Outcome of Sustained Virological Responders With Histologically Advanced Chronic Hepatitis C†,‡,§,¶

Abstract

Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n 5 309) or who experienced breakthrough or relapse (BT/R; n 5 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR 5 0.17, 95% confidence interval [CI] 5 0.06-0.46) or development of liver-related morbidity/mortality (HR 5 0.15, 95% CI 5 0.06-0.38) or HCC (HR 5 0.19, 95% CI 5 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR. Conclusion: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. (HEPATOLOGY 2010;52:833-844)

TGF-β signal shifting between tumor suppression and fibro-carcinogenesis in human chronic liver diseases

“…In chronic hepatitis, HCC occurrence clearly depends on continued presence of hepatitis viruses and chronic inflammation. In contrast, patients with cirrhosis have relatively low but real risks of HCC occurrence and hepatic decompensation despite SVR [10,11].…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Several studies and a meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage [79,80]. However, a reduction in the risk of HCC does not necessarily indicate improvement in overall survival, and interferon is less effective in patients with cirrhosis.…”

Interleukin 28b Gene Polymorphisms as a Predictor of Treatment Response in Egyptians With Chronic Hepatitis C.

“…While up to 80% of the genotype 2 and 3 infected and 40-50% in genotype 1 patients can be cured, the response rate of genotype 4 in many clinical repots is showing SVR rates exceeding 60% 14 . Once achieved, an SVR is associated with long-term clearance of HCV infection, which is regarded as a virologic ''cure,'' as well as with improved morbidity and mortality 18 .…”