donor liver trasplantation

N. Yi; K. Suh; H. Lee; W. Shin; J. Yoon; K. Lee 

 

Introduction

Adult living donor liver transplantation (ALDLT) had shown comparable outcome to the deceased donor recipients because of being better risk candidates. However, outcome of very ill patients with high MELD score is fairly elusive especially in small grafts (< 0.8% of graft-to-recipient weight ratio, GRWR) in ALDLT.

 

Methods

Between 1999 and 2005, consecutive 167 hepatitis B virus-infected recipients underwent ALDLT at our center. Based on pre-transplant MELD, recipients were stratified as low risk (≤25, Group L, n=105) and high risk (>25, Group H, n=62). To analyze the risk of graft size in very ill patients, patients were divided HR (high risk group; MELD score >25 and GRWR < 0.8%), LR (low risk group; MELD >25 or GRWR <0.8%), and NR (no risk group; MELD ≤25 and GRWR ≥ 0.8%) group. Primary end points were one-year patient survival. Post-transplant follow-up was 32.6 months.

 

Results

Mean MELD scores were 17.1 in Group L and 32.6 in Group H. In pre-transplant recipients’ dada, Group H more frequently had uncontrolled ascites (50.0%), encephalopathy (64.5%), bacterial peritonitis (48.4%), and UNOS status 2A (38.7%) than Group L (27.6%, 30.5%, 27.6% and 4.8%) (p<0.05). Accompanying hepatocellular carcinoma (HCC) was more common in Group L (61.0%) than in Group H (22.6%) (p=0.000). Mean hospital stay were 33 days in Group L and 47 days in Group H (p=0.000). One-year patient survival rate (1-YSR) was 86.7% in Group L and 83.8% in Group H, respectively (p=0.48). There was no significant difference in 1-YSR among HR (72.7%), LR (84.6%), and NR (88.5%) group, respectively (p=0.278). Multivariate analysis revealed accompanying HCC and early transplant year to be risk factors of with poor 1-YSR (p<0.05).

 

Conclusion

·        In summary, outcome including 1-YSR of Group H in ALDLT was similar to group L.  In subgroup analyses high risk group had lower 6 mo survival than the others, but its 1-YSR was similar to the others.  In addition,  accompanying HCC and the year of transplant , but not MELD score (≥ 25) must not be excluded in ALDLT candidates. 

·        However, during early post-transplant period critical care must be given if they had small for size graphs.

·        Accumulation of center’s experience may improve the early post-transplanted survival in very ill patients in ALDLT.

 


621. Use of Donation-after-Cardiac-Death (DCD) Donors for Combined Liver and Kidney Transplantation

W. R. Hewitt; J. Stauffer; M. Mai; H. Grewal; L. Arasi; B. Rosser; D. Kramer; J. Canabal; J. H. Nguyen; H. Wadei; N. Ahsan; D. Willingham; A. Keaveny; J. Aranda-Michel; D. M. Harnois; R. Satyanarayana; R. C. Dickson; T. Gonwa; C. B. Hughes 

 

Renal failure is a common complication of end-stage liver disease and is increasingly recognized among candidates for liver transplantation (LT). Outcomes are clearly superior when such patients undergo combined liver and kidney transplantation (LKT). However, this approach increases the demand for kidney donors. Donation after cardiac death (DCD) successfully expands the donor pool to provide isolated kidney and liver allografts. We sought to investigate the outcomes after combined LKT with DCD and non-DCD organs at our institution.

 

METHODS:

A retrospective review of all patients who received an LT at our center from 04/2000 until 02/2007 was conducted. A total of 1361 LTs were performed during that time. Of these, 39 (2.9%) had a LKT transplant, 9 received DCD organs. Liver and kidney graft cold ischemia times (CIT) were recorded. These patients were then analyzed and their outcome was compared to the 30 non-DCD LKT.

 

RESULTS:

In the LKT recipients 41.0% were diabetic, 48.7% required renal replacement therapy (RRT) pre-transplant and 33.3% required RRT post-operatively. None of the transplants utilized HBcAb-positive grafts and 1 non-DCD recipient received a HCV-Ab + graft. There was no significant difference in patient characteristics or transplant outcomes other than initial hospital length of stay (LOS).*

 

The one-year patient survival for DCD LKT was 88.9% compared to 83.3% with non-DCD LKT. The one-year liver and kidney graft survival for the DCD group was 77.8% and 88.9%, respectively. Glomerular Filtration Rate at one year after LKT was 55.0 ± 30.4 and 46.8 ± 18.3 ml/min for non-DCD (n=20) and DCD (n=4) grafts, respectively.

 

CONCLUSION:

The use of DCD organs for solitary liver transplant or solitary kidney transplant is well described. The combination of the two has not been well defined. Despite the higher incidence of need for RRT and longer hospital stay the utilization of DCD donors provides comparable graft and patient survival and should be considered for patients requiring combined liver and kidney transplants.

 

Pt Characteristics

 

DCD (n=9)

non-DCD (n=30)

p-value

Age at Tx (yrs)

56.3 ± 10.2

55.3 ± 8.9

0.77

Donor Age (yrs)

32.4 ± 13.4

34.9 ± 16.4

0.68

MELD

25.2 ± 6.7

22.4 ± 6.2

0.24

RRT post-Tx

5 (56%)

8 (27%)

0.11

Liver CIT (hr)

6.27 ± 1.4

7.0 ± 1.3

0.18

Kidney CIT (hr)

8.2 ± 2.3

9.7 ± 1.9

0.06

LOS (d)

23.1 ± 14.3

12.7 ± 9.6

0.02*

 


624. Does Health Related Quality of Life Correlate with the Model for End Stage Liver Disease Score Before Liver Transplantation?

E. T. Castaldo; R. T. Russell; I. D. Feurer; C. Pinson 

 

Introduction:

With minimal existing data our primary aim was to correlate the model for end-stage liver disease (MELD) score pretransplant and quality of life after liver transplantation (LT).

 

Methods:

A single institution prospective study of all patients undergoing first time LT over a 4-year period was conducted. Patients were given the SF-36 at 1, 3, 6, or 12 months post-LT. MELD was calculated the day of LT. Simultaneous multiple regression-based path analysis was used to test the effects of MELD, diabetes, diagnosis, length of stay (LOS), time post-LT, rejection, and the contemporaneous Karnofsky performance score (KPS), on the physical component (PCS) and mental component (MCS) summary scales of the SF-36.

 

Results:

There were 209 participants. Diabetes, LOS, and rejection were associated with worse KPS (p≤0.02) whereas time post-LT was associated with an improved KPS (p<0.01). Factors influencing quality of life measured by PCS and MCS of the SF-36 are shown in the table.

 

Conclusions:

Increasing MELD score was associated with improvement in PCS. MELD did not affect MCS. Functional performance, measured by KPS, had the largest effects on post-LT quality of life. Since good quality of life can be expected even with higher MELD scores, they should not discourage transplantation.

 

Factors Influencing Quality of Life

Variable

PCS

MCS

MELD

β=0.16, p=0.01

NS

Diabetes

NS

NS

Cholestatic Cirrhosis

β=0.12, p=0.05

NS

Acute Hepatic Failure

NS

NS

Neoplasm

β=0.23, p<0.01

NS

Autoimmune Disease

β=0.18, p<0.01

β=0.16, p=0.02

LOS

NS

NS

Time post-LT

β=0.16, p=0.01

NS

Rejection

NS

NS

KPS

β=0.49, p<0.01

β=0.25, p<0.01

Values shown are standardized correlation coefficients. Note: NS = non significant.

 


625. Should donor organs and recipients be matched in liver transplantation? An analysis of the United Kingdom and Ireland Liver Transplant Database

M. F. Dawwas; D. Collett; K. M. Barber; C. J. Watson; J. M. Neuberger; A. E. Gimson 

 

BACKGROUND

The prevailing practice of matching liver transplant donors and recipients according to their respective risks of graft failure is predicated on the tacit assumption that the adverse effects of a high-risk graft are minimized in a low-risk recipient. The evidence-base supporting this practice is currently unclear.

 

METHODS

Using the UK and Ireland National Transplant Database, we examined the effect of the interaction between donor characteristics and recipient characteristics on the risk of graft loss (defined as graft failure or death whichever occurred first) among adult first single-organ liver transplant recipients in the two countries between 1 March 1994-31 October 2006 (n=6,658). Donors were categorised as high- or low-risk using the 75th centile of the UK and Ireland Donor Risk Index (UKDRI) as a threshold. Recipient risk was categorised as high, medium or low using the highest, middle two and lowest quartiles of the MELD score, respectively. Cox regression models including UKDRI and MELD with and without their interaction terms were fitted and compared using the likelihood-ratio test to determine whether the increased relative risk (RR) of graft loss for high-risk organs was consistent across the MELD categories. RR estimates by UKDRI in high, medium and low MELD categories were derived from Cox models including the interaction terms, stratified by transplant centre, with and without adjustment for other recipient risk factors and year of transplant.

 

RESULTS

Recipients in the lowest MELD score quartile received a significantly greater proportion of high-risk livers than those in the highest MELD quartile (27.4% vs. 21.9%, p<0.001). High-risk donor organs conferred a greater risk of graft loss across all recipient risk categories (table 1). The magnitude of the risk increase was similar in the first year but was modestly greater in high-risk recipients thereafter.

 

CONCLUSIONS

Both high- and low-risk recipients experience a significantly greater, albeit unequal, risk of graft loss when receiving high-risk organs. Given their substantially different mortality risks without transplantation, these results question the wisdom of the current practice of allocating high-risk organs to low-risk recipients in preference to high-risk recipients.

 

ENDPOINT

MELD CATEGORY

UKDRI/MELD Interaction

Low

Medium

High

RR (95%CI)

P-value

RR (95%CI)

P-value

RR (95%CI)

P-value

P-value

Overall

unadjusted

 

adjusted

1.30 (1.05-1.60)

1.33 (1.07-1.65)

<0.02

 

<0.01

1.43 (1.21-1.70)

1.48 (1.25-1.76)

<0.001

 

<0.001

1.81 (1.50-2.18)

1.85 (1.52-2.24)

<0.001

 

<0.001

0.03

 

0.03

90 days

unadjusted

 

adjusted

2.01 (1.47-2.73)

2.23 (1.64-3.04)

<0.001

 

<0.001

1.98 (1.58-2.46)

2.16 (1.73-2.71)

<0.001

 

<0.001

2.00 (1.59-2.52)

2.09 (1.65-2.65)

<0.001

 

<0.001

0.9

 

0.9

1 year

unadjusted

 

adjusted

1.59 (1.22-2.06)

1.72 (1.32-2.24)

<0.001

 

<0.000

1.62 (1.33-1.98)

1.75 (1.44-2.14)

<0.001

 

<0.001

1.83 (1.47-2.26)

1.90 (1.52-2.37)

<0.001

 

<0.001

0.5

 

0.7

3 years

unadjusted

 

adjusted

1.36 (1.08-1.70)

1.43 (1.13-1.80)

<0.009

 

<0.003

1.49 (1.24-1.80)

1.58 (1.31-1.90)

<0.001

 

<0.001

1.70 (1.38-2.08)

1.74 (1.41-2.16)

<0.001

 

<0.001

0.3

 

0.3

5 years

unadjusted

 

adjusted

1.33 (1.08-1.65)

1.38 (1.11-1.72)

<0.008

 

<0.004

1.42 (1.18-1.70)

1.48 (1.23-1.78)

<0.001

 

<0.001

1.73 (1.43-2.11)

1.77 (1.45-2.17)

<0.001

 

<0.001

0.1

 

0.1

 


626. Liver Transplantation for Hepatocellular Carcinoma : Validation of a new Prognostic Score Predicting Overall Survival

T. Decaens; F. Roudot-Thoraval; H. Badran; C. Meyer; F. Durand; R. Adam; O. Boillot; C. Vanlemens; J. Gugenheim; S. Dharancy; P. Bernard; P. Compagnon; Y. Calmus; J. Hardwigsen; C. Ducerf; G. Pageaux; M. Hilleret; O. Chazoullieres; D. Cherqui; C. Duvoux 

 

Aim:

To provide a new prognostic score for refining the prediction of disease-free survival after LT for HCC, using variables assessable pre-operatively and to compare the prognostic value of this model with Milan criteria.

 

Patients and Methods:

The prognostic model was derived from the multivariate Cox model analysis of a series of 373 patients (training cohort (TC)) without portal thrombosis, transplanted for HCC (1988-1998) in 14 centers. 3 independent predictors were identified: maximal diameter (p<0.0001), tumor differentiation (p<0.0001) and number of nodules (p=0.0001). Regression coefficients were estimated for each class of the variables, and a discrete prognostic score was derived. The score was subsequently simplified by linear transformation of the regression estimates. Two different prognostic groups were identified on the TC: group A < 3 points and group B > 4 points. The score was subsequently tested in a validation cohort (VC) of 128 patients transplanted for HCC (1999-2001) in 7 centers.

 

Results:

Overall 5-year survival rate was 61.0±2.6% in the TC and 83.8±2.9% in the VC (p=0.0001). In the TC, 5-year survival was 66.8±3.2% in group ATC and 42.6±5.0% in group BTC (p<0.0001). The difference between the 2 groups persisted in the VC despite an overall better prognosis: 5-year survival: 89.0±3% vs 57.9±11.3% in groups AVC and BVC, respectively (p=0.014). In addition, although 5 year survival was significantly better in group ATC vs group AVC (p= 0.004), it did not differ between group BTC and group BVC (p=0.22). In the VC, (a) among the Milan+ patients, 94 patients were in group A and 4 in group B with a 5-year survival of 87.2±3.4% and 50.0±25.0% respectively (p=0.017) and (b), in Milan negative patients, 15 patients were in group A and 15 in group B with a 5-year survival of 100.0±0.0% and 60.0±12.6%, respectively (p=0.01).

 

Conclusion:

This study shows that the use of a prognostic model taking into account tumor differentiation improves Milan criteria accuracy and suggests that incorporation of tumor differentiation in the decision–making algorithm for selection of HCC candidates must be considered.