Long-term follow-up of hepatitis G virus/GB virus C replication in liver during and after interferon therapy in patients coinfected with hepatitis C and G viruses

We investigated changes in the titers of positive and negative strands of hepatitis G virus (HGV) RNA and hepatitis C virus (HCV) RNA in serum and liver during and 1 to 3 years after interferon therapy in patients with chronic hepatitis C coinfected with HGV/GBV-C. Eight (6%) of 134 patients with chronic hepatitis C treated with interferon were positive for HGV RNA and were examined retrospectively. Titers of positive and negative strands of HGV RNA and HCV RNA were determined by strand-specific reverse transcriptase-polymerase chain reaction. Before therapy, HGV RNA titers in liver were lower than those in serum (P = 0.0169), while HCV RNA titers in liver were significantly higher than those in serum (P = 0.0074). No negative strands of HGV RNA were detected in serum, liver, or peripheral blood mononuclear cells in any patients. With interferon therapy, 5 of the 8 patients lost HCV RNA from serum and liver, with sustained normal liver biochemical values and significant histological improvement. HGV RNA disappeared transiently from serum and liver at the end of therapy in 5 patients, but reappeared again after therapy in 4 of them. Two of the 8 patients naturally lost HGV RNA after completion of therapy. These findings suggest that: (1) HGV/GBV-C does not appear to replicate in liver, serum, or peripheral blood mononuclear cells, (2) detection of HGV RNA in liver and peripheral blood mononuclear cells may be a mere reflection of serum HGV RNA, and (3) the long-term clinical outcome of chronic HGV/GBV-C infection appeared to be benign.