Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.

BACKGROUND: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated. AIM: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients. METHODS: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review. RESULTS: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility. CONCLUSIONS: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

Liver transplantation in alcoholic liver disease current status and controversies.

Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids.

Definition, epidemiology and magnitude of alcoholic hepatitis.

Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology, environmental factors and the host's genetic make-up may also play significant roles that have not yet been entirely explored. Continuing alcohol consumption is a major factor that influences the survival of patients with AH. The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run. This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular.

Management of hepatitis C virus infection in HIV/HCV co-infected patients: clinical review.

Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV mono-infection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti-HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in co-infected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.

Can we predict the degree of fibrosis in chronic hepatitis C patients using routine blood tests in our daily practice?

GOALS: To determine the validity of fibrosis indexes based on simple laboratory tests in daily practice. BACKGROUND: Fibrosis indexes were developed in referral centers using high-quality data. METHODS: We compared the performance characteristics of several such indexes with liver biopsies in a cohort of 490 diverse veterans with chronic hepatitis C from 24 centers. All laboratory tests including interpretation of the liver biopsy were done locally. The following indexes were calculated and correlated with a 5-point fibrosis stage (F0-F4) on liver biopsies: platelet counts (<100 or <150x10(9)/L), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), Pohl score, AST-to-platelet ratio index (APRI) and "Lok's model." RESULTS: Our cohort was predominantly male with 24% blacks, and fibrosis stages of 0, 1, 2, 3, and 4 in 11%, 24%, 28%, 24%, and 13%, respectively. All indexes performed better in predicting advanced (F3-4) than significant (F2-4) fibrosis. When patients with F3-4 were compared to those with F0-2, the area under the receiver operating characteristics curve were 0.534 and 0.641 for platelet count <100 and <150x10(9)/L, respectively, 0.524 for AAR, 0.534 for Pohl score, 0.693 for Lok's model, and 0.765 for APRI. The sensitivity, specificity, and predictive values of APRI and Lok's model were only slightly lower than those reported by the authors using the recommended cutoffs in clinical trial settings. Alcohol use within 12 months, normalization of AST, ALT, and race (blacks/non-blacks) had minimal impact on the performance. CONCLUSIONS: AAR, Pohl, and platelet counts <100x10(9)/L have limited ability to predict significant/advanced fibrosis with area under the receiver operating characteristics curve similar to 0.5. However, platelet counts <150x10(9)/L, Lok's model and APRI performed well for advanced fibrosis in our daily practice setting.

Chronic hepatitis C in Latinos: natural history, treatment eligibility, acceptance, and outcomes.

OBJECTIVES: The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos. METHODS: A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naïve, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study. RESULTS: Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4%vs 3.9%, p < 0.0001) and prior HAV infection (39.9%vs 26.4%, p= 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7%vs 43.2%, p= 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8%vs 28.9%, p= 0.043) and tended to have lower sustained virological response (SVR) rates (14.8%vs 22.5%, p= 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR. CONCLUSIONS: Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR.