Previous observational studies suggested that hepatitis B virus (HBV) preS mutation plays an important role in the existence of HBV-related hepatocellular carcinoma (HCC). However, the results are still debatable. With an increasing number of studies about this topic, this study employed a meta-analysis to identify the association between HBV preS mutation and HCC risk. We searched for eligible studies from PubMed, ProQuest, CINAHL, ScienceDirect and Springer databases to assess the association between HBV mutation and HCC risk. This meta-analysis was conducted using RevMan 5.3 to provide pooled estimate for odds ratio (ORs) with 95% confidence intervals (95% CIs). Twenty-one clinical studies were included in this meta-analysis study which consisted of 1738 participants with HBV-related HCC and 3740 HBsAg-positive patients without HCC. All studies used samples of Asian population. PreS deletion was the most common mutation found in all studies. We found that ORs of HBV overall preS deletion was associated with HCC (OR = 3.28; 95% CI = 2.32-4.65; P <.00001; random-effects model). Each preS1 and preS2 deletion was associated with increased risk of HCC, with OR 2.42 (95% CI = 1.25-4.68, P =.008) and 3.36 (95% CI = 2.04-5.55, P <.00001), respectively. PreS2 start codon mutation was also significantly associated with HCC risk (OR = 2.47; 95% CI: 1.15-5.27; P =.02; random-effect model). The result of this meta-analysis suggested that HBV preS deletion (all, preS1 and preS2) and preS2 start codon mutation might contribute to the increased risk of HBV-related HCC.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalJournal of Viral Hepatitis
Issue number1
Publication statusPublished - Jan 2021


  • hepatitis B virus
  • hepatocellular carcinoma
  • meta-analysis
  • preS mutation


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