Impact Of Hepatic Steatosis On Response To Antiviral Therapy Of Chronic Hepatitis B

Background China has a large amount of chronic hepatitis B(CHB)patients.Long-term nucleos(t)ide analogues(NAs)antiviral therapy can inhibit hepatitis B virus(HBV)replication continuously,significantly reduce the risk of disease progression in CHB patients.In recent years,with changes in lifestyle and diet,the prevalence of nonalcoholic fatty liver disease(NAFLD)in China has shown a significant increasing trend.However,the effect of hepatic steatosis on the efficacy of NAs treatment in CHB patients remains unclear.Objective To investigate the impact of hepatic steatosis on antiviral treatment response in chronic hepatitis B.Methods We retrospectively recruited treatment-naive CHB patients who received Entecavir or Tenofovir for initial antiviral treatment in Department of Infectious Diseases,Nanfang Hospital between January 2017 to December 2018 and collected demographic information,virological,biochemical test results and controlled attenuation parameter(CAP)value before treatment,as well as virological and biochemical test results every 3-6 months(±1.5 months)after treatment.According to CAP value before treatment,patients were divided into NAFLD group(CAP≥238 dB/m)and non-NAFLD group(CAP<238 dB/m)The impact of hepatic steatosis on NAs antiviral treatment response in CHB were retrospectively analyzed by comparing the biochemical and virological indicators of the two groups before and after the treatment,as well as the differences in the cumulative incidence of treatment response.Results A total of 445 CHB patients were enrolled in the analysis,of whom 82(18.4%)had NAFLD.The quantitative levels of HBV DNA and HBsAg in the NAFLD group before treatment tended to be lower than those in the non-NAFLD group(HBV DNA;5.81 vs.6.27 log10 IU/ml,p=0.070;HBsAg:3.28 vs.3.47 log10 IU/ml,p=0.068),and NAFLD group had a significantly lower lever of alanine aminotransferase(ALT)than non-NAFLD group(111 U/L vs.170 U/L,p=0.009).During NAs antiviral treatment,the decrease in HBV DNA level of NAFLD group was lower than that of non-NAFLD group(Month 3:-3.54 log10 IU/ml vs.-4.07 log10 IU/ml,p=0.020;Month 9:-4.37 log10 IU/ml vs.-4.87 log10 IU/ml,p=0.520),the decrease in HBsAg level was lower than that of the non-NAFLD group as well,but not quite significantly(Month 3:-0.18 log10 IU/ml vs.-0.341 log10 IU/ml,p=0.156;Month 9:-0.387 log10 IU/ml vs.-0.504 Iog10 IU/ml,p=0.520);NAFLD group had a significantly lower lever of alanine aminotransferase(ALT)than non-NAFLD group(Month 3:52 U/L vs.37 U/L,p=0.040;Month 6:39 U/L vs.28 U/L,p=0.019).After 3 years of antiviral treatment,the cumulative incidence of HBeAg loss(28.1%vs.57.2%,p=0.042)and ALT normalization(97.5%vs.100.0%,p=0.029)in the NAFLD group were significantly lower than those of non-NAFLD group.Multivariate analysis showed CAP value was independently associated with probability of HBeAg loss(HR:0.994,95%CI:0.988-1.000,p=0.049)and probability of ALT normalization(HR:0.996,95%CI:0.994-0.999,p=0.009).There was no significant difference between NAFLD group and non-NAFLD group in the cumulative incidence rate of virological response(100.0%vs.100.0%,p=0.327),HBsAg decline>1 log(21.9%vs.27.7%,p=0.128)and HBeAg seroconversion(26.4%vs.51.3%,p=0.121).Conclusion Concurrent hepatic steatosis can affect the virological and biochemical indicators of CHB patients.It can reduce the efficacy of NAs treatment in CHB patients to a certain extent.It is necessary to further clarify the underlying mechanism of liver steatosis affecting the efficacy of antiviral therapy in the future.