Cases Of Hepatitis B Virus Reactivation Research Articles

Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with rituximab has been reported increasingly. The aim of this study was to investigate the molecular mechanisms underlying HBV reactivation in an HBsAg-negative patient. HBV was reactivated in a 75-year-old man following chemotherapy with rituximab, without elevation of HBsAg. The patient's full-length HBV genome was cloned and the entire sequence was determined. Transfection studies were performed in vitro using recombinant wild-type HBV (wild-type), the patient's HBV (patient), and two chimeric HBV constructs, in which the preS/S region of the patient and wild-type virus had been exchanged with one another. Secreted HBsAg and intra- and extra-cellular HBV DNA were measured. The number of amino acid substitutions in HBV from this patient was much higher than in previous reports of HBV mutants, such as occult HBV and vaccine escape HBV mutants. Levels of HBsAg and HBV DNA production in vitro were significantly lower in the patient compared to wild-type transfections. From analyses of the chimeric constructs, the altered preS/S region was responsible mainly for this impairment. These results show that highly mutated HBV can reactivate after chemotherapy with rituximab, despite an unusually large number of mutations, resulting in impaired viral replication in vitro. Severe immune suppression, probably caused by rituximab, may permit reactivation of highly mutated HBV. These findings have important clinical implications for the prevention and management of HBV reactivation and may explain partially the mechanism of recent, unusual cases of HBV reactivation.

Prevalence and significance of occult hepatitis B in a liver transplant population with chronic hepatitis C

Occult hepatitis B virus (HBV) infection is defined as the detection of HBV deoxyribonucleic acid (DNA) in the serum or liver tissue of individuals who test negative for hepatitis B surface antigen (HBsAg). We undertook a prospective study to evaluate the significance and course of occult HBV in patients with hepatitis C virus (HCV) cirrhosis undergoing orthotopic liver transplantation (OLT). A sensitive real-time polymerase chain reaction assay was utilized to test for serum HBV DNA at enrollment and for hepatic HBV DNA within the explant liver. Patients were followed with serum HBsAg and HBV DNA post-OLT. A total of 56 patients with HCV cirrhosis were enrolled between October 2002 and July 2004; of these, 44 underwent OLT. The overall prevalence of occult HBV based on positive serum HBV DNA was 16 of 56 (28%), and based on positive hepatic HBV DNA ("occult HBV liver") was 22 of 44 (50%). The presence of serum hepatitis B core antibody (anti-HBc) and a past history of injection drug use correlated with occult HBV.Explant-proven hepatocellular carcinoma (HCC) was found in 13 of 22 (59%) patients with occult HBV liver compared to 8 of 22 (36%) patients without occult HBV liver (P ¼ 0.36, odds ratio 2.5; confidence interval 0.76–8.54 [corrected]. Post-OLT, no cases of HBV reactivation were noted, and there was no significant association between occult HBV and recurrent HCV. In conclusion, occult HBV is far more prevalent in patients with end-stage HCV than would be expected from its prevalence in the general population. Occult HBV infection is strongly associated with the presence of anti-HBc, history of injection drug use, and explant-proven HCC.