Jasmohan S Bajaj, Patrick S Kamath, Florence Wong, Qing Xie, Ramazan Idilman, Mark Topazian, Wai-Kay Seto, Aldo Torre, Peter Hayes, Jacob George, Mario Alvares da Silva, Brian J Bush, Scott Silvey, Ashok Choudhury, on behalf of CLEARED Investigators
Received February 17, 2026 Accepted April 8, 2026 Published online April 15, 2026
Background/Aims Infections with drug-resistant organisms (DROs) are associated with poor outcomes in cirrhosis. Rifaximin, widely used for hepatic encephalopathy (HE) could promote cross-resistance, but data regarding clinical impact are conflicting. Aim: Determine predictors of DROs in a global cirrhosis inpatient cohort focusing on pre-admission rifaximin use.
Methods From the global CLEARED consortium, we focused on cirrhosis inpatients with infections on/during admission. Clinical/demographic/medications especially rifaximin details were recorded. The primary outcome was DRO development. Multivariable regression for DRO development including clinical, medications, and country income were performed.
Results 2,949 infected inpatients (55.3 years, 62.9% male) were included. 12.2% of all and 24.4% of culture-positive infections developed DROs; these patients had higher HE (39 vs.31%,p=0.003), AKI/HRS (25 vs 19%,p=0.006), lactulose(55 vs.47%,p=0.008) and rifaximin use (34 vs 27%,p=0.006) on crude comparisons but country-income distributions were similar. 29.7% were on pre-admission rifaximin, mostly HE-related; they had more advanced cirrhosis and from low/low-middle-income countries. Daptomycin was used in 1.5%, linked with DROs (5.0 vs 1.0%, p<0.0001) without difference in rifaximin use (1.4 vs.1.7%,p=0.61). On adjusted analysis, MELD-Na (1.03,95% CI:1.02-1.04, p<0.001)increased, whereas male sex (0.73,95%CI:0.58-0.92,p=0.008) and HBV (0.65,95%CI:0.45-0.92,p=0.020) decreased DRO. Rifaximin was not associated with DROs overall (OR:1.07, 95%CI:0.80-1.43, p=0.65) or within income strata (High:1.07, 95%CI:0.59-1.92,p=0.82, Upper-middle:1.18,95%CI:0.74-1.85,p=0.49, low/low-middle:1.04, 95%CI:0.60-1.81,p=0.90) despite sensitivity analyses.
Conclusion In this large global cohort of hospitalized patients with cirrhosis and infections, 12% developed infections involving DROs. 30% had pre-admission rifaximin use which was not linked with daptomycin use, or with with DRO development on adjusted analysis overall or across country income groups.
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Liver fibrosis, cirrhosis, and portal hypertension
Backgrounds/Aims Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
Citations
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Endoscopic variceal ligation combined with carvedilol versus endoscopic variceal ligation combined with propranolol for the treatment of oesophageal variceal bleeding in cirrhosis: study protocol for a multicentre, randomised controlled trial Yiling Li, Li Du, Shuairan Zhang, Chuan Liu, Chao Ma, Xiaochao Liu, Huanhai Xu, Zhixu Fan, Shengjuan Hu, Jing Wang, Lichun Shao, Lijun Peng, Huiling Xiang, Xuan Liang, Wenhui Zhang, Hongyun Zhao, Pengyuan He, Jingyi Xu, Qianlong Li, Ling Yang, Yunhai Wu, BMJ Open.2025; 15(4): e093866. CrossRef
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Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
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Linvencovir: Paving the way for functional cure in hepatitis B Jiwon Yang, Jonggi Choi Clinical and Molecular Hepatology.2024; 30(2): 164. CrossRef
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