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Introduction: Emerging evidence suggests that long-term nucleos(t)ide analogue (NA) therapy can be ceased in a selective group of chronic hepatitis B (CHB). This is being gradually implemented in clinical practice. Case Presentation: A 68-year-old man known with a chronic hepatitis B e antigen-positive hepatitis B infection without signs of advanced liver fibrosis or cirrhosis was admitted with acute liver failure. Two months prior to his admission, he ceased his NA therapy. During the admission, NA therapy was restarted, but the liver function worsened. The patient was put on the high-urgency liver transplantation waiting list, and the next day, he was successfully transplanted. However, the patient died 17 days later due to hemorrhagic shock that resulted from intra-abdominal bleeding and acute pancreatitis. Conclusion: Current guidelines suggest that NA therapy can be discontinued in a selective group of CHB patients. However, these guidelines suggest different stopping and follow-up criteria. This case illustrates that NA withdrawal is not without risks and that these differences in recommendations may lead to inadequate management and eventually a fatal outcome. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) α-2b alone or in combination with lamivudine. Methods: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN α-2b (100 μg/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 ± 0.8 years). Results: Of 266 patients enrolled in the initial study, 172 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A–infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P < .001). Conclusions: HBeAg loss after treatment with PEG-IFN α-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A–infected patients. Therefore, PEG-IFN α-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy. [Copyright &y& Elsevier]

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS)., Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time., Results: On the 1 st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001)., Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences., Impact and Implications: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population., (© 2024 The Authors.)

Objectives: Treatment with pegylated interferon (PEG-IFN) alpha-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss., Methods: A total of 91 patients treated with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study. Patients were initially followed up at 4-week intervals and had one additional long-term follow-up (LTFU) visit (mean: 3.03+/-0.77 years 26 weeks post treatment)., Results: Of the 172 patients included, 78 patients (46%) did not have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%) had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss< or =32 weeks had hepatitis B virus DNA of <400 copies/ml significantly more often than did those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis B surface antigen (HBsAg) negativity was also observed significantly more often in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg loss tended to occur more often in patients treated with PEG-IFN and lamivudine combination therapy than in those treated with PEG-IFN alone (35 vs. 21%; P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14)., Conclusions: Early PEG-IFN-induced HBeAg loss results in a high likelihood of HBsAg loss and may be associated with more profound viral suppression during the first 32 weeks of therapy in patients treated with lamivudine combinations.

Background & Aims: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) alpha-2b alone or in combination with lamivudine., Methods: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN alpha-2b (100 mug/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 +/- 0.8 years)., Results: Of 266 patients enrolled in the initial study, 172 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A-infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P < .001)., Conclusions: HBeAg loss after treatment with PEG-IFN alpha-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A-infected patients. Therefore, PEG-IFN alpha-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy.

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is the hallmark of a complete response to antiviral therapy for chronic hepatitis B. In this study, we investigated the frequency of HBsAg loss after treatment with pegylated (Peg)-interferon alpha-2b., Methods: In a multicenter randomized controlled trial, 266 HBeAg-positive patients were treated for 52 wks with Peg-interferon alpha-2b (100 microg/wk) in combination with either lamivudine (100 mg/day) or placebo. Posttreatment follow-up was 26 wks., Results: At the end of follow-up, 95 (36%) of the 266 patients exhibited HBeAg loss, 18 (7%) HBsAg loss, and 16 (6%) HBsAg seroconversion. Addition of lamivudine did not enhance HBeAg loss, HBsAg loss, or development of anti-HBs. All 18 patients who showed HBsAg loss had normal ALT; 11 (61%) of these patients were also hepatitis B virus (HBV) DNA negative (<400 copies/mL) at the end of follow-up. Loss of HBsAg differed according to HBV genotype: 14% for genotype A, 9% for genotype B, 3% for genotype C, and 2% for genotype D (A vs D: p = 0.006)., Conclusions: One year of Peg-interferon alpha-2b for HBeAg-positive patients led to HBsAg loss in 7%. Our study indicates that treatment with Peg-interferon alpha-2b is the best therapy to achieve HBsAg clearance in patients with genotype A.