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Introduction: Racial/ethnic disparities have been previously reported in renal and hepatic disease care; however, acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) despite its complexity requiring a multidisciplinary approach, remains understudied., Methods: To identify unique associations of clinical and sociodemographic factors with mortality and length of stay (LOS) among patients hospitalised with HRS-AKI, hierarchical regression analysis was conducted, along with a mediation analysis to estimate how race-related differences in in-hospital mortality were influenced by payer type, area household income, and clinical severity., Results: Black patients demonstrated a significantly higher odds of in-hospital mortality, compared to their white counterparts, adjusting for (1) sex and age, (2) sex, age, payer type, and area household income and (3) sex, age, and clinical severity [OR 1.16-1.20, 95% confidence intervals (CI) > 1]. Higher mortality rates among Black patients were partially mediated by clinical severity and area household income [proportion mediated (PM): 0.189 0.19 0.192 and 0.16 0.17 0.18 , respectively]. Black patients with HRS-AKI had longer LOS than White patients. Hispanic patients tended to have lower odds of in-hospital mortality [OR: 0.77 0.86 0.97 ] despite their lower income and more severe illness., Conclusion: Our nationwide US study demonstrated that, partly due to higher clinical severity and lower household income, Black patients with HRS-AKI experience higher inpatient mortality, compared to White patients. On the other hand, Hispanics with HRS-AKI have a survival advantage. More awareness is warranted to address racial disparities in HRS-AKI outcomes., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n  = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E / e ' was strongly correlated with serum LBP ( r  = 0.731; P  < 0.001), PRA ( r  = 0.714; P  < 0.001) and GFR ( r  = -0.609; P  < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P  = 0.01 and 53.3 vs. 28.2%; P  = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients., Methods: An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis., Results: The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality., Conclusion: The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Since MELD implementation renal impairment in liver transplant (LT) recipients has become of increasing importance. This is the first study evaluating the course of renal function immediately prior to LT as predictor for long-term renal and overall outcome., Patients and Methods: In this retrospective study, 226 adults undergoing LT at the University Medical Center Hamburg-Eppendorf (2011-2015) were included. The impact of renal function over a period of 3 months prior to LT compared to renal function at the day of LT on long-term renal outcome and survival was assessed., Results: According to GFR at day of LT renal function improved (≥1 CKD stage) in 64 patients (28%), remained stable in 144 (64%) or deteriorated in 18 (8%). Improvement of renal function prior to LT did neither significantly affect 90-day (13% vs. 14%, p = 0.83), nor 5-year post-LT mortality (35% vs. 41%, p = 0.57). 50 patients (22%) with hepatorenal syndrome (HRS) received terlipressin prior to LT, but only 18 (37%) showed prolonged stabilization of renal function (improvement ≥1 CKD stage). Response to terlipressin did neither improve 90-day (p=1), 5-year mortality (p = 0.52) nor long-term renal function (p = 0.843). Nevertheless, need for dialysis pre-LT (59% vs. 34%, p = 0.005) and post-LT (62% vs. 17%, p<0.001) was associated with increased 5-year mortality., Conclusions: Improvement of renal function immediately prior to LT, either spontaneously or following terlipressin therapy, did neither ameliorate long-term renal outcome nor survival in LT recipients. Future studies need to clarify the impact of terlipressin in HRS on the transplant waiting time in LT candidates., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe., Methods: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons., Results: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group., Conclusions: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: It has been reported that transjugular intrahepatic portosystemic shunting (TIPS) might be utilized as a salvage option for hepatorenal syndrome (HRS), while randomized controlled trials are pending and real-world contemporary data on inpatient mortality is lacking., Methods: We conducted an observational retrospective cohort study from the National Inpatient Sample from 2005 to 2014. We included all adult patients admitted with HRS and cirrhosis, using ICD 9-CM codes. We excluded cases with variceal bleeding, Budd-Chiari, end-stage renal disease, liver transplant and transfers to acute-care facilities. TIPS' association with inpatient mortality was assessed using multivariable mixed-effects logistic regression, as well as exact-matching, thus mitigating for TIPS selection bias. The exact-matched analysis was repeated among TIPS-only versus dialysis-only patients., Results: A total of 79,354 patients were included. Nine hundred eighteen (1.2%) underwent TIPS. Between TIPS and non-TIPS groups, mean age (58 years) and gender (65% males) were similar. Overall mortality was 18% in TIPS and 48% in dialysis-only cases (n = 10,379; 13.1%). Ninety six (10.5%) TIPS patients underwent dialysis. In-hospital mortality in TIPS patients was twice less likely than in non-TIPS patients (adjusted odds ratio [aOR] = 0.43, 95% CI 0.30-0.62; p < 0.001), with similar results in matched analysis [exact-matched (em) OR = 0.39, 95% CI 0.17-0.89; p < 0.024; groups = 96; unweighted n = 463]. Head-to-head comparison showed that TIPS-only patients were 3.3 times less likely to succumb inpatient versus dialysis-only patients (contrast aOR = 0.31, 95% CI 0.20-0.46; p < 0.001), with similar findings post-matching (emOR = 0.22, 95% CI 0.15-0.33; p < 0.001; groups = 54, unweighted n = 1457)., Conclusions: Contemporary, real-world data reveal that TIPS on its own, and when compared to dialysis, is associated with decreased inpatient mortality when utilized in non-bleeders-HRS patients. Further randomized studies are needed to establish the long-term benefit of TIPS in these patients.

Background: Hepatorenal syndrome type 1 (HRS-1), a form of acute kidney injury (AKI) in cirrhosis, has a median survival of days to weeks if untreated. The impact of reduction in AKI stage on overall survival in cirrhosis, independent of HRS reversal, is unclear., Methods: The Randomized, placEbo-controlled, double-blind study to confirm the reVERSal of HRS-1 with terlipressin study assessed terlipressin versus placebo, both with albumin, as treatment for HRS-1 for ≤14 days. Renal dysfunction severity was categorized by AKI stage at enrollment. Baseline patient characteristics were evaluated as predictors of AKI improvement using a multivariate model; the association between AKI stage reduction and 90-day survival was assessed using linear regression., Results: A total of 184 patients (terlipressin: n = 91; placebo: n = 93) with similar numbers in AKI Stages 1-3 (terlipressin/placebo, Stage 1: n = 25/26; Stage 2: n = 35/33; Stage 3: n = 31/34) were included. Predictors of AKI improvement were absence of alcoholic hepatitis, baseline serum creatinine and male gender. Overall survival was not significantly different across AKI stages (range 53-65%). In patients with no AKI worsening, 90-day survival was consistently better when AKI improved independent of HRS reversal, regardless of the initial AKI stage, with patients with Stage 1 at initial diagnosis achieving the greatest clinical benefit. A significant association was observed between AKI reduction and overall 90-day survival (P = 0.0022)., Conclusions: A reduction in AKI stage, independent of HRS reversal, was sufficient to improve overall survival in patients with HRS-1. The goal for HRS-1 treatment should be less stringent than absolute HRS reversal., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first-line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking., Aims: To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals., Methods: This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events., Results: Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2-24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety-day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001)., Conclusion: Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90-day survival., (© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: Spontaneous splenorenal shuntis a type of portosystemic shunt that develops frequently in the setting of chronic portal hypertension. It remains controversial whether shuntinterventions during liver transplant improve transplant outcomes., Materials and Methods: We conducted a retrospective comparison between deceased-donor liver transplant recipients who received spontaneous splenorenal shunt intervention and those who did not at a tertiary center between 2012 and 2017. Primary outcomes of interest included intraoperative transfusion requirement, hospital length of stay, acute kidney injury posttransplant, portal vein thrombosis, thrombocytopenia, and 1-year graft and patient survival., Results: Of 268 liver transplant recipients, 50 (18.6%) had large spontaneous splenorenal shunts pretransplant, with 45 patients having available radiologic and outcome data. Nine of 45 patients (20%) received shunt intervention, including pretransplant balloonoccluded retrograde transvenous obliteration (n = 5), intraoperative ligation of the left renal vein (n = 3), and intraoperative direct shunt ligation (n = 1). Demographic data, clinical characteristics, and Model for End-Stage Liver Disease scores were not different between the intervention and the nonintervention groups. Intraoperative transfusion, length of hospitalization, portal vein thrombosis, thrombocytopenia, and 1-year graft and patient survival were also similar between the 2 groups. However, the rate of posttransplant acute kidney injury was significantly lower in patients in the intervention group (0 cases vs 12 cases; odds ratio = 0.73; 95% confidence interval, 0.59-0.90). Patients with no SRS intervention (n = 36) were followed radiologically for 1 year posttransplant, with follow-up data showing complete resolution of spontaneous splenorenal shunt in just 4 patients (15%) and no changes in the remaining patients., Conclusions: Peritransplant interventions for spontaneous splenorenal shunt may reduce posttransplant acute kidney injury. In patients without intervention, spontaneous splenorenal shunt predominantly persisted 1 year posttransplant.

Introduction: Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress-or lack thereof-in improving outcomes of type 1 HRS over time., Methods: We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019., Results: Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4-43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2-51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94-1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96-1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95-1.20, p = 0.26) and 0.97 (95% CI 0.85-1.12, p = 0.70)., Conclusion: Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.

Background: Patients with hepatorenal syndrome carry a high short-term mortality. Early diagnosis and treatment are essential for patients' outcome. Nevertheless diagnosis of HRS remains difficult. First-line therapy terlipressin is often associated with severe complications. Biomarkers become more on focus for an early diagnosis. Objective: The aim of this study was to test the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for HRS patients and prognostic value for therapy responding patients. Material and methods: NephroCheck ® measures urinary concentrations of TIMP-2 and IGFBP-7, both indicating stress of renal cells and associated with induction of cell cycle arrest. 22 HRS patients and 30 patients with normal kidney function were included. [TIMP-2]·[IGFBP7] was measured using NephroCheck ® . HRS patients receiving terlipressin were also examined. Results: [TIMP-2]·[IGFBP7] values did not differ significantly (1.3 ± 2.09 vs. 1.03 ± 1.03; p  = 0.55). Furthermore, there was no significant difference of [TIMP-2]·[IGFBP7] regarding response of terlipressin (1.32 ± 2.39 vs. 0.81 ± 1.05; p  = 0.56). Low [TIMP-2]·[IGFBP7] values were significantly associated with higher mortality ( p  = 0.01). Conclusions: The results of this study suggest that [TIMP-2]·[IGFBP7] is not suitable for diagnostic of HRS and prediction of therapy response, but there might be evidence for prognostic value of [TIMP-2]·[IGFBP7] in regard to mortality of liver cirrhosis patients.

Background: Several lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS-AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS-AKI is lacking., Aim and Methods: To characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia-induced AKI and 58 patients with HRS-AKI., Results: HRS-AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL-6, IL-8, TNF-α, VCAM-1, fractalkine and MIP-1α. The inflammatory response was not related to presence of bacterial infection, concomitant acute-on-chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF-α and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS-AKI had higher levels of IP-10 and VCAM-1 compared to those with resolution of HRS-AKI. VCAM-1 was also an independent predictor of 3-month mortality. A systems biology analysis approach showed that the inflammatory status of HRS-AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease., Conclusion: Hepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes., (© 2018 The Authors. Liver International Published by John Wiley & Sons Ltd.)

Background: Hepatorenal syndrome (HRS) is associated with a poor prognosis. In HRS type 1, loss of renal function is rapidly progressive, while HRS type 2 is characterised by chronic ascites and more moderately elevated renal parameters. While treatment with terlipressin/albumin is well established in type 1, its effectiveness in chronic HRS is less clear., Objective: The aim of this study was to evaluate the effectiveness of terlipressin/albumin treatment in patients with HRS type 2., Methods: All patients with a first episode of HRS between April 2013 and February 2016 were included in this observational study. Relevant clinical and laboratory parameters were recorded and patients were followed., Results: A total of 106 patients with HRS were included. With terlipressin therapy reversal of HRS types 1 and 2 was achieved in 48% and 46% of patients ( p  = 0.84) with relapse rates of 8% vs 50% ( p  = 0.001). Overall survival (OS) and survival free of liver transplantation (LTx) were similar in HRS types 1 and 2 ( p  = 0.69; p  = 0.64). In multivariate analysis response to treatment was independently associated with better OS in HRS type 2, in addition to established risk factors such as lower Model for End-Stage Liver Disease score, absence of hepatic encephalopathy and eligibility for LTx., Conclusion: A terlipressin treatment course seems to be justified in selected patients with HRS type 2, especially in countries and settings with long transplant waiting lists. In addition treatment response might also help to identify HRS type 2 patients with a more favourable outcome.

Background: Liver disease is a major cause of mortality, with high numbers of hospital deaths, and disproportionately affects people younger than 65 years. This study aims to examine the place of death and factors associated with hospital death for people who died from liver disease., Method: We did a national population-based, observational study using the National Death Registration Database from the Office for National Statistics, 2001-14. All non-accidental adult deaths (hospital and non-hospital) from liver disease in England were included. Explanatory variables were underlying cause of death, contributory causes of death (number and specific causes), age at death, sex, marital status, year of death, index of multiple deprivation, rural or urban settlement, and residential region. We applied modified Poisson regression models to assess the strength of association between hospital death and explanatory variables using an adjusted prevalence ratio (PR)., Findings: 135 953 decedents were included, of whom 56 065 (41·2%) died from alcohol-related liver disease. Annual deaths from liver disease increased from 7811 in 2001, to 11 017 in 2014. Hospitals were the main place of death (66·9% [95% CI 66·6-67·1]) for patients who died from liver disease. The proportion of hospital deaths reduced from 71·5% in 2001 to 60·0% in 2014. After adjusting for sociodemographic factors, patients who died from alcohol-related liver disease had the highest chance of hospital death; people who died from liver cancer were less likely to die in hospital than people with alcohol-related liver disease (adjusted PR 0·61 [95% CI 0·60-0·61]). People with four or more contributory causes of death were more likely to die in hospital than those with no contributory causes (1·45 [1·42-1·47]). Patients with sepsis (1·24 [1·23-1·25]), hepatorenal syndrome (1·22 [1·21-1·22]), and peritonitis (1·18 [1·17-1·20]) had higher chances of hospital death than those without these respective contributory causes, and those with alcohol-related disorders (0·67 [0·66-0·69]) had lower chances of hospital death., Interpretation: The high risk of hospital death in patients with sepsis, hepatorenal syndrome, or peritonitis warrants further investigation, and the low chance of hospital death in patients with alcohol-related disorders also needs to be explored. Prevention strategies and end-of-life care services are urgently needed to prevent and tackle harms from liver disease., Funding: National Institute of Health Research Health Services and Delivery Research Programme, and Collaboration for Leadership in Applied Health Research and Care South London., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Enterobacteriaceae are now the predominant pathogens isolated in patients with liver cell failure associated with bloodstream infections. We conducted a retrospective cohort study of patients who were admitted for the diagnosis of hepatorenal failure (HRF) between June 1999 and May 2008 to investigate the risk factors of Enterobacteriaceae bacteremia (EB). EB was defined as the isolation of an EB species from at least one blood culture within three months following diagnosis of HRF. Variables were collected from the medical records and analyzed in relation to EB. Twenty-four (32.5%) of the 73 patients developed EB. The origin of EB was abdominal in 21% of the patients, urinary in 12.5%, pulmonary in 16.5%, and primary in the remaining patients (50%). Two-thirds of EB occurred within 10 days following the development of HRF. The main pathogens were Escherichia coli (44%), Enterobacter species (20%) and Klebsiella pneumoniae (22%). Eighteen patients (75%) with EB died. Variables significantly associated with EB after multivariate analysis were a model for end-stage liver disease score >20 [odds ratio (OR): 2.84, P <0.02], posthepatitis B liver cirrhosis (OR: 4.72, P <0.05), posthepatitis C liver cirrhosis (OR: 3.48, P <0.05), and initial level of serum creatinine on admission to intensive care unit (OR: 2.56, P <0.02). EB is a frequent and severe complication of HRF. Patients with posthepatitis cirrhosis B and C, higher serum creatinine, and severe liver cell failure score have a high risk of developing EB., Competing Interests: None

Tubular dysfunction is an important feature of renal injury in hepatorenal syndrome (HRS) in patients with end-stage liver disease. The pathogenesis of kidney injury in HRS is elusive, and there are no clinically relevant rodent models of HRS. We investigated the renal consequences of bile duct ligation (BDL)-induced hepatic and renal injury in mice in vivo by using biochemical assays, real-time polymerase chain reaction (PCR), Western blot, mass spectrometry, histology, and electron microscopy. BDL resulted in time-dependent hepatic injury and hyperammonemia which were paralleled by tubular dilation and tubulointerstitial nephritis with marked upregulation of lipocalin-2, kidney injury molecule 1 (KIM-1) and osteopontin. Renal injury was associated with dramatically impaired microvascular flow and decreased endothelial nitric oxide synthase (eNOS) activity. Gene expression analyses signified proximal tubular epithelial injury, tissue hypoxia, inflammation, and activation of the fibrotic gene program. Marked changes in renal arginine metabolism (upregulation of arginase-2 and downregulation of argininosuccinate synthase 1), resulted in decreased circulating arginine levels. Arginase-2 knockout mice were partially protected from BDL-induced renal injury and had less impairment in microvascular function. In human-cultured proximal tubular epithelial cells hyperammonemia per se induced upregulation of arginase-2 and markers of tubular cell injury., Conclusion: We propose that hyperammonemia may contribute to impaired renal arginine metabolism, leading to decreased eNOS activity, impaired microcirculation, tubular cell death, tubulointerstitial nephritis and fibrosis. Genetic deletion of arginase-2 partially restores microcirculation and thereby alleviates tubular injury. We also demonstrate that BDL in mice is an excellent, clinically relevant model to study the renal consequences of HRS. (Hepatology 2018; 00:000-000)., (© 2018 by the American Association for the Study of Liver Diseases.)

Background and Aims: This study aimed to create a risk scoring model for death from cirrhosis and hepatorenal syndrome, improve the detection rate of high-risk groups, and provide clinical evidence for early intervention treatment., Patients and Methods: We retrospectively recruited 196 patients with cirrhosis and hepatorenal syndrome between 1 January 2013 and 31 July 2014 at Beijing Ditan Hospital, Capital Medical University, China. The clinical information, biochemical values, age, and sex of the patients were included in the multivariate logistic regression model for screening independent risk factors. The model was validated in 56 patients with cirrhosis and hepatorenal syndrome between 1 August 2014 and 31 December 2014 at Beijing Ditan Hospital, Capital Medical University, China., Results: The death risk prediction scoring model included the following four independent risk factors: liver cancer, neutrophil above 70%, alanine aminotransferase higher than 40 U/l, and creatinine higher than 127 mmol/l. The sum death risk score ranged from 0 to 5: 0-2 identified patients with a lower risk of death (mortality rates: 12-41.4%), whereas 3-5 identified patients with a higher risk of death (mortality rates: 48.8-80%). Receiver-operating characteristic curves were constructed for the scoring model and the areas under the curves (AUC) were compared using the z-test. The AUC of the scoring model was 0.843. In addition, the AUC of validated model in 56 patients was 0.742., Conclusion: The scoring model can accurately predict mortality risk in patients with hepatorenal syndrome.

Background: The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking., Aims: To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites., Methods: Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence., Results: Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%)., Conclusions: Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

Background: The aim of this study was to predict the occurrence of hepatorenal syndrome (HRS) and death in patients with advanced cirrhosis and ascites., Patients and Methods: We retrospectively evaluated 2-year data of 78 patients with cirrhosis and ascites (Child-Pugh B/C: 45/43). The mean arterial pressure (MAP) and cardiac output (CO) were measured in all patients just before administration of 2 mg of terlipressin and 30 min later. Systemic vascular resistance (SVR) was calculated as MAP/CO. ΔMAP, and ΔCO, and ΔSVR were defined as the percentage change of MAP, CO, and SVR, respectively, after terlipressin injection. Plasma renin activity (PRA) and plasma aldosterone were evaluated at baseline. Two multivariate models were used: one excluding (model 1) and one including (model 2) the Model of End-stage Liver Disease score., Results: Higher ΔSVR, Model of End-stage Liver Disease score, and PRA were related independently to the severity of cirrhosis. Independent predictors of HRS at 12 and 24 months were ΔSVR (models 1/2: P=0.008/0.01 and 0.01/0.02, respectively), ΔCO (models 1/2: P=0.01/0.03 and 0.03/0.04, respectively), and PRA (models 1/2: P=0.04 and model 1: P=0.04, respectively). ΔSVR at 12 and 24 months (models 1/2: P=0.005/0.01 and 0.01/0.03, respectively) and ΔCO at 24 months (models 1/2: P=0.02/0.01, respectively) were related independently to survival. Patient groups with significantly higher probability of HRS and mortality were identified by certain cutoffs of ΔSVR (20.6 and 22.8%, respectively) and ΔCO (-10.6 and -11.8%, respectively). ΔSVR and ΔCO independently predicted survival in patients with the most advanced cirrhosis and infection-related survival., Conclusion: An increase in SVR by at least 20% and a decrease in CO at least 10% in response to terlipressin could predict HRS and mortality in patients with advanced cirrhosis.

Background: Hepatorenal syndrome is a severe complication of advanced liver diseases with a dismal prognosis., Aims: This systematic review and meta-analysis aims to explore the efficacy and safety of transjugular intrahepatic portosystemic shunt for the treatment of hepatorenal syndrome., Method: Publications were searched via PubMed and EMBASE databases. The pooled proportion and mean difference were calculated by using a random-effect model., Results: Nine publications were included, in which 128 patients with hepatorenal syndrome were treated with transjugular intrahepatic portosystemic shunt. The pooled short-term and 1-year survival rates were 72% and 47% in type 1 hepatorenal syndrome and 86% and 64% in type 2 hepatorenal syndrome. No lethal procedure-related complications were observed. The pooled rate of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt was 49%. The pooled rate of renal function improvement after transjugular intrahepatic portosystemic shunt was 93% in type 1 hepatorenal syndrome and 83% in any type of hepatorenal syndrome. After transjugular intrahepatic portosystemic shunt, serum creatinine, blood urea nitrogen, serum sodium, sodium excretion, and urine volume were significantly improved; by comparison, serum bilirubin slightly increased, but the difference was not statistically significant., Conclusion: Limited evidence suggested a potential survival benefit of transjugular intrahepatic portosystemic shunt in patients with hepatorenal syndrome but with a high incidence of hepatic encephalopathy., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment., Material and Methods: Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for &gt; 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival., Results: Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX)., Discussion: The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

Background and Objectives: Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status., Design, Setting, Participants, & Measurements: Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed., Results: Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis ( P =0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis ( P =0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed)., Conclusions: Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017&#95;11&#95;09&#95;CJASNPodcast&#95;18&#95;1&#95;A.mp3., (Copyright © 2018 by the American Society of Nephrology.)

Background: Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with hepatorenal syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs., Objectives: To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with hepatorenal syndrome., Search Methods: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016)., Selection Criteria: Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for hepatorenal syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups., Data Collection and Analysis: Three authors independently extracted data. The primary outcomes were mortality, hepatorenal syndrome (persistent hepatorenal syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains., Main Results: We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials.Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on hepatorenal syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of hepatorenal syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of hepatorenal syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses., Authors' Conclusions: This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.

Background: Hepatorenal syndrome is a potentially reversible renal failure associated with severe liver disease. The disease is relatively common among people with decompensated cirrhosis. Terlipressin is a drug that increases the blood flow to the kidneys by constricting blood vessels. The previous version of this systematic review found a potential beneficial effect of terlipressin on mortality and renal function in people with cirrhosis and hepatorenal syndrome., Objectives: To assess the beneficial and harmful effects of terlipressin versus placebo/no intervention for people with cirrhosis and hepatorenal syndrome., Search Methods: We identified eligible trials through searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Science Citation Index Expanded, and manual searches until 21 November 2016., Selection Criteria: Randomised clinical trials (RCTs) involving participants with cirrhosis and type 1 or type 2 hepatorenal syndrome allocated to terlipressin versus placebo or no intervention. We allowed co-administration with albumin administered to both comparison groups., Data Collection and Analysis: Two review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcomes were mortality, hepatorenal syndrome, and serious adverse events. We conducted sensitivity analyses of RCTs in which participants received albumin, subgroup analyses of participants with type 1 or type 2 hepatorenal syndrome, and Trial Sequential Analyses to control random errors. We reported random-effects meta-analyses with risk ratios (RR) and 95% confidence intervals (CI). We assessed the risk of bias based on the Cochrane Hepato-Biliary Group domains. We graded the quality of the evidence using GRADE., Main Results: We included nine RCTs with a total of 534 participants with cirrhosis and ascites. One RCT had a low risk of bias for mortality and a high risk of bias for the remaining outcomes. All included trials had a high risk of bias for non-mortality outcomes. In total, 473 participants had type 1 hepatorenal syndrome. Seven RCTs specifically evaluated terlipressin and albumin. Terlipressin was associated with a beneficial effect on mortality when including all RCTs (RR 0.85, 95% CI 0.73 to 0.98; 534 participants; number needed to treat for an additional beneficial outcome (NNTB) 10.3 people; low-quality evidence). Trial Sequential Analysis including all RCTs also found a beneficial effect of terlipressin. Additional analyses showed a beneficial effect of terlipressin and albumin on reversal of hepatorenal syndrome (RR 0.63, 95% CI 0.48 to 0.82; 510 participants; 8 RCTs; NNTB 4 people; low-quality evidence). Terlipressin increased the risk of serious cardiovascular adverse events (RR 7.26, 95% CI 1.70 to 31.05; 234 participants; 4 RCTs), but it had no effect on the risk of serious adverse events when analysed as a composite outcome (RR 0.91, 95% CI 0.68 to 1.21; 534 participants; 9 RCTs; number needed to treat for an additional harmful outcome 24.5 people; low-quality evidence). Non-serious adverse events were mainly gastrointestinal, including diarrhoea (RR 5.76, 95% CI 2.19 to 15.15; 240 participants; low-quality evidence) and abdominal pain (RR 1.54, 95% CI 0.97 to 2.43; 294 participants; low-quality evidence).We identified one ongoing trial on terlipressin versus placebo in participants with cirrhosis, ascites, and hepatorenal syndrome type 1.Three RCTs reported funding from a pharmaceutical company. The remaining trials did not report funding or did not receive funding from pharmaceutical companies., Authors' Conclusions: This review suggests that terlipressin may be associated with beneficial effects on mortality and renal function in people with cirrhosis and type 1 hepatorenal syndrome, but it is also associated with serious adverse effects. We downgraded the strength of the evidence due to methodological issues including bias control, clinical heterogeneity, and imprecision. Consequently, additional evidence is needed.

Background Acute hepatic dysfunction in the form of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) is a disease with a high risk of mortality and requires interdisciplinary intensive care. Aim This article explains the nomenclature, pathophysiology, prognosis and possible treatment options of ALF and ACLF, including the possibilities of extracorporeal liver support therapy at the point of liver transplantation (LTx). Method Narrative review with a selective literature review and representative case studies. Results/Corner Points ALF and ACLF may have several causes and are associated with high mortality. The causes of ALF must be accurately diagnosed because targeted treatment options are available. Both ALF and ACLF may require a liver transplantation for the patient's survival. For ALF and ACLF there are different criteria for decision-making on liver transplantation and graft allocation. For extracorporeal liver support therapy, two methods have been established (MARS [molecuar adsorbent recirculating system] and FPSA [fractionated plasma separation and adsorption] Prometheus ® ). Both approaches may have the potential to increase the probability of survival of patients with ALF or ACLF. In some cases they can be used for bridging to liver transplantation, in individual cases also for primary poison elimination, e.g. after Amatoxin ingestion. Both methods are not suitable for long-term therapy. Conclusion Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are serious diseases with a high risk of mortality. Affected patients should receive immediate interdisciplinary intensive care in a (tertiary) centre with the aim to clarify the cause of the disease as well as possible treatment options with respect to available extracorporeal liver support therapy and liver transplantation., Competing Interests: Interessenkonflikt: Nein., (Georg Thieme Verlag KG Stuttgart · New York.)

Background & Aims: Clinical course and risk factors of death in non-spontaneous bacterial peritonitis (SBP) infections are poorly known. We assessed the prevalence of acute kidney injury (AKI) and type-1 hepatorenal syndrome (HRS), hospital, 30-day and 90-day mortality and risk factors of death in 441 decompensated patients., Methods: Analysis of 615 non-SBP infections (161 urinary infections (UTI), 95 cellulitis, 92 suspected infections, 92 bacteraemias, 84 pneumonias, 21 bronchitis, 18 cholangitis, 15 spontaneous empyema, 13 secondary peritonitis, 24 other)., Results: Ninety-six percent of infections solved. AKI and type-1 HRS were developed in 37% and 9% of infections respectively. Overall hospital, 30-day and 90-day mortality rates were 11%, 12% and 18% respectively. Clinical course and mortality differed markedly across infections. Endocarditis, osteoarticular infections, pneumonia, spontaneous bacteraemia, cholangitis, secondary peritonitis and UTI showed higher rates of AKI. Prevalence of type-1 HRS was not significantly different among infections. Endocarditis, secondary peritonitis, pneumonia and bacteraemia showed lower rates of renal impairment resolution and higher hospital mortality associated with AKI (42% vs 12%, P<.0001) or type-1 HRS (71% vs 27%, P=.003) than the rest of infections. Age (HR: 1.04), serum sodium (HR: 0.91), serum bilirubin (HR: 1.06), INR (HR: 1.91), hepatic encephalopathy (HR: 2.44), ascites (HR: 3.06) and multidrug-resistant isolation (HR: 2.27) at infection diagnosis were independent predictors of death during hospitalization., Conclusions: Non-SBP infections constitute a heterogeneous group regarding clinical course and prognosis. Endocarditis, secondary peritonitis, pneumonia and bacteraemia show worse prognosis. The combination of data of liver and renal dysfunction and of the type of infection allows the identification of patients with poor prognosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several drugs have been studied to improve outcomes for patients with hepatorenal syndrome, but trials have reported variable efficacy. We aimed to compare the efficacy of different management strategies for type 1 hepatorenal syndrome., Methods: For this systematic review and network meta-analysis, we searched Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for papers published up to June 9, 2016. We selected randomised controlled trials of adults (>18 years) with decompensated cirrhosis and type 1 hepatorenal syndrome that compared the efficacy of active vasoactive drugs (terlipressin, midodrine, octreotide, noradrenaline, and dopamine; alone or in combination) with placebo or each other. The primary outcome was reduction in short-term mortality. Secondary outcomes were reversal of hepatorenal syndrome, relapse of hepatorenal syndrome after initial reversal, and adverse events. We did pairwise and network meta-analyses to produce odds ratios (ORs) and 95% CIs. We used the GRADE criteria to appraise quality of evidence., Findings: We identified 13 randomised controlled trials done in 739 adults with type 1 hepatorenal syndrome. All participants received supportive therapy with albumin. Moderate-quality evidence might support the use of terlipressin over placebo for reduction of short-term mortality (OR 0·65, 95% CI 0·41-1·05), whereas only low-quality evidence supported the use of noradrenaline, midodrine plus octreotide, and dopamine plus furosemide over placebo to reduce mortality, and no ORs for any of the comparisons versus placebo were significant. Moderate-quality evidence supported the use of terlipressin over midodrine plus octreotide (OR 26·25, 95% CI 3·07-224·21) to reverse hepatorenal syndrome, with low-quality evidence supporting the use of noradrenaline over placebo (4·17, 1·37-12·50) and over midodrine plus octreotide (10·00, 1·49-50·00) for this outcome. A median of 16% (range 5-20) of terlipressin-treated patients, and 33% (range 6-40) noradrenaline-treated patients with reversal of hepatorenal syndrome had recurrence on discontinuation of therapy. A median of 8% (range 4-22) terlipressin-treated patients required discontinuation of therapy due to serious adverse events., Interpretation: Terlipressin with albumin might reduce short-term mortality compared with placebo in patients with type 1 hepatorenal syndrome. Terlipressin with albumin and noradrenaline with albumin are both superior to midodrine plus octreotide with albumin for reversal of hepatorenal syndrome. Pragmatic clinical trials of terlipressin with albumin are warranted to evaluate real-world effectiveness and safety in patients with type 1 hepatorenal syndrome., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Patients with end-stage liver disease (ESLD) who develop hepatorenal syndrome (HRS) have very high mortality rates. For patients with HRS type I, median survival without specific therapy is only 2 weeks. Due to worsening clinical condition in such patients secondary to uremia and hepatic disease, some form of renal replacement therapy (RRT), either intermittent hemodialysis IHD or continuous veno-venous hemodialysis (CVVHD), must be instituted. However, the literature regarding the survival benefits of the hemodialysis for the worsening renal failure in liver cirrhotic patients remains limited. In this review, we performed a meta-analysis of nine different studies done in the last 2 decades that included 464 patients with end-stage liver disease with renal failure who received either pretransplantation or post-transplantation CVVHD. Survival of the patients was then analyzed with respect to patients with end-stage liver disease without renal failure that underwent liver transplantation (LT). Outcomes for the patients with pre-LT CVVHD were comparable with those of liver transplant recipients without renal failure. However, patients requiring post-LT hemodialysis for prolonged periods showed poor outcomes and a tendency to progress to chronic kidney disease. In all selected studies, patients with post-transplantation CVVHD for a prolonged period had a 3-year survival rate of ≤40%. This review highlights the role of pretransplantation CVVHD in selected patients with HRS who could achieve significantly better survival rates compared with patients without any renal replacement therapy or patients with post-transplantation CVVHD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Hepatorenal syndrome (HRS) represents a severe form of renal injury in cirrhotic patients with ascites in the absence of certain triggers., Methods: Patients with cirrhosis and ascites were longitudinally screened for renal dysfunction. HRS was diagnosed by an increase in serum creatinine (SCr) by ≥100% to ≥1.5 mg/dl. If specific triggers (i.e. nephrotoxins, parenchymal kidney damage, hypovolaemia, infections) were found, these cases were defined as specifically triggered acute kidney injury (sAKI)., Results: Four hundred ninety-seven cirrhotic patients were screened for AKI and we identified 71 patients with HRS and 84 with sAKI. The most common triggers of sAKI were parenchymal damage in 33%, nephrotoxins in 30% and hypovolaemia in 29%. sAKI patients showed significantly more often complete remission than HRS patients (51% vs. 13%, P < 0.001), whereas persisting impairment of renal function was more common in HRS than in sAKI (56% vs. 37%, P = 0.006). Short-term (30 days) mortality was significantly higher in HRS than in sAKI (62% vs. 45%, P = 0.038). Remission rates and mortality varied between sAKI triggers. Transplant-free survival (TFS) was not significantly, but numerically lower in HRS than in sAKI [14 (IQR: 2-99) vs. 36 (IQR: 5-371) days; P = 0.102]., Conclusion: Patients with HRS show worse outcome and higher 30-day mortality than patients with severe triggered AKI. Different triggers of sAKI seem to influence prognosis. Prospective data are needed to implement effective screening and treatment algorithms for kidney injury in patients with cirrhosis and ascites., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: In patients with cirrhosis and hepatorenal syndrome (HRS), terlipressin has been used either as continuous intravenous infusion or as intravenous boluses. To date, these two approaches have never been compared. The goal of this study was to compare the administration of terlipressin as continuous intravenous infusion versus intravenous boluses in the treatment of type 1 HRS. Seventy-eight patients were randomly assigned to receive either continuous intravenous infusion (TERLI-INF group) at the initial dose of 2 mg/day or intravenous boluses of terlipressin (TERLI-BOL group) at the initial dose of 0.5 mg every 4 hours. In case of no response, the dose was progressively increased to a final dose of 12 mg/day in both groups. Albumin was given at the same dose in both groups (1 g/kg of body weight at the first day followed by 20-40 g/day). Complete response was defined by decrease of serum creatinine (sCr) from baseline to a final value ≤133 μmol/L, partial response by a decrease ≥50% of sCr from baseline to a final value >133 μmol/L. The rate of adverse events was lower in the TERLI-INF group (35.29%) than in the TERLI-BOL group (62.16%, P < 0.025). The rate of response to treatment, including both complete and partial response, was not significantly different between the two groups (76.47% versus 64.85%; P value not significant). The mean daily effective dose of terlipressin was lower in the TERLI-INF group than in the TERLI-BOL group (2.23 ± 0.65 versus 3.51 ± 1.77 mg/day; P < 0.05)., Conclusion: Terlipressin given by continuous intravenous infusion is better tolerated than intravenous boluses in the treatment of type 1 HRS. Moreover, it is effective at doses lower than those required for intravenous bolus administration., (© 2015 by the American Association for the Study of Liver Diseases.)

Objective: The aim of this study was to compare the efficacy and costs of terlipressin and noradrenaline for the treatment of hepatorenal syndrome from the perspective of the Brazilian public health system and that of a major private health insurance., Methods: Comparison of efficacy was performed through a systematic review with a meta-analysis of randomized-controlled trials using a random-effects model. Economic evaluation was carried out through cost minimization., Results: Four studies (154 patients) were included in the meta-analysis. There was no evidence of a difference between treatments with terlipressin or noradrenaline in terms of 30-day survival (risk ratio=1.04, 95% confidence interval=0.84-1.30, P=0.70). From the perspective of the public health system, costs of the treatments with terlipressin or noradrenaline were Int$7437.04 and Int$8406.41, respectively. From the perspective of the private health insurance, costs of treatments with terlipressin and noradrenaline were Int$13,484.57 and Int$15,061.01, respectively., Conclusion: There was no evidence of superiority between treatment strategies using terlipressin or noradrenaline in terms of the survival of patients with hepatorenal syndrome, but the strategy using terlipressin was more economical under two different perspectives.

Hepatorenal syndrome (HRS) is one of the leading causes of hospitalizations in patients with chronic liver disease (CLD). We conducted a retrospective national database study to determine the epidemiology of HRS in hospitalized patients with CLD. Data from a Nationwide Inpatient Sample were extracted from 2002 to 2012 using ICD-9-CM codes related to CLD and HRS. The following outcomes were examined: in-hospital mortality, total charges, length of stay (LOS), patient demographics, procedures, complications, and comorbidities. Statistical analysis including regression was performed to examine factors associated with HRS. During 2002-2012, hospital discharges related to CLD increased from 407,246 to 836,475 with an increase of 37.9% for HRS as a complication in this population. Patients with CLD and HRS had worse outcomes compared with patients with CLD without HRS. This was manifested as a higher mortality rate (32.0% vs 10.3%), increased LOS (median 7 vs 5 days), and increased hospital costs (median $16,000 vs $11,000). Logistic regression demonstrated that HIV/AIDS (adjusted OR 2.9, 95% CI 2.2 to 3.9), pneumonia (aOR 2.8, 95% CI 2.3 to 3.2), and esophageal variceal bleeding (aOR 1.9, 95% CI 1.7 to 2.0) were associated with higher mortality in patients with HRS. Conversely, liver transplantation (aOR 0.1, 95% CI 0.1 to 0.1), transjugular intrahepatic portosystemic shunt (aOR 0.5, 95% CI 0.4 to 0.6), and hospitalization in the Midwest region of the USA (aOR 0.7, 95% CI 0.6 to 0.7) were associated with reduced mortality. The incidence of HRS in hospitalized patients with CLD increased during 2002-2012. HRS is associated with significant mortality and morbidity in these patients., (Copyright © 2016 American Federation for Medical Research.)

Background/aims: Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade., Methods: We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis., Results: Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods., Conclusions: The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Background: Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes., Methods: Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose., Results: Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period., Conclusions: This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.

Background and Aims: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS)., Methods: We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated., Results: Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients., Conclusion: This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

There is little information on the effects of treatment with vasoconstrictors plus albumin in patients with type 2 hepatorenal syndrome (HRS), particularly those awaiting liver transplantation (LT). This study reports the effects of treatment of type 2 HRS in patients on the waiting list for LT. We included 56 patients with type 2 HRS who were awaiting LT. Out of these 56 patients, 31 were treated with terlipressin and albumin. Nineteen (61%) of these 31 patients had response to therapy, and 11 of them relapsed after treatment withdrawal. There were no differences in mortality on the waiting list between responders and nonresponders. Among the 46 (82%) patients who underwent transplantation, 15 underwent transplantation with reversal of type 2 HRS, whereas the remaining 31 underwent transplantation with type 2 HRS. There were no significant differences in serum creatinine or estimated glomerular filtration rate between the 2 cohorts of patients at 3, 6, and 12 months after transplantation. There were no significant differences regarding development of acute kidney injury, need for renal replacement therapy, frequency of chronic kidney disease 1 year after transplant, length of hospitalization, and survival. In conclusion, treatment of patients with type 2 HRS with terlipressin and albumin does not appear to have beneficial effects either in pretransplantation or in posttransplantation outcomes., (© 2015 American Association for the Study of Liver Diseases.)

Hepatorenal syndrome is a condition associated with very high mortality that may be reverted in some cases with vasoconstrictors. Terlipressin has generally been considered standard treatment, but noradrenaline has been postulated as alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded noradrenaline and terlipressin probably have similar effects on reverting hepatorrenal syndrome and decreasing mortality, but noradrenaline is associated with less adverse effects, and has lower costs.

Background and Aims: Hepatorenal syndrome is a severe complication of cirrhosis and associates with significant mortality. Vasoconstrictor medications improve renal function in patients with hepatorenal syndrome. However, it is unclear to what extent changes in serum creatinine during treatment may act as a surrogate for changes in mortality. We have performed a meta-analysis of randomized trials of vasoconstrictors assessing the association between changes in serum creatinine, taken as a continuous variable, and mortality, both while on treatment and during the follow-up period for survivors., Methods: The electronic databases of PubMed, Web of Science and Embase were searched for randomized trials evaluating the efficacy of vasoconstrictor therapy for treatment of HRS type 1 or 2. The relative risk (RR) for mortality was calculated against delta creatinine. The proportion of treatment effect explained (PTE) was calculated for delta creatinine., Results: Seven trials enrolling 345 patients were included. The correlation between delta creatinine and ln (RR) was moderately good (R2 = 0.61). The intercept and parameter estimate indicated a fall in creatinine while on treatment of 1 mg/dL resulted in a 27% reduction in RR for mortality compared to the control arm. In patients surviving the treatment period, a fall in creatinine while on treatment of 1 mg/dL resulted in a 16% reduction in RR for post-treatment mortality during follow-up. The PTE of delta creatinine for overall mortality was 0.91 and 0.26 for post-treatment mortality., Conclusions: Changes in serum creatinine in response to vasoconstrictor therapy appear to be a valid surrogate for mortality, even in the period following the completion of treatment.

Unlabelled: Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival., Conclusion: Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS., (© 2015 by the American Association for the Study of Liver Diseases.)

Background: Type 2 hepatorenal syndrome (HRS2) is a functional renal impairment complicating end-stage liver disease. Although it is reversible after liver transplantation, long-term posttransplant outcomes in HRS2 patients remain ill-defined., Methods: Retrospective, matched case-control (1:2) study of all adult HRS2 patients transplanted in our institution between 2000 and 2012. The HRS2 patients were identified from our electronic transplant database, and matched with controls for the following variables: age, sex, etiology, diabetes mellitus, and year of transplant., Results: Forty-two HRS2 patients were compared to 83 controls. At the time of transplant, HRS2 patients had an estimated glomerular filtration rate of 41 ± 1 mL/min per 1.73 m. The HRS2 patients had greater intraoperative packed red blood cell transfusion (P = 0.002), and longer intensive care unit (P = 0.01) as well as total hospital length of stay (P = 0.03). Reversal of HRS2 occurred in 88.1% patients, 5.7 ± 0.5 days after transplantation. Although HRS2 patients had lower initial exposure to calcineurin inhibitors, a greater proportion of HRS2 patients had chronic kidney disease stage 3 (CKD3) at 3 (53.8% vs 28.4%; P = 0.007) and 12 months (59.5% vs 38.2%; P = 0.03) compared to controls. One-year survival was similar between the 2 groups (log-rank P = 0.82). On multivariate analysis, pretransplant HRS2 was associated with CKD3 at 3 (odds ratio, 3.73; 95% confidence interval, 1.54-9.03; P = 0.004) and 12 months (odds ratio, 3.23; 95% confidence interval, 1.37-7.64; P = 0.007) after transplantation., Conclusions: Liver transplantation reverses HRS2 in the majority of patients with survival outcomes comparable to matched controls, despite longer stays in intensive care unit and in hospital. Pretransplant HRS2 is associated with early posttransplant CKD3, despite calcineurin-inhibitor minimization.

Background: The principle of treating-to-target has been successfully applied to many diseases with significant improvement in patient care and as a useful guidance for healthcare providers. Appreciation of the central role for arterial vasodilatation in the pathogenesis of hepatorenal syndrome (HRS) has led to routine use of vasoconstrictors in combination with albumin in patients with HRS. An appropriate target to guide such therapy, however, has not yet been established., Aims: The purpose of the current study was to identify a suitable target that can predict clinical outcome and guide the medical management of type 1 HRS, a condition associated with very poor prognosis., Methods: A total of 85 patients with type 1 HRS who received a combination therapy of vasoconstrictors and albumin were enrolled. A potential therapeutic target was identified by univariate and multivariate logistic regression analyses. The treat-to-target concept to guide the management of HRS was then tested via a retrospective cohort study., Results: A change in mean arterial pressure (MAP) during treatment was identified as a sole independent predictor for patient survival. Compared with mild or no increase in MAP, achievement in a marked increase in MAP of more than 10 mmHg in these patients was associated with better overall survival and transplant-free survival. Increased MAP to higher than 15 mmHg did not result in further improvement in clinical outcome., Conclusions: A treat-to-target concept by the use of a specific goal of MAP is feasible and may potentially guide the medical management of type 1 HRS.

Hepatorenal syndrome type 1 (HRS1) is acute renal failure in the setting of advanced cirrhosis, and it results from hemodynamic derangements, which should be fully reversible after liver transplantation. However, the rate of hepatorenal syndrome (HRS) reversal and factors predicting renal outcomes after transplantation have not been fully elucidated. The aim of this study was to assess outcomes of HRS1 patients after liver transplantation and factors predicting HRS reversal. A chart review of all liver transplant patients with HRS1 (according to International Ascites Club criteria) at Toronto General Hospital from 2001 to 2010 was conducted. Patient demographic data, pretransplant and posttransplant laboratory data, and the presence of and time to posttransplant HRS reversal (serum creatinine < 1.5 mg/dL) were extracted from the center's transplant electronic database. Patients were followed until death or the end of the 2011 calendar year. Sixty-two patients (mean age, 54.7 ± 1.2 years; mean Model for End-Stage Liver Disease score, 35 ± 1) with HRS1 (serum creatinine, 3.37 ± 0.13 mg/dL) at liver transplant were enrolled. Thirty-eight patients received midodrine, octreotide, and albumin without success and subsequently received renal dialysis. One further patient received dialysis without pharmacotherapy. After liver transplantation, HRS1 resolved in 47 of 62 patients (75.8%) at a mean time of 13 ± 2 days. Patients without HRS reversal had significantly higher pretransplant serum creatinine levels (3.81 ± 0.34 versus 3.23 ± 0.14 mg/dL, P = 0.06), a longer duration of HRS1 {25 days [95% confidence interval (CI), 16-42 days] versus 10 days (95% CI, 10-18 days), P = 0.02}, a longer duration of pretransplant dialysis [27 days (95% CI, 13-41 days) versus 10 days (95% CI, 6-14 days), P = 0.01], and increased posttransplant mortality (P = 0.0045) in comparison with those whose renal function recovered. The only predictor of HRS1 nonreversal was the duration of pretransplant dialysis with a 6% increased risk of nonreversal with each additional day of dialysis. In conclusion, our study suggests that patients with HRS1 should receive a timely liver transplant to improve their outcome., (© 2015 American Association for the Study of Liver Diseases.)

Spontaneous bacterial peritonitis (SBP) is an infection of patients with cirrhosis and ascites. This peculiarity is due to the frequent intestinal translocation that allows bacteria to cross the intestinal barrier, colonizing the ascitic fluid. In cirrhosis, SBP is inferior only to urinary tract infections. It is prevalently sustained by Gram-negative bacteria such as Escherichia coli and Klebsiella. Risk factors for developing SBP are advanced age, refractory ascites, variceal bleeding, renal failure, low albumin levels (below 2.5 g/ml), bilirubin over 4 mg/dl, Child-Pugh class C and a previous diagnosis of SBP. Thus, this is an indication for a long-term antibiotic prophylaxis with norfloxacin. Renal failure - especially the hepatorenal syndrome - complicates SBP in about 20% of cases independently of the efficacy of the antibiotic therapy. The mortality of these patients is about 90%. Infusion of albumin significantly reduces the incidence of hepatorenal syndrome and consequently the risk of death. Long-term quinolonic prophylaxis as well as increased antibiotic therapies are causing the emergence of multidrug-resistant agents as frequent causes of SBP. In such cases, the antibiotic sensitivity to quinolones is low, and European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam. Collection of blood, urine and ascitic fluid for cultures is important for bacterial recognition, possibly before starting an empirical antibiotic therapy. Indeed, the probability of positive cultures rapidly vanishes when they are performed during already implemented antibiotic administration. It is important to know that a failure of the first-line therapy is associated with an increased probability of death., (© 2015 S. Karger AG, Basel.)

Combined liver-kidney transplantation (CLKT) in children is uncommon and outcomes have not been well defined. Using the Scientific Registry of Transplant Recipients, data were analyzed on 152 primary pediatric CLKTs performed from October 1987 to February 2011, to determine their outcome in the largest series reported to date. Patient survival was 86.8%, 82.1% and 78.9% at 1, 5 and 10 years, liver graft survival was 81.9%, 76.5% and 72.6%, and kidney graft survival was 83.4%, 76.5% and 66.8%. By way of comparison, the Registry was queried for pediatric patient survival following isolated liver transplantation (LT) during the same time frame: 86.7%, 81.2% and 77.4% and following isolated kidney transplant (KT): 98.2%, 95.4% and 90% at 1, 5 and 10 years. In patients having undergone CLKT, primary hyperoxaluria was associated with reduced patient (p = 0.01), liver graft (p = 0.01) and kidney graft survival (p = 0.01). Furthermore, graft outcome following CLKT improved over the past decade (p = 0.04 for liver, p = 0.02 for kidney), but this did not translate into improved patient outcome (p = 0.2). All in all, our results confirmed that survival following LT was less than following KT, and that CLKT offered similar patient survival to isolated LT., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Aim: Leptospirosis, endemic in India, is complicated by jaundice and renal failure. Whether leptospirosis could result in a worsening of preexisting chronic liver disease (CLD) is not known. Aim of the study was to analyze the clinical profile and natural course of leptospirosis in decompensated CLD in comparison to those acquiring the infection in an otherwise healthy individual., Methods: Cases were patients with liver cirrhosis who presented with fever and/or jaundice and were screened and found positive for leptospirosis. Controls were patients diagnosed to have leptospirosis during the same period, but in the absence of liver disease. Both cases and controls were followed up until recovery or death., Results: Thirty-one patients had cirrhosis of the liver, and 91 controls had leptospirosis. Significantly more number of cirrhotics had jaundice (87.1 % vs. 16.5 %; p = 0.001), elevated blood urea (41.9 % vs. 18.7 %; p = 0.01), and serum creatinine (41.9 % vs. 19.8 %; p = 0.03) compared to the controls. There were four deaths due to hepatorenal dysfunction and coagulopathy in cirrhotics and no deaths in the control group (4 vs. 0; p = 0.001)., Conclusion: Leptospirosis should be considered as yet another important cause of acute-on-chronic liver failure in endemic areas associated with poor outcome. Death is often due to hepatorenal dysfunction.

Aim: To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders., Methods: The link between Metabolic Syndrome and non-alcoholic fatty liver disease is currently demonstrated. Various metabolic disorders and the Metabolic Syndrome (the association of ≥ 3 metabolic disorders) have been recently described as a risk factor of perioperative mortality in major liver resection. Patients who passed away during perioperative course of major liver resection and presenting with the association of ≥ 2 metabolic disorders without any other known cause of liver disorders were reviewed., Results: From January 2001 to May 2010 in a tertiary centre, ten patients presenting with ≥ 2 metabolic disorders without any other known cause of liver disorders died during perioperative course of major liver resection. The same four-consecutive-steps sequence of events occurred, including jaundice. The analysis of this series suggested a rapidly deteriorating congestive liver resulting in an increased portal hypertension leading to hepatorenal syndrome and lately to multiorgan failure (mimicking septic collapse) as the mechanism leading to exitus. The acute portal hypertension is mainly related to the surgical procedure. The chronic portal hypertension is indeterminate. Patients with ≥ 2 metabolic disorders should be considered as potentially presenting with portal hypertension possibly evolving towards hepatorenal syndrome; thus, they should be considered as having a high perioperative risk and should be carefully evaluated before undergoing major liver resection., Conclusion: As fibrosis was not present or marginal in liver specimens, the real cause of portal hypertension in patients with multiple metabolic disorders should be investigated with further studies.