Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with endstage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.

BACKGROUND & AIMS:Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events. METHODS:We performed a retrospective analysis of consecutive patients with NAFLD (n [ 1039) with a histologic diagnosis of F3-F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19-63 months). RESULTS:Based on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.

Summary Background & Aim Non‐alcoholic fatty liver disease (NAFLD), and especially fibrotic non‐alcoholic steatohepatitis, is associated with high risks of liver‐related events (LRE) and extrahepatic events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy‐proven NAFLD stratified according to baseline severity of fibrosis. Methods Two thousand one hundred thirty‐five patients with biopsy‐proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause‐specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with liver fibrosis severity estimated by liver stiffness measurement by transient elastography was also enrolled. Results Observed CIFs indicated that the 60‐month probabilities of LRE and EHE were 0.2% and 3% in F0‐F1, 2% and 3.8% in F2 and 9.7% and 6.4% in F3‐F4 patients, respectively. The cause‐specific Cox model indicated that in F0‐F1 and F2 patients, age > 50 years (HR 2.7) was the only predictor of LRE, while age > 50 years (HR 2.96), previous cardiovascular events (CVE, HR 2.07), and previous extra‐hepatic cancer (HR 2.36) were independent risk factors for EHE. In F3‐F4 patients, age > 55 years (HR 1.73), obesity (HR 1.52), PLT < 150 000/mmc (HR 3.66) and log(GGT) (HR 1.77) were associated with LRE, while age > 55 years (HR 1.74) and previous CVE (HR 2.51) were independent predictors of EHE. Predicted CIFs for HE and EHE in F0‐F1, F2 and F3‐F4 patients stratified the risk of events. The results were externally replicated. Conclusion The likelihood of EHE in NAFLD patients is relevant and increases according to the severity of liver fibrosis, while the risk of LRE is negligible in F0‐F1, low but clinically relevant in F2 and high in F3‐F4 patients.