Resolution of Hepatitis C Infection

Abstract & Commentary

Synopsis: Studies on HCV infection resolution show that PBMC HCV-RNA may remain, despite clearance of the virus from plasma.

Source: Wawrzynowicz-Syczewska M, et al. Infection. 2004;32:138-143.

Hepatitis C infection is usually asymptomatic, but with insidious progression. This paper from Poland features the outcomes of a series of patients with acute hepatitis C in order to determine the resolution or progression of disease. In the 10-year period from 1988-1998, 159 patients were recognized with acute HCV, 77 of which were eventually enrolled into the study. In 46, an incubation period could be determined. Past hepatitis B infection was detected in 19. Of the 77 patients, 23 (30%) became spontaneously negative for serum HCV-RNA and had no elevation of ALT. All but 3 of these patients were still anti-HCV antibody positive. Of the 30% who were negative for routine HCV viral load analysis, 2 had positive HCV in peripheral blood mononuclear cell (PBMC) assay.

Comparison of HCV-RNA(+) and HCV-RNA(-), by univariate analysis, revealed that HCV clearance was associated with higher hepatic enzymes and a history of alcohol abuse. Multiple other analysis showed the same associations.

There were 45 liver biopsies available for review. None showed severe inflammation. Clinically silent cirrhosis was present in 19%. Mild or minimal forms of chronic hepatitis was the common finding. Factors that were associated statistically with advanced liver histologic findings included male gender, heavy alcohol consumption, increased iron stores measured as serum ferritin (particularly with levels > 115 ng/mL), and older age at time of exposure.

Comment by Joseph F. John Jr., MD

This study is unusual because Wawrzynowicz-Syczewska and colleagues found a number of patients with a history of acute HCV that had a median time after acute infection of 8 years. A unique aspect of the study was the use of HCV detection in PBMCs, an approach that showed patients with negative viral loads , done by routine testing, may still have detectable HCV using PBMC analysis. This finding suggests that perhaps more rigorous searches for latent HCV infection, possibly using PBMC assays, will have implications for future antiviral chemotherapy.

Ironically, the more icteric the initial episode, the more likely the spontaneous resolution. Wawrzynowicz-Syczewska et al emphasize this finding, suggesting that early lymphocyte stimulation allows a better cell-mediated response to infection.

The issue of fibrosis/cirrhosis is more confusing. In this study, about 20% of patients had histologic evidence of cirrhosis. Recall that the findings of inflammation were so minimal that the progression of the disease to fibrosis/cirrhosis involves other factors, Wawrzynowicz-Syczewska et al would argue, more than the inflammatory response.

Dr. John is the Chief of Medical Subspecialty Services at Ralph H. Johnson Veterans Medical Center and a Professor of Medicine at the University of South Carolina, Charleston.