Diagnosis and management of hepatic encephalopathy: The French recommendations.

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Baclofen Combined With Psychosocial Care is Useful and Safe in Alcohol-Related Cirrhosis Patients: A Real-Life Multicenter Study.

BACKGROUND: Alcohol-related cirrhosis is a frequent and difficult-to-treat disease. Despite the low hepatic metabolism of baclofen, data on its use in this subgroup are scarce. The French multicenter Observatory of patients treated with Baclofen for Alcohol DEpendence real-life cohort assessed: (a) prescription modalities of baclofen in liver units; (b) safety profile of baclofen; and (c) declared alcohol intake, biological markers of excessive alcohol intake and hepatic function at 12 months. METHODS: All consecutive patients with cirrhosis who received baclofen to reduce alcohol consumption or maintain abstinence were prospectively included. Psychosocial management was always associated. Clinical and biological data were collected every 3 months for 1 year. RESULTS: Between November 2013 and December 2016, 71 in- or outpatients were included from 10 liver units. Of the patients, 25% had ascites. After 12 months, 52 patients (73%) were still being followed, and 41 (57.7%) were still receiving baclofen at a mean dosage of 75 mg/day (r30-210). The overall declared consumption decreased from 100.2 to 14.7 g/day (P < 0.0001), and 29 patients (40.8%) reached abstinence. Significant improvement in the usual biomarkers of excessive alcohol intake (AST, GGT and MCV) and liver function (Prothrombin ratio (PTr), albumin levels) were observed. The usual side effects such as drowsiness were frequent (22%) but no serious adverse events (AEs) or overt encephalopathy related to baclofen was reported. CONCLUSION: In this 1-year follow-up series, baclofen was combined with psychosocial treatment in patients with cirrhosis and was well tolerated. This treatment was associated with a significant decrease in declared alcohol consumption as well as improvement in hepatic function.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

Consensus care recommendations for alfapump® in cirrhotic patients with refractory or recurrent ascites.

BACKGROUND: The alfapump® is an implantable class III medical device that pumps ascitic fluid from the peritoneal space to the urinary bladder from where it is excreted. The pump reduces or abrogates the need for repeated paracentesis in patients with recurrent or refractory ascites. AIMS: To improve outcomes for alfapump® implantation and pre- and post-implant patient management in both clinical trial and real-world settings by development of consensus recommendations. METHODS: The alfapump® working group consisting of hepatologists and surgeons with extensive experience in implantation of the alfapump® and patient management met on two occasions: (1) to determine the key areas where recommendations should be made; and (2) to discuss the experiences of the working group within those areas and formulate draft statements. Developed statements were submitted to the group and consensus sought on relevance and wording through a collaborative iterative approach in order to consolidate the recommendations into consensus statements. Only recommendations agreed upon unanimously were included. RESULTS: Twenty-three consensus recommendations were developed in the areas of pre-implantation procedure, (three statements), surgical implant procedure (11 statements), immediate post-implant care (three statements) and long-term management (six statements). CONCLUSIONS: The consensus statements are a valuable reference resource for physicians managing patients with the alfapump® and for those considering management strategies for patients with refractory ascites.

The Current Status of Granulocyte-Colony Stimulating Factor to Treat Acute-on-Chronic Liver Failure.

Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.

Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study.

BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases < 0.6 × ULN (OR = 7.1; CI: 1.3; 36.7). Thirty-nine patients stopped therapy after a median biochemical response of 48.6 months. Twenty-four of them had a biopsy before treatment withdrawal: 21 were histological responders. The cumulative rate of relapse was 25% at 64 months. CONCLUSIONS: This study indicates that older age, mild-to-moderate fibrosis at diagnosis and serum aspartate aminotransferases in the lower range of normal are independent predictors of histological response in AIH with prolonged biochemical response. The relapse rate after treatment withdrawal may be limited to 25% at 64 months when patients are selected on the basis of prolonged biochemical remission and, when available, histological response.

Albumin in decompensated cirrhosis: new concepts and perspectives.

The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.

Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients.

BACKGROUND & AIMS: The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage. METHODS: Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry. RESULTS: 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR = 4.39; 95%CI = 1.79-10.76) or MELD (OR = 8.24; 95%CI = 3.19-21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, P = 0.089). CONCLUSIONS: In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.

Accuracy of calprotectin using the Quantum Blue Reader for the diagnosis of spontaneous bacterial peritonitis in liver cirrhosis.

AIM: We aimed to evaluate the accuracy of the dosage of calprotectin in ascitic fluid (AF) using the Quantum Blue assay, for the prompt diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: We prospectively collected 236 AF samples from 119 cirrhotic patients hospitalized in two French centers between May 2016 and May 2017. Bloody and chylous/cloudy AF, and secondary peritonitis were excluded. SBP was diagnosed if neutrophils in AF were >250/mm3 using standard cytology. The Quantum Blue Reader selectively measured the calprotectin antigen (MRP8/14) in 12 min within the measurable range from 0.18 to 1.80 µg/mL; values outside this range were registered as 0.17 and 1.81 µg/mL. RESULTS: A total of 36 AF were considered as SBP (15.2%). SBP had higher median levels of calprotectin than non-SBP (1.81 vs. 0.25 µg/mL, P < 0.001). Calprotectin levels were positively correlated with neutrophils in AF (r = 0.57, P < 0.001) and C-reactive protein (r = 0.43, P < 0.001), but not with the Child-Pugh and Model for End-Stage Liver Disease scores. The optimal threshold of calprotectin to diagnose SBP was set at 1.51 µg/mL (80th percentile of calprotectin), yielding sensitivity, specificity, and positive and negative predictive values of 86.1%, 92.0%, 65.9%, and 97.3%, respectively. Only one asymptomatic patient with SBP had a low calprotectin level, but a high serum C-reactive protein level that strongly suggested an ongoing infection. We also showed that intraclass correlation coefficients for inter- and intra-observer agreement were excellent, with 0.95 and 0.89, respectively. CONCLUSIONS: The dosage of calprotectin in AF using the Quantum Blue assay is a rapid and reliable method of ruling out SBP in hospitalized cirrhotic patients.

Albumin Use in Patients With Cirrhosis in France: Results of the "ALBU-LIVE" Survey: A Case for Better EASL Guidelines Diffusion and/or Revision.

INTRODUCTION: The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. METHODS: All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. RESULTS: Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. CONCLUSIONS: In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients.

OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm3. Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P<0.001) and 7.2% in patients with symptoms suggestive of SBP (3% in outpatients vs. 11.3% in inpatients; P<0.001). The κ value for inter-reader agreement was 0.81 (95% confidence interval: 0.77-0.84) when using the "trace" threshold. Considering discordant results (n=131) as positive to interpret the diagnostic performance of the strip at the "trace" threshold, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.7, 57.1, 12.0, and 99.1%, respectively. At this "trace" threshold, sensitivity and NPV were both 100% in outpatients, and 89.5 and 97.9% in inpatients, respectively. At the "small" threshold, sensitivity, specificity, PPV and NPV were 81.0, 85.9, 25.9 and 98.7%, respectively. CONCLUSIONS: The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.

Copeptin is an independent prognostic factor for transplant-free survival in cirrhosis.

BACKGROUND & AIMS: Copeptin is a stable cleavage product of the arginine vasopressin (AVP) precursor and is equimolarly secreted with AVP. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. We aimed to investigate the association between severity of cirrhosis and copeptin concentrations and to confirm whether copeptin is of prognostic significance in cirrhosis. METHODS: One hundred and eighty-four cirrhotic patients hospitalized in two tertiary referral centres were studied. Serum copeptin was measured in samples obtained at hospital admission. Differences in serum copeptin between Child-Pugh classes were evaluated using the Kruskal-Wallis test. Cox proportional hazard regression and Kaplan-Meier analyses were performed to evaluate associations of copeptin and other possible prognostic factors with 6- and 12-month mortality. RESULTS: Median serum copeptin (interquartile range) increased significantly through Child-Pugh classes A [5.4 (3.1-10.7) pmol/L], B [9.6 (6.0-17.3) pmol/L] and C [13.8 (5.8-34.1) pmol/L, P < 0.01]. Patients with serum copeptin >12.3 pmol/L displayed significantly higher mortality rates at 6 and 12 months as compared to those with serum copeptin ≤12.3 pmol/L (Log-rank test: P < 0.01). Serum copeptin >12.3 pmol/L was significantly associated with mortality, particularly at 6 months, independently of age, clinical parameters and Model for End stage Liver Disease (MELD), MELD-sodium and Child-Pugh score. CONCLUSIONS: Serum copeptin concentration increases significantly along with the severity of cirrhosis as defined by the Child-Pugh classification. A high serum copeptin concentration predicts survival, particularly at 6 months, independently of liver-specific scoring systems in a heterogeneous population of hospitalized cirrhotic patients.

Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial.

BACKGROUND & AIMS: Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. METHODS: A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 µmol/L). The secondary endpoint was 3-month survival rate. RESULTS: Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. CONCLUSIONS: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.