Successful HCV virus eradication is durable

Posted on April 15, 2015

Study reconfirms that successful anti-HCV therapy translates into increased patient survival at least in chronically infected patients with advanced stages of fibrosis. Achieving SVR did not entirely prevent hepatic decompensation or HCC, which adds further credence to continued long-term surveillance for HCC in SVR patients.

Long-term complications of chronic hepatitis C infection including liver cirrhosis, portal hypertension and hepatocellular carcinoma (HCC) are resulting in increasing rates of mortality. Successful anti-viral treatment of hepatitis C prolongs life expectancy, reduces liver-related deaths and the incidence of hepatocellular carcinoma (HCC) in patients with advanced stages of fibrosis, as compared with patients without a successful HCV eradication. While the clinical benefit of HCV therapy in patients with advanced liver fibrosis is established, the benefit in patients with mild liver disease is less clear. Results of a study of all-cause and liver-related mortality, incidence of HCC and liver failure or liver transplantation in SVR and nonsustained virological responders (non-SVR) to anti-viral therapy with different stages of fibrosis, were recently published in the journal Alimentary Pharmacology and Therapeutics (Rutter K et al. Aliment Pharmacol Ther 2015; 41: 521–531). In total, 714 patients (276 females) with chronic hepatitis C who received at least 1 course of anti-viral therapy at a single tertiary referral center between 1990 and 2012 were regularly followed and retrospectively analyzed.

  • 551 patients with SVR: male/female = 325/226, mean age: 50.2 ± 11.9 (years ± SD); HCV genotype 1: 324 (58.8%), HCV-2: 19 (3.5%), HCV-3: 145 (26.3%), HCV-4: 57 (10.3%), no HCV genotype available: 6 (1.1%). Median follow up duration of 6.6 (1–21.1) years. Of the 551 patients with SVR, 546 (99%) had undetectable HCV RNA at the end of follow-up.
  • 163 patients without SVR: male/female = 113/50, mean age: 55.5 ± 11.7 (years ± SD); HCV genotype 1: 134 (82.2%), HCV-3: 3 (1.8%); HCV-4: 25 (15.4%), HCV genotype missing: 1 (0.6%). Median follow up duration of 9.0 (1–19.9) years.

Non-SVR was identified as an independent predictor of HCC in a Cox analysis adjusted for sex, age and advanced fibrosis (HR: 2.36 (95% CI: 1.07–5.23); P = 0.034)

  • Ten patients who had a SVR developed HCC (1.8%) with a follow-up time of 4.1 (1.0–7.2) years, compared with 19 (11.7%, P < 0.001) patients were non-SVR with a follow-up time of 4.8 (0.8–12.3) years.
  • 24/29 patients who suffered from HCC had fibrosis stage 3 or 4 (SVR: 8/10, non-SVR: 16/19) and 23/29 patients had a pre-treatment liver cirrhosis (SVR: 7/10, non-SVR: 16/19), respectively.

Non-SVR was identified as an independent predictor of hepatic decompensation in a Cox analysis adjusted for sex, age and advanced fibrosis (HR: 2.62 (95% CI: 1.18–5.81); P = 0.018)

  • Hepatic decompensation occurred in 29 patients (4%; including eight patients with HCC; 10 female, mean age: 58.6 ± 11.1 years; median follow-up time of 4 (0.1–11) years).
  • The pre-treatment liver biopsy showed advanced fibrosis (F3) in 2 and cirrhosis (F4) in 27 patients.
  • Nine patients had SVR (1.6%) and 20 were non-SVR (12.3%, P < 0.001).

Non-SVR was identified as an independent risk factor of death or liver transplantation in a Cox analysis adjusted for sex, age and advanced fibrosis (HR: 3.46 (95% CI: 1.91–6.29), P < 0.001)

  • Of the 48 patients (female 17, mean age: 60 ± 12 years) who died during follow-up, 15 had a SVR and 33 did not achieve a viral eradication (P < 0.001).
  • Occurrence of HCC or other liver disease-related complications was the cause of death in 16 patients.
  • Five- and 10-year mortality rate was 1.8% (10/551) and 2.7% (15/551) in the SVR group, in contrast to 8.6% (14/163) and 19.1% (31/163) in the non-SVR group (P < 0.001).

The results of this study reconfirm that a successful anti-HCV therapy translates into increased patient survival at least in chronically-infected patients with advanced stages of fibrosis. Achieving SVR did not entirely prevent hepatic decompensation or HCC, which adds further credence to continued long-term surveillance for HCC in SVR patients, especially if they have additional risk factors for developing HCC such as cirrhosis, male gender, advanced age, occult hepatitis B (or anti-HBc positivity), alcohol consumption, diabetes mellitus or steatosis.

While a survival benefit could not be demonstrated within the follow-up period for SVR patients with early stages of fibrosis, the impact of HCV treatment in these patients is difficult to assess and longer follow-up periods might be needed. The authors noted that prevention of cirrhosis is a relevant goal of therapy in patients with less advanced liver disease and those with earlier stages of liver disease, as they are more likely to respond to IFN-based and IFN-free treatments. In addition, HCV infection might contribute to extrahepatic morbidity. The authors concluded the following: “our study reconfirms that successful viral eradication is durable. Furthermore, achieving a sustained virological response improves survival in patients with advanced liver disease due to HCV infection. The risk of development of HCC or liver failure is decreased but not completely prevented. Thus, patients should have further follow-up after achieving a SVR.”


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