ABSTRACT Aims The tolerance of patients with compensated hepatitis B cirrhosis to interferon (IFN) therapy remains controversial. Therefore, this study aimed to evaluate the safety of pegylated interferon‐alpha in chronic hepatitis B (CHB) patients with compensatory cirrhosis. Methods Data from two prospective cohorts (the OASIS Project and CHESS 2306) from January 2018 to January 2024 were synthesized and analyzed. Patients with Child‐Pugh Class A hepatitis B cirrhosis who received IFN‐based therapy (n = 920) were included. The control groups included patients with compensated hepatitis B receiving nucleos(t)ide analog (Nuc) monotherapy (n = 714) and patients without cirrhosis receiving IFN‐based therapy (n = 4111), respectively. Propensity score matching was used to control for confounding factors; 566 versus 566 cases were analyzed among patients with cirrhosis treated with IFN‐based therapy or Nuc monotherapy, and 785 versus 785 cases were analyzed among patients with and without cirrhosis treated with IFN‐based therapy. Primary outcomes included decompensation events, and secondary outcomes included severe adverse events, overall adverse events, and treatment‐related hospitalizations or deaths. Results In patients with hepatitis B virus‐related cirrhosis, the incidence of decompensation events was similar between IFN‐based therapy and Nuc monotherapy (6/566 [1.1%] vs. 3/566 [0.5%], p = 0.506). No hospitalizations or deaths were associated with adverse events during the observation period (48 weeks). The incidences of severe adverse events were similar in patients with cirrhosis under IFN‐based therapy or Nuc monotherapy (severe neutropenia: 1/450 [0.2%] vs. 0/378 [0], p = 0.999; severe thrombocytopenia: 4/435 [0.9%] vs. 0/296 [0], p = 0.153; severe alanine aminotransferase level elevation: 1/523 [0.2%] vs. 1/458 [0.2%], p = 0.999; and severe total bilirubin [TBIL] level elevation: 5/419 [1.2%] vs. 3/385 [0.8%], p = 0.727). The incidences of severe adverse events were similar between patients with and without cirrhosis receiving IFN‐based therapy, except that severe TBIL level elevation was more frequent in patients with cirrhosis who already had mildly to moderately elevated TBIL levels at baseline than in those without (6/153 [3.9%] vs. 0/118 [0], p = 0.040). Conclusion IFN‐based therapy demonstrates favorable safety in Child‐Pugh A compensated cirrhosis. It did not increase decompensation events or severe adverse events compared to Nuc monotherapy, and adverse event profiles were largely similar between cirrhotic and non‐cirrhotic patients, except for a higher risk of severe hyperbilirubinemia in those with pre‐existing TBIL elevation. ClinicalTrials.gov identifier: NCT04896255. Chinese Clinical Trial Registry number: ChiCTR2500107592.
INTRODUCTION:The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS:In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months. RESULTS:Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) vs 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] vs 0% [0/120, 0%-3.1%]). DISCUSSION:Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov , NCT04850950.
The role of intra-arterial tenecteplase for acute large vessel occlusion (LVO) stroke after successful endovascular therapy is uncertain. To assess the efficacy and safety of intra-arterial tenecteplase in patients with successful endovascular therapy (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2b to 3) after endovascular therapy. This was a prospective, open-label, blinded end point, randomized trial. Recruitment took place between February 16, 2023, and March 23, 2024, with final follow-up on July 4, 2024. The study was conducted across 19 centers in China. Patients with acute anterior circulation LVO treated between 4.5 and 24 hours from the time that the patient was last known to be well were included. After successful endovascular recanalization, defined as eTICI 2b or greater, patients were randomized to receive intra-arterial tenecteplase at 0.125 mg/kg (n = 126) or standard medical treatment (n = 129). The primary end point was excellent outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0 to 1 (range, 0 [no symptoms] to 6 [death]). There were a total of 7 secondary efficacy end points (mRS score of 0-1 at 90 days, mRS score at 90 days, mRS score of 0-2 at 90 days, mRS score of 0-3 at 90 days, National Institutes of Health Stroke Scale score of 0-1 or improved ≥10 points at 36 hours, European Quality of Life Visual Analogue Scale score at 90 days, time to maximum volume > 6 s at 24 hours, and infarct core volume change from baseline) and 3 safety end points, including symptomatic intracranial hemorrhage (sICH) within 48 hours, any intracranial hemorrhage within 48 hours, and all-cause mortality within 90 days. Among 256 patients who were randomized (median [IQR] age, 71.6 [61.3-79.2] years; 113 [44.1%] females), 255 (99.6%) completed the trial. The rate of patients with an mRS score of 0 to 1 at 90 days was 40.5% in the intra-arterial tenecteplase group (n = 51) and 26.4% in the standard medical treatment group (n = 34) (relative risk, 1.44 [95% CI, 1.06-1.95]; P = .02). Of 7 prespecified secondary efficacy end points, none showed a significant difference. Intra-arterial tenecteplase after endovascular therapy did not increase the incidence of sICH within 48 hours after treatment compared with standard medical treatment (5.6% vs 6.2%; relative risk, 0.95 [95% CI, 0.36-2.53]; P = .92). Mortality at 90 days was 21.4% with intra-arterial tenecteplase and 21.7% with standard medical treatment (relative risk, 0.76 [95% CI, 0.40-1.43]; P = .78). In patients with acute LVO presenting between 4.5 and 24 hours of symptom onset, intra-arterial tenecteplase after successful thrombectomy had a greater likelihood of excellent neurological outcome at 90 days without increasing the risk of sICH or mortality. However, because none of the secondary efficacy analyses supported the primary finding, further trials are needed to confirm the results. ClinicalTrials.gov Identifier: NCT05624190
