Sequencing of human‐viral DNA junctions in hepatocellular carcinoma from patients with HCV and occult HBV infection

Abstract

DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.

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

“…The prevalence of occult infection seems to be closely related to the prevalence of HBV infection in different parts of the world. Several investigators have shown an intermediate to high occurrence of HBV occult infection, both in serum and in liver tissue (1,2,4,(8)(9)(10)(11)(12)(13)(14)(15). In Brazil, particularly in the Southeast region, the prevalence of HBV infection is very low (21) and this may have contributed to our results of an HBV occult infection rate close to zero.…”

“…Cirrhosis is considered to be the most important risk factor for HCC. 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).…”

Clinicopathologic Features and Outcome After Liver Resection for Hepatocellular Carcinoma in Patients with Concurrent Versus Previous Chronic Hepatitis B

“…[10][11][12][13][14][15][16][17][18] Futhermore, HBV has been detected in the hepatic tissue of some patients after Tumor-free survival rates after liver resection for hepatocellular carcinoma. Circles, 58 patients whose sera were positive for hepatitis B surface antigen but negative for antihepatitis C virus antibody (group A).…”

Occult Hepatitis B (OBH) in Clinical Settings

“…Furthermore, in a direct examination using cassette-ligation-mediated PCR in the junctions between HBV DNA and human DNA, the integration of HBV DNA was identified in 10 out of 34 HCC patients, all of whom were OHB positive. Four of these integrations were observed in chromosome 11q (78). Altogether, clear evidence exists that OHB infection HBV maintains its pro-oncogenic properties in case of occult HBV infection, possibly by integrating with the host genome, the synthesis of pro-oncogenic proteins by free intra-hepatic HBV genomes (33, 36, 47, 52, 64, 69), or by progression from through cirrhosis to hepatocellular carcinoma (73).…”