Sustained Virological Response Was Durable After Several Years in Patients With Hepatitis C

Risk for recurrence was greater in high-risk and HIV coinfected patients.

Results from an analysis of 43 studies involving more than 9,000 patients showed that for low risk patients treated for hepatitis C, the 5-year risk of recurrence following sustained virological response was less than 1%.

Fourteen studies evaluating high risk patients and four evaluating patients with hepatitis C/HIV coinfection showed a much high risk for recurrence in these patient populations.

“In patients without ongoing high-risk behavior, relapse and/or reinfection was very low,” Graham S. Cook, MD, told Infectious Disease Advisor. Cooke, a clinical senior lecturer of infectious diseases at Imperial College London, was one of the study’s coauthors. “In other words, cure was durable with the health benefit that brings including a reduced risk of cancer, death and end stage liver disease. However, in high risk groups, particularly intravenous drug users and HIV-positive men who have sex with men, there was a significant chance of reinfection within 5 years–up to 15% in HIV-positive men who have sex with men. This tells us that infection with HCV offers inadequate protection to reinfection unlike many other infectious diseases.”

Studies have shown that sustained virological response, defined as absence of virus in the blood 12 or 24 weeks after the completion of antiviral therapy, is associated with improved outcomes for patients with hepatitis C, including reduced risk for hepatocellular carcinoma and improved overall survival. Nonetheless, treatment uptake for patients with chronic hepatitis C has been low because of treatment complexities and poor success rates.

The researchers conducted a meta-analysis of studies collected in the MEDLINE database from 1990 to March 2015. Simmons et al analyzed studies that examined hepatitis C recurrence post-sustained virological response to provide summary estimates of the recurrence rate by risk group and to evaluate the contribution of late relapse and of reinfection to the recurrence rate.

This meta-analysis included 43 studies looking at low-risk patients (N=7,969), 14 studies that considered high risk patients (N=617), and four studies that evaluated patients (N=309) with coinfection.

In 39 studies, low risk patients were treated with interferon or pegylated interferon, either in combination with ribavirin or as monotherapy. In 3 other studies, patients were treated with pegylated interferon, ribavirin, and a direct acting antiviral drug. The final study did not specify the treatment regimen.

The mean average follow-up after sustained virological response was 3.9 years (range, 1.0–8.7 years).

There were 108 reports of hepatitis C observed in reviewed studies. Following random effects meta-analysis, the pooled estimate for the recurrence rate was 1.85 per 1,000 person years of follow-up (95% CI, 0.71 to 3.35). Based on this pooled estimate, the researchers concluded that the 5-year recurrence risk was 0.95% (95% CI, 0.35% to 1.69%).

The pooled estimate was 0.82 per 1,000 person years of follow-up (95% CI, 0.08 to 2.05) for late relapse, for a 5-year rate of late relapse of 0.40% (95% CI, 0.35% to 1.05%). Researchers did not find incidence of reinfection.

Among high risk patients, there were 12 studies that included only patients with chronic hepatitis C and two that included patients with acute and chronic infections. Patients received interferon or pegylated interferon with or without ribavirin in 9 studies and  interferon or pegylated interferon plus ribavirin or a direct acting antiviral drug. Four studies did not specify the antiviral regimen.

Average mean follow-up after sustained virological response was 2.8 years.

With 42 recorded recurrences, the pooled estimate for recurrence was 22.32 per 1,000 person years of follow-up (95% CI, 13.07 to 33.46). Researchers observed a low level of heterogeneity (I2 = 27.3%).

Based on the pooled estimate, the 5-year recurrence rate was 10.67% (95% CI, 6.38% to 15.66%), which researchers explained was likely driven more by reinfection, 19.06 per 1,000 person years of follow-up (95% CI, 11.42 to 28.16) rather than late relapse.

“We need interventions for behavioral change, but they have limited effect,” said Dr Cooke. “Expanding treatment into high risk populations has the potential to reduce reinfection by reducing the number of infectious people out there.”


1. Simmons B, Saleem J, Hill A, et al. Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis. Clin Infect Dis J. 2016; oi: 10.1093/cid/civ948.