{"doi":"10.1002/cld.1182","title":"Nonselective Beta‐Blockers in Portal Hypertension: Why, When, and How?","abstract":"Answer questions and earn CME Content available: Author Interview and Audio Recording In the past three decades, nonselective beta-blockers (NSBBs) have been the cornerstone in the management of portal hypertension (PH) in patients with cirrhosis. PH in cirrhosis initially develops as a result of increased hepatic resistance (architectural distortion and intrahepatic vasoconstriction). This initial increase in pressure leads to splanchnic vasodilation resulting in an increased portal venous inflow and a further increase in portal pressure. In addition, vasodilation leads to decreased effective arterial blood volume and to compensatory neurohormonal activation resulting in sodium and water retention from the kidneys, plasma volume expansion, and an increase in cardiac output (hyperdynamic circulation). This further augments portal venous inflow and pressure, thereby creating a vicious cycle1 (Fig. 1). NSBBs were first shown to reduce portal pressure in patients with variceal hemorrhage in 1980.2 In contrast with cardioselective beta-blockers whose affinity is specific for β1 (located in cardiac muscles), NSBBs such as propranolol or nadolol have a similar affinity for β1 and β2 (located in splanchnic vessels). Blocking β1 results in decreased cardiac output, and blocking β2 results in splanchnic vasoconstriction, both of which contribute to decreasing portal pressure. Carvedilol, a newer NSBB, additionally blocks α1-adrenergic receptors, which decreases intrahepatic resistance, with a consequent greater reduction in portal pressure.1 The effect of NSBBs depends on the stage of cirrhosis and PH. In compensated cirrhosis, PH is initially mild with a hepatic venous pressure gradient (HVPG) of 6 to 10 mm Hg. With the onset of the hyperdynamic circulation, HVPG increases to >10 mm Hg, a threshold identified as being “clinically significant PH (CSPH)” because it is the main predictor of cirrhosis decompensation.3 NSBBs play a major role in the treatment of PH in patients in whom hyperdynamic circulation has developed, that is, those with CSPH and those who have bled from varices4 (Fig. 2). We will discuss the major indications of NSBBs and future directions. Currently, guidelines recommend NSBBs or endoscopic variceal ligation (EVL) to prevent first variceal hemorrhage (primary prophylaxis) in patients with high-risk varices. High-risk varices are defined as medium-to-large varices, varices of any size with red wale marks, or varices of any size in patients with Child class C.5 Treatment selection is based on patient and provider preference, but guided by data on benefits and risks. When used for primary prophylaxis, NSBBs have also been shown to decrease decompensation, as opposed to EVL, which is a local treatment and does not alter the disease progression. NSBBs can additionally decrease intestinal permeability and bacterial translocation.6-8 Also, once a patient is on NSBBs, the risk for bleeding is reduced similarly to eradication of the varices with EVL, and thus repeat endoscopy is not required.9 The risks or drawbacks of each approach, however, are real. Thus, it is important to individualize treatment selection based on contraindications, tolerance, side effect profile, and patient preference (Fig. 3). In patients who have previously bled from varices, combination therapy with NSBBs and EVL is recommended.5 Multiple trials have demonstrated the benefits of combination therapy over either of these treatments alone. Interestingly, NSBBs have been shown to be the key component of the combination therapy and drive the majority of the benefit.1 Despite their proven efficacy, there is hesitancy in using NSBBs in patients with decompensated cirrhosis with ascites, because retrospective studies have shown increased mortality in these patients.10 Despite initial concerns, recent meta-analyses showed an overall survival benefit with appropriate dosing of NSSBs in subgroup analyses of patients with ascites or even refractory ascites.11","journal":"Clinical Liver Disease","year":2022,"id":259636,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281372,"name":"Guadalupe García–Tsao","orcid":"0000-0002-6175-8216","position":1,"is_corresponding":false},{"id":247306,"name":"Elliot B. Tapper","orcid":"0000-0002-0839-1515","position":2,"is_corresponding":false},{"id":309091,"name":"Anahita Rabiee","orcid":"0000-0002-8833-3592","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T00:25:58.993402Z","pmid":"35355838","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}