Treatment of HCV cirrhosis--simple or not quite so?

Hepatitis C virus (HCV) infection is a major global health problem with 170 million carriers worldwide and 12-13 million HCV carriers in India. Of the 16250 blood units screened, the prevalence of HCV infection was 0.44% (72/16250) in healthy blood donors at our centre. In addition, of all the chronic liver disease patients (chronic hepatitis and cirrhosis) that come to us around 20% have been attributed to HCV infection (unpublished). The World Health Organisation estimates that 3% of the world’s population is infected with the hepatitis C virus (HCV), about 20% of whom will go on to develop cirrhosis. Currently there are possibly 7.8 million cases of HCV cirrhosis in the world which may rise to 13.8 million by 2015. Patients who have compensated cirrhosis are at risk for progression of disease and clinical deterioration. Estimated rates for the development of clinical deterioration (decompensation), hepatocellular carcinoma (HCC), and death from liver disease in patients with compensated cirrhosis are 3.6% to 6.0% per year, 1.4% to 3.3% per year, and 2.6% to 4.0% per year, respectively. Worldwide, HCV-associated end-stage liver disease is the most common indication for liver transplantation in adults. A total of 43% of the over 6000 liver transplants done in 2004 in USA were performed in patients with chronic hepatitis C (CHC) related liver disease. Fortunately effective drugs are available for treating CHC even when they have progressed to a stage of cirrhosis. Clinical trials have identified various viral and host factors that are predictive of response to pegylated interferon (pegIFN) and ribavirin (RBV). The strongest predictor of nonresponse to HCV treatment is infection with genotype 1, which has a significantly lower sustained virological response (SVR) rate compared with genotype 2 and 3 infections. Additional negative predictors for response include high viral load (>800,000 IU/mL) especially with genotype 1, age more than 40 years, high body mass index, insulin resistance or diabetes mellitus, African American heritage, HIV-HCV co-infection, inability to achieve rapid virological response (RVR) and early virological response (EVR) and advanced fibrosis or cirrhosis. Patients who have early-stage (noncirrhotic) disease generally achieve better virologic response than those who have bridging fibrosis or cirrhosis. Response is poorer in patients with cirrhosis because of poor tolerance, higher side effects, dose reductions of drugs and dropouts. Still anti-viral treatment is recommended in these patients because it can reduce the occurrence of complications (decompensation), including HCC and also reduce the post-transplant HCV recurrence. Treatment for patients with Child’s status C is usually recommended in specialised centres with facilities for liver transplantation. In this issue of the journal, Butt et al report sustained virological response (SVR) and predictive factors in 66 patients with cirrhosis due to genotype 3 HCV infection treated with pegIFN and RBV. Sixty one (92.4%) patients had Child’s A cirrhosis and 5 (7.6%) Child’s B. Thirty three (50%) patients received pegylated interferon alfa-2a (180 μg /week) with ribavirin and 33 (50%) received pegylated interferon alfa 2b (1 μg /kg/week) with ribavirin, both groups for one year. EVR was reached in 44 (66.7%), and end of treatment response (ETR) in 46 (69.7%); the overall SVR was achieved in 38 (57.6%) patients. Factors predictive of SVR were age (p value = 0.03), treatment naive status (p value = 0.04) and EVR (p value<0.001). Five patients were unable to complete the treatment due to side effects or cytopenias. They concluded that treatment of patients with HCV genotype 3, compensated cirrhosis, with pegylated interferon and ribavirin is effective and well tolerated. The study provides useful data from the Indian subcontinent where the predominant HCV genotype is 3 and where there is significant load of HCV-related cirrhosis. But at the same time, their study does raise a few important issues. Firstly there are mixed reports of response rate in patients with compensated HCV cirrhosis. In one study from Pakistan itself, 21 (13 male) of 94 patients with HCV-associated HCC received standard interferon therapy for a total of 24 weeks. All patients had cirrhosis with genotype 3 and were treated before the diagnosis of HCC. Fourteen (66.7%) of these patients had an end of treatment response but relapsed after discontinuation of treatment, with no sustained viral response. On the other hand in an Indian study, 28 patients with HCVrelated compensated cirrhosis (predominant genotype 3) treated with combination therapy of peg interferon alfa-2b (1 μg/kg/week) plus oral ribavirin (10-12 μg/kg/day) were analysed. Department of Hepatology Post Graduate Institute of Medical Education and Research, Chandigarh, India