Clinical Study Of Entecavir In Patients With Chronic Hepatitis B With Low-level Viremia

Objective: Compare the efficacy and safety of entecavir(ETV)in treating chronic hepatitis B hypoviremia in patients who have been treated with entecavir(ETV).Continue using entecavir,switch to tenofovir alfenamida fumarate(TAF),or switch to entecavir combined with tenofovir fumarate for treatment of 12,24,and 48 weeks,and explore the relevant factors affecting hypoviremia among the three treatment regimens.Methods: A retrospective study was conducted on 246 chronic hepatitis B patients who had been treated with ETV for 48 weeks at Qingdao University Affiliated Hospital from July 2020 to October 2022 and developed hypoviremia.They were divided into three groups,including 86 patients who continued to use ETV,83 patients who switched to TAF,and 77 patients who switched to ETV combined with TAF.The complete virology response rate(CVR rate)and the level of serum hepatitis B virus deoxyribonucleic acid(HBV DNA)load decline were observed at the 12 th,24th and 48 th weeks after treatment in the three groups;The clearance rate of hepatitis B virus surface antigen(HBs Ag),the negative conversion rate of hepatitis B virus e antigen(HBe Ag),and the serological conversion rate of HBe Ag;Changes in levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL);The incidence of liver fibrosis and cirrhosis,as well as liver cancer;Changes in renal function,blood phosphorus,blood calcium,creatine kinase levels,and incidence of adverse events.Analyze and explore the relevant influencing factors that still lead to LLV after 48 weeks of treatment with three different regimens.Results:1.CVR rate in ETV group,TAF group and combined group was 17.4%,42.2% and 61.0%at 12 weeks,respectively,and the difference was statistically significant(P < 0.001);18.6%,57.8% and 72.7% at 24 weeks,respectively,and the difference was statistically significant(P < 0.001);29.1%,73.5% and 90.9% at 48 weeks,respectively,and the difference was statistically significant(P < 0.001).At 12 weeks,24 weeks and 48 weeks of treatment,there were statistically significant differences between the three groups(P <0.05).2.The median HBV DNA load(log10 IU/ml)reduction was 0.16(0.05,0.45),0.94(0.29,1.41)and 1.18(0.53,1.66)at 12 weeks in the ETV,TAF and combined groups,respectively,and the overall distribution was statistically different(P < 0.001);0.17(0.03,0.46),1.35(0.71,1.65)and 1.49(1.08,1.89)at 24 weeks,respectively,and the overall distribution was statistically different(P < 0.001);0.34(0.04,1.28),1.49(1.11,1.85)and1.65(1.38,2.11)at 48 weeks,respectively,and the overall distribution was statistically different(P < 0.001).At 12 weeks,24 weeks and 48 weeks of treatment,there were statistically significant differences between the three groups(P < 0.05).3.There was no significant difference in HBs Ag clearance rate,HBe Ag negative rate and HBe Ag seroconversion rate between the three groups at weeks 24 and 48(P > 0.05).4.At weeks 12,24 and 48 of ALT,AST and TBIL,there was no statistically significant difference in the distribution of median levels among the three groups(P > 0.05).Compared at baseline and before and after 48 weeks in the three groups,there was no statistically significant difference in the distribution of median ALT,AST,and TBIL levels in the ETV group(P > 0.05);there was a significant difference in median ALT and AST levels between the TAF and combined groups(P < 0.05),and there was no significant difference in TBIL levels(P > 0.05).5.There was no significant difference in APRI and FIB-4 at 24 and 48 weeks in the three group(P > 0.05).One patient in TAF group developed liver cancer at 24 weeks,and no liver cancer occurred within 48 weeks in ETV group and combined group,with no statistical difference among the three groups(P > 0.05).No new cirrhosis within 48 weeks in the 3 groups.6.There was no significant difference in e GFR,serum phosphorus,serum calcium,creatine kinase and incidence of adverse events between the three groups at 24 and 48weeks(P > 0.05).There was a statistically significant difference in the overall distribution of e GFR levels at baseline and 48 weeks between the three groups(P = 0.003);there was no statistically significant difference in the overall distribution between the ETV and combined groups(P > 0.05).There was no statistically significant difference in the incidence of adverse events within 48 weeks among the three groups(P > 0.05).7.Young age was an independent risk factor for persistent low-level viremia in patients who continued ETV(OR = 1.046,95% CI: 1.001-1.127,P < 0.05).In patients switched to TAF,high HBV DNA load levels were an independent risk factor for sustained low-level viremia(OR = 0.142,95% CI: 0.048-0.421,P < 0.001).High HBV DNA load levels were a risk factor for sustained low-level viremia in patients receiving ETV in combination with TAF(OR = 0.239,95% CI: 0.059-0.966,P < 0.001).Conclusion:1.In ETV-treated patients with chronic hepatitis B LLV,switching to TAF or ETV combined with TAF is superior to continuing ETV in terms of CVR rate and HBV DNA load reduction;the combination can achieve CVR at a greater rate and earlier than switching to TAF alone.2.Switching to TAF or combination reduces ALT and AST levels compared with continuing ETV.Switching to TAF improved renal function to some extent compared to continuing ETV or combination therapy.3.Young age is an independent risk factor for LLV following ETV use,and high HBV DNA load levels are a risk factor for switching to TAF or combination therapy.3.Young age is an independent risk factor for LLV with continued ETV,and high HBV DNA load levels are risk factors for LLV with switching to TAF or combination therapy.