Clinical significance of pre‐S mutations in patients with genotype C hepatitis B virus infection

Abstract

We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation

“…HBV variants with pre-S deletions were identified in both liver explant and blood samples. In general, these variants are often observed in patients with advanced disease, such as liver cirrhosis and HCC (12,13). This is consistent with the findings of this study, as the subject evaluated here had end-stage liver disease prior to a liver transplantation.…”

“…The mRNAs of these envelope proteins are transcribed from a single ORF; however, each has its own initiation codon (11). In general, the number of pre-S mutations can increase during the progression of CHB (12), and pre-S mutations are more prevalent in patients with HCC and liver cirrhosis (13). It has also been shown that NA treatments can select viral variants whose genomes encode truncated surface proteins, which could, in turn, accelerate liver disease progression (14).…”

Pre-S2 Deletions of Hepatitis B Virus and Hepatocellular Carcinoma in Children

“…Our study showed a significantly higher rate of pre-S2 deletions in the children of the HCC group than in the group with chronic HBV infection. The meaning of our results is unique and not merely in agreement with the studies in adults, because we found that pre-S2 deletions in HBV genomes did not necessarily take decades to accumulate, as in adult patients with advanced liver diseases (1,(15)(16)(17)(18)(19)(20)(21)(22); they emerged in nearly half of the young children with HBV-related HCC that developed in a relatively short period of time.…”

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

“…Previous data also demonstrated that T1753A/G/C mutations occurred later than the double BCP mutations in the natural course of chronic HBV infection (Takahashi et al, 1999). Regarding pre-S deletion, it has been shown in several reports that such mutant is an important risk factor of HCC (Chen et al, 2006;Choi et al, 2007). In vitro studies have also showed that intracellular accumulation of pre-S mutant proteins can modify HBV protein expression, induce ER stress and increased DNA damage (Hsieh et al, 2004).…”