Glasgow Alcoholic Hepatitis Score Research Articles

Prognostic and diagnostic scoring models in acute alcohol-associated hepatitis: A review comparing the performance of different scoring systems.

Alcohol-associated hepatitis (AAH) is a severe form of liver disease caused by alcohol consumption. In the absence of confounding factors, clinical features and laboratory markers are sufficient to diagnose AAH, rule out alternative causes of liver injury and assess disease severity. Due to the elevated mortality of AAH, assessing the prognosis is a radical step in management. The Maddrey discriminant function (MDF) is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials. A MDF > 32 indicates a poor prognosis and a potential benefit of initiating corticosteroids. The model for end stage liver disease (MELD) score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF. The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course. Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model. Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis. AAH presenting as acute on chronic liver failure (ACLF) is so far prognosticated with ACLF-specific scoring systems. New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH. Acute kidney injury (AKI) is one possible complication of AAH and is significantly associated with increased AAH mortality. Predicting AKI and alcohol relapse are important steps in the management of AAH. The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality, emphasize the most useful tools in prognostication and review predictors of recurrence.

Predictive Ability of Different Scoring Models in Severe Alcoholic Hepatitis

ABSTRACT Introduction: Alcoholic hepatitis is a major health problem which carries a high mortality despite treatment. Predicting severity of disease is of utmost importance to avoid overzealous and unnecessary treatment with steroids in each and every case. Maddrey’s discriminant function (DF) may not always be reliable in predicting such prognosis. Aim of the Study: To observe the predictive ability of Glasgow alcoholic hepatitis score (GAHS), age, bilirubin, international normalized ratio (INR) and creatinine (ABIC) score, model for end stage liver disease (MELD) score, and Lille’s score in determining the prognosis in severe alcoholic hepatitis. Materials and Methods: Patients of severe alcoholic hepatitis were enrolled in this study as per inclusion and exclusion criteria and a DF score of >32. Once the decision to initiate corticosteroids was made, DF scores, MELD scores, GAHS scores, and ABIC scores were calculated on the day on initiation of therapy. On day 7, patients were re-assessed and Lille score was calculated in addition. Follow-up was obtained on repeat out-patient visit or telephonically after every 2 weeks till 90 days or till mortality, whichever occurred first. Statistical Analysis: The scores were compared among the survival and mortality groups to see association between mortality and severity of scores using Chi-square test of significance. Cut-offs providing a composite of best sensitivity, specificity, negative predictive value, and positive predictive value were derived on the basis of data of our study. P value of ≤ 0.05 was taken as a cut-off for significance. Results: Our study comprised 30 patients with severe alcoholic hepatitis. At the end of 90-day follow-up, 23 patients survived with 7 (23%) mortalities because of liver failure and sepsis. On day 7, barring the ABIC score (0.713), the areas under curve of all scores were above 0.8 and were hence of comparable efficacy. Lille score performed the best at assessing treatment response but had the limitation of not being applicable at day 1. Conclusion: Severe alcoholic hepatitis carries a bad prognosis. Cut-offs of DF and MELD need to be raised, whereas they need to be lowered in the case of GAHS, ABIC, and Lille score to improve the predictive value of score. Steroid-treated patients should be evaluated preferably with Lille score for a better prediction of survival.

Assessment of fecal microbiota transplantation as add on therapy in management of severe alcoholic hepatitis at tertiary care centre in North India

Background and aim: Severe alcoholic hepatitis (SAH) demands definitive management therapy with long term survival benefit. As alcohol induced intestinal dysbiosis is central to the development of SAH, there is an intense effort in recent past to explore the therapeutic potential of modulating gut microbiota. With this background, the current study was performed to assess whether, the inclusion of Fecal Microbiota Transplantation (FMT) with current Standard of Care (SOC) in steroids eligible SAH patients, leads to any survival benefit and/ or improvement in various prognostic scores. Methods: In this randomized prospective study, group A had 10 patients of SAH who were provided standard of care (SOC) and 10 in group B were imparted Fecal Microbiota Transplantation (FMT) along with SOC. Survival and prognostic scores viz. Child Pugh Turcotte (CTP), Model for End Stage Liver Disease (MELD), MELD sodium (MELD Na), Glasgow Alcoholic Hepatitis score (GAHS) and Maddrey's Discriminant Function (mDF) were evaluated at 1 and 3 months. Overall survival at 6 months was assessed. Results: Overall, 11(55%) patients were steroid- responsive (Lille score>0.45); 6 of group A and 5 of group B. At baseline, mean serum protein was significantly higher in group A (6.58±0.57gm/dL) than group B (5.94±0.55gm/dL). Group B had significantly higher leucocyte count, urea level and GAHS at 1st (8.67±0.5) and 3rd (6.67±0.58) month. Mortality was similar (20%) at 1 month, 70% in group B and 50% in group A at 3 months. At 6 months, mortality was significantly higher in group B (90%) than A (70%) (p=0.007). Conclusion: No survival benefits seen with addition of FMT to SOC in SAH. Significant higher leucocyte count at 1st and 3rd month and higher mortality at 6 months was observed after addition of FMT which might point towards the propensity to cause sepsis.

The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Clinical diagnosis of alcoholic hepatitis in Tongliao City, Inner Mongolia

Objective: To explore the current status of alcoholic hepatitis diagnosis by clinicians' in China. Methods: Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases. Results: Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively. Conclusion: Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.

Determinants of Short- and Long-Term Outcomes of an Australian Cohort of Patients Admitted with Alcoholic Hepatitis.

Alcoholic hepatitis is a common condition with high mortality. This study aimed to firstly describe the presentation, treatment, and short- and long-term outcomes of an Australian cohort of patients admitted to hospital with alcoholic hepatitis and secondly to validate existing prognostic models. This is a retrospective study of consecutive patients admitted with alcoholic hepatitis to a major academic liver center in Melbourne, Australia, between January 1, 2010, and December 31, 2019. Cases were identified through appropriate International Classification of Diseases version 10 coding as well as review of non-coded patients with compatible biochemistry. Baseline demographic data, alcohol consumption, laboratory values, treatment, and outcomes at 30days, 90days, and 12months post-diagnosis were collected from electronic medical records. Mortality data were extracted from an independent state government death registry. In total, 126 patients (72 males [57%], median age 51years) were included in the final analysis. Ninety-five (75%) were cirrhotic at diagnosis, 81 (64%) met criteria for severe alcoholic hepatitis, and 41 (33%) had an infection during their index admission. 54% of eligible patients were treated with corticosteroids. 30-day and 12-month mortality rates were 8.7% and 27.1%, respectively, with hepatic encephalopathy (hazard ratio 5.45) and neutrophil-to-lymphocyte ratio (hazard ratio 1.09) independent markers for 12-month mortality on Cox regression analysis. Glasgow alcoholic hepatitis score outperformed other major prognostic models for short-term mortality. The 12-month mortality rate of 27% following alcoholic hepatitis is lower than previously reported studies, with hepatic encephalopathy and neutrophil-to-lymphocyte ratio predictive of long-term outcome.

Comparison of prognostic scores for alcoholic hepatitis: a retrospective study

AimTo explore the prognostic value of modified Discriminant Function (mDF), Glasgow Alcoholic Hepatitis Score (GAHS), Model of End Stage Liver Disease (MELD), Age-Bilirubin-International Normalized Ratio-Creatinine score (ABIC), and the Lille Model for the 28- and 90-day mortality in patients with alcoholic hepatitis.MethodsThis retrospective study enrolled patients treated for alcoholic hepatitis in Dubrava University Hospital between January 2014 and May 2018. The diagnosis was established based on histology findings or the combination of patient´s history of ongoing alcohol consumption before hospitalization, serum bilirubin above 50 mmol/L, and aspartate transaminase to alanine transaminase ratio greater than 1.5. We calculated mDF, MELD, GAHS, and ABIC on the first and seventh day of hospitalization (including the Lille model).ResultsIn total, 70 patients were enrolled. ABIC at admission most accurately predicted the 28-day mortality, with a cut-off of 9.92 (AUC 0.727; 95% CI 0.608-0.827, P = 0.0119), while GAHS most accurately predicted the 90-day mortality, calculated both at admission (cut off >7, AUC 0.765, 95% CI 0.639-0.864, P < 0.0001) and after seven days of hospitalization (cut-off >8, AUC 0.835 95% CI 0.716-0.918, P < 0.0001). Modified DF was able to predict the 28- and 90-day mortality only when calculated after seven days of hospitalization.ConclusionThere is a need for better prognostic indicators for patients with AH.

The diagnostic and prognostic significance of liver histology in alcoholic hepatitis.

Liver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial. To assess the utility of liver biopsy in the assessment of clinically severe AH METHODS: The histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores. The STOPAH trial recruited 1068 patients; biopsies were obtained in 182 (17%). One hundred and sixty-one biopsies were adequate for histological assessment and 140 (87%) were diagnostic for ASH. Only three biopsies (2%) did not have histological features of alcohol-related liver injury. In biopsies performed prior to randomisation, ASH was identified in 92.5% of patients meeting clinical trial definitions of severe AH. In biopsies with ASH, taken before or within 48hours of randomisation, survival differences between Alcoholic Hepatitis Histological Score (AHHS) groups were not significant: comparison of mild / moderate (91%: 21 of 23 patients) with severe (78%: 29 of 37 patients) groups: P=0.18. The AHHS was not superior to clinical scores of prognosis: area under the curve for 28-day mortality was 0.728, compared with 0.799 for the Glasgow alcoholic hepatitis score and 0.728 for the MELD score. Liver histology taken before treatment rarely changes the diagnosis in patients meeting strict criteria for a clinical diagnosis of AH. The AHHS is similar to clinical scores in determining prognosis. Clinical trial registration EudraCT reference number: 2009-013897-42. ISRCTN reference number: 88782125. MREC number: 09/MRE09/59. 9143.

Comparison of conventional scoring systems versus MAGIC score to predict short-term mortality in patients hospitalized for alcoholic hepatitis

Background Multiple prognostic models are available to predict mortality in alcoholic hepatitis (AH) which are of modest benefit, but the best model remains unexplored. Methods This is a retrospective analysis (2012–2015) of AH patients. Conventional prognostic scoring systems viz. Maddrey’s Discriminant Function (mDF), Age Bilirubin International Normalized Ratio and Creatinine (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), and the Model for End-stage Liver Disease score (MELD), were compared with Model for AH to Grade the Severity in an Asian patient cohort (MAGIC) score, using area under the ROC curves for ascertaining 30/90-day mortality. Results Eighty-eight patients (100% male); mean (SD) age of 45.6 (7.6) years with a follow-up of 80.7 (45.1) days were included. The 30 and 90-day mortality were 21 (23.9%) and 42 (47.7%), respectively; the commonest cause being sepsis in 22 (48.9%) patients. Survival probabilities for mDF < 32 and mDF > 32 were 100% and 42.25% ± 4.46%, respectively (p = .001). The mean (SD) scores of mDF, MELD and GAHS were significantly higher in deceased patients 70.8 (26.5), 23.4 (5.2), 8.1 (1.01), respectively, as compared to those who survived 40.8 (23.1), 18.9 (5.1), 7.3 (0.9), respectively; p = .001. ABIC and MAGIC scores were higher among the deceased, but were not significant. mDF had the best predictive AUROC value 0.872, followed by MELD 0.772, and MAGIC 0.626, respectively. mDF was significantly superior in comparison to MAGIC score (p < .001). Conclusion This study showed that mDF had a better predictive performance than other scoring systems in patients with AH.

Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis.

Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH. Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628). Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively). In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.

Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis.

Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7days to assess "response". To assess the prognostic and therapeutic implications of baseline neutrophil-to-lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan-Meier analysis was used to assess survival. Log-rank test and odds ratio (OR) were used for comparative analysis. Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90-day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety-day survival was not affected by prednisolone treatment if NLR < 5 or > 8 but mortality was reduced with prednisolone treatment when the NLR was 5-8 (21.0% cf. 34.5%; P=0.012). Prednisolone treatment increased the chance of Lille response if the NLR was ≥5 (56.5% cf. 41.1%: P=0.01; OR 1.86) but increased the risk of day 7 infection (17.3% cf. 7.4%: P=0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P=0.008; OR 3.46) if the NLR was>8. Incorporation of NLR into a modified Glasgow alcoholic hepatitis score (mGAHS) improved the AUC to 0.783 and 0.739 for 28-day and 90-day outcome, respectively. The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5-8). The mGAHS has a good predictive value for 28- and 90-day outcomes.

Biomarkers of Macrophage Activation and Immune Danger Signals Predict Clinical Outcomes in Alcoholic Hepatitis.

Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients in four US academic medical centers. Plasma from AH patients had a significant increase in gut microbial translocation indicators (endotoxin, bacterial 16S ribosomal DNA) and host response indicators (soluble cluster of differentiation 14 [sCD14] and lipopolysaccharide binding protein [LBP]) compared to controls. Patient MELD score and Glasgow Alcoholic Hepatitis score (GAHS) correlated with endotoxin levels. AH patients also had a significant increase in high mobility group protein 1 (HMGB1), a sterile danger signal molecule, and osteopontin (OPN), a multifunctional phosphoprotein involved in neutrophil activation, compared to controls. Increased levels of OPN positively correlated with increasing MELD score, GAHS, and LBP levels. Consistent with these results, AH patients had significantly increased circulating levels of macrophage activation (sCD163 and sCD206) markers compared to healthy controls, and sCD163 and sCD206 significantly and positively correlated with OPN, HMGB1, and LBP levels as well as with MELD score and GAHS. These findings indicate a connection between microbial translocation, immune cell activation, and AH severity. Plasma sCD14, OPN, sCD163, and sCD206 levels were significantly higher in nonsurvivors than survivors. In multivariate regression models, we identified sCD14, sCD163, and OPN as independent predictors of 90-day mortality, infection, and organ failure development, respectively. Conclusion: Our study suggests that sCD14, LBP, OPN, sCD163, and sCD206 are biomarkers to indicate severity and predict clinical outcomes in AH.

THU-262-A modified Glasgow alcoholic hepatitis score incorporating the neutrophil-to-lymphocyte ratio is superior to other baseline scores of prognosis in alcoholic hepatitis

THU-262-A modified Glasgow alcoholic hepatitis score incorporating the neutrophil-to-lymphocyte ratio is superior to other baseline scores of prognosis in alcoholic hepatitis

The soluble mannose receptor (sMR) is elevated in alcoholic liver disease and associated with disease severity, portal hypertension, and mortality in cirrhosis patients.

Background and aimsHepatic macrophages (Kupffer cells) are involved in the immunopathology of alcoholic liver disease (ALD). The mannose receptor (MR, CD206), expressed primarily by macrophages, mediates endocytosis, antigen presentation and T-cell activation. A soluble form, sMR, has recently been identified in humans.We aimed to study plasma sMR levels and its correlation with disease severity and survival in ALD patients.MethodsWe included 50 patients with alcoholic hepatitis (AH), 68 alcoholic cirrhosis (AC) patients (Child-Pugh A (23), B (24), C (21)), and 21 healthy controls (HC). Liver status was described by the Glasgow Alcoholic Hepatitis Score (GAHS), Child-Pugh (CP) and MELD-scores, and in AC patients the hepatic venous pressure gradient (HVPG) was measured by liver vein catheterisation. We used Kaplan-Meier statistics for short-term survival (84-days) in AH patients and long-term (4 years) in AC patients. We measured plasma sMR by ELISA.ResultsMedian sMR concentrations were significantly elevated in AH 1.32(IQR:0.69) and AC 0.46(0.5) compared to HC 0.2(0.06) mg/L; p<0.001 and increased in a stepwise manner with the CP-score (p<0.001). In AC sMR predicted portal hypertension (HVPG ≥10 mmHg) with an area under the Receiver Operator Characteristics curve of 0.86 and a high sMR cut-off (>0.43 mg/l) was associated with increased mortality (p = 0.005).ConclusionThe soluble mannose receptor is elevated in alcoholic liver disease, especially in patients with AH. Its blood level predicts portal hypertension and long-term mortality in AC patients.

Application of prognostic scores in the STOPAH trial: Discriminant function is no longer the optimal scoring system in alcoholic hepatitis

'Static' prognostic models in alcoholic hepatitis, using data from a single time point, include the discriminant function (DF), Glasgow alcoholic hepatitis score (GAHS), the age, serum bilirubin, international normalized ratio and serum creatinine (ABIC) score and the model of end-stage liver disease (MELD). 'Dynamic' scores, incorporating evolution of bilirubin at seven days, include the Lille score. The aim of this study was to assess these scores' performance in patients from the STOPAH trial. Predictive performance of scores was assessed by area under the receiver operating curve (AUC). The effect of different therapeutic strategies upon survival was assessed by Kaplan-Meier analysis and tested using the log-rank test. A total of 1,068 patients were studied. The AUCs for the DF were significantly lower than for MELD, ABIC and GAHS for both 28- and 90-day outcomes: 90-day values were 0.670, 0.704, 0.726 and 0.713, respectively. 'Dynamic' scores and change in 'static' scores by Day 7 had similar AUCs. Patients with consistently low 'static' scores had low 28-day mortalities that were not improved with prednisolone (MELD <25: 8.6%; ABIC <6.71: 6.6%; GAHS <9: 5.9%). In patients with high 'static' scores without gastrointestinal bleeding or sepsis, prednisolone reduced 28-day mortality (MELD: 22.2% vs. 28.9%, p = 0.13; ABIC 14.6% vs. 21%, p = 0.02; GAHS 21% vs. 29.3%, p = 0.04). Overall mortality from treating all patients with a DF ≥32 and Lille assessment (90-day mortality 26.8%) was greater than combining newer 'static' and 'dynamic' scores (90-day mortality: MELD/Lille 21.8%; ABIC/Lille 23.7%; GAHS/Lille 20.6%). MELD, ABIC and GAHS are superior to the DF in alcoholic hepatitis. Consistently low scores have a favourable outcome not improved with prednisolone. Combined baseline 'static' and Day 7 scores reduce the number of patients exposed to corticosteroids and improve 90-day outcome. Alcoholic hepatitis is a life-threatening condition. Several scores exist to determine the outcome of these patients as well as to identify those who may benefit from treatment. This study looked at the performance of existing scores in patients who had been recruited to the largest alcoholic hepatitis clinical trial: STOPAH. 'Static' scores are calculable at the start of assessment. The three newer static scores (ABIC, GAHS and MELD) were shown to be superior to the oldest score (DF). ABIC and GAHS could also identify patients who had a survival benefit 28 days after starting prednisolone treatment. 'Dynamic' scores relate to the change in disease over the first week of treatment. Combination of the 'static' scores 'with the 'dynamic' scores or change in 'static' scores allowed identification of patients who could benefit from prednisolone up to 90 days.

Time course of compromised urea synthesis in patients with alcoholic hepatitis

Objectives: Alcoholic hepatitis (AH) markedly decreases the urea synthesis capacity. We aimed to investigate the time course of this compromised essential liver function in patients with AH and its relation to treatment and survival.Materials and methods: Thirty patients with AH were included in a prospective cohort study. We measured the substrate-independent urea synthesis capacity, i.e., the functional hepatic nitrogen clearance (FHNC), in the patients at study entry and again at three months (survivors/available: n = 17). Patients with severe disease (Glasgow Alcoholic Hepatitis Score ≥9, n = 17) were randomized to receive either prednisolone or pentoxifylline and were in addition examined after 14 days (n = 9).Results: FHNC (normal range = 25–45 L/h) was markedly decreased at study entry (median = 5.6 (IQR = 3.0–9.6) L/h) and increased by three-fold in survivors at three months (15.1 (12.0–22.9) L/h; p < .001). In patients with severe AH, FHNC was also increased after 14 days of pharmacologic treatment and showed the greatest increase in the patients taking prednisolone (prednisolone 25.4 (20.6–26.2) L/h vs. pentoxifylline 12.3 (8.0–15.3) L/h; p = .05). FHNC at study entry was lower in 90-day non-survivors than in survivors (p = .04).Conclusions: The decrease in the urea synthesis capacity in patients with AH was the most marked in short-term non-survivors and partly recovered in survivors at three months. In patients on pharmacologic treatment, recovery was observed already after 14 days, and it was nearly complete in those on prednisolone. Thus, metabolic liver failure in AH seems to be prognostically important, is potentially reversible, and may recover more rapidly following treatment with prednisolone.

A prognostic evaluation and management of alcoholic hepatitis

Alcoholic hepatitis (AH) is an acute and severe form of alco1holic liver disease associated with high morbidity and mortality of 30-50% worldwide, severity ranging from asymptomatic derangement of liver biochemistries to fulminant liver failure or death. Rapidly progressing jaundice and coagulopathy in prolonged excessive alcohol abusers with or without fever, malnutrition, and tender liver are the clinical hallmarks. The prognostic models (Model for end-stage liver disease, Maddrey's discriminant function [MDF], age, serum bilirubin, INR, creatinine [ABIC], Glasgow Alcoholic Hepatitis Score [GAHS], Lille's Score) not only predict the short term mortality, but also guide the clinicians to choose appropriate specific therapy (corticosteroid or pentoxifylline) and as a stopping rule if there is no significant benefits of it. MDF Score is commonly followed in clinical practice, score of >32 would predict short term mortality of around 20-30% at 1 month and 30-40% within 6 months after presentation. The GAHS on day 1 can predict 28 day overall survival outcome accuracy of 81%, which is comparatively higher than MDF Score. Moreover, ABIC Score categorizes risk of deaths (based on 90 days) into low risks (0%), intermediate risk (30%), and high risk (75%). Corticosteroid and pentoxifylline have significant benefits in decreasing mortality (corticosteroid improves survival on 28 day and 84 day of 78% and 59%) in severe disease state (MDF >32 or Lille's Score >0.45 or GAHS >9). Corticosteroid is the initial treatment of choice with infections screening before initiating; however, pentoxifylline is better preferred in case of AH with severe infections and hepatorenal syndrome. Additionally, combination of corticosteroids and N-acetylcysteine decreases development of hepatorenal syndrome, infections, and short-term mortality. However, the Lille Score after corticosteroid therapy of >0.45 after day 7 indicates poor responders or >0.56 indicates null responders. Therefore, in these cases, either therapy has to be stopped or changed to pentoxifylline. In treatment failure cases, liver transplantation is the ultimate option. However, the facilitating of this service in most transplant centers is a challenge. Beside these specific therapies, alcohol abstinence and recommendation of nutritional supplements with high calorie, protein diet and vitamin E, C, thiamine regardless of other treatment plays a prime role in preventing disease progression and survival benefits even in pre and post-transplant cases.

Review article: recent insights into clinical decision-making in severe alcoholic hepatitis.

Alcoholic hepatitis is a severe acute manifestation of alcoholic liver disease with a high mortality. Management of patients with this condition has been a matter of controversy for many years; however, recent clinical studies have sought to improve the clinical approach to these patients. To use these recent studies in order to guide clinical management. A MeSH search of Medline was performed to specifically identify recent studies which influenced clinical diagnosis, assessment and management of alcoholic hepatitis. Fulfilment of clear clinical criteria including a minimum threshold of bilirubin, defined periods of jaundice and alcohol ingestion negates the need for liver biopsy in most patients. Corticosteroids improve short-term mortality only (28 day) with other factors such as abstinence likely to be significant in long-term outcome. Pentoxifylline is not an effective treatment. The Glasgow Alcoholic Hepatitis Score (GAHS) score can identify those patients likely to benefit from corticosteroids, but scores that include the evolution of bilirubin over 1 week of such treatment (such as the Lille Score) define "response". Underlying infection may contribute towards corticosteroid nonresponse and needs to be actively sought out and treated. Liver transplant remains controversial; however, it has been shown to be feasible in alcoholic hepatitis. Recent studies have helped to define patients who may benefit from corticosteroid treatment. However, there remains a need for more accurate scores of prognosis and treatment response, and a clear need for alternative treatments for those patients not responding to corticosteroid therapy.

PS-150 - Time course of compromised urea synthesis in patients with alcoholic hepatitis

AbstractObjectives: Alcoholic hepatitis (AH) markedly decreases the urea synthesis capacity. We aimed to investigate the time course of this compromised essential liver function in patients with AH and its relation to treatment and survival.Materials and methods: Thirty patients with AH were included in a prospective cohort study. We measured the substrate-independent urea synthesis capacity, i.e., the functional hepatic nitrogen clearance (FHNC), in the patients at study entry and again at three months (survivors/available: n = 17). Patients with severe disease (Glasgow Alcoholic Hepatitis Score ≥9, n = 17) were randomized to receive either prednisolone or pentoxifylline and were in addition examined after 14 days (n = 9).Results: FHNC (normal range = 25–45 L/h) was markedly decreased at study entry (median = 5.6 (IQR = 3.0–9.6) L/h) and increased by three-fold in survivors at three months (15.1 (12.0–22.9) L/h; p < .001). In patients with severe AH, FHNC was also increased after 14 days of pharmacologic...

Alcoholic Hepatitis Severity Scores; Which Score Is Better? Evidence From Meta-analysis of 5 Different Scoring Systems

Introduction: We performed a systematic review and a meta-analysis of studies comparing various scoring systems to predict severity of and short-term mortality from alcoholic hepatitis. Methods: To be included in the current meta-analysis articles had to (1) report mortality in AH patients, (2) report AH severity by 2 or more scoring models, and (3) report area under curve (AUC) of each model. AUC from different studies were pooled using a MedCalc meta-analysis program for the following severity scoring systems (1) Model for End Stage Liver Disease (MELD), (2) Maddrey discriminant function (mDF), (3) Glasgow Alcoholic Hepatitis Score (GAHS), (4) Child-Turcotte-Pugh (CTP), and (5) Age, Bilirubin, International Normalization Ratio and Creatinine (ABIC). The analysis was stratified according to 28 and 90 day (D) mortality. Results: On 28 d mortality, AUC comparing MELD and DF from 9 studies did not show difference, 0.837 (0.779-0.895) vs. 0.803 (0.747-0.860), P=0.41. Comparisons were also non-significant on 28d mortality for DF vs. CTP from 3 studies: 0.774 (0.697-0.850) vs. 0.711 (0.559-0.864), P= 0.47), for ABIC vs. GAHS from 5 studies: 0.768 (0.714-0.823) vs. 0.772 (0.721-0.824), P= 0.92, and for MELD vs. GAHS from 4 studies: 0.768 ( 0.714-0.823) vs. 0.780 (0.713-0.0.846), P=0.78. Analysis on 90 d mortality showed similar results comparing AUC using MELD and DF from 7 studies: 0.802 (0.758-0.846) vs. 0.790 (0.782-0.797), P=0.6, comparing ABIC vs. GAHS from 7 studies: 0.765 (0.716-0.815) vs. 0.758 (0.711-0.805), P=0.84, and comparing MELD vs. GAHS from 6 studies:0.779 (0.725-0.832) vs. 0.746 (0.695-0.797), P= 0.38. Conclusion: Existing severity scores used in clinical practice are comparable in predicting severity and prognosis of alcoholic hepatitis. However, none of the scoring systems is ideal. Prospective studies are needed as basis for deriving scoring systems and/or biomarkers for better stratification of severity and prognosis of patients with alcoholic hepatiits.