Does HCV Really Go Away?
Abstract & Commentary
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center. Dr. Kemper reports no financial relationships to this field of study.
Synopsis: HCV may persist and replicate in the liver and PBMCs of healthy, anti-HCV antibody-positive, serum HCV RNA-negative patients who have persistently normal ALT levels. These patients should be followed up, because they have an ongoing viral infection.
Source: Carreño V, et al. Detection of Hepatitis C Virus (HCV) RNA in the Liver of Healthy, Anti-HCV Antibody-Positive, Serum HCV RNA-Negative Patients with Normal Alanine Aminotransferase Levels. J Infect Dis. 2006:194:53-60.
A small number (5% to 15%) of fortunate people who become acutely infected with HCV appear to clear their infection with no residual evidence of HCV viremia and normal transaminases. Suspicions are, however, being cast on whether HCV can ever be, in fact, completely cleared from the body. Studies have shown that patients successfully treated with antiviral therapy who achieve sustained undetectable levels of plasma HCV RNA may still harbor occult intrahepatic virus. Other investigators have identified HCV RNA in the peripheral blood mononuclear cells (PBMC) of a few patients who apparently cleared their viremia and developed anti-HCV antibodies, either naturally or in response to antiviral treatment.
Carreño and colleagues in Madrid, Spain, examined liver biopsies from 12 patients with anti-HCV antibodies by recombinant immunoblot assay and negative serum HCV RNA (Amplicor HCV, version 2.0, Roche Diagnostics). Two of the patients had a remote history of blood transfusion more than 25 years earlier. The remaining patients had no history of hepatitis and no risk factor for HCV. During a mean follow-up of 29 ± 20 months, none of the patients developed clinical or laboratory evidence of HCV infection. Serum transaminases remained normal; they continued to have undetectable plasma HCV RNA, and all 12 remained HCV antibody positive.
Commentary
Surprisingly, despite this lack of evidence for residual HCV infection, 10 of 12 (83%) liver biopsies were positive for genomic HCV RNA. All 10 of these specimens also demonstrated positive antigenomic HCV RNA strands, indicating occult replication. All 10 individuals had genotype 1b, raising concerns about possible cross-contamination in the lab, but nucleotide sequencing revealed distinct clones.
Genomic HCV RNA was also detected in the PBMCs of 6 of 12 patients (50%) (all of whom had positive liver biopsies); anti-genomic RNA was identified in 5 of these.
Despite a lack of clinical or other laboratory evidence of infection, histopathology in one patient revealed chronic active hepatitis and stage 1 fibrosis. Other potential causes of liver disease were ruled-out in this individual. Three patients had steatohepatitis or steatosis (2 were overweight and one was diabetic). The remaining 6 patients with positive intrahepatic HCV RNA had normal or minimal histologic changes.
HCV may persist and replicate in the liver and PBMCs of healthy, anti-HCV antibody-positive, serum HCV RNA-negative patients who have persistently normal ALT levels. These patients should be followed up, because they have an ongoing viral infection.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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