Impact of occult hepatitis B virus infection or hepatitis B virus DNA integration on efficacy of chronic hepatitis C treatment with peginterferon and ribavirin: where are we?

Occult hepatitis B virus (HBV) infection is defined as the presence of HBV DNA in the liver, with or without detectable HBV DNA in the serum of individuals tested negative for hepatitis B surface antigen (HBsAg). As both HBV and hepatitis C virus (HCV) share similar modes of transmission, HBV and HCV coinfection is a well-known clinical entity. Likewise, a high prevalence of occult HBV infection, ranging from 11% to 95%, has been reported in patients with chronic hepatitis C (CHC). 1–6 These findings raised a series of clinical questions, including its pathogenic and carcinogenic role and possible impact on HCV treatment response. Cacciola and colleagues conducted a retrospective study in Italy and found that among 66 of the 200 patients with CHC and negative serum HBsAg, but detectable HBV DNA in the liver biopsy tissue, 46 were antiHBc positive and 20 were negative for all HBV markers (P<0.001). The frequency of cirrhosis was significantly higher in CHC patients with occult HBV infection compared with those without occult HBV infection (22/66, 33% vs. 26/134, 19%; P=0.04). The authors concluded that occult HBV infection occurs frequently in patients with CHC and may have clinical significance.4 Another recent study conducted in France reported that only 4.4% (5/113) of patients with CHC and negative serum HBsAg had detectable HBV DNA in the liver biopsy tissue.7 Kao and colleagues conducted a similar study in Taiwan and found that, in 210 patients with CHC and negative serum HBsAg, 32 (14.8%) had HBV DNA in their sera, which was comparable to 100 healthy controls (15/100, 15%). HBV DNA was not detected in the sera of patients negative for serological markers of HBV infection. They concluded that, in patients with CHC, the prevalence of occult HBV infection did not parallel the severity of liver disease (14.5% in patients with chronic hepatitis, 8% in patients with liver cirrhosis, and 22% in patients with hepatocellular carcinoma). 8 Clearly, these results are not consistent, and it should be noted that in these studies different methods were used to determine occult HBV infection and all these reports are cross-sectional studies. Therefore, additional prospective studies are required to confirm whether occult HBV infection accelerates the progression of liver injury in patients with CHC. Another important clinical question is whether occult HBV infection could impact the treatment response in patients with CHC. Unfortunately, the present data related to this issue have also been inconsistent. Although some studies reported that occult HBV infection may provoke a reduction in the response rate to interferon (IFN) therapy in patients with CHC,4–6,8,9 the opposite results have also been reported. In the study by Cacciola et al4 in Italy, CHC patients with negative HBsAg but detectable intrahepatic HBV DNA were found to have a higher nonresponse rate to conventional IFN monotherapy compared with those without occult HBV infection (26/55; 47% vs. 7/28; 25%), but this was not statistically significant (P=0.06). Another study in France reported that the sustained virological response (SVR) rate to conventional IFN combined with ribavirin was significantly lower in CHC patients with negative HBsAg, but positive serum HBV DNA, compared with those without occult HBV infection (11/40; 28% vs. 65/144; 45%; P<0.05). This was also true in those with HCV genotype 1 infection (42% vs. 58%, P=0.004). The same results were also reported in patients who were HBsAg negative and anti-HBc positive, especially in those with HCV genotype 1 and 4 infection, although the sample size was very small.7 However, another study