Analysis Of Antiretroviral Treatment And Liver-Related Complications In Chronic Hepatitis B Patients Based On Real-World Data

PART 1.HBV DNA AND LIVER-RELATED COMPLICATIONS IN CHRONIC HEPATITIS B PATIENTS TREATED WITH DIFFERENT DRUGSObjective: Chronic hepatitis B(CHB)is a major global public health problem.Although antiviral drugs have been widely used in recent years,Liver-related complications associated with CHB infection such as hepatocellular carcinoma(HCC)still occur.In addition,there is still controversy about the therapeutic effect of various drugs on CHB and the effect of liver-related complications,especially between entecavir(ETV)and tenofovir(tenofovir disoproxil fumarate,TDF),which are the two first-line drugs recommended by clinical guidelines.This study compared and analyzed the effects of different antiviral drugs on HBV DNA virological response in CHB patients,and also compared whether the Liver-related complications are distinct in different drug treatments.Methods: This study was a retrospective study that included and analyzed the data of 3658 CHB patients treated with different drugs in The Second Affiliated Hospital of Chongqing Medical University between January 2006 and July 2021.Included patients had HBV DNA greater than5 log10 IU/ml at the start of treatment and excluded patients diagnosed with cirrhosis and other liver-related complications before treatment and within 6 months after treatment initiation.Results: We screened 3658 patients from the Integrated Clinical Data Systems of Chronic Hepatitis B(ICDS-CHB)database of Chongqing Medical University,and 60,29,168,2547,and 735 patients received Adefovir(ADV),Lamivudine(LAM),Telbivudine(LDT),ETV and TDF treatment.In total,3539 patients were treated with NAs and 119 patients were treated with IFN.Among them,patients receiving ETV treatment had a higher proportion of males(p < 0.001)and were significantly older than those receiving TDF(p < 0.001).In HBV DNA correlation analysis,we found that compared with patients receiving nucleos(t)ide analogues(NAs)and TDF,patients treated with ETV and interferon(IFN)had a higher rate of HBV DNA relapse(p < 0.001).In addition,patients treated with ETV were significantly more likely to develop liver-related complications than those treated with TDF(p < 0.001).COX proportional hazards model showed that male(HR=1.149,log-rank-p=<0.001)and age >40(HR=1.9,log-rank-p=<0.001)were significantly associated with liver-related complications.Conclusions: Compared with ETV therapy,TDF therapy is associated with a lower risk of HCC,which may be related to age,male,etc.Compared with patients treated with NAs,patients treated with IFN did not develop HCC,but this may be due to the difference in the scale of data between the two groups,and further research is needed to clarify.PART 2.EFFECTS OF AGE AND BASELINE HBEAG IN CHRONIC HEPATITIS B PATIENTS RECEIVED NUCLEOS(T)IDE ANALOGUESObjective: Advances in antiviral therapy over the past few decades have greatly improved outcomes in chronic hepatitis B(CHB),but challenges persist.In current CHB studies,the effects of HBeAg seroconversion and age on CHB patients are not well established.In this study,we analyzed data on HBeAg and age at different baselines in patients treated with entecavir and tenofovir to explore their impact on the development of liver-related complications.Methods: This study was a retrospective study that included and analyzed 2547 and 735 patients treated with entecavir and tenofovir.And grouped by age <18 years,18-30 years,31-40 years,41-50 years,>50 years and HBeAg(+)& ALT(+),HBeAg(+)& ALT(-)and HBeAg(-).Results: Among the ETV-treated patients grouped by age,the patients in the >50 group had the largest proportion of patients with virological response during the follow-up period(383,72.3%),and the smallest proportion of patients with virological re-positivity(99,18.7%),Kaplan-Meier analysis showed that >50 years group was more likely to achieve virological response than 18-30 years,31-40 years and 41-50 years group,this phenomenon was also observed in patients ≤40 years and >40 years,and with TDF-treated patients.In addition,patients aged >40 years had statistically significant differences with patients ≤40 years in the total number of liver-related complications,HCC,and cirrhosis(p < 0.001).Among ETV-treated patients grouped by baseline HBeAg and ALT,Kaplan-Meier analysis showed that the HBeAg(-)group was more likely to obtain virological response than the HBeAg(+)& ALT(+)and HBeAg(+)&ALT(-)groups(p < 0.001),similar results were observed in TDF-treated patients.Pairwise comparison analysis showed that the incidence of liver-related complications in HBeAg(+)& ALT(-)group and HBeAg(-)group was significantly higher than that in HBeAg(+)& ALT(+)group(p=0.002,p<0.001).Conclusion: Patients >50 years of age and HBeAg-negative were more likely to achieve a virological response,while HBeAg-positive and ALT-normal,HBeAg-negative and older patients were more likely to develop liver-related complications.PART 3.ANALYSIS OF HEPATITIS B SURFACE ANTIGEN SEROCLEARANCE IN PATIENTS EXPERIENCED NUCLEOSIDE ANALOGS OR INTERFERON MONOTHERAPYObjective:Little is known about the difference in durability of HBs Ag seroclearance induced by nucleoside analogs(NAs)or by interferon(IFN).In the present study we analyzed the difference in persistence between HBs Ag seroclearance induced by NAs and IFN monotherapy.Methods:A real-world,retrospective cohort study was conducted.Patients were assigned into two groups: NAs monotherapy induced HBs Ag seroclearance subjects and IFN monotherapy induced HBs Ag seroclearance subjects.A total of 198 subjects,comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced,who achieved HBs Ag seroclearance were included in this study.The patients who had at least one negative HBs Ag result after 6 months from HBs Ag seroclearance was defined as "confirmed seroclearance".Results:The one-year probability of confirmed HBs Ag seroclearance were significantly different in patients with NAs monotherapy and IFN monotherapy(0.960(with 95% CI 0.922-0.999)vs.0.691(with 95% CI0.523-0.913),log-rank-p<0.001).The probabilities of confirmed HBs Ag seroclearance within one year and follow-up was higher in IFN monotherapy patients with HBs Ab than the patients without HBs Ab[0.825(95% CI 0.631-1.000)vs.0.539(95% CI 0.306-0.951),log-rank test,p=0.051;0.839(95% CI 0.657-1.000)vs.0.489(95% CI0.251-0.953),log-rank test,p=0.024],it means patients with HBs Ag seroconversion induced by IFN have a lower HBs Ag recurrence rate.73.3%(11 of 15)HBs Ag recurrence occurred within 1 year after HBs Ag seroclearance.Conclusion: Our study thus provided novel insights into the durability of HBs Ag seroclearance induced by NAs or IFN monotherapy.In particular,the HBs Ag seroreversion rate was relatively high in IFN monotherapy subjects.The presence of HBs Ab was significantly correlated with a longer durability of functional cure induced by IFN treatment.And continued follow-up for 1 year after HBs Ag seroclearance is necessary.