Abstract
Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p < 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p < 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.
Highlights
Hepatitis B virus (HBV) infection is a public health challenge that affects more than 250 million people worldwide (WHO, 2017)
chronic hepatitis B (CHB) patients continuously using monotherapy of the firstline Nucleos(t)ide analogs (NAs) entecavir or tenofovir disoproxil fumarate for at least weeks were selected for propensity score matching (PSM) with IBM SPSS Statistics software (IBM SPSS Statistics, IBM, Chicago, IL, United States) to control for confounding factors, such as age, sex, diagnosis, baseline HBV DNA and type of NAs
For subgroup analysis, even though the proportions of primary nonresponse, partial virological response, and hepatitis B reactivation were lower in heterozygous carriers than in wild-type controls among patients taking ETV, only the percentage of primary nonresponse was found to be significantly lower (OR, 0.87; 95% 95% confidence intervals (CI), 0.79–0.97; p 0.013)
Summary
Hepatitis B virus (HBV) infection is a public health challenge that affects more than 250 million people worldwide (WHO, 2017). Oral nucleos(t)ide analog (NA) therapy is currently the mainstream form of anti-HBV treatment. Viral suppression with NAs therapy directly affects the prognosis of CHB patients. All patients included in this study received either the nucleoside analog ETV or nucleotide analog TDF (Chen and Liaw, 2016). These triphosphorylated NAs compete with endogenous deoxynucleoside triphosphates (dNTPs) for incorporation into the viral DNA chain and terminate its elongation immediately (Fung et al, 2011) or at 2 or 3 nt downstream of incorporation (ETV) (Langley et al, 2007)
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