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 an...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.展开更多
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 i...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.展开更多
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...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%.展开更多
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...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.展开更多
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...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.展开更多
Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of...Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.展开更多
HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients expe...HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients experiencing higher liver-related morbidity,hospitalization rates,and mortality than those with HBV monoinfection.Surprisingly,an increasing number of studies have shown that hepatitis B surface antigen(HBsAg)clearance rates in HIV/HBV coinfection can reach over 10%,which is significantly higher than in HBV monoinfection.In this review,we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection,including baseline HBsAg levels,baseline HBV DNA levels,baseline CD4+T cell-counts,and immune reconstitution inflammatory syndrome-related hepatic flare.Based on current evidence,we further discuss a potential mechanism for HBsAg clearance:HIV-induced immunodeficiency,particularly the depletion of CD4+T cells,may unexpectedly disrupt preexisting HBV-specific tolerance.After antiretroviral therapy(ART)in HIV/HBV coinfected individuals,partial immune system reconstitution occurs,and the reconstituted immune system,no longer tolerized by HBV,effectively clears HBV-infected hepatocytes,triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance.Additionally,emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve:PD-1/PD-L1 pathway inhibition,cytokine induction promoting immune cell recruitment and an inflammatory environment,and natural killer(NK)cell functional remodeling.These collective observations highlight the important role of immune modulation in HBV clearance,providing insights that can facilitate the development of a functional HBV cure.Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.展开更多
文摘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.
基金Supported by Tianjin Health Industry Key Project,No.15KG113Tianjin Science Foundation of China,No.17JCYBJC26100
文摘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.
基金Supported by National Key Research and Development Program of China,No.2023YFC2308105.
文摘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%.
基金supported by Project from the Science&Technology Commission of Chongqing,China(No.cstc2018jcyjAX0027,cstc2018jscx-msybX0376,cstc2020jcyj-msxmX0159,and cstc2020jscx-dxwtBX0022)Chongqing Municipal Education Commission,China(No.KJQN201800422)+3 种基金Intelligent Medicine Project from Chongqing Medical University,China(No.ZHYX202028)111 Project,China(No.D20028)National Key Research and Development Project,China(No.2018YFE0107500)Chongqing Talents Program,China(No.CQYC202005013).
文摘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.
基金supported by the National Key Research and Development Program of China(No.2022YFC2304800)Science and Technology Project of Guangzhou(Nos.2023A03J0792,20220020285)+2 种基金National Natural Science Foundation of China(No.82072265)Science and Technology Program of Guangzhou(No.202102020074)Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases(No.2021-2023)
文摘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.
文摘Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.
基金supported by the National Key Research and Development Program of China(2022YFC2304800)the Guangzhou Science and Technology Plan Project(2025 Basic and Applied Basic Research Project,No.2025A04J4146).
文摘HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients experiencing higher liver-related morbidity,hospitalization rates,and mortality than those with HBV monoinfection.Surprisingly,an increasing number of studies have shown that hepatitis B surface antigen(HBsAg)clearance rates in HIV/HBV coinfection can reach over 10%,which is significantly higher than in HBV monoinfection.In this review,we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection,including baseline HBsAg levels,baseline HBV DNA levels,baseline CD4+T cell-counts,and immune reconstitution inflammatory syndrome-related hepatic flare.Based on current evidence,we further discuss a potential mechanism for HBsAg clearance:HIV-induced immunodeficiency,particularly the depletion of CD4+T cells,may unexpectedly disrupt preexisting HBV-specific tolerance.After antiretroviral therapy(ART)in HIV/HBV coinfected individuals,partial immune system reconstitution occurs,and the reconstituted immune system,no longer tolerized by HBV,effectively clears HBV-infected hepatocytes,triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance.Additionally,emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve:PD-1/PD-L1 pathway inhibition,cytokine induction promoting immune cell recruitment and an inflammatory environment,and natural killer(NK)cell functional remodeling.These collective observations highlight the important role of immune modulation in HBV clearance,providing insights that can facilitate the development of a functional HBV cure.Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.
