Treatment of hepatitis C virus-related cirrhosis: A randomized, controlled trial of interferon alfa-2b versus no treatment

Abstract

To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-␣2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P F .02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, ␣-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 ؎ 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis. (HEPATOLOGY 1999;29:1870-1875.)Cirrhosis is a common complication of chronic hepatitis C, affecting approximately 20% of patients followed up for more than 10 years. 1 Currently identified risk factors for cirrhosis in hepatitis C virus (HCV)-infected patients are age at contamination, duration of infection, degree of histological activity, and alcohol consumption. 2,3 Natural history of HCVrelated cirrhosis is jeopardized by a high incidence of hepatocellular carcinoma (up to 5% per year) 4-7 and hepatic decompensation (up to 25% at 4 years). 4,6,7 Mortality rate is about 15% to 20% at 4 years. HCV-related cirrhosis accounts for 30% of liver transplantation in adults. 1 A treatment able to halt the progression of liver disease once cirrhosis is established but not yet complicated would be of great interest. Current data on the efficacy of interferon (IFN) therapy in patients with HCV-related cirrhosis are conflicting. Cirrhosis is a marker of a poor response to IFN therapy. 8 However, when genotype and serum viral load are taken into account, it is unclear that cirrhosis has any independent value in predicting a poor response to IFN therapy. 8 It has been recently suggested that IFN therapy can prevent the subsequent development of hepatocellular carcinoma, 9 but this contention is not supported by all studies. [5][6][7] In addition, the effects of IFN therapy on mortality rate and probab...

Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis: A retrospective study

“…However, the rates of SVR in our study is consistent with those obtained in similar patients using this schedule of treatment, 36 and might be justified by the sole inclusion of a cohort of patients with "early" stage of cirrhosis with moderate of portal hypertension and, of a high proportion of patients infected by "easy-to-treat" genotype 2. 37 In conclusion, our data show that, in patients with HCV-related histologically proven cirrhosis, the achievement of a SVR following IFN treatment was associated with a reduction in liver-related mortality and with a lower risk of liver-related complications and occurrence of HCC.…”

Hepatocellular carcinoma and hepatitis C in the United States

“…61 The rest of the studies, mostly retrospective and nonrandomized, suggested a moderate decrease in the risk for HCC among HCVinfected patients treated with interferon. 54,8,[62][63][64][65][66][67][68][69] In general, the reported preventive effect of interferon alfa therapy was less marked in European studies than in studies from Japan. The benefit was better appreciated in patients with sustained response than nonresponders.…”

Does chemotherapy prevent HCV-related hepatocellular carcinoma? Cons

“…In 1995, a small randomized controlled trial (RCT) showed a decrease in the incidence of HCC in patients with HCV cirrhosis compared with untreated controls [8]. In the wake of this study, several controlled trials [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] were performed. These studies, often assessed retrospectively, collected cohorts of a relatively small size and having a marked degree of heterogeneity, making it difficult to assess the actual level of benefit obtained by IFN treatment.…”