Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis.

Lille score at Day 7 (LM7) helps to predict the outcome of patients with severe alcoholic hepatitis (sAH) undergoing corticotherapy. Several scores such as Maddrey's discriminant function (MDF), MELD, ABIC, and GAHS are used for a 28-day mortality prognosis. Our study aimed to evaluate if the assessment of the Lille score at 4 days (LM4) is as useful as the Lille score at Day 7 (LM7) to predict response to corticosteroids and 28-day mortality and evaluate the utility of severity scores at admission for predicting the prognosis of patients with liver cirrhosis (LC) and severe alcoholic hepatitis (sAH). A retrospective study was performed, and all consecutive patients with AH and MDF > 32 without contraindications to corticosteroids were included. Prognostic scores were evaluated at admission, and 28-day mortality was assessed. Response to corticotherapy was assessed by LM4 and LM7. Results: A total of 55/103 patients with sAH (51.5%) had MDF > 32 and received corticosteroids. There was no difference between the proportion of patients with a responder LM4 versus LM7 (27% vs. 36%, p = 0.31). The mean value for LM4 was 0.64 ± 0.3 versus 0.60 ± 0.3 for LM7 (p = 0.48). Precisely 90.3% of patients were correctly identified as responders or not by LM4 compared with LM7. The best model for predicting 28-day mortality was composed of MELD and LM4/LM7, with an accuracy of 0.90 for both combinations. Conclusion: LM4 could be used instead of LM7 for predicting response to corticosteroid therapy in patients with sAH and LC, as well as 28-day mortality. Using LM4, we could avoid prolonged use of this therapy and its complications.

Alcoholic hepatitis: Towards an era of personalised management.

Alcoholic hepatitis should be suspected in every patient with excessive chronic alcohol consumption and recent onset of jaundice. Diagnosis of alcoholic hepatitis is based on clinical and laboratory findings, and confirmed by a liver biopsy when available. Several scores are available to assess severity and prognosis of alcoholic hepatitis. The 1-month mortality of patients with severe alcoholic hepatitis, as defined by Maddrey's discriminant function, is 20-30%. Therefore, severe alcoholic hepatitis should be treated with a 28-day course of oral prednisolone after systematic screening for infection. In this review, we discuss diagnosis of alcoholic hepatitis, the different scores to assess severity of the disease, indications for corticosteroid therapy and alternative therapeutic options for non-responders to medical therapy.

A Combination of N-Acetylcysteine and Prednisone Has No Benefit Over Prednisone Alone in Severe Alcoholic Hepatitis: A Retrospective Analysis.

INTRODUCTION: In this study, we assessed whether there were any survival advantages with a combination treatment of intravenous N-acetylcysteine (NAC) and prednisone over prednisone alone in those with severe alcoholic hepatitis [discriminant function (DF) ≥ 32]. PATIENTS AND METHODS: Between January 1, 2013, and February 28, 2019, we identified 68 patients (mean age 47.2 years ± 10.1, 57% women, 65% cirrhosis, MELD score 28.1 ± 6.6) with alcoholic hepatitis, and of those, 21 (31%) received prednisone and 47 (69%) received prednisone + NAC. Lille score ≥ 0.45 was considered a poor response. Renal insufficiency was defined as GFR < 60 ml/min/1.73m2 calculated on two separate occasions. RESULTS: DF (74.2 ± 33.6 vs. 56.9 ± 15.9, p = 0.09) was similar, but MELD (29.2 ± 6.3 vs. 25.5 ± 6.4, p = 0.03) scores were higher in the combination group. The overall 30-day and 90-day mortality was 13.2% (9/68) and 20.6% (14/68), respectively. Women were more likely (OR 4.86, 95% CI 1.62-14.59) to respond to treatment based on Lille score compared to men, but the type of treatment regimen had no effect on Lille score (OR 0.84, 95% CI 0.25-2.78). Treatment regimen had no effect on both adjusted and unadjusted survivals. Multivariate analysis, after adjusting for confounding variables, confirmed these observations. DF + renal insufficiency had the highest AUROC (0.86) to predict mortality. CONCLUSION: The combination treatment of NAC + prednisone is not better than prednisone alone in patients with severe alcoholic hepatitis.

Prognostic Value of Neutrophil-lymphocyte Ratio in Patients with Severe Alcoholic Hepatitis.

Background Prednisolone is considered the cornerstone treatment for severe alcoholic hepatitis (AH). However, its use is limited by the increased risk of infection in an already immunocompromised patient population. Among patients with severe AH, there exists a group of non-responders who do not benefit from prednisolone therapy. Day-4 Lille score is a widely employed prognostic model used to identify this non-responder subgroup. The present study evaluates the prognostic ability of the inflammatory marker, the neutrophil-lymphocyte ratio (NLR), as a stand-alone model and in conjunction with the day-4 Lille score. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AH. Demographic and biochemical data at diagnosis were collected to calculate Maddrey's discriminant function (MDF) and model for end-stage liver disease (MELD) score upon admission and also on day 4. Receiver operating characteristic (ROC) curves were plotted for day-4 NLR and day-4 Lille score for prediction of 90-day mortality, and optimal cut-off values were determined. Patients were then subcategorized into groups based on the generated optimal cut-off values. Categorization was validated by comparing the mortality rate in each group with the chi-squared test. We then performed a multivariate analysis for prediction of 90-day mortality using day-4 Lille score and day-4 NLR, constructing a new prediction score based on the odds ratio (OR). The ROC curve of the new score was plotted and the area under a curve (AUC) was reported and compared with previously validated scores. Results Our analysis demonstrated that both day-4 NLR and Lille score individually predicted 90-day mortality with statistical significance (p: 0.049, p: <0.001, respectively). The ROC analysis of day-4 Lille score for the prediction of 90-day mortality revealed an AUC of 0.819 with an optimal cut-off value of 0.45 (sensitivity: 83.3%, specificity: 76.1%). Day-4 NLR had an AUC of 0.756 with an optimal cut-off value of 12.3 (sensitivity: 66.7%, specificity: 78.1%) The combined day-Lille-NLR model with a cut-off of 0.55 had an AUC of .889, which was higher than day-4 Lille score and NLR independently. Conclusion Day-4 NLR is an easily assessed prognostic model of mortality in alcoholic hepatitis. However, it often underperforms relative to day-4 Lille score. Combining these two models to create a "modified" Lille score adds increased performance characteristics to the prediction of outcomes/mortality. The "modified" Lille score presented in this study can be used to further cut down the number of non-responders who are often forced to undergo costly and potentially harmful treatment courses.

Alcoholic Hepatitis: A Review.

Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty changes in the liver which can develop into inflammation, fibrosis and ultimately cirrhosis with continued, excessive drinking. Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality that can occur in patients with steatosis or underlying cirrhosis. The pathogenesis of ALD is multifactorial and in addition to genetic factors, alcohol-induced hepatocyte damage, reactive oxygen species, gut-derived microbial components result in steatosis and inflammatory cell (macrophage and neutrophil leukocyte) recruitment and activation in the liver. Continued alcohol and pro-inflammatory cytokines induce stellate cell activation and result in progressive fibrosis. Other than cessation of alcohol use, medical therapy of AH is limited to prednisolone in a subset of patients. Given the high mortality of AH and the progressive nature of ALD, there is a major need for new therapeutic intervention for this underserved patient population.

Acute Alcoholic Hepatitis.

Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival.

Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids.

AIM: To determine whether infection in patients with acute severe alcoholic hepatitis (AAH) treated with corticosteroids is associated with increased mortality. METHODS: Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections (body temperature > 38 °C or < 36 °C for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis. RESULTS: Seventy-two patients were included in the final analysis (mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15 (21%), 23 (32%) and 31 (43%) at day 28, day 90 and 1 year respectively. 36 (50%) had a clinically relevant infection during their hospitalisation (23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites (31%) and bacteraemia (31%) followed by urinary tract (19%) and respiratory tract (8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia (22%) and Enterococcus (20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality. CONCLUSION: Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality.

The Worsening Profile of Alcoholic Hepatitis in the United States.

BACKGROUND: Alcoholic hepatitis (AH) is a major cause of liver-related hospitalization. The profile, treatment patterns, and outcomes of subjects admitted for AH in routine clinical practice are unknown. Also, it is not known whether these are changing over time. This study is thus aimed to identify temporal trends in hospitalization rates, clinical characteristics, treatment patterns, and outcomes of subjects admitted for AH in a routine clinical setting. METHODS: A retrospective analysis of adults admitted for AH from 2000 to 2011 was performed using an anonymized EMR database of patient-level data from 169 U.S. medical centers. RESULTS: (i) EPIDEMIOLOGY: The proportion of baby boomers admitted for AH increased from 2000 to 2011 (26 to 31%, p < 0.0001). (ii) CLINICAL: The median Model for End-Stage Liver Disease (MELD) score increased over time from 12 to 14 (p = 0.0014) driven mainly by increased international normalized ratio (1.2 to 1.4, p < 0.0001). The median Charlson Comorbidity Index increased from 0 to 1 (p < 0.0001) with increased diabetes, chronic obstructive pulmonary disease, and heart disease. (iii) COMPLICATIONS: The following increased from 2001 to 2011: Gastrointestinal bleed-7 to 10% (p = 0.03); hepatic encephalopathy-7 to 13% (p < 0.0001); hepatorenal syndrome-1.8 to 2.8% (p = 0.0003); sepsis-0 to 6% (p < 0.0001); and pancreatitis-11 to 16% (p = 0.0061). (iv) Treatment patterns and mortality: Eight to 9% of subjects received steroids while pentoxifylline use increased to 2.2%. In those with MELD ≥ 22, mortality remained between 19 and 20% and only steroids modestly improved survival in this subset. CONCLUSIONS: Severe AH continues to have a high mortality. The severity and comorbidities and complications associated with AH have worsened. Drug therapy remains suboptimal.

Hepatitis E infection in patients with severe acute alcoholic hepatitis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is a known cause of acute-on-chronic liver failure in developing countries, but its implication in Western countries remains unknown. HEV burden in the setting of severe acute alcoholic hepatitis (AAH) was assessed. METHODS: Patients admitted for severe AAH from 2007 to 2013, with available sera and histologically proven AAH, were included and managed according to current European guidelines. At admission, clinical and biological characteristics were collected; HEV serology and RNA detection were retrospectively performed. RESULTS: Eighty-four patients were included. Mean age was 50.8 ± 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 ± 11.4 and 73.3 ± 37. Liver biopsy showed mild, moderate and severe hepatitis in 25 (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to 61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille score: 0.78 ± 0.21). During hospitalization, 24 patients (28.6%) died and 11 (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV infection and 21 (25%) markers of past HEV infection. Patient with acute infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids were given to two patients without any response. The third patient died. None were transplanted. CONCLUSIONS: A substantial proportion of patients with severe AAH had markers of acute HEV infection, with similar clinical presentation and outcomes. Larger studies are needed to evaluate HEV impact on AAH management, resistance to steroids, and outcome.

Prognosis and treatment of patients with acute alcoholic hepatitis.

Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders.

Liver transplantation for alcoholic hepatitis. Current situation and future.

Alcoholic hepatitis (AH) is a life-threatening disease, especially in its severe forms, with a 30-40 % mortality rate at 1 month in the absence of treatment. Severe forms are traditionally defined by Maddrey discriminant function >32. Until now, only corticosteroids have provided a significant benefit to survival in severe AH patients. Non-responders to corticosteroid therapy can be identified after 7 days of treatment when the Lille score is above 0.45, and this concerns about 40 % of patients with AH. With so few therapeutic alternatives for severe AH, the debate on liver transplantation (LT) has reopened. However, the latter indication for LT is facing several difficulties such as the 6-month abstinence rule ordinarily required for alcoholic diseases, risk of alcohol relapse and comprehensive fear of a drop in donations. Inversely, transplanted AH patients have a significantly improved survival, and an excess risk of alcohol relapse has not been demonstrated. Solutions can certainly be found in order to improve severe AH survival without causing a loss of opportunity for LT for other indications by good selection according to strict criteria.