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Summary: Background: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. Aims: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. Methods: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high‐dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low‐dose PPI group) for each outcome. Results: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high‐dose PPI group. High‐dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38–2.11, p < 0.001). This result was reproducible after propensity score‐matching (PSM) (aHR = 1.90, 95% CI = 1.49–2.44, p < 0.001). High‐dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66–2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70–2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43–2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31–2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02–2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95–2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12–1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28–2.37, p < 0.001). Conclusions: The use of high‐dose PPI was independently associated with increased risks of mortality and cirrhotic complications. [ABSTRACT FROM AUTHOR]

Background & Aims: Non‐selective β‐blockers (NSBBs) and endoscopic variceal‐ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high‐risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. Methods: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing‐risk, time‐to‐event meta‐analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. Results: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard‐ratio (sHR) = 1.05, 95% CI = 0.75–1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11–2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. Conclusions: In patients with compensated cirrhosis and high‐risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. Aims: To assess the treatment and renal/bone safety outcomes following the switch to TAF. Methods: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T‐scores (L‐spine) by bone absorptiometry by 24 months after switch to TAF. Results: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T‐score improved significantly from −1.43 ± 1.36 to −1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9–89.5 ± 16.3 mL/min/1.73 m2, p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T‐score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T‐score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). Conclusions: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable. [ABSTRACT FROM AUTHOR]

Simple Summary: Trans-arterial radioembolization (TARE) can effectively treat patients with locally advanced hepatocellular carcinoma (HCC). However, TARE is not widely used in clinical practice due to the lack of consensus on how to select the best candidates for this therapy. Therefore, it is crucial to find predictive biomarkers or clinical parameters that can differentiate the patients who will respond well to TARE and improve their outcomes. Low skeletal muscle mass (LSMM) is one of the factors that affects the prognosis of HCC patients and has been extensively studied in relation to different treatments. We used a semi-automated program that has been validated and proven to be reliable for assessing LSMM. In this study, we aimed to identify prognostic factors, including pre-treatment LSMM, for survival outcomes in patients with HCC undergoing TARE. Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90-loaded microspheres. This was a multi-center retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT), and 126 (36.3%) were classified as LSMM. The median overall survival (OS) was 28.1 months (95% CI, 24.8–35.7), and median progression-free survival was 8.0 months (95% CI, 6.4–9.4). Multivariate Cox regression analysis revealed that LSMM (hazard ratio [HR], 1.36; 95% CI, 1.00–1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33–2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04–1.92, p = 0.03), and albumin–bilirubin grade (2–3) (HR 1.74; 95% CI, 1.24–2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment LSMM independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates. [ABSTRACT FROM AUTHOR]