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Whether tubular injury develops in patients with acute kidney injury owing to hepatorenal syndrome (AKI-HRS) is controversial. We performed repeated measurements of biomarkers of tubular injury during a 14-day period in 60 patients with cirrhosis and AKI (34 with AKI-HRS meeting the classical definition of type 1 HRS and 26 with AKI owing to acute tubular necrosis, AKI-ATN). Nineteen of 34 patients had resolution of AKI-HRS, while the remainder had persistent AKI-HRS. The persistence of AKI-HRS was associated with remarkably high short-term mortality. There were no significant differences in urinary NGAL or IL-18 between patients with resolution vs those with persistent AKI-HRS throughout the 14-day period. By contrast, biomarker levels were significantly lower in AKI-HRS, even if persistent, compared to AKI-ATN. These findings are highly suggestive of lack of significant tubular injury in AKI-HRS and could be of value in the clinical decision between combined liver-kidney or liver transplantation alone in patients with cirrhosis and AKI candidates to transplantation.

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

OBJECTIVES: Alcoholic hepatitis (AH) is a severe condition characterized by a marked inflammatory response and high short-term mortality. Endothelial dysfunction (ED) is an early event in vascular and inflammatory disorders. The aim of this study is to evaluate ED in AH patients. METHODS: Prognostic value of ED biomarkers was evaluated in patients with severe AH (n = 67), compensated alcoholic cirrhosis (n = 15), heavy drinkers without liver disease (n = 15) and controls (n = 9), and in a validation cohort of 50 patients with AH. Gene expression of ED markers was analyzed in liver tissue. RESULTS: Plasma levels of ED markers such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin and von Willebrand factor (vWF) increased along alcohol-related liver disease (ALD) progression. Intergroup analysis showed a significant increase of these markers in AH patients. In addition, VCAM-1 showed a positive correlation with Maddrey, MELD and ABIC scores and inflammation parameters (i.e. C-reactive protein and LPS levels). Importantly, levels of VCAM-1 were higher in patients with increased mortality and were independently associated with short-term survival (90-day) when adjusted by ABIC score. These results were confirmed in an independent cohort of AH patients. In addition, severe AH patients showed altered hepatic expression of ED markers. CONCLUSIONS: In this study we show that advanced ALD and particularly severe AH is associated with an increase of ED biomarkers, which correlate with patient outcomes. These results suggest that ED may be a pathogenic event in AH and highlight endothelial factors as potential biomarkers in AH.

BACKGROUND AND AIMS Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Background & Aims Acute kidney injury (AKI) is common in cirrhosis and is associated with poor prognosis. In patients who survive after AKI, it is not known whether the acute injury leads to chronic impairment of kidney function (chronic kidney disease [CKD]). The aim of the study was to determine the frequency of CKD at 3 months after an AKI episode and its effects on patient outcomes. Methods Patients admitted for complications of cirrhosis during a 6.5-year period were evaluated using the same protocol, with assessment of kidney function at regular intervals during and after hospitalization. CKD was defined as estimated glomerular filtration rate (eGFR) Results A total of 409 patients (168 with AKI and 241 without AKI) were included. After 3 months, 97 patients with AKI and 188 patients without AKI had survived. Of the 97 patients with AKI, 24 had developed CKD at 3 months compared to only 2 of the 188 patients without AKI (25% vs. 1%, odds ratio 31; p Conclusions CKD frequently develops in patients with cirrhosis who survive AKI and has a negative impact on relevant clinical outcomes. The transition from AKI to CKD is common and should be considered a high-risk condition in patients with cirrhosis. Lay summary Episodes of acute impairment of kidney function are common in patients with cirrhosis. This study shows that the development of chronic impairment of kidney function is frequent in patients surviving these acute episodes and that it is associated with a higher risk of developing other complications of cirrhosis and to a higher rate of 3-month hospital readmissions.

Background and aims Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. Methods One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). Results Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). Conclusion Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.

Impairment of kidney function is common in acute-on-chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill-defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI-on-CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p 0.001 vs. ACLF). Frequency of CKD alone was low and similar in both groups (4% and 3%, respectively); only a few patients with ACLF (4%) had no kidney dysfunction. AKI in ACLF was associated with poor kidney and patient outcomes compared with no ACLF (AKI resolution: 54% vs. 89%; 3-month survival: 51% vs. 86%, respectively; p 0.001 for both). Independent predictive factors of 3-month survival were Model for End-Stage Liver Disease-Sodium score, ACLF status, and urine neutrophil gelatinase-associated lipocalin (NGAL). AKI is almost universal in patients with ACLF, sometimes associated with CKD, whereas CKD alone is uncommon. Prognosis of AKI depends on ACLF status. AKI without ACLF has good prognosis. Best predictors of 3-month survival are MELD-Na, ACLF status, and urine NGAL.

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.