Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

Motorized Power Spiral Enteroscopy (MSE): Is Routine Bougienage of the Upper Esophageal Sphincter (UES) Necessary?

Introduction Wire-guided bougienage of the upper esophageal sphincter (UES) was performed routinely before per-oral motorized power spiral enteroscopy (MSE). In the present study, we aimed to answer the clinical question of whether routine bougienage of UES is required. Methods This was a retrospective study that included 20 patients who underwent antegrade spiral enteroscopy for various indications. The feasibility and safety of anterograde MSE without prior bougie dilatation of the upper esophageal sphincter were assessed. The technical success rate (TSR), diagnostic yield, and adverse events (AEs) were also assessed. Results In 16 out of the 20 patients, a spiral enteroscope was taken directly across UES into the esophagus without a prior bougie dilatation. The spiral enteroscope could not be negotiated across UES only in one patient, and bougie dilatation was done. The technical success rate was 100%. The diagnostic yield was 80%. Four patients reported AEs. Conclusions MSE had a good technical success rate and diagnostic yield. Routine dilatation of the UES before the procedure may be unnecessary.

Nutritional therapy for persistent cognitive impairment after resolution of overt hepatic encephalopathy in patients with cirrhosis: A double-blind randomized controlled trial.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) reflects cognitive impairment in patients with liver cirrhosis and is associated with poor prognosis. We assessed the effects of nutritional therapy on cognitive functions, health-related quality of life (HRQOL), anthropometry, endotoxins, and inflammatory markers in cirrhotic patients with MHE. METHODS: In a double-blind randomized controlled trial, cirrhotic patients with MHE were randomized to nutritional therapy (group I: 30-35 kcal/kg/day and 1.0-1.5 g of protein/kg/day) and no nutritional therapy (group II: diet as patients were taking before) for 6 months. MHE was diagnosed based on psychometric hepatic encephalopathy score (PHES). Anthropometry, ammonia, endotoxins, inflammatory markers, myostatin, and HRQOL were assessed at baseline and after 6 months. Primary endpoints were improvement or worsening in MHE and HRQOL. RESULTS: A total of 150 patients were randomized to group I (n = 75, age 46.3 ± 12.5 years, 58 men) and group II (n = 75, age 45.2 ± 9.3 years, 56 men). Baseline PHES (-8.16 ± 1.42 vs -8.24 ± 1.43; P = 0.54) was comparable in both groups. Reversal of MHE was higher in group I (73.2% vs 21.4%; P = 0.001) than group II. Improvement in PHES (Δ PHES 4.0 ± 0.60 vs -4.18 ± 0.40; P = 0.001), HRQOL (Δ Sickness Impact Profile 3.24 ± 3.63 vs 0.54 ± 3.58; P = 0.001), anthropometry, ammonia, endotoxins, cytokines, and myostatin levels was also significantly higher in group I than group II. Overt hepatic encephalopathy developed in 6 patients in group I and 13 in group II (P = 0.04). CONCLUSIONS: Nutritional therapy is effective in treatment of MHE and associated with improvement in nutritional status, HRQOL, ammonia, endotoxins, inflammatory markers, and myostatin levels.

Validity and Reliability of the European Organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 in Indian Patients With Corrosive-Induced Benign Refractory Esophageal Strictures.

Background The European organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 (EORTC QLQ-OG 25) is designed for patients with esophagogastric cancer. Its performance has never been tested with benign disorders. A health-related quality-of-life questionnaire does not exist for patients with benign corrosive-induced esophageal strictures. Hence, we evaluated the EORTC QLQ-OG 25 in Indian patients with corrosive strictures. Methods The English or Hindi version of QLQ-OG 25 was administered to 31 adult patients undergoing outpatient esophageal dilation at GB Pant hospital, New Delhi. These patients had refractory or recurrent esophageal strictures due to corrosive ingestion and had not undergone reconstructive surgery. Score distribution was analyzed, and item performance was determined based on floor and ceiling effects. Convergent validity, discriminant validity, and internal consistency were checked. Results The average time to finish the questionnaire was 6.70 minutes. Most scales fulfilled convergent validity (corrected item-total correlation >0.4), barring the Odynophagia scale and one item of the Dysphagia scale. Most scales exhibited divergent validity except for odynophagia and one item of dysphagia. Cronbach's alpha was >0.70 for all scales except odynophagia. Responses to questions evaluating taste, cough, swallowing saliva, and talking were highly skewed and had prominent floor effects. Overall, the questionnaire demonstrated good internal consistency, convergent validity, and divergent validity in benign corrosive-induced refractory esophageal strictures patients. Conclusion The EORTC QLQ-OG 25 can be satisfactorily used in patients with benign esophageal strictures to assess health-related quality of life.

A double blind randomized controlled trial to assess efficacy of nutritional therapy for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis.

BACKGROUND AND AIM: Overt hepatic encephalopathy (OHE) has high risk of recurrence and is associated with poor survival. The role of nutrition therapy is well documented in cirrhosis, but its efficacy in preventing the recurrence of OHE has not been studied. METHODS: In double blind RCT, we randomly assigned 150 patients with liver cirrhosis, with history of OHE in recent past to receive nutrition therapy (group I) or no nutrition therapy (group II) and followed up for 6 months. The primary efficacy end points were occurrence of breakthrough episodes and time to breakthrough episode of OHE. Secondary end points were OHE related hospitalizations and time to hospitalization involving OHE. Other parameters included anthropometry, changes in serum cytokines (IL-1, IL-6, IL-10, and TNF-α), endotoxin and myostatin. RESULTS: There was significant reduction in occurrence of breakthrough episodes of OHE in group I [10 vs 36, hazard ratio 0.20; P < 0.001], OHE-related hospitalization [8 vs 24, hazard ratio 0.27; P < 0.001)]. Times to breakthrough episode of OHE and OHE-related hospitalization were longer in group I. At the end of 6 months, inflammatory and anthropometry parameters showed significant improvement in group I compared with worsening of serum albumin, anthropometric parameters, IL-6, IL-10 and TNF-α in group II. At the end of 6 months, ascites (50 vs 66, P = 0.01), gastrointestinal bleed (2 vs 11, P = 0.007), and jaundice (16 vs 41, P < 0.001) were lower in group I. CONCLUSIONS: Treatment with nutrition therapy prevented recurrence of OHE and decreased OHE-related hospitalizations as compared with no nutrition therapy.

Comparing Myelosuppression Frequency in Indian Inflammatory Bowel Disease Patients: A Randomized Trial of Full Dose Versus Gradual Escalation of Thiopurines.

INTRODUCTION: We aimed to compare the frequency of myelosuppression in patients initiating azathioprine (AZA) at full dose versus those undergoing gradual dose escalation. METHODS: Forty patients with inflammatory bowel disease were recruited over one year and randomized into two groups of 20. Group A initiated AZA at a full dose of 2 mg/kg, while group B started at 1 mg/kg with subsequent dose increases at regular intervals. RESULTS: Seventeen patients from each group were included in the final analysis. During follow-up, two patients (11.8%) from group A and four patients (23.5%) from group B experienced relapses (p=0.65). Myelosuppression occurred in two patients (11.8%) from each group. Absolute neutrophil counts in group A tended to have lower median values than those in group B, particularly four weeks after AZA initiation. Univariate analysis identified serum proteins, albumin, and bilirubin as significantly associated with leukopenia, but these factors were not significant according to multivariate analysis. CONCLUSIONS: The incidence of myelosuppression was similar between the groups. Patients with full-dose initiation of AZA had numerically fewer relapses during the follow-up period.

Endoscopic retrograde cholangiopancreaticography-related complications - Experience from tertiary care teaching centre over half a decade.

Introduction: Endoscopic retrograde cholangiopancreaticography (ERCP) is an essential therapeutic procedure with a significant risk of complications. Data regarding the complications and predictors of adverse outcomes such as mortality are scarce, especially from India and Asia. We aimed to look at the incidence and outcome of complications in ERCP patients. Materials and Methods: This study is a retrospective analysis of prospectively collected data of all the patients who underwent ERCP and had a complication from January 2012 to December 2018. Data were recorded in predesigned pro forma. The data analysis was done by appropriate statistical tests. Results: : A total of 17,163 ERCP were done. A total of 570 patients (3.3%) had complications; perforation (n = 275, 1.6%) was most common followed by pancreatitis (n = 177, 1.03%) and bleeding (n = 60, 0.35%). The majorities of perforations were managed conservatively (n = 205, 74.5%), and 53 (19%) required surgery. Overall, 69 (0.4%) patients died. Of these, 30 (10.9%) patients died with perforation. Age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.005-1.07) and need of surgery (OR: 5.11, 95% CI: 1.66-15.77) were the predictors of mortality in patients with perforation. The majority pancreatitis were mild (n = 125, 70.6%) and overall mortality was 5.6% (n = 10). Conclusion: ERCP complications have been remained static over the years, with perforation and pancreatitis contributing the most. Most perforations can be managed conservatively with good clinical outcomes.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial.

BACKGROUND AND AIMS: Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. APPROACH AND RESULTS: In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n = 70) or placebo, lactulose, and rifaximin (n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. CONCLUSIONS: Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.

Prevalence of and Factors Associated with Sleep-Wake Abnormalities in Patients with Cirrhosis.

BACKGROUND & AIMS: Sleep-wake abnormalities [poor nighttime sleep and excessive daytime sleepiness (EDS)] are common in patients with cirrhosis. The aim of this study was to assess the prevalence of sleep-wake abnormalities and clinical factors associated with these abnormalities in a group of patients with cirrhosis. METHODS: 1098 patients with cirrhosis [Child Turcotte Pugh (CTP) class A, 22.2%; CTP class B, 29.2% and CTP class C, 48.6%], with either no ascites or mild ascites controlled on diuretics, and no history of or current overt hepatic encephalopathy were included in the study. RESULTS: Poor nighttime sleep and EDS were found in 569 (51.8%) and 489 (44.5%) patients respectively. On multivariate analysis, factors associated with poor nighttime sleep were CTP class C (vs. class A), presence of minimal hepatic encephalopathy (MHE), intermediate or evening type of diurnal preference category (vs. morning type), high risk for obstructive sleep apnea (OSA), diuretic use, presence of major depression, and presence of generalized anxiety disorder (GAD). Factors associated with EDS on multivariate analysis were CTP class B and C (vs. class A), intermediate or evening type of diurnal preference category (vs. morning type), high risk for OSA, presence of major depression, and presence of GAD. CONCLUSIONS: Sleep-wake abnormalities are common in patients with cirrhosis. CTP status, diurnal preference chronotype, risk of OSA, major depression and GAD are associated with both poor nighttime sleep and EDS. MHE and diuretic use are associated with poor nighttime sleep, but not with EDS.

COVID-19 Rapid Antigen Test: Role in Screening Prior to Gastrointestinal Endoscopy.

BACKGROUND/AIMS: The severe acute respiratory syndrome coronavirus 2 pandemic has affected the gastrointestinal (GI) endoscopy units globally owing to the risk of transmission. We present our data on the use of rapid antigen test (RAT) as a screening tool prior to endoscopy to prevent the transmission of coronavirus disease (COVID-19). METHODS: This study was a retrospective analysis of patients who underwent any GI endoscopic procedure from July 2020 to October 2020 at a tertiary referral center in New Delhi, India. All patients underwent screening for COVID-19 using RAT, and endoscopy was performed only when the RAT was negative. The data are presented as numbers and percentages. RESULTS: A total of 3,002 endoscopic procedures were performed during the study period. Only one endoscopic procedure was performed in a COVID-19 positive patient. A total of 53 healthcare workers were involved in conducting these procedures. Only 2 healthcare workers (3.8%) were diagnosed COVID-19 positive, presumably due to community-acquired infection, during this period. CONCLUSION: The COVID-19 RAT is easily usable as a simple screening tool prior to GI endoscopy during the COVID-19 pandemic.

Duodenal strongyloidiasis - Our 15-year histopathological experience at a tertiary gastrointestinal centre.

In order to emphasise the importance of histopathology in the clinically unsuspected diagnosis of duodenal strongyloidiasis, we report six cases diagnosed on duodenal biopsies identified from the database over a period of 15 years, and clinical, endoscopic and histopathological findings were analysed retrospectively. Four were elderly males and the remainder young females. Only one patient had an underlying immunocompromised state. Three presented with cholestatic jaundice and simulated hepatobiliary malignancy. In all cases, endoscopy provided non-specific findings. Only one case showed a predominant eosinophilic infiltrate. Eggs, larvae and adult forms of strongyloides were seen in crypts and showed intense basophilic staining on HE stain. It is concluded that since mostly undetected clinically, duodenal biopsy serves as the first step in the diagnosis of strongyloidiasis. Hepatobiliary manifestations, though very infrequent, should raise the suspicion for strongyloidiasis and thus necessitate the need for duodenal biopsy.

Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus.

Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.

Utility of N-acetylcysteine in ischemic hepatitis in cirrhotics with acute variceal bleed: a randomized controlled trial.

BACKGROUND AND AIMS: Ischemic hepatitis (IH) following acute variceal bleed (AVB) carries an ominous prognosis. N-Acetylcysteine (NAC), a potent anti-oxidant, may prevent IH by improving tissue oxygen delivery and improving hepatic hypoxia. METHODS: Consecutive cirrhotics with AVB were prospectively randomized to receive either standard of care (SOC) plus NAC intravenously for 72 h(at 150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, followed by 6.25 mg/kg for 67 h) (Group A, n = 107) or SOC alone (Group B, n = 107). RESULTS: Baseline characteristics were comparable. IH developed more frequently in Gr.B 25(23%) than A-15(14%); p = 0.08). Incidence of IH increased with severity of liver disease. Binary logistic regression analysis showed reduced incidence of IH in Gr.A than B [odds ratio (OR) 0.33, 0.11-0.93] patients after controlling for other significant factors. The incidence of acute kidney injury (AKI) was also reduced in Gr.A [OR 0.34, 0.15-0.75]. Development of IH was significantly associated with increased deaths due to liver failure at 6 weeks [subdistribution hazard ratio (SHR) 21.6, 7.4-62.8]. On multivariate competing risk analysis, significantly lower deaths due to liver failure (SHR 0.33, 0.11-0.97) were noted in Gr.A than B. CONCLUSIONS: One in five patients with acute variceal bleed develops ischemic hepatitis which is associated with worse outcomes. NAC therapy averts deaths due to liver failure by preventing IH and reduces AKI and is, therefore, recommended for cirrhotics with acute variceal bleed. TRIAL REGISTRATION: Clinicaltrials.gov no: NCT02015403.

ERCP-related perforation: an analysis of operative outcomes in a large series over 12 years.

BACKGROUND: Perforation is a rare but serious adverse event of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the predictors of morbidity and mortality after surgical management of ERCP-related perforation (EP). METHODS: The records of patients with EP requiring surgical intervention at a tertiary referral center in a 12-year period (2004-2016) were retrospectively analyzed for demography, indications for ERCP, risk factors, timing and type of surgical repair, post-operative course, hospital stay, and outcome. Multiple logistic regression was used to identify the parameters predicting survival. RESULTS: Of 25,300 ERCPs, 380 (1.5%) had EP. Non-operative management was successful in 330 (86.8%) patients. 50 (13.2%) patients were operated for EP. Out of 50, the perforation was detected during ERCP (intra-procedure) in 32 patients (64%). In 30 patients (60%), the surgery was performed within 24 h of ERCP. Twenty patients underwent delayed surgery (after 24 h of ERCP) following the failure of initial non-operative management. The delayed surgery after an unsuccessful medical treatment had a detrimental effect on morbidity, mortality and hospital stay. Post-operative duodenal leak was the only independent predictor of 90-day mortality (p = 0.02, OR = 9.1, 95% CI 1.52-54.64). Addition of T-tube duodenostomy (TTD) to the primary repair for either type I or type II perforations increased post-operative duodenal leak (type I, p = 0.048 and type II; p = 0.001) and mortality (type I, p = 0.009 and type II, p = 0.045). CONCLUSION: Although EP is a rare event, it has a serious impact on morbidity and mortality. Delaying of surgery following failed non-operative management worsens the prognosis. Addition of TTD to the repair is not helpful in these patients.

Endoscopic cystogastrostomy versus surgical cystogastrostomy in the management of acute pancreatic pseudocysts.

Background: Studies comparing surgical versus endoscopic drainage of pseudocyst customarily include patients with both acute and chronic pseudocysts and the endoscopic modalities used for drainage are protean. We compared the outcomes following endoscopic cystogastrostomy (ECG) and surgical cystogastrostomy (SCG) in patients with acute pseudocyst. Methods: Seventy-three patients with acute pseudocyst requiring drainage from 2011 to 2014 were analysed (18 patients excluded: transpapillary drainage n = 15; cystojejunostomy n = 3). The remaining 55 patients were divided into two groups, ECG n = 35 and SCG n = 20, and their outcomes (technical success, successful drainage, complication rate and hospital stay) were compared. Results: The technical success (31/35 [89%] vs. 20/20 [100%] P = 0.28), complication rate (10/35 [28.6%] vs. 2/20 [10%]; P = 0.17) and median hospital stay (6.5 days [range 2-12] vs. 5 days [range 3-12]; P = 0.22) were comparable in both the groups, except successful drainage which was higher in surgical group (27/35 [78%] vs. 20/20 [100%] P = 0.04). The conversion rate to surgical procedure was 17%. The location of cyst towards tail of pancreas and presence of necrosis were the main causes of technical failure and failure of successful endoscopic drainage, respectively. Conclusion: Surgical drainage albeit remains the gold standard for management of pseudocyst drainage; endoscopic drainage should be considered a first-line treatment in patients with acute pseudocyst considering the reasonably good success rate.

Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis.

BACKGROUND & AIMS: In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites. METHODS: We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites. RESULTS: Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective ß-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22-0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32-0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16-0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29-0.75). No heterogeneity was observed among studies. CONCLUSIONS: In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective ß-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.