Male Hepatitis B Virus Carriers Research Articles

Cytochrome P450 1A1 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis B carriers.

Cigarette smoking has been associated with increased risk of hepatocellular carcinoma (HCC) in some epidemiological studies. Cytochrome P450 1A1 (CYP1A1) is involved in the biotransformation of tobacco-derived polycyclic aromatic hydrocarbons (PAHs) into carcinogenic metabolites. The aim of this study was to determine whether CYP1A1 polymorphisms were related to HCC risk among chronic hepatitis B virus (HBV) carriers. Genotypic variants of CYP1A1 were determined using polymerase chain reaction in 81 incident cases of HCC and 409 controls nested in a cohort study of 4841 male chronic HBV carriers. No overall association between CYP1A1 genotypes and HCC was observed. The presence of the MspI (odds ratio (OR) 3.15, P= 0.0196) or Ile-Val (OR 1.99, P= 0.0855) variant allele of CYP1A1 increased HCC risk among smokers, but posed no increased risk among non-smokers. The smoking-related HCC risk was most pronounced among those who had a susceptible allele of the CYP1A1 and a deficient genotype of glutathione S-transferase M1, which detoxifies PAH electrophilic metabolites produced by CYP1A1. In the absence of the Ile-Val variant allele, the MspI polymorphism was still associated with smoking-related HCC. This study suggests that tobacco-derived PAHs play a role in HCC risk among chronic HBV carriers, and CYP1A1 polymorphism is an important modulator of the hepatocarcinogenic effect of PAHs. The MspI and Ile-Val polymorphisms of CYP1A1 may have different mechanisms for increasing susceptibility to smoking-related HCC. © 1999 Cancer Research Campaign

Successful treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non-Hodgkin’s lymphoma

Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for malignant lymphoma, are at high risk of mortality from reactivated HBV infection. We report a case of a 29-year-old male chronic HBV carrier who developed fulminant reactivated HBV infection following intensive chemotherapy for stage IVB large cell B-cell non-Hodgkin's lymphoma associated with extensive central nervous system and bone marrow involvement. Prior to chemotherapy the patient had normal liver function tests and was negative for HBV DNA by semiquantitative PCR assay. Fulminant HBV reactivation was confirmed following clinical deterioration, massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850 U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued. Symptoms and liver function tests improved within days and HBV DNA became negative within 12 weeks. Our patient later died from relapsed lymphoma but without evidence of reactivated HBV infection. We advise that lamivudine should be considered during intensive chemotherapy treatment of chronic carriers of HBV.

Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection.

Hepatitis B virus (HBV) and HIV infections share risk-factors; therefore coinfection is common. Interactions have been reported but controlled studies have been limited. Our objective was to study the effect of HIV infection on the natural history of chronic HBV infection and the reverse effect of the HBV carrier state on HIV infection. Prospective observational cohort study. Open-access outpatient HIV/genitourinary medicine clinic at a Central London hospital. Total of 152 untreated homosexual male HBV carriers and 212 HBV surface antigen-negative controls (41.4 and 70.3% HIV-seropositive, respectively). The rate of loss of serum HBV e antigen (HBeAg) and its reappearance in HIV-infected and HIV-uninfected HBV carriers; serum HBV DNA levels measured by dot-blot hybridization assay), HBV DNA polymerase activity and liver transaminase activities, the progression of HIV infection to symptomatic disease or AIDS in HIV-infected compared with HBV-HIV coinfected patients. In HIV-infected HBV carriers, serum HBV DNA polymerase activity was higher, alanine aminotransferase was lower and loss of serum HBeAg (mean follow-up, 2.8 years) occurred at a lower rate when compared with HIV-uninfected HBV carriers (estimated relative hazard, 0.39; 95% confidence interval, 0.161-0.942) Concomitant chronic HBV infection had no detectable effect on the rate of progression of HIV disease after correction for lead-time bias. This study strengthens the evidence for a significant effect of HIV infection on the natural history of chronic HBV infection, which by prolonging the period of infectivity could have an important impact on the epidemiology of HBV infection in regions, or patient groups, with high HIV seroprevalence. There was no evidence of an important effect of HBV carriage on HIV disease progression.

Effect of human immunodeficiency virus (HIV) infection on chronic hepatitis B hepatic viral antigen display

Immunofluorescent and immunoperoxidase monoclonal antibody-based techniques were used to demonstrate hepatitis B e antigen (HBeAg) and hepatitis B c antigen (HBcAg) display in the liver biopsy specimens of 45 chronic hepatitis B virus (HBV) carriers. Anti-human immunodeficiency virus (anti-HIV)-positive HBV carriers had many more HBe- and HBc-positive hepatocyte nuclei than anti-HIV-negative carriers (P less than 0.0003 and less than 0.02, respectively), and HBV-DNA levels were slightly, but not significantly, increased in the positive subjects. The number of HBe- and HBc-positive nuclei were positively correlated with serum HBV-DNA levels (P less than 0.05 comparing high serum HBV-DNA levels of greater than 2880 pg/ml and levels of 1-480 pg/ml), and were negatively correlated with disease activity (P less than 0.05 comparing those with severe chronic active hepatitis (CAH) and those with mild CAH and chronic persistent hepatitis (CPH]. These results indicate that male homosexual HBV carriers, positive for anti-HIV, may be immunosuppressed before there are clinical signs of immunodeficiency, and this allows an increased level of replication of at least one other virus (HBV).

A follow-up study of hepatitis B virus carriers at hospital.

For the purpose of clarifying the relation between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), a follow-up study of 1,614 HBV carriers (910 males and 704 females) was conducted at Kure National Hospital from 1970 to 1984. During the follow-up period (40.3 months on average), 247 HBV carriers died. Deaths from HCC and liver cirrhosis (LC) numbered 99 of 168 males (58.9%) and 38 of 79 females (48.2%), the chi-square test revealing no sex difference. Of 142 deaths from malignant neoplasm, HCC accounted for 52 of 96 males (54.2%) and 19 of 46 females (41.3%), the chi-square test again revealing no sex difference. The adjusted odds ratio of death from HCC among HBV carriers (1,614) with respect to HBV non-carriers (176,909) in this hospital during the study period (14-years) was 9.52 (males 7.94, females 13.39). The expected number of deaths was calculated based on the population of Hiroshima Prefecture (1978-1980) as a standard. The adjusted O/E (observed number/expected number) ratio of death from HCC was 6.66 for males and 12.13 for females, and the adjusted O/E ratio of death from LC was 5.41 for males and 11.02 for females. These findings suggest that HBV is a high risk factor of both HCC and LC, and, unlike the general population, female HBV carriers may have a rather higher risk of death from HCC and LC than male HBV carriers.

Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer.

In order to confirm the close association between chronic hepatitis B virus (HBV) infection and primary hepatocellular carcinoma (PHC) in Japan, 8,646 male hepatitis B surface antigen (HBs Ag)-positive blood donors (GPT less than or equal to 35 Karmen units) were followed up. Twenty liver cancer cases were observed during the follow-up period (average 6.2 years), the expected number calculated on the basis of age-specific incidence rates among the general population being 3.03. Therefore, the observed to expected ratio of liver cancer was 6.60, that is significantly higher than 1.0. During the same follow-up period, a total of 76 deaths were observed, of which 20 were due to liver cancers and 9 to liver cirrhoses, meaning that nearly 40% of deaths among the study subjects due to chronic liver diseases. Drinking and smoking habits in the liver cancer cases were compared with those observed in healthy male HBV carriers. A strong positive association between drinking habits and liver cancer was observed and there was a significant dose-response relationship after adjustment for cigarette smoking habits. A high risk of liver cancer was also observed among heavy smokers, but a significant dose-response relationship could not be found between smoking habits and liver cancer, partly because of the limited number of the study subjects. These findings suggest that HBV is a major etiologic agent of PHC in Japan where the HBs Ag prevalence rate is about 2%, and alcohol drinking and cigarette smoking may promote the process of HB viral hepato-carcinogenesis.