Correlation between mutations in the interferon sensitivity-determining region of NS5A protein and viral load of hepatitis C virus subtypes 1b, 1c, and 2a.

In the present study, we analyzed the possible relationship between interferon (IFN) sensitivity-determining region (ISDR) sequence variation of various hepatitis C virus (HCV) subtypes and serum HCV titers in Indonesian patients without IFN treatment. The viremia titers (mean +/- standard deviation) of HCV subtype 1b (HCV-1b) isolates with low (three or fewer) and high (four or more) numbers of ISDR mutations were 5.4 +/- 0.6 and 4.2 +/- 0.9 log(10) RNA copies/ml, respectively, with the difference between the two groups being statistically significant (P < 0.01). Similarly, the viremia titers of HCV-1c isolates with low and high numbers of ISDR mutations were 5.3 +/- 0.6 and <3.0 +/- 0.0 log(10) RNA copies/ml, respectively, with the difference between the two groups being statistically significant (P < 0.01). Also, the virus titers of HCV-2a isolates with low and high numbers of ISDR mutations were 4.3 +/- 0.7 and 3.5 +/- 0.4 log(10) RNA copies/ml, respectively, with the difference between the two groups being statistically significant (P < 0.01). Thus, our results demonstrated that virus load in Indonesian patients infected with HCV-1b, HCV-1c, or HCV-2a correlated inversely with the number of mutations in the ISDR sequence, implying the possibility that the ISDR sequence plays an important role in determining the levels of HCV viremia.

Viral load in Indonesian patients with chronic liver disease and in blood donors infected with different subtypes of hepatitis C virus.

The viral load of different hepatitis C virus (HCV) subtypes, including the globally distributed HCV-1b and the unique Indonesian subtype HCV-1c, was analyzed using serum samples obtained from Indonesian blood donors and patients with chronic liver disease. The mean viral load of HCV-1c was comparable with that of HCV-1b, suggesting that HCV-1c is as pathogenic as HCV-1b. On the other hand, the mean viral load of HCV-2a was lower than that of HCV-1b or HCV-1c, with this result being consistent with previous observations. Interestingly, some HCV-2a strains were associated with a high viral load that was almost equivalent to that of HCV-1b and HCV-1c. This result implies the possibility that there exists a minor fraction of HCV-2a strains that cause higher levels of viremia compared with the majority of ordinary HCV-2a strains.

Prevalence of GB virus C/Hepatitis G virus infection among various populations in Surabaya, Indonesia, and identification of novel groups of sequence variants.

A molecular epidemiological study was performed to investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among various populations in Surabaya, Indonesia. The prevalence of GBV-C/HGV RNA, determined by reverse transcription-PCR for a portion of the NS3 region of the viral genome, was 2.7% (4 of 150) among randomly collected blood donor sera, which were all negative for both hepatitis B virus surface antigen and antibodies against hepatitis C virus (HCV). On the other hand, the prevalence among anti-HCV-positive blood donors was 17.8% (13 of 73), with the ratio being significantly higher than that observed with the anti-HCV-negative blood donors (P < 0.001). A high prevalence of GBV-C/HGV infection was also observed among patients with chronic liver disease, such as chronic hepatitis (5.7%), liver cirrhosis (11. 5%), and hepatocellular carcinoma (7.0%), and patients on maintenance hemodialysis (29.0%). No correlation was observed between GBV-C/HGV viremia and serum alanine aminotransferase levels in the populations tested, suggesting the possibility that GBV-C/HGV does not cause apparent liver injury. Phylogenetic analysis of sequences of a portion of the 5' untranslated region and the E1 region of the viral genome identified, in addition to a previously reported then novel group of GBV-C/HGV variants (group 4), another novel group of variants (group 5). This result suggests that GBV-C/HGV can be classified into at least five genetic groups. GBV-C/HGV isolates of group 4 and group 5 were each shown to comprise approximately 40% of the total Indonesian isolates.