Session Title: Liver Transplantation: Immunosuppression, Outcomes, and Complications

Session Type: Poster Sessions

Location: West Hall (Moscone West Convention Center)

Start time: Sat, Nov 01 - 2:00 PM

 

Liver Transplantation – General

 

540. Predictors of patient and graft survivals following orthotopic liver transplantation (OLT) in patients with HCV cirrhosis. 

P. K. Jalal; N. S. Becker; P. Shroff; N. L. Sussman; C. O'Mahony; J. A. Goss; R. Stribling; J. M. Vierling.

 

Background:

HCV cirrhosis is the most common indication for OLT in the U.S. and is associated with decreased long-term patient and graft survivals. In contrast to the known impact of recurrent HCV, other predictors of HCV patient and graft survivals remain poorly defined.

 

Aim:

To identify variables that predict patient and graft survivals in patients transplanted for HCV.

 

Methods:

We performed a retrospective observational cohort study using the UNOS database for adult liver transplants (>18 yrs). Patients with multiorgan transplantation or retransplantation were excluded. Predictors of patient and graft survival in HCV patients transplanted in the MELD era (2002-2007) were identified using univariate and multivariate analyses.

 

Results:

·        Overall adult recipients 1991-2007:  59,605

·        Of these 25,052 (42%) adult patients were HCV+, and 12,351 (50%) were transplanted in the MELD era.

·        Univariate analyses identified nine variables as prognostic indicators for patient and graft survivals.

o       Donor age > 60 years

o       Serum Creatinine >1.5 mg/dl

o       African American race

o       ICU stay at transplantation

o       Recipient age >60 years

o       Cold ischemia >6 hours

o       Diabetes mellitus

o       Female gender

o       Serum albumin <2.5 g/dl. 

 

Conclusions:

·        Multivariate analysis identified nine predictors of both patient and graft survivals after OLT for HCV cirrhosis in the MELD era.

·        Only four variables can be potentially modified before OLT: albumin <2.5 (an indicator of malnutrition), creatinine >1.5, donor age >60 yrs and cold ischemia time >6 h.

·        The impact of prospective modification of these variables on patient and graft survivals after OLT for HCV should be systematically studied.

 

Variable

Patient Survival
HR (95% CI)

p value

Graft Survival
HR (95% CI)

p value

Donor age > 60 yrs

1.71 (1.51 - 1.93)

<0.001

1.73 (1.56 - 1.93)

<0.001

Serum creatinine > 1.5 mg/dL

1.41 (1.26 - 1.57)

<0.001

1.26 (1.14 - 1.39)

<0.001

AA Race

1.36 (1.18 - 1.57)

<0.001

1.39 (1.22 - 1.57)

<0.001

ICU Stay at transplantation

1.33 (1.13 - 1.57)

0.001

1.28 (1.10 - 1.48)

0.001

Recipient age > 60 yrs

1.32 (1.17 - 1.50)

<0.001

1.14 (1.02 - 1.27)

0.021

Cold ischemia > 6 hrs

1.25 (1.12 - 1.39)

<0.001

1.24 (1.13 - 1.35)

<0.001

Diabetes Mellitus

1.19 (1.06 - 1.34)

0.004

1.13 (1.02 - 1.26)

0.021

Female gender

1.18 (1.06 - 1.31)

0.003

1.14 (1.04 - 1.25)

0.007

Serum albumin < 2.5 g/dL

1.17 (1.06 - 1.30)

0.002

1.11 (1.02 - 1.21)

0.02

 


Liver Transplantation – Epidemiology

 

545. Racial Disparities in Patient Survivals After Pediatric Liver Transplantation.  

N. S. Becker; O. A. Taylor; J. Anguay; N. L. Sussman; C. O'Mahony; J. A. Goss.

 

Introduction:

Recent studies have demonstrated that adult African-American recipients of orthotopic liver transplantation (OLT) have poor patient survivals when compared to Caucasian recipients. Little is known about racial differences in pre-transplant variables and outcomes after pediatric OLT. The purpose of this study is to examine post-OLT graft and patient survivals in transplant recipients age 17 and under.

 

Methods:

The United Network for Organ Sharing (UNOS) dataset was obtained for the years 2002-2007. Data was extracted for all pediatric (<18 years of age) primary OLT recipients (n=2,967). Racial differences in pre-transplant variables were examined. Graft and patient survivals stratified by racial group were calculated and compared.

 

Results:

Data was available for 2,700 pediatric transplant recipients. Caucasians (CA) were the largest racial group (55%), followed by Hispanics (HA) (22%), African-Americans (AA) (17%), and Asians (AsA) (5%). Comparing racial groups, AA and HA were more likely to have a diagnosis of fulminant hepatic failure then were CA or AsA. AsA were more likely to have a listing diagnosis of biliary atresia. HA were younger at time of transplant, and HA and AA were more likely to be female. There were no significant differences among racial groups in % of patients transplanted at Status 1, PELD/MELD score at transplant, or % of patients undergoing multiorgan transplant (all p-values >0.05) (Table 1). Overall 30-day mortality was 3.7% and was similar among racial groups (p=0.180). Three-year graft survivals were similar: CA: 76%, AA: 76%, HA: 80% and AsA: 85%; p=0.308. Likewise, patient survivals did not differ among racial groups, with 3-year patients survivals for CA, AA, HA, and AsA of 86%, 83%, 87%, and 92%, respectively, p=0.448.

 

Discussion:

Although racial disparities in outcomes after liver transplantation exist in the adult population, this study does not demonstrate any such inequality in the pediatric population. Examining differences between the pediatric and adult OLT populations may help to elucidate why such disparities are observed in adults.

 

Table 1

 

Caucasians

African-Americans

Hispanics

Asians

p-value

% Status 1

28%

31%

34%

29%

0.06

% Fulminant

10%

14%

16%

9%

<0.01

% Biliary Atresia/ Cholestatic Liver Disease

35%

39%

35%

45%

0.03

Mean PELD/MELD

20±13

21±11

21±14

22±13

0.55

% Multiorgan

15%

13%

12%

7%

0.07

Mean Age

5.3±5.9

5.2±6.0

4.0±5.3

4.9±5.8

<0.01

% Ventilated

7%

10%

10%

7%

0.11

% Female

49%

57%

53%

50%

0.02

 


Liver Transplantation – General

 

547. Wide Disparity in Substance Use Policies for Liver Transplant Candidates at U.S. Centers.  

R. S. Mangus; J. Andersen; A. L. Hall.

 

Introduction

Discussion at the recent Transplantation Ethics conference (Chicago, 2008) brought to light a disparity in substance use policies among U.S. liver transplant centers. These disparities were found to exist not only among the criteria for listing for individual centers, but also among the requirements held by governmental and private payers. This study is a review of the written substance use policies for liver transplant candidates at U.S. transplant centers.

 

Methods

Using the database from the United Network for Organ Sharing (UNOS), all U.S. adult liver transplant centers performing 10 or more transplants in 2007 were identified. These centers were individually contacted to request a copy of the written substance use policy for liver transplant recipients. A data extraction sheet was then developed to allow comparison of these policies. Substances of interest included alcohol, tobacco, marijuana, prescription narcotics and illegally obtained substances of abuse.

 

Results

There were 96 centers identified and all were contacted. Of the responding centers, 20% had no formal written substance use policy. Among those centers with a written policy, 100% require complete abstinence from alcohol prior to transplantation. The required alcohol abstinence period ranged from a maximum of 1-year down to an “unspecified period determined on a case-by-case basis.” 50% of centers allow exceptions to this abstinence period if hepatocellular carcinoma (HCC) is present. There are 23% of centers which provide some sort of second chance policy for patients who drink alcohol after a previous agreement to stop alcohol intake. 19% of centers require complete abstinence from tobacco for all recipients, 12% require tobacco abstinence in cases of lung disease and 69% permit tobacco use. Marijuana use was specifically prohibited in 92% of centers, and 8% do not routinely test patients for this substance. Nearly all centers offered a second chance policy for those testing positive for marijuana while listed. All centers exclude patients with current illicit drug use, but the required abstinence period varies from 1-year down to 1 negative screen. The use of narcotic pain pills was specifically addressed in the policies at many centers, though this did not universally exclude patients from listing. For patients with a history of recent substance abuse, 85% of centers require completion of a formal treatment program, while 15% do not.

 

Discussion

A national substance use policy for liver transplantation would be beneficial to establish expectations for recipients, transplant centers and payers, and to remove the current disparity in this area of transplantation.

 


Liver Transplantation – Epidemiology

 

548. Relationship between Recipient Race and Transplant Center as Predictors of Outcome following Liver Transplantation. 

Y. Lim; R. Pedersen; W. K. Kremers; W. Kim.

 

Background:

The impact of recipient race on the outcome after liver transplantation (LTx) has been debated. While previous studies documented poorer survival in non-white recipients, we have demonstrated that race had no effect on post-LTx survival in select, academic centers in the US (Hepatology 2007;1491), which may suggest a barrier in access to LTx for minority patients.

 

Aim:

We examined recipient race and transplant center as predictors of post-LTx outcome.

 

Methods:

Individual data on all adult single-organ primary LTx recipients between 2003 and 2005 were obtained from the Organ Procurement and Transplantation Network. The relationship between patients' race, pre-LTx clinical and payer status and post-LTx survival was analyzed.

 

Results:

There were 11,565 recipients that met the inclusion criteria, consisting of 8,817 Caucasian (CA), 896 African (AA), 401 Asian/Pacific Islander (AP) and 1,451 Other (O) race. Compared to CA, AA recipients were younger (mean age 49.3 vs. 52.9 years), more likely to have HCV (56% vs. 42%) and Medicaid (18% vs. 11%), less likely to have alcoholic liver disease (7% vs. 18%) and private insurance (60% vs. 66%). No difference in short-term patient and graft survival was found between CA and AA: Patient [graft] survival at 3 months was 94[91]% for CA, 95[91]% for AA, 96[92]% for AP, and 94[91]% for O. However, signficant differences were found by 2 years post-LTx: Patient [graft] survival was 83[79]% for CA, 80[73]% for AA, 87[80]% for AP, and 85[80]% for O (p=0.01 for patient survival, <0.01 for graft survival). These differences were partially explained by the center - the unadjusted hazard ratio for mortality in AA was 1.22 (p=0.01), which decreased to 1.19 (p=0.04), compared to CA. However, the final model (Table) which included stratification on center and adjustment for recipient age, diagnosis, payer and pre-LTx MELD, AA still had a 1.24-fold increase in mortality and 1.33-fold increase in graft failure compared to CA. No difference was found for AP or O race.

 

Conclusion:

In the current era, recipient race has no impact on short-term post-LTx survival. However, long-term outcome is decreased in AA, which was not explained by the center, payer or preLTx disease severity.

 

 

Patient Survival

Graft Survival

 

HR

95% CI

HR

95% CI

AA

1.24

1.03-1.50

1.33

1.14-1.56

AP

0.81

0.59-1.12

1.05

0.81-1.36

O

0.86

0.72-1.02

0.91

0.78-1.06

HCV

1.34

1.20-1.49

1.24

1.13-1.36

Public Insurance

1.19

1.05-1.35

1.13

1.01-1.27

MELD

1.02

1.02-1.03

1.02

1.01-1.02

HR=hazard ratio CI=confidence interval

 


Liver Transplantation – General

 

555. Outcomes and Resource Utilization during Hospitalization for Liver Transplantation in the United States and the impact of MELD: A Nationwide Study. 

G. Arora; S. Vadhavkar; G. Singh; G. D. Friedman; G. Triadafilopoulos.

 

Background and Aims:

Liver transplantation (LT) is an efficacious, yet costly treatment for end–stage liver disease and liver cancer. We aimed to determine secular trends and association of clinical and demographic variables with the outcomes related to LT hospitalization –mean hospital length of stay (LOS), mean total hospitalization charges (THC), in–hospital mortality (IHM) and fraction of patients discharged home (FDH). A secondary aim was to test whether the introduction of MELD–based organ allocation system in February 2002 affected these outcomes (1998–2001 vs. 2002–2005).

 

Methods:

The Nationwide Inpatient Sample (NIS) is a 20% stratified random sample of all–payer inpatient stays in all US community hospitals. We studied all adult inpatient records in NIS from 1998 to 2005 containing an ICD–9 procedure code for LT. Covariates included age, gender, race, Charlson comorbidity score, median income level, expected payer, and presence or absence of acute viral hepatitis (AVH), chronic viral hepatitis (CVH), alcoholic liver disease, other liver diseases, hepatocellular carcinoma (HCC) and hepatic encephalopathy (HE). LOS and THC results were stratified according to the discharge type–routine (–R) or non–routine (–NR).

 

Results:

LOS–R showed a downward secular trend (p=0.03). Presence of HCC decreased LOS-R by 27% while that of HE increased it by 75%. LOS–NR remained stable over the study period and was similarly affected by HCC (–21%) and HE (+43%). THC–R (p=0.06) and THC–NR (p=0.03) both revealed upward secular trends and were associated with CVH (+23%; +15%), HCC (–12%; –10%) and HE (+34%; +21%). IHM remained stable and HE increased its odds by 42%. FDH, too, remained stable and its odds were increased by HCC (36%) and decreased by increasing age (2%/year), CVH (25%), HE (43%) and Medicare as the expected payer (24%). Differences in outcomes pre– and post–MELD for LT and compared with those in all–cause hospitalizations are shown in the Table. The odds of FDH in LT patients were 20% less in the post–MELD period.

 

Conclusion:

LT hospitalization outcomes overall remained stable and compared favorably to those of all–cause hospitalizations. The post–MELD period was associated with less in–hospital mortality but higher likelihood of non–home discharge.

 

Outcome

Pre–MELD

Post–MELD

Percentage Change/OR

LOS-LT

23.43

22.94

-2.10%

LOS-AC

4.68

4.63

-1.17%

THC-LT

$880799

$1041187

+18%

THC-AC

$60979

$83137

+36%

IHM-LT

8.32%

7.00%

OR 0.84

IHM-AC

2.413%

2.174%

OR 0.90

LT-Liver Transplantation AC-All-cause Hospitalization

 


Liver Transplantation – General

 

558. The duration of pre-transplant abstinence is an independent predictor of problem drinking post liver transplantation. 

P. Tandon; K. J. Goodman; M. M. Ma; W. Wong; A. L. Mason; G. Meeberg; D. Bergsten; M. Carbonneau; V. G. Bain.

 

Background:

Liver transplantation for alcoholic liver disease (ALD) can be complicated by abusive or “problem” drinking (PD) post-transplant. The disparity between the growing transplant waiting list and donation rates underscores the importance of identifying predictors for these patients. We hypothesized that a longer duration of pre-transplant abstinence would lead to less PD following transplantation. Accordingly, the objectives of this study are to analyze a North American cohort of patients with ALD with or without a secondary diagnosis of liver disease to estimate (i) the incidence of PD and its predictors (ii) the impact of PD on patient survival.

 

Methods:

We conducted a retrospective review of all patients transplanted for alcohol induced liver disease at our center between January 1991 and May 2007 surviving > 3 months post-transplant. PD was defined as either any drinking to intoxication or >20 grams/day in women and >40 grams/day in men on at least 2 separate occasions. We used Cox proportional hazards regression to estimate risk ratios and Kaplan-Meier curves with log rank analysis to compare survival.

 

Results:

In total, 213 patients with ALD were studied from a total of 707 patients in the liver transplant program. Of 213 eligible transplant patients, 42 were excluded. Of the 171 remaining patients, 78% were male with a mean (±SD) age of 52.2 ± 7.6 years. Fifty-three percent of patients had co-existing causes of liver dysfunction. The mean follow-up time was 64.8 ± 42.6 months. The mean pre-transplant abstinence was 40.4 ± 51.6 months. A total of 41 patients (24%) drank alcohol following transplantation and of these 22 (13% of the total) developed PD. Pre-transplant abstinence duration was the only independent predictor of PD post-transplant with the risk of PD decreasing by 5% for every incremental month of pre-transplant abstinence. Eighteen percent of patients died during the course of the study but there was no survival difference noted between PD and non-drinkers.

 

Conclusions:

The risk for PD decreases with increasing pre-transplant abstinence. Our data supports pre-transplant abstinence as the most important predictor of post-transplant recidivism, however, the optimal period of required abstinence remains unclear. Patients with durations of abstinence <18 months may benefit from more intensive follow-up and rehabilitation post-transplant.

 

Risk of recidivism increases with shorter pre-transplant abstinence duration

 

≤ 6 months
(n=8)

7-12 months
(n=33)

13-17 months
(n=34)

18-35 months
(n=43)

≥ 36 months
(n=53)

trend
p value

RR (95% CI) of problem drinking (PD)

8.5
(1.4, 51)

5.9
(1.3, 27)

4.3
(0.9, 22)

1.3
(0.2, 9.1)

1.0 (referent)

0.013

Risk of PD

38%

27%

18%

5%

4%

0.001

 


Liver Transplantation – General

 

562. Outcomes of Liver Transplantation in Combined Hepatitis C and Hepatocellular Carcinoma Are Not Inferior to Hepatitis C Alone. 

A. Raza; G. Ramaraju; R. Razack; A. Shareef; K. Desai; D. Wilson; A. N. de la Torre; A. Fisher; A. Samanta; B. Koneru.

 

Purpose:

To determine if outcomes of liver transplantation (LT) in hepatitis C virus (HCV) recipients are further worsened by the presence of hepatocellular carcinoma (HCC-HCV).

 

Methods:

Using a retrospective case-control design, cases of HCC-HCV liver recipients transplanted between 1990 and 2006, with 1-year minimum follow-up, were matched to HCV controls in 1:1.5 ratio based on age, gender, ethnicity and year of transplant. Graft and patient survival outcomes until 12/31/07 were based on Kaplan-Meier estimates. The effects of donor risk index (DRI), warm ischemic time (WIT), pre-operative calculated MELD score, HCC recurrence, HCV recurrence, and histological rejection on outcomes were examined in multivariate analyses and Cox proportional hazard modeling. Significance was set at p <0.05.

 

Results:

Sixty-five cases of HCC-HCV were matched to 100 controls; females comprised 13.9%, African Americans 10.3%, and Hispanics 23.6%. Mean ages were 53.3 +/-7.2 and 52.6 +/-6.8 years in HCC-HCV and HCV, respectively. 78% in HCC-HCV and 76% in HCV were transplanted in the year 2000 or after. Median DRI (1.33 vs. 1.39), WIT (41 vs. 41 min), proportion with histological hepatitis (65.6 vs. 57.1%), and histological rejection (55.9 vs. 48.1%) were similar between the two groups. Calculated median MELD was significantly lower in HCC-HCV group (16 vs. 19, p<0.01). Most patients with HCC-HCV received no post transplant chemotherapy. Most patients with HCV recurrence were started on HCV therapy. Median follow up was 42.8 months in HCC-HCV and 53.8 months in HCV. Retransplantation rates were 9.2 vs. 9.0%. Five HCC-HCV patients developed tumor recurrence and four subsequently died. Graft and patient survivals in HCC-HCV were better than HCV at 1, 3, and 5 years (graft= 86, 71, 69% vs. 77, 67, 57%, p=0.07; patient= 88, 75, 72% vs. 82, 73, 63%, p=0.14), but did not reach significance. In multivariate analyses, DRI, HCV recurrence, and HCC recurrence had significant impact (p<0.05) on graft survival for the study population. DRI (p<0.01) and HCC recurrence (p<0.05) had significant impact on patient survival. Cox modeling revealed increasing DRI (p=0.011) and HCV recurrence (p=0.003) worsened graft survival, while patient survival worsened with HCC recurrence and higher DRI (p=0.024; p=0.048).

 

Conclusions:

1)     Graft survival in HCC-HCV patients is better than in HCV patients when controlled for age, gender, ethnicity and year of transplant.

2)     Differences in DRI, MELD, and HCV recurrence do not explain the observed improvement in graft survival in the HCC-HCV group.

3)     HCC-HCV liver recipients do not comprise a high-risk group in comparison to HCV without HCC.

 


Liver Transplantation – General

 

566. Health related quality of life predicts survival in liver transplant candidates. 

M. B. Fallon; R. Tanikella; G. Philips; S. M. Kawut; M. J. Krowka; R. S. Brown; J. F. Trotter; S. Zacks; K. E. Roberts; V. Shah; N. Kaplowitz; L. Forman; K. M. Wille; M. Mohd.

 

Introduction:

Health related quality of life(HRQOL) is an important measure of the impact of chronic illness and can help guide interventions to improve well-being. However, whether HRQOL predicts mortality in patients evaluated for liver transplantation (LT) is unknown. We assessed whether HRQOL predicts mortality in patients evaluated for LT.

 

Methods:

We administered the Liver Disease Quality of Life questionnaire(LDQOL 1.0) that includes the SF-36 (Version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease(PVCLD) study, a multi-center prospective cohort study of patients evaluated for LT in seven US academic centers between 2003-2006. Survival was assessed until December 31, 2006. Cox-proportional hazards modeling was used to investigate the association between HRQOL and all-cause mortality. For each HRQOL scale the risk of death was measured in patients grouped based on tertile of the scale with the highest tertile used as a referent. LT status was a time-dependent covariate.

 

Results:

There were 258 patients in the cohort (mean age 54 ± 9.7, 36% female, 93% white). There were 434 person-years of follow-up. 49 of the 258 patients (19%) died. Three patients were lost to follow-up. 153 patients(59%) were listed for LT and 78(30%) underwent LT. Among the SF-36 summary scores, cirrhotics in the lowest tertile of physical component summary score (PCS) had a significantly higher risk of death (Hazard ratio 4.1, 95% CI [1.7 – 9.6]) after adjusting for age, gender, MELD and transplant status. Likewise, patients in the lowest tertile of all scales related to PCS - physical functioning (2.7, [1.2 – 6.2], role limitations due to physical problems (3.2, [1.4 – 7]), bodily pain (2.9, [1.3 – 6.7]) and general health (3.7, [1.7 – 8]) had a significantly higher risk of death. Cirrhotics in the lowest tertile of scales related to mental component summary score - vitality (2.7, [1.3 – 5.9]), social functioning (2.5, [1.2 – 5.3]) and mental health (2.4, [1.1 – 5.4]) also had a significantly higher risk of death. Among the liver disease specific scales, patients in the middle tertile of effects due to liver disease (4, [1.6 – 9.8]) and health distress due to liver disease (3.1, [1.3 – 7.5]) and patients in the lowest tertile of hopelessness due to liver disease had a significantly higher risk of death (3.3, [1.4 – 7.6]).

 

Conclusions:

Self reported HRQOL significantly predicts all-cause mortality independent of disease severity. Hence interventions directed towards improving HRQOL of cirrhotic patients may be helpful in improving outcomes in end stage liver disease.

 


Liver Transplantation – Epidemiology

 

586. Liver Transplantation Trends and Survival in the Asian Population. 

N. Kemmer; V. C. Zacharias; T. E. Kaiser; G. W. Neff.

 

Studies to address ethnic minorities in Liver Transplantation (LT) have traditionally focused on African Americans and Hispanics. Although, the Asian population accounts for 4.4% of the US population, there is limited information on transplantation trends for this ethnic group.

 

Aim:

The Aim of this study is to evaluate the transplantation trends and determine survival patterns of Asian LT recipients.

 

Method:

Using the UNOS database, we identified all adult LT recipients (age > 18 yrs) between 1998 and 2007. The data collected included demographics, diagnosis, survival data and UNOS region. Statistical analysis was done using Kaplan-Meier (KM) and log-Rank tests for survival analysis.

 

Results:

During the study period, 1953 patients received LT, accounting for 4.1% of all adult LT. Of these, there were 1286 (65.8%) males with a median age of 55 (range 18 – 75). The underlying liver disease was hepatitis B (28.1%), Hepatitis C (18.4%), HCC (17.9%), AHN (11.3%), Idiopathic (3.7%), Alcohol (3.3%), PBC/PSC (3.0%), and others (14.3%). A significant regional variation was observed ranging from 2.6% in Region 10 to 39.6% in Region 5. Additionally there was a significant difference for patient and graft survival between Asian and non-Asian group (see Table I, p<0.001)

 

Conclusion:

(1) Regional variation and differences in liver disease pattern was seen among Asian population with HBV-HCC being the most common.

(2) Overall LT recipients of Asian ethnicity have a significant survival advantage especially at (5yr) in comparison to non-Asian groups.

 

YEAR

ASIAN

AA

HISPANIC

CAUCASIAN

PATIENT

 

 

 

 

1

89%

84%

88%

87%

3

81%

72%

80%

79%

5

76%

65%

74%

73%

GRAFT

 

 

 

 

1

84%

79%

83%

83%

3

76%

65%

75%

74%

5

71%

57%

68%

67%

 


Session Title: Liver Transplantation: Donor and Allocation Issues

Session Type: Poster Sessions

 

Location: West Hall (Moscone West Convention Center)

Start time: Sat, Nov 01 - 2:00 PM

 

Liver Transplantation – General

524. Hepatitis C Positive Liver Transplant Recipients who Receive Grafts from Donors with Hepatitis C Antibodies have Similar Outcomes to Hepatitis C Negative Donors. 

P. G. Northup; M. A. McBride; T. M. Schmitt; C. K. Argo; T. L. Pruett.

 

Background:

Organ donors are screened for the hepatitis C antibody (anti-HCV) and if positive the organs are often discarded. Sometimes these organs are transplanted under extended criteria donation. It was the aim of this study to assess the outcomes of anti-HCV positive liver grafts.

 

Methods:

The United Network for Organ Sharing / Organ Procurement and Transplantation Network dataset was used to find all adult liver transplantations with donors who were anti-HCV positive from January 1, 1994 to February 6, 2008. Status 1 transplantations were excluded. Patient and graft survival were assessed in separate analyses accounting for both donor and recipient anti-HCV status. Multivariable proportional hazards survival models were constructed to adjust for factors known to affect post-transplant survival.

 

Results:

70,071 liver transplantations were analyzed. 23,972 (34.2%) involved anti-HCV positive recipients and 1, 313 (1.87%) had anti-HCV positive donors. 77% of anti-HCV positive grafts were transplanted into anti-HCV positive recipients while the remainder (33%) went to HCV negative recipients.

Overall donor risk between groups, as measured by the DRI, were statistically different but the absolute difference as negligible (1.83 in the HCV + group vs. 1.80 in the HCV-group, p=0002).  The best survival was achieved in the transplants with neither the recipient nor donor being affected by HCV with five year survival of 73.0%.  The worst survival was in the recipient negative, donor positive group (63.7%).  There was no statistical difference in adjusted hazard of death in HCV + recipients regardless of donor HCV status (donor HCV- HR=1.228, 95% CI 1.189-1.269 vs. donor HCV+  HR=1.269, 95% CI 1.112-1.450, p=0.,53).

 

Conclusions:

After adjusting for other pre- and post- transplant facto4rs, there does not appear to be an increased risk of post-transplant mortality in HCV + recipients when using well selected donors with the antibody to HCV at the time of donation. 

 

Discussion:

The aim of this study was to assess the outcome of HCV+ liver grafts using the largest dataset with the longest follow-up available in the U.S.  Over 70, 000 liver transplantations were analyzed including more than 27,000 transplants since the initiation of the MELD allocation system in 2002, an era which has not been analyzed with regard to HCV+ donors.  Not surprisingly, we found the best outcomes were observed when both recipient and donor were negative for HCV.  After adjusting for known mortality risk factors in a HCV+ recipients using multivariable proportional hazards survival models, we found that a potential recipient with HCV cirrhosis is not subjected to excess mortality if a HCV+ liver allograft is used.  As expected, HCV-recipients of HCV+ donors had the worst outcomes, but these events were understandably rare and were likely under extreme circumstances not borne out by a database analysis such as this. 

 


Liver Transplantation – Epidemiology

 

526. The Impact of MELD Allocation Policy on Racial Disparities in Access to Liver Transplantation. 

M. L. Volk; G. Warren; J. A. Marrero; M. Heisler.

 

Prior to implementation of the Model for End-stage Liver Disease (MELD) allocation policy, racial disparities in access to liver transplantation were documented at several stages of the process including referral, listing, and transplant.

 

Aim:

The aim of this study was to determine whether implementation of the MELD policy eliminated disparities in access to transplantation once patients are placed on the waiting list.

 

Methods:

Data from the United Network for Organ Sharing (UNOS) was analyzed for all adults on the waiting list for transplantation between 1997-2007 (n=110,042). The two largest minority groups, African-Americans and Hispanics, were compared to Caucasians. Endpoints included 1) probability of receiving a transplant, and 2) probability of removal from the waiting list for death or being too sick. Regression models were fitted for each endpoint during the pre-MELD and post-MELD eras.

 

Results:

During the pre-MELD era (1997-2001), African-Americans were less likely to receive a transplant (OR 0.8, 95% CI 0.74-0.86) and more likely to be removed from the waiting list (OR 1.32, 95% CI 1.22-1.42) than Caucasians. In the post-MELD era (2002-2007), African-Americans are now more likely to receive a transplant, but still more likely to be removed from the waiting list than Caucasians. These differences can be largely attributed to the higher MELD scores among African-Americans, as demonstrated by the multivariate analysis in Table 1. Hispanics were less likely to receive a transplant (OR 0.87, 95% CI 0.82-0.93) and more likely to be removed from the waiting list (OR 1.24, 95% CI 1.16-1.33) than Caucasians during the pre-MELD era. These differences persisted during the post-MELD era despite adjustment for severity of liver disease, as shown in Table 1.

 

Conclusion:

The MELD allocation policy has improved disparities in access to liver transplantation for African-Americans, but not for Hispanics. Further research is needed to explain this discrepancy.

 

Table 1: Multivariate analysis of waiting list endpoints for African-Americans and Hispanics (relative to Caucasians) during the post-MELD era.

 

 

Odds of Transplantation

Odds of Removal

OR

95% CI

OR

95% CI

African-American

1.06

1.00-1.12

0.85

0.79-0.92

Hispanic

0.75

0.72-0.79

1.15

1.08-1.21

MELD

1.04

1.04-1.04

1.07

1.07-1.07

 


Liver Transplantation – Epidemiology

 

534. Race/Ethnicity and Geographic Disparities in Waitlisting and Waitlist Outcomes in the Post-MELD Era.  

C. J. Sonnenday; M. J. Englesbe; J. Kubus; A. K. Mathur; R. M. Merion.

 

Background:

Marked disparities have been reported in rates of liver transplantation (LT) by race/ethnicity and geographic region in the U.S. Some have suggested that the MELD-based allocation system, which is based upon objective laboratory data, might lessen these disparities.

 

Methods:

OPTN data were used to investigate the rates of waitlist (WL) death and LT among candidates listed in the three years prior to (n=34477) and following (n=34811) implementation of MELD-based allocation in 2002. Demographics of LT candidates were compared to U.S. Census Bureau-based national and regional population data. Multivariable Cox models were fitted to test the association of race/ethnicity with WL mortality and LT rates, adjusted for multiple characteristics. The interaction of race and OPTN region was also tested.

 

Results:

Overall, African-Americans were underrepresented as transplant candidates (7%) compared to their proportion in the U.S. population (13%, P<0.001). Significant regional differences in race/ethnicity existed between LT candidates and the general population; African-Americans and Hispanics were significantly underrepresented in 9 and 4 of the 11 OPTN regions, respectively (P<0.01). In the MELD era, rates of LT increased and WL death decreased among all candidate groups. African-American and white candidates had similar LT rates in both the pre- and post-MELD eras. However, in a multivariable analysis, the LT rate was 10% lower for Hispanics and 17% lower for Asians, compared to whites (both P<0.001). African-American candidates had an 18% higher rate of WL death vs. whites in the pre-MELD era (P<0.001), and this disparity increased to 27% under MELD–based allocation (P<0.001)(TABLE). Racial/ethnic disparities in WL death rates also varied significantly by OPTN region (range of hazard ratios for WL death=0.59-1.43 by race/ethnicity and OPTN region; P<0.0001). The regional differences in LT and WL death rates by race/ethnicity were unchanged in the MELD era.

 

Conclusions:

MELD-based liver allocation has not eliminated disparities by race/ethnicity in WL death rates and access to LT. These disparities are especially large across OPTN regions.

 

WL DEATH RATES (multivariable model)

 

PRE-MELD

POST-MELD

RACE/ETHNICITY

HR

95% CI

HR

95% CI

WHITE

1.0

REFERENCE

0.97

0.93-1.01

AFRICAN-AMERICAN

1.18*

1.09-1.28

1.21†

1.11-1.33

HISPANIC

1.03

0.97-1.10

1.01

0.94-1.07

ASIAN

0.97

0.93-1.01

0.83#

0.73-0.95

P<0.001 vs. white (pre-MELD); †P<0.001 vs. white (post-MELD); # P=0.006 vs. white (post-MELD) 

 


Session Title: Cell Death, Oxidant Stress, and Drug Toxicity

Session Type: Poster Sessions

 

Location: West Hall (Moscone West Convention Center)

Start time: Sat, Nov 01 - 2:00 PM

 

Disease Progression – General

358. Fulminant hepatic failure associated with chewing khat.  

M. H. Chapman; J. O'Beirne; D. W. Patch; A. P. Dhillon; G. Borges; A. Crozier; M. Y. Morgan.

 

Background

Chewing leaves of the khat plant (Catha edulis) is a widespread cultural habit in East Africa. Its amphetamine like constituents, cathine and cathinone, induce euphoria and alertness. While its association with psychiatric morbidity is well established, association with other medical sequelae is not. We report five cases of presumed khat-induced fulminant hepatic failure (FHF).

 

Methods & Results

Details of five Somali patients with unexplained FHF were reviewed. All regularly chewed khat and presented with jaundice, lethargy and abdominal discomfort. Three had had previous admissions for unexplained hepatitis and resumed their khat habit after discharge. Apart from jaundice, there were few distinguishing clinical features. Laboratory data indicated severe liver dysfunction (Table). Histology showed acute severe hepatitis with confluent panlobular necrosis, architectural collapse, mixed inflammatory response including eosinophils with no elastic fibre deposition; some showed venulitis. The patients who died had autopsy evidence of hypertrophic cardiomyopathy consistent with previously described cardiac effects of khat1.

 

Frozen samples of khat leaves and liver from one patient were analysed using an HPLC-PDS-MS2 system. The main component in khat leaves was cathinone (516±12μg/g) with trace quantities of cathine and its metabolite pseudoephedrine. Cathinone was also detected in the liver in a concentration of 29±1μg/g; the metabolite profile in liver matched the leaves. No heavy metals or pesticides were identified in the leaves or liver.

 

Summary

There is strong presumptive evidence that the liver injury in these patients was Khat-related viz:

1)     Absence of other identifiable cause of liver injury,

2)     Positive re-challenge in three cases

3)     Histopathological features reminiscent of ecstasy-related hepatotoxicity with which Khat shares biochemical similarities

4)     Identification of khat in the liver sample

5)     Khat induces hepatotoxicity in animals2

 

The mechanism of the liver injury remains unclear, but is likely to be idiosyncratic.

In conclusion, khat should be considered as a cause of unexplained liver injury particular in immigrants from East Africa. Patients with liver disease should be counselled against its use.

 

References

1. Al-Habori et al, J Ethnopharm 2002(83);209

2. Saha & Dollery, J R Soc Med 2006(99);316

 

Case

Sex

Age

Khat use

Bilirubin
mg/dl

ALT
IU/L

AST
IU/L

ALP
IU/L

Albumin
g/L

INR

Outcome

1

M

36

Daily for 10 years

9.6

1589

1543

231

38

1.5

Died

2

F

36

3/week for 10 years

14.9

X

2346

230

29

1.9

OLT

3

F

32

2/week for 4 years

16.9

796

X

193

35

2.2

OLT

4

M

28

3/week for 8 years

14.6

2314

3250

213

34

1.2

OLT

5

M

34

2/week for 9 years

11.58

76

246

244

21

2.7

OLT

 


Disease Progression – General

 

369. Assessing Hepatotoxicity of Thiazolidinediones (TZDs), Metformin, and/or Statin Therapy in Chronic Hepatitis C (HCV) Patients. 

H. Han; A. S. Boxer; M. Adler; J. L. Matloff; D. C. Carriero; M. Vachon; D. T. Dieterich.

 

Purpose:

Patients over the age of 40 with Hepatitis C (HCV) have a three-fold higher prevalence of Type 2 diabetes (T2DM) than those without HCV. In addition, glucose abnormalities are associated with a poorer virologic response in chronic HCV patients. Attempts to improve insulin sensitivity prior to or during combination pegylated interferon and ribavirin therapy may result in a higher rate of viral response to HCV treatment.

 

Aim:

The aim of the study is to assess hepatic safety of insulin sensitizers such as TZDs and metformin, and/or cholesterol lowering agents like statins when used in patients with chronic HCV, prior to HCV treatment.

 

Methods:

IRB-approved, retrospective chart review from 2002 to 2007 of patients at a liver clinic in our center with chronic HCV treated with at least one of the study medications. We examined variations in ALT, AST, GGT, HDL, LDL and total cholesterol, triglycerides (TG), HbA1C, and calculated HOMA-IR at baseline and after 3 to 6 months of therapy. The Student T-Test was used to compare pre-treatment and post-treatment parameters.

 

Results:

Fifty-two patients (73% males, ages 36-68), of which 32 were on TZDs, 14 on metformin, and 6 on statins, were included for analysis. Compared to the pre-treatment, the post-treatment group evidenced a decreased trend in all biochemical parameters except for TG and HDL cholesterol. There was a statistically significant (p<0.05) decrease in calculated HOMA-IR from 7.37 (8.28) to 2.40 (0.87) after 3 to 6 months of treatment, and HbA1C declined from 5.44 (1.11) to 5.29 (0.82) %. ALT, AST, and GGT levels improved from 83.56 (82.47) to 65.92 (46.04) IU/L, 78.44 (66.76) to 65.77 (42.11) IU/L, and 139.48 (132.60) to 136.84 (202.38) IU/L, respectively. Total and LDL cholesterol also showed a trend downwards from pre-treatment (167.63 [37.69] and 82.65 [29.73] mg/dL, respectively) to post-treatment (162.55 [35.16] and 77.86 [27.21] mg/dL, respectively). TG and HDL values trended up from 163.85 (97.52) to 171.04 (127.99) mg/dL and from 49.59 (17.91) to 49.93 (19.99) mg/dL, respectively. There was no significant change in BMI from pre-treatment, 28.38 [5.72], to post-treatment, 28.04 [4.24] kg/m^2. No patients discontinued medications because of liver-related side effects.

 

Conclusions:

The decreasing trends in ALT, AST, GGT, and total cholesterol with the use of TZDs, metformin, and/or statins demonstrate the relative safety of these agents in HCV patients. The significant decrease in calculated HOMA-IR with insulin sensitizers given before HCV therapy may indicate a role for them in improving treatment response in HCV patients. A randomized study is underway.


Session Title: IASL Posters

Session Type: Poster Sessions

 

Location: Default

Start time: Sat, Nov 01 - 2:00 PM

 

Diagnostic Tools – Biochemical/Imaging

457. Fibrotest Fibromax: International Standardization Of Biochemical Markers Measurements For Results Concordance Between Laboratories. 

D. Messous; R. Morra; M. Munteanu ; T. Poynard; B. Hainque; F. Imbert-Bismut.

 

Background:

World-wide utility of fibrosis blood markers is limited by the variability of results depending on analytical systems used to perform the assays. Analytical standardized methods should now be adapted to the different analyzers in order to improve harmonization of FibroTest- Fibro-Max score results between different laboratories.Objective:

 

Aim:

The aim was to assess the impact of the international analytical standardization on result transferability between various analyzers of FibroTest-FibroMax components [alpha2-macroglobulin (A2M), haptoglobin (HPT), apolipoprotein A1 (APOA1), GGT, total bilirubin (TBILI), ALT, AST, total cholesterol (TC), triglycerides (TG) and fasting glucose (GLU)].

 

Methods:

GGT activities were measured according to standardized methods, as ALT and AST when pyridoxal 5-phosphate (P5P) was used as activator. A2M, HPT, APOA1 assays used standardized reagents against Certified Reference Materials (CRM 470, SP1-01). TBILI assays were performed according to diazoreaction, TC, TG were assessed according to a Trinder reaction. For glucose assay, blood has to be collected on a glycolysis inhibitor. 1) ALT assays were conducted on 13 analyzers from the different manufacturers, using P5P or not. 2) Result transferability of Fibrotest- Fibromax components was tested between analyzers from the various manufacturers: Beckman, Roche Diagnostics, Siemens -Dade-Behring, KoneLab, Bayer, Abbott). Referent analytical systems were for proteins BN2 from Dade- Behring and Modular from Roche Diagnostics for the others components.

 

Results:

ALT results: The impact on ActiTest results of ALT measured without P5P was of 10% (p<0.05). Proteins results: in spite of the same reference material used to titrate the reagents, the A2M assays results obtained on Immage (Beckman) were 40% upper and required antibody change. A2M results obtained with turbidimetric assays are dependent on the reagents used. ApoA1 results obtained with the analyzers from Beckman, Olympus, Bayer manufacturers were 15% up to 18 % lower and results have to be corrected. With these exceptions, protein results concordance was excellent on the different analyzers appraised. Others FibroTest-FibroMax components: transferability of CT, TG, and GLU were excellent (median slope range was from 1.00 to 1.08). For FibroTest-FibroMax scores, significant differences in fibrosis stages and inflammation grades were noticed between the laboratories when non standardized methods were employed.

 

Conclusion:

Standardized conditions have to be used to perform the assays of blood markers especially for combination components. P5P have to be used for the correct measurement of ALT and AST activities.

 


HCV Disease Progression – General

 

470. The Impact Of Alcohol Abuse, HCV  Infection And Liver Dysfunction On Neuropsychological And Neurophysiological Profile Of Patients With Liver Cirrhosis. 

F. Campagna; S. Schiff; M. Ruzzoli; A. Biancardi; D. Mapelli; P. Pujatti; D. Pavanello; P. Angeli; A. Gatta; P. Amodio.

 

Background and aim.

Neuropsychological and EEG alterations are ascribed to minimal hepatic encephalopathy (MHE) in cirrhotic patients. Chronic alcohol abuse and HCV infection can act as confounders since they may impair brain functioning. Aim of the study was to identify the influence of these confounders in the evaluation of patients with liver cirrhosis.

 

Material and methods.

Neuropsychological profile and EEG spectral parameters were studied in 6 groups of subjects to allow a two ways ANOVA design:

a)     30 healthy subjects,

b)    30 non-cirrhotic subjects with HCV-hepatitis,

c)     30non-cirrhotic chronic alcohol abusers,

d)    30 subjects with HCV-related cirrhosis,

e)     30subjects with alcohol-related cirrhosis,

f)      30 subjects with no alcohol, no viral related cirrhosis.

 

All groups were matched for age; the cirrhotic patients were matched for the liver insufficiency. All groups underwent extensive neuropsychological investigation and quantified EEG analysis.

 

Results.

·        Alcohol misuse alone had a detrimental effect on Phoemic Verbal Fluency (PVF) and Interference Tasks

·        Cirrhosis had detrimental effect on the TMT(B-A) and Phoemic Verbal Fluency

o       Alcohol increased the detrimental effect of cirrhosis on the TMT-A and TMT-B

·        HCV infection per se showed a trend for reduced performance in the Interference Tasks

·        Cirrhosis had a detri8mental effect on the TMA (B-A) and PVT

o       HCV infection did not have additive detrimental effect on the neuropsychological profile of patients with liver cirrhosis.

Neurophysiological Evaluation

·        Cirrhosis influenced every EEG spectral measures (MDF, Absolute Spectral Power, Delta, Theta, Alfha, and Beta relative power)

·        Alcohol misuse alone did not show any significant influence, but it showed a trend for an additive detrimental effect on the MDF, Absolute Sprectral Power, Delta and Beta relative power of patients with liver cirrhosis. 

·        HCV infection per see influenced the Absolute Spectural Power and an interaction cirrhosis-HCV infection was found (p<0.05)

 

Conclusions.

1.     The consequences of chronic alcohol misuse are highly evident on memory interference tasks;

2.     Alcohol abuse had a synergic effect with cirrhsois in damaging executive functions;

3.     The influence of HCV infection, if any, was negligible;

4.     The EEG changes were found to be mainly related to the factor ‘cirrhosis.’

 


Diagnostic Tools – General

 

475. Sex-specific Association between Alcohol, Body Size and Serum Aminotransferase Levels: The Rancho Bernardo Study. 

R. Loomba; R. Bettencourt; E. Barrett-Connor.

 

Background:

It is unclear if men and women have a differential effect of alcohol (ETOH) dose & BMI on serum ALT & AST in older community-dwelling adults in the US.

 

Aim:

To examine the sex-specific association of ETOH dose & BMI on serum ALT & AST in a population-based cohort of older adults.

 

Methods:

A cross-sectional study of 2466 individuals (mean age 70 yr, BMI-24.5 kg/m2, 54% F) of the Rancho Bernardo Study who attended a research visit in 1984-87. Current ETOH use was recorded. BMI & LFT were measured. Sex-specific odds (OR[95% CI]) of raised ALT & AST, defined as ≥ 19 U/l in women & ≥30 U/l in men, were calculated to assess dose response associations with ETOH: 0-1 drink/day, 1-2 drinks/day, 2-3 drinks/day, > 3 drinks/day vs. no ETOH (referent). OR was used to assess the association of obesity (BMI ≥30) & overweight (BMI 25 < 30) vs. normal wt. (BMI 18.5-25) with raised serum ALT & AST. Joint effects of ETOH and obesity were also examined.

 

Results:

In multiply-adjusted analyses, the only statistically significant independent association of ETOH dose with raised ALT & AST was in the 80 men (OR 2.5[95% CI,1.3-4.7]) & 29 women (OR 2.9[95% CI,1.3-6.3])who reported >3 drinks/day. Those drinking less than this amount showed no elevation in either ALT or AST. Among the 96 obese men & 107 obese women, there was a significantly higher odds of raised ALT but not AST. Obese individuals who drink >3 drinks/day had higher odds of elevated serum ALT (see figure) & AST.

 

Conclusions:

In these community based sample older in older adults, there was a threshold association of raised serum ALT & AST at >3 drinks/day, consistent for both men & women. Obesity and high alcohol consumption is more strongly associated with serum ALT than AST in both sexes.  Obese individuals had an increased odds of raised serum ALT at lower levels of ETOH use. 

 

Given the current obesity epidemic, these results may have important public health implications.  

 

 


Diagnostic Tools – Biochemical/Imaging

 

477. Non-invasive Prediction of Liver Fibrosis in Nonalcoholic Fatty Liver Disease. 

L. A. Adams; J. George; E. Rossi; D. van der Poorten; J. G. Kench; B. DeBoer; G. C. MacQuillan; G. P. Jeffrey.

 

Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disorder worldwide, however only a small proportion of individuals develop significant liver damage. Staging is thus vital for prognosis and management however, currently requires liver biopsy. We examined the accuracy of three non-invasive models, namely Hepascore (HS), Fibrotest (FT) and the AST to Platelet Ratio Index (APRI) in predicting different levels of fibrosis in patients with NAFLD.

 

Methods:

Serum was taken from NAFLD patients at the time of liver biopsy and analysed for the components of the non-invasive models. Liver biopsies were staged according to the Kleiner classification. Fibrosis was classified as significant (F2-4), advanced (F3-4) and cirrhosis (F4). Accuracy was determined by area under the receiver operator characteristic (AUROC)curve analysis. Cutoffs were determined according to the highest Youden Index (sensitivity + specificity -1).

 

Results:

119 patients (54% male) with a mean (SD) age of 48.7 (13.0) years were assessed. 44 (37%) were overweight (BMI 25-29.9 kg/m2), 53 (44.0%) were obese (BMI>30 kg/m2) and 38 (32%) were diabetic. Significant fibrosis was present in 50 (42%), advanced fibrosis in 29 (24.4%) and cirrhosis in 10 (8.4%). The AUROC of all three indices were similar for significant and advanced fibrosis, however APRI was significantly less accurate for cirrhosis. Specifically, the AUROC curve for significant fibrosis for HS, FT and APRI were 0.75 (95% CI 0.66-0.84), 0.72 (95% CI 0.62-0.81) and 0.73 (0.64-0.82) respectively. For advanced fibrosis, the AUROC for HS, FT and APRI were 0.82 (95% CI 0.72-0.93), 0.82 (95% CI 0.73-0.92) and 0.78 (95% CI 0.68-0.88) respectively. For cirrhosis, the AUROC for HS, FT and APRI were 0.94 (95%CI 0.90-0.98), 0.94 (95% CI 0.89-0.99) and 0.67 (95% CI 0.46-0.87). The highest Youden Index and positive predictive value (PPV) for significant fibrosis was provided by HS (see table). For the diagnosis of cirrhosis, the highest Youden Index for HS, FT and APRI was 0.87, 0.81 and 0.35 respectively. At the cutoff provided by the peak Youden Index, the PPV for HS, FT and APRI was 42%, 52% and 16% respectively, whereas the NPV were 100%, 99% and 96% respectively.

 

Conclusion:

·        Hepascore and fibrotest have equivalent accuracy in determining liver fibrosis in NAFLD.

·        API has lower accuracy in predicting cirrhosis in NAFLD..

 

Diagnostic characteristics of noninvasive markers for significant fibrosis

 

Youden Index

Sens

Spec

PPV

NPV

Hepascore

0.50

56%

94%

88%

75%

Fibrotest

0.33

73%

60%

57%

75%

APRI

0.42

72%

70%

64%

78%

 


HCV Diagnostic Tools – General

 

501. Fibrotest Or Fibroscan For Evaluation Of Liver Fibrosis In Hemophilia Patients Infected With Hepatitis C. 

Y. Maor; P. Halfon; D. Bashari; G. Penaranda; G. Morali ; R. Klar; S. Bar-Meir; U. Martinowitz; R. Oren.

 

Introduction:

The use of non-invasive markers of fibrosis is particularly desirable in hepatitis C (HCV)-infected hemophilia patients. Significant fibrosis was estimated by both by Fibrotest (FT) and Fibroscan (FS) in a high proportion of hemophiliacs. Direct comparison between these tests has not been performed.

 

Aim:

To estimate liver fibrosis by FT and FS in HCV-infected hemophilia patients.

 

Methods:

FT and FS were performed up to three month apart in different laboratories that were unaware of the results of the alternative test. Liver Stiffness Measurements (LSM) was performed at three points on the right lobe of the liver. Two validated algorithms were used to improve evaluation of fibrosis by these non-invasive markers (1, 2).

 

Results:

Fifty-seven hemophilia patients with HCV were evaluated by FT and FS. LSM could not be obtained in two patients: obesity- 1, surgical scars- 1.

See Table

 

Using the two algorithms additional fourteen patients could be reliably estimated for fibrosis stage ≥2 by combining FT and FS scores.

 

Conclusions:

·        A high proportion HCV-infected hemophilia patients were estimated with significant or advanced stages of liver fibrosis using both FT and FS.

·        Nevertheless, the individual agreement between modalities was only fair, and improved in more advanced stages of fibrosis.

·        Practical indicators of the accuracy of FT and FS may improve estimation of fibrosis in this population.

 

References:

1. Bourliere M, et al. J Viral Hepat 2006;13:659-70.

2. Lucidarme D, et al. Hepatol 2007:318A.

 

Comparison between FT and FS for evaluation of liver fibrosis in hemophiliacs with HCV

Fibrosis Stage

> 2

> 3

= 4

FibroTest(%)

27 (49)


20 (36)


11 (20)

FibroScan(%)

30 (54)

18 (33)

8 (15)

Kappa

0.24

0.32

0.44

Concordance (%)

34 (62)

38 (69)

47 (85)

 

 


HCV Disease Progression – General

504. The Illness Intrusiveness of a Hepatitis C Diagnosis. 

M. B. Murphy.

 

Aim:

The aim of this pilot study was to describe the Illness Intrusiveness of a diagnosis of Hepatitis C virus (HCV) in adults. Infection with HCV affects an estimated 4 million Americans and 170 million worldwide. The disease becomes chronic in up to 85% of those who are infected. Care for the patient with HCV is typically delivered in specialty clinics and the focus of care is usually on treatment. Less attention is given to the experience of adjusting to the diagnosis.

 

Illness intrusiveness refers to the degree to which an illness or its treatment interferes with important elements of a patient’s life, especially the ability of the individual to continue participation in valued activities or interests. Illness intrusiveness compromises psychological well being in chronic diseases. The Illness Intrusiveness Rating Scale (IIRS) measures the extent of the interference of a chronic disease in important life domains.

 

Thirty patients diagnosed with HCV who presented to a Hepatology clinic for evaluation of their disease participated in the study. Internal consistency of the IIRS for this sample was determined using Cronbach’s alpha (r = 0.94). Mean total IIRS score was 35.46, SD = 20.38. The total possible range of scores was from 13 to 91; the range of scores for the study sample was 13-91. Subscale scores for the IIRS were obtained by calculating item means. For the Instrumental subscale, the mean was 3.05 (SD=1.95). For the Intimacy subscale the sample mean was 1.3 (SD=1.01). The Relationships and Personal Development subscale mean was 2.47 (SD=1.5). The mean IIRS score for this population was slightly lower than the mean IIRS scores of subjects with more symptomatic chronic conditions such as hyperhidrosis and bipolar disorder, and higher than patients with insomnia. In addition to the IIRS, study subjects were asked to describe their HCV illness experience. Responses included ‘shock’, ‘concern’, ‘depressed’,’increased stress’,‘devastated’, ‘anxiety’, ‘scared’ , and ‘worry about the future’, which suggest a strong negative emotional response to receiving a diagnosis.

 

Conclusion

Results of this study indicate that future research with this population is warranted in order to identify the true nature of the impact of the diagnosis of HCV. QOL , uncertainty of illness , and anxiety and depression indices may provide additional insight .

 


HCV Treatment – Pegasys

 

512. Alfa-2a monotherapy could be a treatment option for Chronic Hepatitis C in Patients Infected with HCV Genotype 2. 

K. Takaguchi; T. Nagano; M. Wato; N. Baba; T. Seno; T. Inaba; S. Watanabe; K. Kawai.

 

Background and Aims

Peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy has become the global standard treatment for chronic hepatitis C virus (HCV) infection. However, PEG-IFN monotherapy remains a treatment option in Japan depends on patient demographics and baseline characteristics. Also PEG-IFN monotherapy is still indicated for patients who are RBV intolerant or anemic. This study investigated the efficacy of PEG-IFN monotherapy in Japanese patients infected with HCV genotype 2.

 

Methods

We analyzed the data from 64 naïve patients with chronic hepatitis C who were treated with peginterferon alfa-2a monotherapy for HCV genotype 2 infection at our hospital between January 2004 and September 2005. 33 patients were male and 31 patients were female (mean age 55.9 ± 12.2 years, mean body weight 59.8 ± 11.0kg);38 patients had low baseline viral load(LVL:<500KIU/mL) and 26 patients had high baseline viral load(HVL: ≥500KIU/mL). Distribution of HCV subtypes were 2a (n=47), 2b(n=15) and 2ab(n=2). Liver biopsy was performed in 53 patients.(F1: 15 patients ,F2: 26 patients,F3:11 patients,,F4: 1 patient). Patients received peginterferon alfa-2a 90 or 180μg subcutaneously once a week, 48 weeks. Doses were modified according to the hematological test results. 23 patients were treated shorter duration due to the adverse events.

 

Results

A sustained virologic response (SVR) was observed in 67.2% of all patients as well as 68.1%, 60.0%, and 100% of those infected with HCV genotype 2a, 2b, and 2ab, respectively. In patients with LVL, 71% of patients achieved an SVR. 39.7%, 74.6%, 85.9%, and 93.5% of all patients achieved HCV RNA negative at week 4, 8, 12, and 24, respectively. Positive predict value (PPV) for SVR in each time points were 94.4%(17/18), 76.9%(10/13), 0%, 0% at week 4.8.12.and 24 in patients with LVL. And PPVs for SVR in each time points were 85.7%(6/7), 77.8%(7/9), 40%(2/5), 25%(1/4) at week 4.8.12.and 24 in patients with HVL.

 

Conclusions

Peginterferon alfa-2a monotherapy produced a high rate of SVR in patients infected with HCV genotype 2 specially in patients with LVL (71%) or undetectable HCV-RNA by week 8 (≥77%). Peginterferon Alfa-2a monotherapy could be a treatment option for patients with HCV Genotype 2 and intolerant with RBV combination therapy.