Characterization of hepatitis B virus reverse transcriptase sequences in Chinese treatment naive patients.

BACKGROUND AND AIMS: The hepatitis B virus (HBV) reverse transcriptase (RT) plays an important role in viral replication. The aim of the present study was to characterize profiles of the RT region and to construct a database for further studies. METHODS: Serum samples were obtained from 328 treatment naive patients chronically infected with HBV in five Chinese cities. Mutation status, genotypes and deep sequence analysis were carried out by amplifying and sequencing the RT region. RESULTS: The base usage in the RT region differed at the mono- and dinucleotide level and thymidine dominated. The higher the variability of the strain was, the more it replicated. No significant clustering was found between our HBV RT sequences and those isolated 10 years ago (achieved from genebank). Nucleotide analogue resistance related mutants exist. The M204V/I mutation was found in 1.8% of the strains, 1.2% had L180M+ M204V/I, 0.6% had A181T/V, and only one had all three mutations. Minor strain mutants were found in 9.3% of the samples studied. The genotype B patients made up 36.6% (88.7% B2) and were mostly found in southern China, 63.4% (92.2% C2) were genotype C, and only one was genotype D. The average age of HBeAg positive genotype B patients was 29.5 +/- 10.4 years, for genotype C it was 36.1 +/- 10.9 (P < 0.001). CONCLUSION: Primarily antiviral resistance related mutant strains do exist in treatment naïve patients. Without antiviral pressure, HBV strains evolved at a normal speed. In depth sequence analysis implied that viral replication might be correlated with its variability, which needs to be further investigated.

[Histological changes in the livers of chronic hepatitis B patients with persistently normal serum alanine transaminase levels].

OBJECTIVE: To study the histological changes in livers of chronic hepatitis B (CHB) patients with persistently normal serum ALT levels (PNAL). METHODS: 274 CHB patients who had percutaneous liver biopsies and had a detectable viral load (lower limit of detection is 10(3) copies/ml) in our department between October 2003 and February 2007 were included in this study. Among these patients, 139 had PNAL, group A, (with at least 3 normal serum ALT levels, with intervals of more than two months over a period of 12 or more months before the biopsy). The other 135 patients, group B, had abnormal serum ALT levels during the same period. The histological changes in the livers of the two groups of patients were compared. RESULTS: Sixty-six (47.5%) patients with PNAL had normal liver histology, but significant pathohistological changes such as significant necroinflammation, fibrosis and/or cirrhosis were found in 33 (23.7%) patients. Thirteen (9.4%) had established cirrhosis. When compared to patients within (0-0.75)x upper limit of normal (ULN) ALT, patients within (0.76-1.00)x ULN ALT had higher scores of histological changes (43.5% vs. 19.8%, P < 0.05). In the PNAL group, scores of histological changes increased sharply in parallel with an age increase of older than 40 yrs. However neither viral loads nor HBeAg statuses of the PNAL patients had any predictive meaning to the scores of the histological findings. CONCLUSIONS: 23.7% of our CHB patients with PNAL, regardless of what their HBeAg statuses or viral load levels were, had significant liver pathohistological changes. Liver biopsies should be considered in CHB patients with PNAL, especially those older than 40 yrs and with a higher ALT within (0.76-1) x ULN.

Hepatitis B virus of genotype C persistence after recovery from acute hepatitis B virus infection in Japan.

BACKGROUND/AIMS: this study aimed to determine the viremia status after clinical, biochemical and serological recovery from acute hepatitis B viral (HBV) infection. METHODS: we detected serum HBV-DNA in 19 patients with acute hepatitis B during followed-up 6-43 months after onset, and analyzed HBV genotypes. RESULTS: 13 (72%) of 19 patients had detectable HBV DNA at the point of 6 months after onset, and four (33%) of 12 patients had persisted viremia for more than 1 year although they were recovery with normalization of alanine transaminase (ALT), disappearance of hepatitis B surface antigen (HBsAg) and appearance of antibody against HBsAg (anti-HBs). Eighteen (95%) of 19 patients were infected with HBV genotype C, one (5%) with genotype B. CONCLUSIONS: these results suggest genotype C of HBV is the predominant genotype of acute hepatitis B in Nagasaki region in Japan. HBV can persist in the serum for more than one year after complete clinical and serological recovery from acute viral hepatitis.