Sunday Liver Transplantation Topic Forum

 

201. Non-utilization of livers from deceased donors who successfully donate another solid organ: How often and the role of donor age and obesity

G. Sayuk; T. Leet; M. Schnitzler; P. H. Hayashi

 

Background:

Livers from deceased donors who donate at least one other solid organ are not always utilized.

 

Hypothesis:

Increased donor age and obesity leads to liver non-utilization in donors who successfully donate another organ.

 

Aim:

To determine the proportion of liver non-utilization and associated risk factors in these deceased donors.

 

Methods:

We did a nested, case-control study using the UNOS deceased donor database from 1987 to 2005. Only those donating at least one solid organ were included. Donation was defined as engraftment into a recipient. A case was a donor whose liver was not engrafted (LNE); controls were donors whose liver was engrafted (LE). We did univariate & multivariate analyses with donor age & obesity (BMI>30 kg/m2 or 95th weight percentile for pediatric donors) variables. Covariates included non-heart beating donor (NHBD), inotropic support, serum Na, death by cardiovascular or intracranial bleed event (CV/ICH), viral serologies, cancer, diabetes, hypertension, AST, bilirubin, blood group, race & gender. Similar analyses were done for LNE subgroups: liver not recovered (NR), recovered but not transplanted (RNT), recovered not for transplant (RN4T), consent (for liver) not obtained (cNO) or requested (cNR).

 

Results:

LNE occurred in 25% (23,373) of 91,362 deceased donors who successfully donated another organ. This percent has fallen significantly over time (’87-90: 48%, ’91-95: 29%, ’96-00: 21%, ’00-05: 16%, p<0.05). Of LNE’s, 12,788 (55%) were NR, 5258 (23%) were RNT, 2414 (10%) were cNR (for liver), 2141 (9%) were cNO, & 772 (3%) were RN4T. On univariate analysis, increased age & obesity were associated with LNE (p<0.05). On multivariate analysis, increased age (e.g. OR: 2.5, 2.2-2.9, p<0.01 for 50-60 year olds) and obesity (OR 2.1, 1.9-2.3, p<0.01) remained significant. Significant covariates included NHBD, high bilirubin, high AST, positive anti-HBc and antiHCV serologies. Adjusted population attributable risks were highest for age over 49 (13.7%), obesity (8.8%) & elevated AST (16.7%). Analysis across 5-year intervals and for LNE subgroups NR, RNT and RN4T yielded similar results. cNO & cNR were associated with NHBD, CV/ICH, bilirubin and AST, but not age or obesity.

 

Summary:

LNE in these otherwise suitable donors has declined over time but remains significant. LNE was associated with age & obesity, but LNE from lack of consent was not.

 

Conclusion:

The decline in LNE is likely due to the rise in demand for livers and use of extended criteria. Further decreases in LNE may be hindered by aging and increased obesity in the general population. Lack of consent in LNE should be explored further.


202. Overall and post-liver transplant (OLT) outcomes of patients listed for HBV-hepatocellular carcinoma (HCC) are similar to those listed for HBV-cirrhosis: data from the US HBV-OLT study

S. N. Wong; R. Reddy; E. Keeffe; S. Han; R. Perrillo; T. Tran; T. Pruett; A. S. Lok

 

Background:

Patients with HCC receive higher MELD scores and may be transplanted earlier than those with cirrhosis, potentially decreasing mortality on the waiting list. However, survival post-OLT may be reduced by recurrence of HCC.

 

Aims:

To compare the rates of major outcomes (OLT, death, disease [HBV and HCC] recurrence) between patients listed for HBV-cirrhosis (Gp 1) and patients listed for HBV-HCC (Gp 2), and to determine independent predictors of death and disease recurrence.

 

Methods:

All HBV patients with cirrhosis or HCC listed for primary OLT in the US HBV-OLT study were included. Survival, disease recurrence, and probability of OLT were estimated by Kaplan-Meier analysis. Significant factors on univariate analysis were entered into a Cox regression hazard model.

 

Results:

A total of 279 patients (Gp 1=183; Gp 2=96) were included. Gp 2 patients were older and more likely to be Asians, while Gp 1 patients had more severe liver impairment (MELD 15 vs. 9.5; p<0.001). After a median follow-up of 29 months (12-46, 25-75% quartile) from listing, 17 patients in Gp 1 and 4 in Gp 2 died before OLT and 10 and 8 died after OLT. Overall survival was similar despite a higher rate of OLT in Gp 2. MELD score at listing (Hazard ratio [HR]: 1.1; 95% CI: 1.05-1.14) and being transplanted (HR: 4.5; 95% CI: 1.97-10.15) were independently associated with overall survival. Ninety-four (51%) Gp 1 and 74 (77%) Gp 2 patients underwent OLT. Two Gp 2 and no Gp 1 patient were delisted due to worsening disease. After a median of 18 months (9-33, 25-75% quartile) post-OLT follow-up, 5 Gp 1 and 7 Gp 2 patients had HBV recurrence, and 6 Gp 2 patients had HCC recurrence. Post-OLT survival, HBV recurrence, and disease recurrence-free survival were similar in the 2 groups. HCC recurrence (HR: 5.7; 95% CI: 1.03-31.36) was the only independent predictor of post-OLT survival (p=0.046).

 

Conclusions:

Despite more advanced liver disease and a lower rate of OLT, overall survival of patients listed for HBV-cirrhosis was comparable to those listed for HBV-HCC, possibly related to beneficial effects of antiviral therapy. Higher MELD scores and absence of OLT predicted overall mortality, while recurrence of HCC adversely affected post-OLT survival.

 

Probability (%)

Gp 1

Gp 2

p-value

Overall survival*

97, 86, 76

90, 85, 72

0.859

Death without OLT*

8, 12, 24

5, 5, 19

0.538

OLT*

35, 53, 66

62, 83, 86

<0.001

Post-OLT survival^

93, 90

91, 83

0.615

HBV recurrence^

2, 10

6, 11

0.421

Disease recurrence^

2, 10

12, 19

0.062

Disease recurrence-free survival^

93, 82

84, 78

0.328

 

 

 

 


204. Race Influences Access to Liver Transplantation and Mortality on the Waiting-List

O. Khokhar; N. Ganeshan; L. Johnson; k. Shetty

 

African-Americans(AA)are believed to have reduced access to various medical therapies; however, objective race-specific data examining utilization of liver transplantation(LT)are sparse.

 

Aims :

To compare AA and Caucasians with regard to (a) severity of liver disease at the time of listing for LT, as measured by the Model for End-stage Liver Disease (MELD)score (b) mortality on the waiting list.

 

Methods:

This was a retrospective analysis of the United Network for Organ Sharing (UNOS) database on OLT registrants from 1997 to 2001, aged between 18 and 70 years. Individuals lacking information on the variables essential for calculation of the MELD score were excluded,as were those designated as Hispanic. The Mann-Whitney t-test was used to compare continuous variables, and the log-rank test to compare means. The Kaplan-Meier method was used to compute transplant-free survivals on the waiting list.

 

Results :

A total of 4853 patients were included, over 85% of these were Caucasian, and 60% were male. African-Americans accounted for 7.5% of those listed. The overall rate of deceased donor transplantation was 28.5%, and the mortality rate on the waiting list was 23.3%. The mean MELD score among AA at the time of listing was 23 compared to 16 in Caucasians, p=0.034.Mortality on the waiting list was significantly higher among AA than among Caucasians ( 28. 5 % vs 21.7%, p = 0.02) The rate of transplantation at 4 years from the time of listing was similar among AA and Caucasians,as was the time to transplantation.This data is summarized in table 1. Predictors of mortality on the waiting list were: age > 55 yrs, AA race, MELD score.

 

Conclusions

(1) AA have a lower rate of registration on the LT waiting list than would be expected from their representation in the US population (2) AA are listed at a more advanced stage of disease severity, i.e higher MELD scores, than are Caucasians, presumably due to delayed diagnosis and referral for transplantation. (3) The mortality of AA on the waiting list is significantly higher than that of Caucasians (4) Once listed for OLT, AA have similar rates of transplantation and waiting times. Our data suggests a marked disparity in referral patterns and access to liver transplantation among different racial groups, resulting in greater mortality without benefit of transplantation in African-Americans.

 

 

All Races

African-Americans

Caucasians

p Value

MELD score at listing

17

23

16

0.03*

Mortality on Waiting-List (%)

23.3

28.5

21.7

0.02*

Time to OLT (days)

307

282

314

NS

Rate of OLT within 4 years(%)

28.5

28

29.4

NS

 


205. Psychosocial Characteristics of Living Liver Donors

A. Bhushan; S. Cotler; S. J. Cotler

 

Living liver donors (LD) volunteer to undergo a major surgery for the sole purpose of helping a loved one. The behavioral and psychological features of this fascinating group of people have not been well characterized.

 

Aim

The aim of this study was to use a behavioral health inventory to gain insight into the traits of LD.

 

Methods:

Living liver donor candidates were asked to complete the Millon Behavioral Medicine Diagnostic (MBMD) during the evaluation process. The MBMD is a validated, 164 item survey that provides a detailed assessment of behavioral health domains. Computer scoring generates normalized standard scores on a 100 point scale with 0-35 representing low values and >85 representing high values. Accompanying interpretative reports address negative health habits, psychiatric status, style of coping with illness, stress moderators, treatment prognostics, and psychosocial attitudes. LD demographic data, post-operative pain medication use, and number of post-operative outpatient visits were collected.

 

Results:

Subjects consisted of 11 LD who completed the MBMD. Six (55%) were female, 9 (82%) were White, and 2 (18%) were African American. Four (36%) subjects were married and 7 (64%) were single. Only 3 (27%) had more than a high school education. All of the LD had successful recoveries. LD had standard scores of 25±14 for anxiety and 22±16 for depression, well below the normative mean. The personality profiles consisted of standard scores for sociability (67±13) and confidence (74±13) that were well above the normative mean. In qualitative analysis, LD presented themselves as calm, nonchalant, self-assured, and as people who did not take illness very seriously. Moreover, illness apprehension scores were low (29±18). Standard scores on the category of problematic compliance were strikingly elevated (64±29), whereas reported pain sensitivity was quite low (22±10). The sample was dichotomized between deep spiritual and religious convictions (5/11) and those who reported a complete absence of spirituality (5/11). There were no consistent relationships among the MBMD domains and post-operative pain medication use, length of hospital stay, or number of follow-up outpatient visits.

 

Conclusions:

The MBMD generated detailed psychosocial profiles of living liver donors that could be useful in assessing liver donor candidates. The LD in this sample were well-adjusted, sociable, confident, nonconforming, and independent. The LD presented themselves as calm and nonchalant, suggesting a certain amount of bravado and optimistic expectations about their post-operative recovery.

 

 


206. Use Of Ethambutol And A Quinolone In Ppd Positive Patients With Advanced Cirrhosis Before Or After Liver Transplantation.

M. LaRocque; R. Lalonde; P. Ghali; N. Hilzenrat; J. Barkun; P. Metrakos; J. Tchervenkof; M. Deschenes

 

Background:

The 1st and 2nd line treatments for latent tuberculosis (TB) are isoniazid for 9 months or rifampin for 4 months respectively. Both are hepatotoxic. Patients under consideration for liver transplantation who have a positive PPD need treatment for latent TB because the future use of antirejection drugs constitutes a very high risk for TB reactivation. We have evaluated the combination of ethambutol (EMB) 15mg/kg and a quinolone in PPD positive patients with advanced liver disease or early after liver transplantation when unable to tolerate the first or second line anti TB treatment.

 

Objective:

To describe the outcome of 17 patients with advanced liver disease or who are early after liver transplantation treated with EMB and either 500mg of Ofloxacin (OFLOX) or 400mg of levofloxacin (LEVO) for a positive PPD.

 

Methods:

After obtaining ethics approval, a retrospective analysis of data from the Royal-Victoria Hospital transplant clinic (Montreal, Canada) database was performed. Hospital records were used to validate some data.

 

Results:

We reviewed 17 patients with a positive PPD who were treated with EMB and either OFLOX (15 pts) or LEVO (2 pts). There were 7 women and 10 men, mean age 58 years old. Six patients underwent treatment shortly before and 11 underwent treatment after liver transplantation. Patients received anti-TB treatment for 9 to 12 months, except for one who died of acute graft failure shortly after transplantation, and thus received therapy for only 7 months. Median follow-up was 32 months. No reactivation of TB was observed. Routine ophthalmologic examination did not detect any cases of optic neuritis. There was no decline in Child-Pugh score of any patient, except the one who died of acute graft failure. Five patients died in the post transplant period, none from TB or adverse effects attributed to EMB, OFLOX or LEVO. Two died of recurrent hepatitis C, one of an angiosarcoma, one of sepsis and one of graft failure.

 

Discussion:

The combination of EMB and a quinolone has been used to treat latent TB with presumed drug-resistant bacteria. This is, to our knowledge, the first report of its use in the context of advanced liver disease and liver transplantation, when first and second line regimens were contraindicated. The regimen was well tolerated and appears to have successfully prevented reactivation of TB. We propose that the combination of EMB plus an anti-TB quinolone seems to be an effective and safe alternative therapy in those patients.