Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).

[Spontaneous bacterial peritonitis].

AIM OF STUDY: Spontaneous bacterial peritonitis (SBP) is the most frequent infectious complication of liver cirrhosis with serious consequences. Initially, SBP is always treated with empirical, not targeted, antibiotic therapy. Since a retrospective study performed in our department showed suboptimal effectiveness (only 40 %) of empirical antibiotic therapy in accordance with the EASL guidelines, a decision was made to change the protocol. The aims of this prospective study were to determine: (1) the incidence and characteristics of SBP in real clinical practice - in a liver unit of a tertiary hospital, (2) the effectiveness of new antibiotic therapy selected based on analysis of the spectrum of pathogens and their resistance to antibiotics as identified in a retrospective cohort study on SBP carried out in our department, (3) mortality, and to compare these findings with the literature data. MATERIAL AND METHODS: A prospective cohort observational pragmatic study. SETTING: Department of Hepatology, Gastroenterology and Liver Transplantation, 2nd Internal Clinic, Slovak Medical University and F. D. Roosevelt Teaching Hospital with Polyclinic in Banska Bystrica. Time interval: November 2012-August 2013. INCLUSION CRITERIA: hospitalization for liver cirrhosis, ascites ≥ grade 2, informed consent. The study was approved by the local ethics committee. EXCLUSION CRITERIA: malignancy, secondary bacterial peritonitis. DIAGNOSIS: SBP was defined by the count of neutrophil leukocytes in ascites ≥ 250/mm3). Positive ascitic fluid culture was not a necessary condition for the diagnosis. From each patient, 10 mL of ascitic fluid were sampled into two blood culture bottles, anaerobic and aerobic. Therapeutic response: defined as a decrease in NeA to 25 % of the baseline value after 48-72 hours, in accordance with the EASL guidelines. The absence of response was indication for change of the antibiotic therapy strategy. Empirical antibiotic therapy: The drug of choice was piperacillin/tazobactam 4 g/0.5 g i.v. every 8 hours for 5 days. Additionally, 20% human albumin at doses of 1.5 g/kg of patient weight on day 1 and 1.0 g/kg of patient weight on day 3 from the diagnosis was administered. If there was no response, (a) second choice antibiotic therapy according to analysis of the spectrum of pathogens and their resistance as identified in the former retrospective study on SBP, that is, ertapenem 1g i.v. every 24 hours for 5 days, or (b) targeted antibiotic therapy according to analysis of ascitic fluid culture performed in the meantime was initiated. RESULTS: The inclusion criteria were met by 65 patients (99 episodes); the incidence of SBP was 9 out of 99 episodes (9.1 %); 5 out of the 9 cases had positive bacterial culture (56 %), with most of bacteria being Gram-positive (4 out of 5 cases, 89 %). Therapeutic response was documented in 7 out of the 9 cases (78 %). The in-hospital mortality of patients with SBP was 11 %. CONCLUSIONS: SBP was detected in one out of ten patients with cirrhotic ascites. The selection of empirical therapy in accordance with the principles of antibiotic stewardship led to an increase in therapeutic response to more than 75 %. Effective treatment of SBP is a prerequisite for reduction of mortality.

Concomitant diverticulosis among patients undergoing liver transplantation. Does it influence the length of hospitalization after the procedure?

Aim of the study: We tried to assess the influence of concomitant diverticulosis and other factors, e.g., Child-Pugh (C-P) and MELD scores, viral etiology, and presence of alcoholic disease, on short-term results of liver transplantation (LT) with an emphasis on duration of patient's hospitalization. Material and methods: This prospective study was performed on 206 cirrhotic patients who were selected for LT. In order to assess the presence of diverticculosis we performed colonoscopy. Results: The duration of hospitalization after LT did not differ significantly between patients with and without diverticulosis (27.5 [21.0-33.5] vs. 24.0 [18.0-32.0] days, p = 0.28). Patients with C-P class C were hospitalized longer in comparison to the class B patients. It is reflected in the positive correlation between C-P score and days of hospitalization (r = 0.22, p = 0.002). Patients with diverticulosis were significantly older (59.6 [51.1-63.3] vs. 52.9 [43.8-59.2] years, p = 0.03). Alcoholic liver disease (ALD) was associated with a greater risk of diverticulosis (OR = 3.89, 95% CI [1.13-15.87], p = 0.04). Conclusions: Presence of diverticulosis among subjects undergoing LT did not influence the duration of hospitalization after the procedure. Significantly longer hospitalization was observed in patients with the most advanced liver disease according to C-P score. To determine the exact impact of diverticulosis on short-term results of LT additional studies are required.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Acute-on-chronic liver failure: a single-centre experience.

AIM OF THE STUDY: We set out to determine the applicability of acute-on-chronic liver failure (ACLF) diagnostic criteria and characteristics of thus defined ACLF sub-cohorts in a real-life clinical context. MATERIAL AND METHODS: Retrospective charts' analysis of consecutive patients hospitalized with decompensated liver disease. Inclusion criteria: acute decompensation, informed consent. Exclusion criteria: malignancy. Diagnostic tools: 1st phase - CLIF-SOFA score calculated manually; 2nd phase - CLIF-C ACLF score calculated at www.efclif.com. RESULTS: Of 432 hospitalized patients aged 52 years, 41% were female, with MELD 20, 32% patients had acute decompensation (AD); main triggers were alcoholic hepatitis (38%), infections (26%), and variceal bleeding (23%). Of patients with AD, ACLF grades 0-3 was present in 64%, 19%, 13%, and 4%, respectively. In hospital mortality according to final AD/ACLF grade in ACLF 0-3 was 7.5%, 42%, 47%, and 80%, respectively (p < 0.0001). CONCLUSIONS: Diagnosing ACLF is nowadays easy; it helps to stratify patients at admission, and refine risk stratification at day 7. The main trigger of AD/ACLF in this region is alcohol. Currently, there are no ACLF-specific treatments; however, timely intensive supportive care can influence the prognosis. Even though still elusive and controversial, the ACLF concept can help systematize management of patients admitted with acute decompensation of advanced chronic liver disease.