Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

Normal vitamin D levels are associated with spontaneous hepatitis B surface antigen seroclearance

AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneousHBsAg seroclearance.HBsAg seroclearance. RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (>35 years) OR = 1.7 (95%CI: 1.25-2.8, P=0.05), serum vitamin D levels (>20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P=0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P=0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P=0.04) were also associated with spontaneous HBsAg seroclearance. CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer

AIM To assess the impact of hepatitis B surface(HBs Ag) seroclearance on survival outcomes in hepatitis B-related primary liver cancer.METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBs Ag(-) and HBc Ab(+) liver cancer were included in the HBs Ag seroclearance(SC) group. HBs Ag(+) liver cancer patients strictly matched for liver cancer stage(AJCC staging system, 8 th edition), Child-Pugh score, and first diagnosis/treatment method(surgery, ablation and TACE) were assigned to the HBsA g non-seroclearance(NSC) group. Then, clinical, pathological and survival data in both groups were assessed.RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age(P < 0.001) and platelet count(P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma(ICC) and combined HCC-CC(CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups(4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group(P = 0.019), with 1-,3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2%vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage Ⅰ disease in the SC group was lower than that of the NSC group(P = 0.029).CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Durability of Hepatitis B surface antigen seroclearance in patients experienced nucleoside analogs or interferon monotherapy: A real-world data from Electronic Health Record

Little is known about the difference in durability of HBsAg seroclearance induced by nucleoside analogs (NAs) or by interferon (IFN). A real-world, retrospective cohort study was conducted. Patients were assigned into two groups: NAs monotherapy-induced HBsAg seroclearance subjects and IFN monotherapy induced-HBsAg seroclearance subjects. A total of 198 subjects, comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced, who achieved HBsAg seroclearance were included in this study. The one-year probabilities of confirmed HBsAg 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% CI 0.523–0.913), log-rank-P = 4.04e-4). 73.3% (11 of 15) HBsAg recurrence occurred within one year after HBsAg seroclearance. The one-year probabilities of confirmed HBsAg seroclearance were higher in IFN monotherapy patients with anti-HBs than in IFN monotherapy patients without anti-HBs (0.839 (with 95% CI 0.657–1.000) vs. 0.489 (with 95% CI 0.251–0.953), log-rank test, P = 0.024). Our study thus provided novel insights into the durability of HBsAg seroclearance induced by NAs or IFN monotherapy. In particular, the HBsAg seroreversion rate was relatively high in IFN monotherapy subjects. The presence of anti-HBs was significantly correlated with a longer durability of functional cure induced by IFN treatment. And one-year follow-up in HBsAg seroclearance achieved individuals is proper for averting HBsAg seroreversion and other liver disease.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong,China

Background:Hepatitis B surface antigen(HBsAg)clearance is vital for a functional cure of hepatitis B virus(HBV)infection.However,the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus(HIV)remain largely unknown in Guangdong,China.Methods:Between 2009 and 2019,patients co-infected with HBV/HIV undergoing antiretroviral therapy(ART)in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31,2020.The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.Results:A total of 1550 HBV/HIV co-infected patients were included in the study,with the median age of 42 years and 86.0%(1333/1550)males.Further,98.3%(1524/1550)received ART containing tenofovir disoproxil fumarate(TDF)plus lamivudine(3TC).HBV DNA was examined in 1283 cases at the last follow-up.Over the median 4.7 years of follow-up,8.1%(126/1550)patients achieved HBsAg seroclearance,among whom 50.8%(64/126)obtained hepatitis B surface antibody,28.1%(137/488)acquired hepatitis B e antigen seroconversion,and 95.9%(1231/1283)undetectable HBV DNA.Compared with patients who maintained HBsAg positive,cases achieving HBsAg seroclearance showed no differences in age,gender,CD4+T cell count,alanine aminotransferase(ALT)level,or fibrosis status;however,they presented lower HBV DNA levels,lower HBsAg levels,and higher rates of HBV genotype B at the baseline.Multivariate analysis showed that baseline HBsAg<1500 cutoff index(COI)(adjusted hazard ratio[aHR],2.74,95%confidence interval[95%CI]:1.48-5.09),ALT elevation>2×upper limit of normal during the first six months after receiving ART(aHR,2.96,95%CI:1.53-5.77),and HBV genotype B(aHR,3.73,95%CI:1.46-9.59)were independent predictors for HBsAg seroclearance(all P<0.01).Conclusions:Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients.Lower baseline HBsAg levels,HBV genotype B,and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.