Use Of Non-selective Beta-blockers Research Articles

COVID 19: Management of Decompensated Cirrhosis and Liver Transplant Recipients.

COVID 19: Management of Decompensated Cirrhosis and Liver Transplant Recipients.

From the Editor’s Desk…

From the Editor’s Desk…

Assessing the effects of beta-blockers on pancreatic cancer risk: A nested case-control study.

Both β1- and β2-adrenoceptor proteins were detected on the cell surface of pancreatic ductal adenocarcinoma. The current study evaluated the association between beta-blocker use and pancreatic cancer risk. We conducted a nested case-control study in a large population representative database. Each pancreatic cancer case was matched with four controls based on age, sex, practice site, and duration of follow-up using incidence density sampling. Beta-blocker use was defined as any prescription prior to index date and was stratified into non-selective and selective β1 -blockers. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for pancreatic cancer risk associated with beta-blocker use was estimated using conditional logistic regression. The study included 4113 patients with pancreatic cancer and 16 072 matched controls. When compared to never users, there was no association between any beta-blocker use and pancreatic cancer risk (adjusted OR 1.06, 95% CI 0.97-1.16, P = .16). Analysis by receptor selectivity showed use of non-selective beta-blockers for more than 2 years was associated with a reduced pancreatic cancer risk (OR 0.75, 95% CI 0.57-1.00, P = .05). When compared to former users both users of selective β1-blockers and non-selective beta-blockers had a reduced pancreatic cancer risk (OR 0.78, 95% CI 0.67-0.90, P = .001) and (OR 0.67, 95% CI 0.49-0.92, P = .01), respectively. Beta-blocker use was not associated with increased pancreatic cancer risk. However, long-term use of beta-blockers may be associated with decreased pancreatic cancer risk.

Low dose of propranolol treatment is associated with better survival in cirrhotic patients with hepatic encephalopathy.

The use of nonselective beta blockers in cirrhotic patients experiencing complications is controversial. We aimed to investigate the association between propranolol treatment and outcomes for cirrhotic patients with hepatic encephalopathy. Using data from the Taiwan National Health Insurance Research Database, we identified 4754 cirrhotic patients newly diagnosed with hepatic encephalopathy between 2001 and 2010. Among them, 519 patients received propranolol treatment and the other 519 patients without exposure to propranolol were enrolled into our study, both of which were matched by sex, age, and propensity score. The Kaplan-Meier method and time-dependent-modified Cox proportional hazards models were employed for survival and multivariate-stratified analyses. The median overall survival (OS) was significantly longer in the propranolol-treated cohort than in the untreated cohort (3.46 versus 1.88 years, P < 0.001). A dose-dependent increase in survival was observed (median OS: 4.49, 3.29, and 2.46 years in patients treated with propranolol more than 30 , 20-30 , and less than 20 mg/day, respectively [P < 0.001, P = 0.001, and P = 0.079 versus the untreated group]). In addition to reduce the risk of mortality (adjusted hazard ratio, 0.58; P < 0.001), propranolol also diminished the risk of sepsis-related death (adjusted hazard ratio, 0.31; P = 0.006) according to the multivariate analysis. However, the risk of circulatory or hepatic failure was nonsignificantly altered by propranolol treatment. Low dose of propranolol treatment was associated with a better OS in cirrhotic patients with hepatic encephalopathy and its effects were dose dependent.

Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

BackgroundRecent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation.MethodsA single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality.ResultsSixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09–0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality.ConclusionsNSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.

Evaluation of machine learning methodology for the prediction of healthcare resource utilization and healthcare costs in patients with critical limb ischemia-is preventive and personalized approach on the horizon?

Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. Patients ≥ 50years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. The mean age of 3189 eligible patients was 71.9years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians' evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.

Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis.

The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.

Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension

Emricasan, an oral pan-caspase inhibitor, decreased portal pressure in experimental cirrhosis and in an open-label study in patients with cirrhosis and severe portal hypertension, defined as a hepatic venous pressure gradient (HVPG) ≥12 mmHg. We aimed to confirm these results in a placebo-controlled study in patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis. We performed a multicenter double-blinded study, randomizing 263 patients with NASH-related cirrhosis and baseline HVPG ≥12 mmHg to twice daily oral emricasan 5 mg, 25 mg, 50 mg or placebo in a 1:1:1:1 ratio for up to 48 weeks. The primary endpoint was change in HVPG (ΔHVPG) at week 24. Secondary endpoints were changes in biomarkers (aminotransferases, caspases, cytokeratins) and development of liver-related outcomes. There were no significant differences in ΔHVPG for any emricasan dose vs. placebo (-0.21,-0.45,-0.58 mmHg, respectively) adjusted for baseline HVPG, compensation status, and non-selective beta-blocker use. Compensated patients (n= 201 [76%]) tended to have a greater decrease in HVPG (emricasan all vs. placebo, p= 0.06), the decrease being greater in those with higher baseline HVPG (p= 0.018), with a significant interaction between baseline HVPG (continuous, p= 0.024; dichotomous at 16 mmHg [median], p= 0.013) and treatment. Biomarkers decreased significantly with emricasan at week 24 but returned to baseline levels by week 48. New or worsening decompensating events (∼10% over median exposure of 337 days), progression in model for end-stage liver disease and Child-Pugh scores, and treatment-emergent adverse events were similar among treatment groups. Despite a reduction in biomarkers indicating target engagement, emricasan was not associated with improvement in HVPG or clinical outcomes in patients with NASH-related cirrhosis and severe portal hypertension. Compensated patients with higher baseline HVPG had evidence of a small treatment effect. Emricasan treatment appeared safe and well-tolerated. Cirrhosis (scarring of the liver) is the main consequence of non-alcoholic steatohepatitis (NASH). Cirrhosis leads to high pressure in the portal vein which accounts for most of the complications of cirrhosis. Reducing portal pressure is beneficial in patients with cirrhosis. We studied the possibility that emricasan, a drug that improves inflammation and scarring in the liver, would reduce portal pressure in patients with NASH-related cirrhosis and severe portal hypertension. Our results in a large, prospective, double-blind study could not demonstrate a beneficial effect of emricasan in these patients. Clinical Trials.gov #NCT02960204.

Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial.

In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications. 136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70). Within 28days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90days, between the two groups. In ACLF patients with either no or small esophageal varices and HVPG ≥ 12mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28days. CLINICALTRIALS. NCT02583698.

P: 48 Nonselective Beta-blocker Use Is Associated With Increased Hepatic Encephalopathy-Related Readmissions in Patients With Cirrhosis

BACKGROUND: Hepatic Encephalopathy (HE) is a reversible syndrome of impaired brain function that is associated with frequent hospitalizations and decreased survival in cirrhotic patients. Nonselective beta-blockers (NSBB) are the mainstay of pharmacologic treatment for portal hypertension and prevention of variceal bleeding. Due to their effects on hepatic blood flow, we hypothesized that NSBB use would decrease portal flow, leading to increased HE related hospitalizations independent of liver disease severity. This study was done to assess the effect of NSBB use on HE-related readmissions. METHODS: We examined all the patients with cirrhosis admitted at Baylor University Medical Center between January 2013 and July 2018. The outcome measure of HE-related readmissions was analyzed in patients taking NSBB vs. patients not taking NSBB using cox proportional hazard regression model. The model was adjusted for age, sex, Model for End-Stage Liver Disease (MELD) score, selective beta-blocker (SBB) use, ascites, and history of esophageal varices (EV) and transjugular intrahepatic portosystemic shunt (TIPS). The Kaplan-Meier method and log-rank test were used to compare the cumulative incidence of HE-related readmissions between the aforementioned groups. RESULTS: There were 393 patients in this study with a mean age of 58.1 ± 10.2 years and a male predominance. The mean MELD score was 19.6 ± 7.7. The median time between the first admission and future readmission was 1.9 months with interquartile range of 4.8 months. The cumulative incidence of HE-related readmissions was significantly higher in patients taking NSBB compared with patients who were never prescribed NSBB (P &lt; 0.001) (Figure 1). This effect was not seen for patients who were taking SSBs. In multivariate analysis, after adjusting for age, sex, MELD score, SBB use, ascites, history of EV and TIPS, NSBB use was independently associated with increased risk of HE-related re-hospitalizations; Hazard ratio was 2.82 (95% confidence interval: 1.81–4.41). CONCLUSIONS: NSBB use is independently associated with increased HE-related readmissions in patients with cirrhosis, regardless of liver disease severity. Thus, NSBBs should be used cautiously in patients who have experienced a prior HE episode. However, further prospective studies are needed to determine the impact of NSBB on portal hypertension complications.

Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis.

Portal vein thrombosis (PVT), which is associated with reduced portalvein velocity, is considered to be an indicator for worse outcomes in liver cirrhosis. Nonselective beta-blockers (NSBBs), which are widely used for primary and secondary prophylaxis of esophageal variceal bleeding in liver cirrhosis, can significantly decrease the portal vein velocity. We proposed a hypothesis that the use of NSBBs might facilitate the development of PVT in cirrhotic patients. The PubMed, EMBASE, and Cochrane Library databases were searched. Major meeting abstracts and randomized-controlled trials regardingthe use of NSBBs in liver cirrhosis were also hand-searched. The number of patients who developed PVT in groups treated with or without NSBBs was pooled. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Subgroup meta-analyses were performed according to the type of studies,region, and study quality. Meta-regression and sensitivity analyses were performed to explore the source of heterogeneity. Nine of the 6416 retrieved papers were finally included. Overall, meta-analysis demonstrated that NSBBs were significantly associated with the development of PVT (OR 4.62, 95% CI 2.50-8.53; p < 0.00001). The heterogeneity was statistically significant (I2 = 80%; p < 0.00001). Subgroup meta-analyses still demonstrated a significantly positive association of NSBBs with the development of PVT in cohort studies (RR 2.57, 95% CI 1.46-4.51; p = 0.001) and case-control studies (OR 8.17, 95% CI 2.46-27.06; p = 0.0006). Sensitivity analyses based on subgroups find the source of heterogeneity. Based on the systematic review and meta-analysis, we found that the use of NSBBs increased a 4.62-fold risk of PVT in cirrhotic patients.

SAT-089-Evaluating the impact of non-selective beta-blocker use in decompensated cirrhosis based on setting of patient care

SAT-089-Evaluating the impact of non-selective beta-blocker use in decompensated cirrhosis based on setting of patient care

A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis.

Patients with cirrhosis can be stratified by a simple risk score for HE that accounts for changing clinical data; our data also highlight a role for statins in reducing cirrhosis complications including HE. (Hepatology 2017).

Effect of Peri-Operative Selective and Nonselective Beta Blocker Use on Survival in Ovarian Cancer Patients [20A

INTRODUCTION: Preclinical studies have demonstrated that adrenergic agonists mediate tumor growth and invasiveness in ovarian cancer models via the beta-2 adrenergic receptor. Studies have also investigated the clinical impact of beta blocker use on epithelial ovarian cancer (EOC) survival with conflicting results. We aim to understand the association between peri-operative beta blockade and clinical outcomes in EOC patients. METHODS: We conducted an institutional retrospective chart review and examined the effects of beta blocker use on overall survival (OS) and progression free survival (PFS) when looking at peri-operative timing of beta blocker use in EOC. RESULTS: In a cox survival model, women who took a selective beta blocker (SBB) in the peri-operative period were four times more likely to die compared to nonusers when looking at OS (adjusted SBB HR 5.82, 95% CI 1.17-28.91, p=0.031). Although there was no difference in PFS between nonselective beta blocker (NSBB) users and nonusers (adjusted NSBB HR 1.88, 95% CI 0.41-8.60, p=0.414), SBB users were four times more likely to have recurrence of disease compared to nonusers (adjusted SBB HR 4.24, 95% CI 1.23-14.55, p=0.022). CONCLUSION: Compared to never use, SBB use peri-operatively was associated with poorer OS and ever SBB use was associated with poorer PFS in patients with EOC. This is an area that warrants further investigation as preclinical studies would suggest a potential survival benefit, but reports in the literature are conflicting and our data seem to suggest a potential harm with SBB use.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n= 101 (35.6%) received EBL only, while n=180 (63.4%) received EBL+NSBBs. In 482 patients on SP, n=163 (33.8%) received EBL only, while n=299 (62%) received EBL+NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P=0.353) nor mortality (log-rank: P=0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL+NSBB vs EBL alone (log-rank: P=0.247). However, EBL+NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL+NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P=0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P=0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P=0.567). EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6months after EBL.

Considerations of prescribers and pharmacists for the use of non-selective β-blockers in asthma and COPD patients: An explorative study.

Rationale, aims, and objectivesDespite recommendations in prevailing guidelines to avoid the use of non‐selective (NS) β‐blockers in patients with asthma or COPD, on average, 10 patients per community pharmacy receive NS β‐blockers monthly. The aim of our study was to identify the reasons of prescribers and pharmacists to treat asthma and COPD patients with NS β‐blockers.MethodsFifty‐three community pharmacists in the Netherlands selected patients with actual concurrent use of inhalation medication and NS β‐blockers. For at least 5 patients, each pharmacist screened all medication surveillance signals and actions taken at first dispensing. Each pharmacist selected 3 different initial prescribers for a short interview to explore their awareness of the co‐morbidity and reasons to apply NS β‐blockers.ResultsPharmacists identified 827 asthma/COPD patients with actual use of NS β‐blockers. From these, 153 NS β‐blocker prescribers were selected and interviewed (64 general practitioners, 45 ophthalmologists, 24 cardiologists, and 20 other prescribers). One hundred seven prescribers were aware of the drug‐disease interaction of the asthma or COPD co‐morbidity when initiating the NS β‐blocker, and 46 were not. From these, 40 prescribers did not consider the contraindication to be relevant.For 299 patients, medication surveillance signals and actions at first dispensing were retrieved. Patients used predominantly ocular timolol (39.8%), and the oral preparations propranolol (30.8%) and carvedilol (15.1%). In 154 cases, the pharmacy system generated a warning alert.ConclusionsA substantial number of prescribers was unaware of the co‐morbidity or did not regard NS β‐blockers contraindicated, despite prevailing clinical guidelines. Improvement programs should target prescribers' awareness and knowledge of NS β‐blockers in patients with asthma or COPD.

The use of nonselective beta blockers is a risk factor for portal vein thrombosis in cirrhotic patients.

Background/Aim:A reduction in portal vein inflow velocity seems to predispose to the emergence of portal vein thrombosis (PVT). Nonselective β-blockers (NSBBs), used to prevent variceal bleeding, may increase the development of PVT by reducing portal vein inflow velocity. In this retrospective case-control study, we evaluated the risk factors and clinical features of a first event of PVT in 130 cirrhotics, 19 (15%) with (PVT group) and 111 (85%) without PVT (non-PVT group).Patients and Methods:Patient evaluation and NNBB treatment were carried out according to the AASLD guidelines.Results:PVT was prevalently partial (84%) and asymptomatic (84%). Patients with PVT were treated with different regimens, and resolution of thrombosis was observed in about 50% of the cases. In both groups, HCV was the most frequent cause of cirrhosis and Child-Pugh score A was prevalent. Ascites and esophageal varices were more frequent in the PVT group (P = 0.05 and <0.000, respectively). Treatment with NSBBs was significantly more frequent in the PVT group than in the non-PVT group (P < 0.000). PVT was associated with higher prevalence of chronic renal disease (P = 0.002), higher PT impairment (P = 0.003) and lower AST and ALT (P = 0.000). At multivariate logistic regression analysis, history of esophageal varices (P = 0.007) and NSBB treatment (P = 0.0003) were independent risk factors significantly associated with PVT.Conclusions:Esophageal varices and NSBB treatment were independent risk factors of PVT. Larger studies should evaluate the risk between variceal bleeding and portal vein thrombosis of using NSBBs, particularly in the prevention of first bleeding in nonadvanced liver cirrhosis.

The use of non-selective beta-blockers in patients with cirrhosis: more doubts than certainties

Since 1980s non-selective beta-blockers (NSBBs) have become the cornerstone of medical treatment for portal hypertension in cirrhotic patients (1). Yet, the evidence for their efficacy to prevent variceal bleeding is derived from prospective trials which largely excluded patients with refractory ascites and renal failure that are patients in which the use of beta-blockers is nowadays under debate (2).

Beta-blockers in patients with advanced liver disease: Has the dust settled?

Nonselective beta-blockers (NSBBs) have been the backbone for the treatment of portal hypertension in cirrhosis for the last 3 decades. A publication in 2010 of a prospective observational study suggested that NSBBs could increase mortality in patients with refractory ascites. This opened a controversy about the safety and efficacy of NSBBs in patients with advanced liver disease and led to the publication of a large corpus of observational data assessing the safety of NSBBs in patients with advanced cirrhosis. In this article, we briefly review the clinical pharmacology of NSBBs, the pathophysiological basis for the underlying benefits and harms of NSBBs in advanced cirrhosis, and the evidence in favor and against the use of NSBBs in specific scenarios. Finally, we summarize the current recommendations and propose areas of opportunity for future research. Liver Transplantation 23 1058-1069 2017 AASLD.

Beneficial and harmful effects of nonselective beta blockade on acute kidney injury in liver transplant candidates.

Nonselective beta-blockers (NSBBs) have played an important role in the prevention of portal hypertensive bleeding in patients with cirrhosis. However, recent studies have suggested that NSBBs may be harmful in some patients with end-stage liver disease. The purpose of this article is to evaluate the association between use of NSBB and the incidence of acute kidney injury (AKI). We conducted a nested case-control study in a cohort of liver transplant wait-list registrants. Each patient with AKI was matched to a control by the Model for End-Stage Liver Disease-Na score, age, serum creatinine, and follow-up duration. Out of a total of 2361 wait-list registrants, 205 patients developed AKI after a median follow-up duration of 18.2 months. When compared with matched controls, ascites (79.0% versus 51.7%) and non-Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of NSBB use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%; P = 0.08). In multivariate analyses, the impact of nonselective beta blockade on the development of AKI was dependent on the presence of ascites: nonselective beta blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57-6.95), whereas in patients without ascites, NSBB use reduced it (HR, 0.19; 95% CI, 0.06-0.60). Potential benefits and harms of a NSBB in terms of AKI depend on the presence of ascites in liver transplant candidates. NSBB therapy in patients with cirrhosis may need to be individualized. Liver Transplantation 23 733-740 2017 AASLD.