Hepatitis B virus infection and genomic changes from a long-term perspective

Sammanfattning: Hepatitis B virus is a non-cytopathic virus with a small, circular, partially double-stranded DNA of 3.2 kb. It causes acute and chronic inflammatory liver disease and hepatocellular carcinoma (HCC). Retesting of stored sera from an outbreak of acute hepatitis in 1969-72 allowed identification of 126 cases of acute hepatitis B. No chronic carriers expressing hepatitis B surface antigen (HBsAg) could be found among 100 patients at follow-up 25-30 years later. Sixteen patients with documented self-limited acute hepatitis were evaluated further. HBV DNA could not be detected by PCR in serum or PBMCs. However, HBV DNA could be detected in the liver specimens of two patients 30 years after having an acute hepatitis B infection. Both patients had histological signs of minor liver inflammation. When selected genomic sequences of the strains detected in the liver were compared with the primary infecting strains in serum collected 30 years earlier, they were identical. Mutations in the precore and core promoter (cp) regions of the HBV genome have been associated with a lack of detectable hepatitis B e antigen (HBeAg). The precore and cp regions of viral strains from 83 chronic HBV carriers, including 16 carriers sampled during HBeAg seroconversion, were sequenced. The development of precore and cp mutations appeared to be a separate event from the HBeAg seroconversion. Mutations in strains from 16 patients with HBV infection and HCC were analyzed. Sequencing of the preS, S, X, and precore regions showed a high prevalence (50%) of mutations affecting part of the preS2 region which codes for B and T cells epitopes.