High rate of core promoter and precore mutations in patients with chronic hepatitis B

Abstract

BackgroundThe prevalence of precore (PC) and core promoter (CP) mutations in patients with chronic hepatitis B virus (HBV) infection (CHB) and their impact on liver disease is incompletely defined in the United States.MethodsA retrospective chart review using a cross-sectional approach of 1,186 CHB patients was conducted.ResultsOf 926 patients tested for HBV e antigen (HBeAg), 37 % were HBeAg+. Of 194 patients tested for mutations, 80 % had PC or CP mutations or both; 89 % of HBeAg-negative and 56 % of HBeAg+ patients had PC or CP mutations or both (p < 0.001). The mean log10 ALT was significantly lower in patients with both mutations compared to patients without mutations. The mean log10 HBV DNA was significantly lower in patients with only PC mutations (4.82) compared to patients without mutations (5.71, p = 0.019). With the study population divided into four subgroups based on ALT level at time of diagnosis, cirrhosis incidence was significantly higher in patients with ALT 1–2 × ULN and ALT > 2 × ULN compared to patients with ALT ≤ 0.5 × ULN.ConclusionsOur finding that PC and CP mutations may be associated with milder liver disease in some patients could serve as the basis for longitudinal studies to help delineate treatment need and duration in patients with these mutations. If confirmed, the finding of an association between ALT 1–2 × ULN and increased incidence of cirrhosis could call into question guidelines which only recommend treatment with ALT > 2 × ULN.

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

“…However, for some patients the infecting virus strain mutate in the pre-core region to form the so-called pre-core mutant [12] or in the basal core promoter region [13, 14]. Patients infected with these mutants often have active liver disease with elevated HBV DNA levels in serum also after seroconversion to anti-HBe [15, 16].…”

Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities

“…Chronic hepatitis leads to necroinflammation and fibrosis progression, and increases the risk of developing cirrhosis and hepatocellular carcinoma. 297 mutations(Baqai et al, 2015; Chu et al, 2003; Takahashi et al, 298 1995) which transitions later to a dominant, but not pure, HBeAg(À) disease. If infection is transmitted from a person with 300 mixed infection, the person who becomes infected (for example, 301 the child in mother-to-child transmission) develops HBeAg(+) non-replicative phase characterized by normal ALT and low or 309 undetectable HBV DNA or transition directly to HBeAg(À) CHB.…”

Mutations in the Basal Core Promoter and Precore/Core Regions of Hepatitis B Virus in Patients Co-Infected With Human Immunodeficiency Virus

“…The 1762 and 1764 mutations reduce transcription of the PC mRNA by interfering binding of transcription factors, which in turn downregulates HBeAg synthesis. Some studies have shown that genomic mutations at positions 1727G, 1741C, 1761C, 1757A /1764T /1766G, 1773T, 1773T /1775G and 1909C are associated with HCC in HBV-infected patients (15)(16)(17)(18)(19). Several studies have reported an association between CP mutations and increased risk of liver inflammation, cirrhosis (20) and HCC (21).…”

“…The other hotspot CP mutations are 1753A/C/G and 1768A, which are also associated with the increased risk of HCC. BCP mutations are common in HCC patients and there is a high rate of point mutations in this region (particularly dual V131L and K130M) among patients with cirrhosis and HCC (18,(25)(26)(27). In our study, we identified these mutations in two patients that can be indicator of HCC progression.…”