A putative hepatitis B virus splice variant associated with chronic hepatitis and liver cirrhosis

Hepatitis B virus (HBV) pre-S deletion was associated with chronic hepatitis (CH) and liver cirrhosis (LC); however, the type of pre-S deletion associated with these conditions and the mechanism of the generation of pre-S deletion remain unknown. Here, pre-S sequences from asymptomatic carriers (ASCs) and carriers with CH or LC were analyzed. The results indicated that deletion in the S promoter and the C-terminal half of the pre-S1 region was more frequent in CH and LC patients than in ASCs. RNA splicing analysis revealed that one type of pre-S1 deletion mutant, termed spPS1, was derived from splicing. This variant was associated with CH (12.7% vs. 1.8%, P = 0.06) and LC (14.5% vs. 1.8%, P = 0.032) when compared with ASC. In conclusion, spPS1, a putative splice variant; S promoter deletion mutant; and deletion in the C-terminal half of the pre-S1 region were closely associated with CH and LC development.