https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840120409

Interrelationship of blood transfusion, non‐A, non‐B hepatitis and hepatocellular carcinoma: Analysis by detection of antibody to hepatitis C virus

Background The presence of hepatitis B e antigen (HBeAg) in serum indicates active viral replication in hepatocytes. HBeAg is thus a surrogate marker for the presence of hepatitis B virus DNA. We conducted a prospective study to determine the relation between positivity for hepatitis B surface antigen (HBsAg) and HBeAg and the development of hepatocellular carcinoma. Methods In 1991 and 1992, we enrolled 11,893 men without evidence of hepatocellular carcinoma (age range, 30 to 65 years) from seven townships in Taiwan. Serum samples obtained at the time of enrollment were tested for HBsAg and HBeAg by radioimmunoassay. The diagnosis of hepatocellular carcinoma was ascertained through data linkage with the computerized National Cancer Registry in Taiwan and with death certificates. We performed a multiple regression analysis to determine the relative risk of hepatocellular carcinoma among men who were positive for HBsAg alone or for HBsAg and HBeAg, as compared with those who were negative for both. Results...

Hepatitis B e antigen and the risk of hepatocellular carcinoma.

We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm.

Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens.

Summary Worldwide, chronic hepatitis B virus (HBV) infection is the primary cause of cirrhosis and hepatocellular carcinoma and is one of the ten leading causes of death. Traditionally, people with chronic HBV infection have been identified with blood tests for HBV antigens and antibodies. Recently, another group of patients with chronic HBV infection has been identified by sensitive, molecular testing for HBV DNA. Members of this group are often referred to as having occult hepatitis B because they are HBV-DNA positive, but hepatitis B surface antigen negative. Occult hepatitis B occurs in a number of clinical settings. In this review, we examine occult hepatitis B in people co-infected with hepatitis C, in whom occult hepatitis B has been associated with advanced fibrosis and diminished response to interferon α. Although much more research is needed, existing reports justify a heightened awareness of the medical importance and means of testing for occult hepatitis B.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(02)00345-6.pdf

Occult hepatitis B

Background: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. Patients and methods: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of α fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. Results: In total, 426 patients were followed up for 1664 person years; median 225 (range 12–295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14–236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39–23.89; p Conclusion: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.

https://gut.bmj.com/content/gutjnl/53/10/1494.full.pdf

Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840030302

Detection of hepatitis B virus DNA directly in human serum by a simplified molecular hybridization test: comparison to HBeAg/anti-HBe status in HBsAg carriers.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840010102

Michael C. Kew

Papers

Detection of hepatitis B virus DNA directly in human serum by a simplified molecular hybridization test: comparison to HBeAg/anti-HBe status in HBsAg carriers.

Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas