By Liz Highleyman hivandhepatitis.com
Hepatitis C patients who maintain an undetectable plasma HCV RNA level 6 months after completion of interferon-based therapy are generally considered "cured." But 2 recent studies indicate that HCV may persist at low levels in the body, and successfully treated patients remain at risk for liver disease progression.
Low Level HCV
In the first study, reported in the December 23, 2008 advance online edition of Hepatology, Canadian researchers aimed to assess the infectivity of HCV persisting at very low levels using a previously established HCV infection system in human T-cells.
As background, the investigators noted that HCV can persist in the liver, lymphoid cells, and serum of individuals with apparently complete spontaneous or treatment-induced resolution of hepatitis C.
In this study, naive lymphoid cells were exposed to plasma and/or supernatants from cultured peripheral blood mononuclear cells from 9 individuals with apparent sustained virological response (SVR) after completion of antiviral therapy.
Exposed cells were analyzed for HCV RNA positive and negative strands. In selected cases, the researchers also assessed the presence of HCV non-structural protein 5a (NS5a), the appearance of HCV variants, and the release of virions (virus particles) using immunoelectron microscopy.
Results
11 of the 12 established cultures were HCV RNA positive strand-reactive.
4 also expressed the viral replicative strand.
The NS5a protein was detected in the newly infected cells.
Clonal sequencing revealed HCV variants not found in the inoculated plasma or supernatants.
Immunoelectron microscopy demonstrated enveloped HCV particles in plasma used as inocula and in culture supernatant from T-cells exposed to that plasma.
Overall, HCV carried by 3 of the 9 study participants elicited productive infection in vitro.
Based on these findings, the study authors concluded, "HCV persisting at very low levels long after therapy-induced resolution of chronic hepatitis C can remain infectious."
"The retained biological competence of the virus might have implications with respect to the mechanisms of its persistence and the epidemiology of HCV infection," they added.
Molecular Virology and Hepatology Research Group, Division of Biomedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada; Discipline of Laboratory Medicine, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada.
Liver Cancer
Hepatocellular carcinoma (HCC) is a form of primary liver cancer that can develop over time in people with chronic hepatitis C. While effective antiviral treatment has been shown to dramatically lower the risk of HCC, it does not eliminate it completely.
In the January 7, 2009 issue of Cases Journal, Japanese authors described a case of a patient who developed HCC more than a decade after successful treatment.
While there have been several recent reports of HCC developing in chronic hepatitis C patients even after attaining a sustained response to interferon-based therapy, it is not common for HCC to develop more than 10 years after achieving SVR, the authors noted as background.
The present case report involved a 73-year-old Japanese man with chronic hepatitis C who achieved SVR with interferon therapy 13 years ago. The man was admitted to the hospital after he developed multiple large liver tumors, along with marked elevation of tumor biomarkers.
After several diagnostic methods strongly suggested HCC, the authors performed histopathological (tissue) examination, confirming a diagnosis of well-differentiated HCC. Since the man's tumors were well-differentiated, he was able to be successfully treated with intensive combination therapy.
In conclusion, the authors wrote, "Our report highlights the need for careful follow-up for more than 10 years even if the patients with chronic hepatitis C achieve SVR to interferon therapy."
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan
2/06/09
References
SA Macparland, TN Pham, CS Guy, and TI Michalak. Hepatitis C virus persisting after clinically apparent sustained virological response to antiviral therapy retains infectivity in vitro. Hepatology. December 23, 2008 [Epub ahead of print].
T Mashitani, H Yoshiji, M Yamazaki, and others. Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report. Cases Journal 2(1): 18. January 7, 2009.
