Occult hepatitis B virus infection in HBs antigen-negative hepatocellular carcinoma in a Japanese population: Involvement of HBx and p53

Abstract

Hepatitis B virus (HBV) genome was reported to be detected in serum or liver tissues in hepatocellular carcinoma (HCC) patients negative for hepatitis B surface antigen (HBsAg). Hepatitis B x (HBx) and p53 protein were reported to play an important role in HBV-related hepatocarcinogenesis. To clarify latent HBV infection in HBsAg- and anti-hepatitis C virus (anti-HCV)-negative HCC in a Japanese population and involvement of HBx and p53 protein in these patients, we performed the sensitive and specific nested polymerase chain reaction (PCR) and immunohistochemical analysis. Of 1,024 HCC patients we saw between 1974 and 1998, 66 (6.4%) were negative for HBsAg and anti-HCV. Serum DNA was amplified by nested PCR by using specific primers of surface (S), core (C) and X regions in 26 patients negative for HBsAg and anti-HCV. Eighteen (69%) patients were positive for either S, C, or X region and the results of PCR were confirmed by Southern blotting. Of 18 PCR-positive patients, 3 were positive for anti-HBs and 9 were positive for anti-HBc, however, one was negative for any HBV markers. In HBsAg-negative and PCR-positive patients, the positive rates of expression of HBx and p53 were 8/13 (62%) and 7/13 (54%), being comparable to those in HBsAg-positive HCC patients. The results of the present study suggest that high prevalence of HBV infection is observed in HBsAg-negative HCC in a Japanese population and expression of HBx and p53 is consistent with a role, in these patients, for the transforming ability of these proteins.

Lack of correlation between the antibody to hepatitis B core antigen and survival after surgical resection for hepatitis C virus-related hepatocellular carcinoma

“…HBsAg and anti-HBc were detected using commercial enzyme immunoassay kits (Dainabot, Tokyo, Japan) (13). The results of the anti-HBc assays were expressed as the percentage of inhibition, and the specimens were considered to be anti-HBc-positive when the percentage of inhibition was >50% (19).…”

“…The results of the anti-HBc assays were expressed as the percentage of inhibition, and the specimens were considered to be anti-HBc-positive when the percentage of inhibition was >50% (19). HCVAb was assessed using second-generation assays (Dainabot) (13). In the present study, serum HCV RNA levels were tested in 182 (82.0%) out of 222 patients by using a competitive reverse transcription-polymerase chain reaction assay.…”

“…HBV DNA may be present in a latent form, even after seroclearance of HB surface antigen (HBsAg), which is referred to as occult HBV infection (8,13). Anti-HBc is reported to be a surrogate marker for such latent carriers (14).…”

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

“…Therefore, besides having a possible direct oncogenetic effect, occult HBV infection may increase neoplastic transformation in HCV-infected patients (4,8). The oncogenicity of occult HBV infection is related to the transactivating role of the HBx protein and to the ability of HBV to integrate the host genome (16,17). Indeed, some studies have shown that HBV DNA could be detected in HBsAg-negative patients with HCC (18,19).…”

Occult hepatitis B virus infection: A hidden menace?

“…Other patients may have chronic HBV infection for decades leading to liver damage but HBsAg is no longer detectable when cirrhosis or HCC is diagnosed. [19][20][21] The role of occult HBV infection in the etiology of liver disease in seronegative individuals is less clear. Data are scanty and based on case reports or case series.…”