Associations Between Hepatitis B Virus Mutations and the Risk of Hepatocellular Carcinoma: A Meta-Analysis

Abstract

BackgroundThe association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis remains controversial because of conflicting data in the literature. We conducted a meta-analysis of case–control and cohort studies to examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore mutations in relation to the risk of hepatocellular carcinoma (HCC).MethodsWe searched databases for studies of these associations that were published in English or Chinese up to August 31, 2008. HBV mutation–specific odds ratios and relative risks were pooled by use of a random-effects model and stratified by potential confounders. All statistical tests were two-sided.ResultsOf the 43 studies included in this meta-analysis, 40 used a case–control design. The 43 studies evaluated a total of 11 582 HBV-infected participants, of whom 2801 had HCC. Statistically significant summary odds ratios of HCC were obtained for any PreS mutation (3.77, 95% confidence interval [CI] = 2.57 to 5.52), C1653T in EnhII (2.76, 95% CI = 2.09 to 3.64), T1753V (2.35, 95% CI = 1.63 to 3.40), and A1762T/G1764A in BCP (3.79, 95% CI = 2.71 to 5.29). PreS mutations were more strongly associated with an increased risk of HCC in subjects who were infected with HBV genotype C than in those who were infected with HBV genotype B, whereas the opposite was true for A1762T/G1764A. C1653T, T1753V, and A1762T/G1764A were more strongly associated with an increased risk of HCC in hepatitis B e antigen (HBeAg)–positive subjects than in HBeAg-negative subjects. PreS mutations, C1653T, T1753V, and A1762T/G1764A accumulated during the progression of chronic HBV infection from the asymptomatic carrier state to HCC (Ptrend < .001 for each mutation). PreS mutations, C1653T, C1653T + T1753V, and A1762T/G1764A-based combinations of mutations had specificities greater than 80% for the prediction of HCC. The precore mutations G1896A and C1858T were not associated with the risk of HCC, regardless of HBeAg status and HBV genotype.ConclusionsHBV PreS mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. These mutations alone and in combination may be predictive for hepatocarcinogenesis.

Viral Factors and Outcomes of Chronic HBV Infection

“…Independent factors associated with HCC included age, abnormal ALT, HBV DNA ≥ 4 log10 copies per ml, genotype C, and core promoter mutations: C1653T, T1674C / G, T1753V, and A1762T / G1764A (TA). Apart from the T1674C / G mutation, these fi ndings are in agreement with previous studies ( 16 ). A previous meta-analysis found that the frequency of C1653T, T1753V, and TA mutations increased successively from ASC to cirrhosis ( 16 ).…”

“…Apart from the T1674C / G mutation, these fi ndings are in agreement with previous studies ( 16 ). A previous meta-analysis found that the frequency of C1653T, T1753V, and TA mutations increased successively from ASC to cirrhosis ( 16 ). Th is study confi rmed that even aft er adjustment for age (and duration of chronic HBV infection), core promoter mutations are associated with HCC.…”

“…Aft er adjustment for serum HBV DNA level and HBV genotype, the HR and 95 % confi dence interval (95 % CI) of the TA mutation for HCC was 1.73 (95 % CI 1.13 -2.67); by contrast, the HR for the most common precore stop codon mutation (G1896A) was 0.34 (95 % CI 0.21 -0.57). Besides TA mutations, other core promoter mutations have also been reported to be associated with an increased risk of HCC ( 16 ). Th ese other mutations were almost invariably found in association with the TA mutation, suggesting a key role for the TA mutation in hepatocarcinogenesis.…”

Hepatitis B Virus Gene C1653T Polymorphism Mutation and Hepatocellular Carcinoma Risk: an Updated Meta-analysis

“…However, the results have been inconsistent. Up to now, there has been only one published meta-analysis article focusing on the C1653T mutation,and the conclusion is that C1653T is associated with an increased risk of HCC (Liu et al, 2009). With much more studies focusing on the correlation of C1653T mutation with HCC,we update the meta-analysis and product a subgroup analysis to give a more comprehensive understanding on C1653T mutation with HCC risk.…”

Avaliação de fatores virológicos associados ao desenvolvimento de carcinoma hepatocelular (CHC) em pacientes com hepatite B crônica

“…As mutações comumente relatadas associadas ao CHC são mutações na região pré-S/S (pré-S1 e pré-S2) e várias mutações na região pré-core/core: dupla mutação no promotor do core A1762T/G1764A, G1896A, T1753V (A, C ou G) e C1653T (82)(83)(84)(85)(86) …”