Functional cure of hepatitis B in patients with cancer undergoing immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B (CHB). Thus, we aimed to determine the previously unclear impact of ICIs on hepatitis B surface antigen (HBsAg) seroclearance in patients with cancer. Consecutive patients with cancer from 2016 to 2020 (cohort 1, n = 118), and hepatocellular carcinoma from 2020 to 2022 (cohort 2, n = 44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional HBV-HCC cohort (cohort 3, n = 85) not receiving ICIs served as a control group. Factors associated with HBsAg loss or a HBsAg decline >1 log were analyzed. With median follow-up of 17.5 months, 8 (6.8%) patients in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and an additional four in cohort 1 and one in cohort 2 had a HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/ml was associated with HBsAg seroclearance (hazard ratio 6.274, p = 0.028). In the validation cohort, the cumulative incidences of HBsAg loss at months 12 and 24 were 13.0% and 38.4%, respectively, for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p = 0.0267). No case in cohort 3 achieved HBsAg loss within 24 months. Of the 17 cases who achieved HBsAg loss or a decline >1 log, 16 (94.1%) received nucleos(t)ide analogue treatment. The median time to HBsAg loss or HBsAg decline was 16.5 (range 9.6 to 27.5) months. ICIs may accelerate HBsAg seroclearance in patients with cancer and baseline HBsAg <100 IU/ml. This finding provides important information for the design of future trials evaluating the ability of ICIs to induce functional cure in patients with CHB. Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B. Functional cure of hepatitis B was observed in patients with cancer or HCC undergoing ICI treatment, and the cumulative incidence of HBsAg loss was higher compared with controls without ICIs. ICIs may accelerate the HBsAg loss in patients with baseline HBsAg levels <100 IU/ml. This finding provides important information for the design of future ICI trials evaluating the ability of ICIs to induce functional cure in patients with CHB.

Mon HC ，Lee PC ，Hung YP ，Hung YW ，Wu CJ ，Lee CJ ，Chi CT ，Lee IC ，Hou MC ，Huang YH ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients.

Chronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis. We searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint. We included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P<0.001) and the pooled HR for PFS was 0.54 (95% CI: 0.33-0.89 P=0.014). In individuals with HCC who received ICIs, there was no notable link found between HBV or HCV infection and prognosis. However, HBV infection showed a connection with improved tumor response. A higher initial HBV load is linked to worse survival results in HCC patients undergoing ICIs treatment and antiviral therapy can significantly improve its prognosis.

Ji Z ，Li J ，Zhang S ，Jia Y ，Zhang J ，Guo Z ... -  《Frontiers in Immunology》

Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study.

Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis. Between Dec 7, 2011, and Jan 24, 2014, we implemented the prospective PROLIFICA cohort study in The Gambia. Participants with chronic hepatitis B aged 16 years or older were recruited after large-scale, community-based HBV screening; blood bank-based HBV screening in Edward Francis Small Teaching Hospital, Banjul; and prospective follow-up of HBsAg-positive individuals via historical, population-based HBsAg serosurveys in two rural villages (Keneba and Manduar). Participants underwent HBV serology and other laboratory tests, fasting FibroScan, and abdominal ultrasound. Survival data were collected between Dec 7, 2011, and Aug 17, 2021. Between Oct 9, 2018, and Aug 17, 2021, all HBsAg-positive participants enrolled in the 2011-14 cohort were invited for a reassessment. For this analysis, we included HBsAg-positive people and excluded all participants who were eligible for treatment according to the 2012 European Association for the Study of the Liver (EASL) criteria at baseline and those who were treated irrespective of treatment eligibility. The primary outcome was all-cause mortality, assessed in all treatment-ineligible and treatment-naive participants with follow-up data. The secondary outcome, analysed in those who were reassessed, was disease progression, defined as becoming eligible for antivirals per 2017 EASL criteria; having an increase in liver fibrosis of at least one stage; or having a clinical diagnosis of hepatic decompensation or hepatocellular carcinoma. 943 HBsAg-positive people with chronic hepatitis B were recruited to the PROLIFICA study. Of these 943, 58 (6%) fulfilled 2012 EASL treatment eligibility criteria at baseline, 35 (4%) were ineligible for treatment but received antiviral therapy, and 44 (5%) were immediately lost to follow-up. Thus, 806 (85%) participants were analysed for the primary outcome (486 [60%] were male and 320 [40%] were female). After a median follow-up of 6·11 years (IQR 5·34-6·80), 708 (88%) participants were confirmed to be alive at last surveillance, 71 (9%) were lost to follow-up and were censored, and 27 (3%) died, giving an all-cause mortality rate of 582 per 100 000 person-years (95% CI 399-849). Of the 27 people who died, five (19%) had liver-related deaths. Of 708 participants confirmed to be alive, 544 (77%) attended follow-up and were assessed for the secondary outcome. Disease progression occurred in 36 (7%) participants: five (1%) became newly eligible for antiviral therapy per EASL 2017 criteria without liver fibrosis progression; 18 (3%) had liver fibrosis progression alone; 13 (2%) had liver fibrosis progression and newly fulfilled the treatment criteria; and none had hepatic decompensation or developed hepatocellular carcinoma. In multivariable analysis adjusted for sex and age, only a baseline HBV DNA of 20 000 IU/mL or more, compared with the baseline HBV DNA of 2000 IU/mL or lower as the reference, was significantly associated with liver disease progression (odds ratio 5·39, 95% CI 1·37-21·23). Among people with chronic hepatitis B who were ineligible for antiviral therapy in The Gambia, all-cause mortality and liver disease progression were low. The clinical benefit of expanding antiviral therapy in this subgroup of patients remains uncertain. European Commission, Medical Research Council UK Research and Innovation, and Gilead Sciences.

Ndow G ，Shimakawa Y ，Leith D ，Bah S ，Bangura R ，Mahmoud I ，Bojang L ，Ceesay A ，Drammeh S ，Bola-Lawal Q ，Lambert G ，Hardy P ，Ingiliz P ，Haddadin Y ，Vo-Quang E ，Chevaliez S ，Cloherty G ，Bittaye SO ，Lo G ，Toure-Kane C ，Mendy M ，Njie R ，Chemin I ，D'Alessandro U ，Thursz M ，Lemoine M ... -  《The Lancet Gastroenterology &amp; Hepatology》

Favourable Prognosis of Patients With Untreated HBeAg-Negative Chronic Hepatitis B Virus Infection With HBsAg < 100 IU/mL.

Serum hepatitis B surface antigen (HBsAg) < 100 IU/mL has been recently proposed as one of the key criteria of 'partial cure' in patients with chronic hepatitis B virus (HBV) infection. We analysed the clinical prognosis of hepatitis B e antigen (HBeAg)-negative untreated patients with HBsAg < 100 IU/mL and normal alanine aminotransferase (ALT) levels. Five hundred and twenty-one untreated patients with HBeAg negativity, HBsAg < 100 IU/mL and normal ALT levels were included from three hospitals. Spontaneous HBsAg seroclearance, phase transition, liver fibrosis progression and hepatocellular carcinoma (HCC) development were analysed. The median age was 43.0 years, and 62.2% of the patients were male. After a median follow-up of 25.0 months, 52 (10.0%) patients achieved spontaneous HBsAg seroclearance. The annual HBsAg seroclearance rate is 4.2%. Patients with baseline HBsAg ≤ 10 IU/mL (adjusted hazard ratio [aHR] = 3.490, p < 0.001) and male sex (aHR = 1.980, p = 0.041) were more likely to achieve HBsAg seroclearance. Only 4 (0.8%) and 23 (4.8%) patients transitioned to the immune escape phase and HBeAg-negative indeterminate phase, respectively. Baseline serum HBsAg > 10 IU/mL (aHR = 3.846, p = 0.034) and detectable HBV DNA (aHR = 2.672, p = 0.023) were associated with transition to the HBeAg-negative indeterminate phase. No patient developed HCC or had fatal outcomes. HBeAg-negative patients with serum HBsAg < 100 IU/mL and normal ALT levels had a favourable prognosis. HBsAg ≤ 10 IU/mL and male sex were associated with a higher rate of HBsAg seroclearance, while HBsAg > 10 IU/mL and detectable HBV DNA were associated with a higher risk of transition to the indeterminate phase.

Wang J ，Zhang Z ，Yin S ，Zhang S ，Zhu L ，Pan Y ，Fan T ，Cao F ，Xiong Y ，Jiang C ，Wang G ，Yang Y ，Jia B ，Liu J ，Xia J ，Yan X ，Li J ，Zhu C ，Liu X ，Chen Y ，Wu C ，Huang R ... -  《-》