Late relapse after SVR may not be new HCV infection

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Hara K. J Infect Dis. 2013;doi:10.1093/infdis/jit541.

November 11, 2013

Patients with hepatitis C who relapse after achieving sustained virological response may be having a relapse of the initial infection rather than a reinfection with a different strain, recent data published in the Journal of Infectious Diseases suggest.

“In a few individuals, hepatitis C has found a sanctuary site and can remain dormant for a length of time,” Theo Heller, MD, chief of the translational hepatology unit at the Liver Diseases Branch of the National Institute of Diabetes & Digestive & Kidney Diseases, told Infectious Disease News. “This is important both biologically and clinically, even in the approaching era of direct-acting antivirals, where relapse may still be a problem. We already know it can and does occur.”

According to the researchers, the liver is considered one of the sanctuary sites in which HCV RNA can persist after SVR is achieved: “Further studies are needed to elucidate how HCV RNA can be maintained at such low levels of virus for prolonged periods after SVR is achieved.”

In a follow up analysis, the researchers evaluated HCV RNA sequences in serum and liver tissue from 103 patients who achieved SVR after receiving interferon-based therapy between 1985 and 2005. Three of the patients had a late relapse, testing positive for HCV RNA at 8 months, 75 months and 78 months. Four patients had an early relapse and were used as controls.

The serum samples taken before treatment and after relapse were sequenced and compared. Among the early relapse patients, the sequence identity between the pretreatment and relapse samples was more than 99.4%. Among the late-relapse patients, the sequence identity between the samples was more than 98.8%. The genotypes were also identical before treatment and after relapse for both early and late relapsers.

“There are increasing data that cirrhotic patients who are long-term responders to treatment are still at risk for liver cancer,” Heller said. “I believe the findings in this study form part of that spectrum, and suggest that high-risk patients be followed on a regular basis, even after viral clearance.”

Heller said that these findings have raised several important questions that should be the focus of future research. These include why the immune system does not finish off HCV, why the virus persists at low levels for so long, and why it does not clear and recur sooner.

Disclosure: Heller reports no relevant disclosures.

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