Diagnosis Of Alcoholic Hepatitis Research Articles

Serendipity in Medicine-Elevated Immunoglobulin E Levels Associated with Excess Alcohol Consumption

Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The first-year resident who admitted the patient mistakenly ordered a blood test for serum IgE. The result was a markedly elevated −6440 IU/mL. There was no evidence of parasitic infections, atopy or autoimmune disease nor was there any eosinophilia. A literature search showed that elevated IgE levels are associated with alcohol abuse. This association has been forgotten and does not appear in standard reference sources such as UptoDate or Harrison’s Principles of Internal Medicine. This judicious use of examining serum IgE levels may aid in the diagnosis of alcoholic hepatitis.

Histological characteristics in patients admitted to the hospital with alcoholic hepatitis complicated by acute-on-chronic liver failure

Objectives Alcoholic hepatitis (AH) is a frequent precipitating event for the development of acute-on-chronic liver failure (ACLF), a syndrome characterised by organ failures due to immune dysfunction. The histological features of this complication are not well characterized. We investigated whether ACLF has specific histological characteristics. Methods Prospective cohort study in consecutive adult patients admitted between 03-2008 and 04-2021 to a tertiary referral centre with suspected AH. Diagnosis of AH was based on clinical presentation and confirmed by transjugular liver biopsy. All biopsies were assessed by a dedicated liver pathologist, blinded for clinical data and outcome. Diagnosis of ACLF was based on EASL-CLIF criteria. Histological and clinical characteristics of patients with and without ACLF at baseline were compared. Results 184 patients with biopsy-proven AH were enrolled. Median time from hospital admission to transjugular biopsy was 4.5 days (IQR 2-8). At baseline, ACLF was present in 73 patients (39.7%). Out of the 110 patients without ACLF at baseline, 30 (27.3%) developed ACLF within 28 days (median 7.5 days (IQR 2-20)). At baseline, ductular bilirubinostasis (DB) was the only histological feature significantly more frequently present in patients with ACLF compared to patients without ACLF (50.7% vs. 30.6%, p = 0.003). No clear association between histological features and the development of ACLF later on could be demonstrated. Conclusions In this well-defined cohort of patients with biopsy-proven AH, DB was associated with the presence of ACLF. This finding fits with the pathophysiology of this syndrome, which is characterized by systemic inflammation and an increased risk of infections.

The Impact of Metabolic Syndrome on the Prognosis of High-Risk Alcoholic Hepatitis Patients: Redefining Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is characterized by acute symptomatic hepatitis associated with heavy alcohol use. This study was designed to assess the impact of metabolic syndrome on high-risk patients with AH with discriminant function (DF) score ≥ 32 and its effect on mortality. We searched the hospital database for ICD-9 diagnosis codes of acute AH, alcoholic liver cirrhosis, and alcoholic liver damage. The entire cohort was categorized into two groups: AH and AH with metabolic syndrome. The effect of metabolic syndrome on mortality was evaluated. Also, an exploratory analysis was used to create a novel risk measure score to assess mortality. A large proportion (75.5%) of the patients identified in the database who had been treated as AH had other etiologies and did not meet the American College of Gastroenterology (ACG)-defined diagnosis of acute AH, thus had been misdiagnosed as AH. Such patients were excluded from analysis. The mean body mass index (BMI), hemoglobin (Hb), hematocrit (HCT), and alcoholic liver disease/non-alcoholic fatty liver disease index (ANI) were significantly different between two groups (P < 0.05). The results of a univariate Cox regression model showed that age, BMI, white blood cells (WBCs), creatinine (Cr), international normalized ratio (INR), prothrombin time (PT), albumin levels, albumin < 3.5, total bilirubin, Na, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), MELD ≥ 21, MELD ≥ 18, DF score, and DF ≥ 32 had a significant effect on mortality. Patients with a MELD greater than 21 had a hazard ratio (HR) (95% confidence interval (CI) of 5.81 (2.74 - 12.30) (P < 0.001). The adjusted Cox regression model results showed that age, Hb, Cr, INR, Na, MELD score, DF score, and metabolic syndrome were independently associated with high patient mortality. However, the increase in BMI and mean corpuscular volume (MCV) and sodium significantly reduced the risk of death. We found that a model including age, MELD ≥ 21, and albumin < 3.5 was the best model in identifying patient mortality. Our study showed that patients admitted with a diagnosis of alcoholic liver disease with metabolic syndrome had an increased mortality risk compared to patients without metabolic syndrome, in high-risk patients with DF ≥ 32 and MELD ≥ 21. A bivariate correlation analysis revealed that patients with AH with metabolic syndrome were more likely to have infection (43%) compared to AH (26%) with correlation coefficient of 0.176 (P = 0.03, CI: 0.018 - 1.0). In clinical practice, the diagnosis of AH is inaccurately applied. Metabolic syndrome significantly increases the mortality risk in high-risk AH. It signifies that the presence of features of metabolic syndrome modifies the behavior of AH in acute settings, warranting different therapeutic strategies. We propose that in defining AH, patients overlapping with metabolic syndrome may need to be excluded as their outcome is different with regard to risk of renal dysfunctions, infections and death.

Portal Venous Thrombosis in Alcoholic Hepatitis: A Relatively Unknown Association.

Portal venous thrombosis (PVT) is a rare diagnosis in the general population. However, it is seen in patients with liver cirrhosis with an estimated prevalence ranging from 0.6% to 26%. Literature reports that about one-third of PVT cases have an unknown etiology. Identifying the precipitating factors implicated in the development of PVT is imperative as it may help guide therapy. Although the association between liver cirrhosis and PVT has been well established in current literature, there continues to be a relative lack of awareness of alcoholic hepatitis (AH) as a risk factor for PVT. Identifying AH as a trigger for thrombosis can help avoid extended anticoagulation and its complications. In the following case report and brief review, we discuss an uncommon case of a 33-year-old male who came to the hospital emergency department with complaints of nauseousness, abdominal discomfort, and yellow discoloration. Lab investigations showed transaminitis. The diagnosis of AH was established, and an abdominal duplex ultrasound revealed PVT. Heparin drip was started as a part of treatment, which improved his abdominal discomfort. He was eventually discharged on apixaban 5 mg twice daily for 3 months and a repeat abdominal duplex ultrasound in 3 months to check for the resolution of the PVT.

S1315 Are We Following the Guidelines in the Treatment of Patients With Alcoholic Hepatitis?

Introduction: Alcoholic liver disease is one of the leading causes of chronic liver disease worldwide and accounts for up to 48% of cirrhosis-associated deaths in the United States. Corticosteroids provide a short-term survival benefit in about half of treated patients with Severe Alcoholic Hepatitis. The decision is made on the basis of risk stratification by Maddrey or Meld scoring system. We hope to assess how well we are at identifying and treating the patient population at Crozer Chester Medical Center Methods: We did a retrospective review of patients admitted to Crozer Chester Medical Center from October 2021 to January 2017. We filtered patients based on ICD-10 codes for Alcoholic Hepatitis. We included the patient 18 years and above hospitalized at Crozer Chester Medical Center with the diagnosis of alcoholic hepatitis. We excluded the patients who had sepsis on admission, had active hepatitis B or C, had acute kidney injury present on admission, had upper gastrointestinal bleed present on admission, patients requiring steroids due to some other condition. Results: We had an initial sample of 431 patients. After clearing duplicates or missing data entries, we were left with 321 patients. After applying the exclusion criteria, we were left with 60 patients, those who did not have any contraindications to steroid use. 90% (N=54) of those patients had no risk calculation score documented. There was no statistically significant difference between the teaching and non-teaching service regarding risk score documentation (p=0.43). We identified 20 patients from the sample who would have benefited from steroids. Out of those, only 47%(N=8) received steroids. Out of those, only 5 (29%) received prednisolone (Figure). Conclusion: Currently, the American College of gastroenterology guideline recommends using steroids in the high-risk patient population. (2)Various risks calculating criteria like Maddrey's Discriminant Function and MELD score have been developed to determine the patients who fulfill the criteria for severe disease and can benefit from a course of steroids Various strategies can be implemented to improve adherence to guidelines. The scoring system should be documented when admitting patients with alcoholic hepatitis Changes in the electronic medical records can be considered as displaying a popup reminder to calculate the appropriate risk score, to consult a specialist, or to automatically calculate the risk score can be made as it would be beneficial in this maintaining adherence to guidelines.Figure 1.: Steroids given to patients with high Maddrey/Meld score with no contraindications

S1409 Improving Provider Adherence to Nutritional and Metabolic Recommendations in Patients With Acute Alcoholic Hepatitis: A Quality Improvement Initiative

Introduction: Alcoholic hepatitis (AH) is an acute, inflammatory liver disease associated with high morbidity and mortality, both short and long term. Current medical therapy for severe alcoholic hepatitis relies on corticosteroids, which have modest efficacy. Alcohol abstinence is of critical importance but recidivism is high. Efficacious medical treatments for alcoholic hepatitis are lacking. Preliminary and Preclinical studies include use of Antibiotics, IL-1 inhibitors, GCSF and antioxidants. Malnutrition and sarcopenia are common among hospitalized AH patients with negative impact on outcome.[1] Current guidelines generally recommend daily protein intake of 1.2–1.5 g/kg/day and caloric intake of 30- 40 kcal/kg/day in alcoholic hepatitis patients. [2][3] Our objective is to implement methods to facilitate adherence to nutritional recommendations in hospitalized patients with AH. Methods: We conducted a 12-month retrospective study followed by a 3-month prospective interventional study at Presbyterian Medical Center. Chart review was performed to evaluate adherence with nutritional recommendations in patients with AH. A 3-month intervention was performed to improve compliance. This included the creation of a customized best practice advisory alert (BPA) in the Electronic medical record (EMR). The triggers included elevated ALT/AST, bilirubin >3 and documented alcohol use within 8 weeks. Alert encouraged physicians to request a nutrition consult if the diagnosis of AH was appropriate. Results: 105 patients with 82 in the pre- and 23 post-intervention periods were reviewed. No significant difference in patient characteristics and demographics was noted between the 2 groups. The intervention implemented revealed a 79% increase in adherence to nutritional recommendation (P < 0.023). Adherence was quantified as modified diet orders in EMR to include high protein diet ( minimum of 60 grams/daily ) and/or addition of supplemental high protein milk shakes to meals and/or electronic consult to nutritionist. Conclusion: AH has high morbidity and mortality. Current pharmacological options remain limited. Patients with AH are commonly malnourished and sarcopenic. System based auto-generated EMR alerts help increase compliance with the nutritional recommendations as well as enforce evidence-based practices in this select patient population.

Trends in hospitalization for alcoholic hepatitis from 2011 to 2017: A USA nationwide study.

BACKGROUNDSevere alcoholic hepatitis (AH) is one of the most lethal manifestations of alcohol-associated liver disease. In light of the increase in alcohol consumption worldwide, the incidence of AH is on the rise, and data examining the trends of AH admission is needed.AIMTo examine inpatient admission trends secondary to AH, along with their clinical outcomes and epidemiological characteristics.METHODSThe National Inpatient Sample (NIS) database was utilized, and data from 2011 to 2017 were reviewed. We included individuals aged ≥ 21 years who were admitted with a primary or secondary diagnosis of AH using the International Classification of Diseases (ICD)-9 and its correspondent ICD-10 codes. Hepatitis not related to alcohol was excluded. The national estimates of inpatient admissions were obtained using sample weights provided by the NIS.RESULTSAH-related hospitalization demonstrated a significant increase in the USA from 281506 (0.7% of the total admission in 2011) to 324050 (0.9% of the total admission in 2017). The median age was 54 years. The most common age group was 45–65 years (range 57.8%–60.7%). The most common race was white (63.2%–66.4%), and patients were predominantly male (69.7%–71.2%). The primary healthcare payers were Medicare (29.4%–30.7%) and Medicaid (21.5%–32.5%). The most common geographical location was the Southern USA (33.6%–34.4%). Most patients were admitted to a tertiary care center (50.2%–62.3%) located in urban areas. Mortality of AH in this inpatient sample was 5.3% in 2011 and 5.5% in 2017. The most common mortality-associated risk factors were acute renal failure (59.6%–72.1%) and gastrointestinal hemorrhage (17.2%–20.3%). The total charges were noted to range between $25242.62 and $34874.50.CONCLUSIONThe number of AH inpatient hospitalizations significantly increased from 2011 to 2017. This could have a substantial financial impact with increasing healthcare costs and utilization. AH-mortality remained the same.

Alcohol use disorder treatment and outcomes among hospitalized adults with alcoholic hepatitis

Purpose: The burden of alcohol-associated liver disease (ALD) in the United States (US) has continued to worsen in the background of rising rates of alcohol use disorder. Patients with ALD present to care at a late stage, often with the sequela of liver decompensation, such as gastrointestinal bleeding and infection. ALD is now the leading indication for liver transplantation. We aimed to measure the quality of care delivered to hospitalized patients with alcoholic hepatitis (AH) across 3 domains: 1) alcohol-use disorder (AUD) care, 2) inpatient cirrhosis care, and 3) alcohol-associated liver disease (ALD) care—and observe associations between quality of care and outcomes. Methods: We included hospital encounters between January 1, 2016 and January 1, 2019 to a large, diverse integrated health system for AH with active alcohol use within the prior 60 days. The diagnosis of AH was determined based on previously published clinical and laboratory criteria. Quality indicator (QI) pass rates were calculated as the proportion of patients eligible for each indicator who received the QI within the timeframe specified. We then evaluated the association between the receipt of all QIs and 6-month mortality, as well as AUD-specific QIs and 30-day readmission. Results: Of the 179 patients, the median age was 47 years-old, 59.2% were male and 49.2% were non-Hispanic White. The median Model for End-Stage Liver Disease-Sodium score was 25, while the median discriminant function was 33. Patients were followed for an average of 21 months. Overall, 14% of patients died during the index hospitalization while 17.3% died following discharge and 24.8% were re-admitted within 30-days. QI pass-rates were variable across the different domains. Few patients received AUD care—pass rates for receipt of pharmacotherapy and behavioral therapy at 6 months were only 19.1% and 35.1%, respectively. There was a significant association between receiving behavioral therapy and 6-month mortality—3% vs 18%, p = 0.05. Conclusion: The quality of care received during hospital encounters for AH is variable, and AUD-specific therapy is low. Future quality of care initiatives are warranted to link patients to AUD treatment to ensure optimal care and maximize patients survival in this at-risk population.

Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Patient-Friendly Summary of the 2019 AASLD Guidelines.

Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Patient-Friendly Summary of the 2019 AASLD Guidelines.

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.

1095 Presence of Acute Kidney Injury (AKI) at Admission in Severe Alcoholic Hepatitis (SAH) Patients Predicts Mortality: A Single Centre Experience

INTRODUCTION: Severe Alcoholic Hepatitis (SAH) is a life-threatening condition. There are different models to prognosticate patients with SAH. However, the impact of presence of acute kidney injury (AKI), defined as per AKIN criteria in patients with SAH has not been assessed for this region of Asia. Hence we performed a prospective study to evaluate the spectrum of SAH including outcome in hospitalized patients and the impact of AKI on outcome of patients with SAH. METHODS: This study was conducted on consecutive alcoholic hepatitis (AH) patients hospitalised in Gastroenterology Department, SCB Medical College, Cuttack, India between October 2016 and October 2018. On diagnosis of AH, modified Maddrey discriminant function (mDF) was used to detect SAH (mDF score ≥32).Demographic, clinical and laboratory parameters were recorded and survival was compared between patients with and without AKI (as per AKIN criteria) during hospitalisation and also at 28 days and 90 days. RESULTS: 339 patients of AH were included in the study. Out of them, 236 (70%) patients had SAH (DF ≥ 32) and 103 patients (30%) had DF &lt; 32.All patients with SAH were males. 164 (69%) patients with SAH had AKI and72 (31%) did not have AKI at hospitalisation. On comparison between SAH patients with or without AKI, age was comparable between the two groups. However, patients with SAH and AKI had higher MELD UNOS (28.69 ± 8.36 vs 19.50 ± 3.83; P &lt; 0.001), MELD Na+ (30.44 ± 7.56 vs 22.97 ± 4.56; P &lt; 0.001), CTP score (12.46 ± 1.84 vs 11.93 ± 1.50; P = 0.033), DF ((71.18 vs 53.24,IQR; P &lt; 0.001) and ABIC score (3.37 ± 1.47 vs 2.26 ± 0.61; P &lt; 0.001). Furthermore, they had increased prevalence of ACLF as per CANONIC study criteria (73.2% vs 34.7%; P &lt; 0.001), increased duration of hospitalisation (5days vs 4days,IQR; P &lt; 0.001) and decreased survival both at 28days (57.9% vs 80.6%; P &lt; 0.001) and 90days (36% vs 55.6%; P = 0.005). Kaplan–Meier survival curves showed significant differencesin survival between patients with and without AKI both at 28 days (log rank P value &lt; 0.001) and 90 days (log rank P value &lt; 0.001) (Figure 1). CONCLUSION: In our institution, over three fourth of alcoholic liver disease patients had severe AH and three fourth of them had AKI at admission. Patients with AH and AKI had increased proportion of ACLF, longer hospital stay, and decreased survival both at day 28 and 90.

COMPARATIVE STUDY OF AST: ALT RATIO IN LIVER DISEASES IN A TERTIARY CARE HOSPITAL IN BAREILLY

Background: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), the enzymes predominantly found in the hepatocytes, exhibit specific elevations in serum levels in different liver diseases. The ratios of their serum levels (AST: ALT ratio or De Ritis ratio) also exhibit specific patterns providing important diagnostic clues. The objective of the study is to establish the diagnostic utility of the AST: ALT ratio in liver diseases.&#x0D; Material and methods: The present study was conducted to measure the serum levels of these enzymes from the blood samples collected from a total of 60 patients with diagnosis of Alcoholic Hepatitis (AH, n= 18), Viral Hepatitis (VH, n= 18), Obstructive Jaundice (OJ, n= 06) and Chronic Hepatitis (CH, n= 18) to calculate their ratio as Mean ± SD, separately in each disease group. 24 normal healthy individuals were studied as control group. The data was analyzed using SPSS (Version 17.0) software and ‘p’ values were elicited using student-‘t’ test.&#x0D; Results: An AST: ALT ratio of 2.005±0.833, 0.648±0.228, 0.865±0.147 and 1.314±0.305 was observed in AH, VH, OJ and CH respectively. Control group showed a mean AST: ALT ratio of 1.001±0.158. A significant difference (p&lt;0.05) was observed when each case group was compared with control except OJ vs Control where the ‘p’ value was observed &gt;0.05. A significant difference (p&lt;0.05) was observed when comparison was done between any two of the disease groups.&#x0D; Conclusion: AST: ALT ratio can be useful in differentiating the liver diseases.&#x0D; Key words: AST:ALT ratio, De Ritis ratio, Alcoholic Hepatitis, Viral Hepatitis, Obstructive Jaundice and Chronic Hepatitis.

Underestimation of Liver Transplantation for Alcoholic Hepatitis in the National Transplant Database

Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician diagnosis of AH at liver transplantation (LT) listing versus UNOS data entry of AH as listing diagnosis. In a prior study, consecutive early LT recipients transplanted for AH between 2012 and 2017 were identified by chart review at 10 ACCELERATE-AH sites. In this current study, these same LT recipients were identified in the UNOS database. The primary UNOS diagnostic code was evaluated for concordance with the chart-review assignment of AH. In cases where the primary listing diagnosis in UNOS was not AH, we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis of AH and alcoholic cirrhosis in the chart; 12 (15%) due to clinical uncertainty regarding the diagnosis of AH versus acute decompensated alcoholic cirrhosis; and 12 (15%) due to a data entry error. In conclusion, in a large cohort of LT recipients with AH, only 35% were documented as such in UNOS. Increased education and awareness for those performing UNOS data entry, the establishment of specific criteria to define AH in the UNOS database, and the ability to document dates of alcohol use would allow future research on ALD to be more informative.

Metabolomics Discloses a New Non-invasive Method for the Diagnosis and Prognosis of Patients with Alcoholic Hepatitis

Introduction and Aims: Alcoholic hepatitis is the most severe manifestation of alcoholic liver disease. Unfortunately, there are still some unresolved issues in the diagnosis and management of this disease, such as the need of histological diagnosis, an accurate prognostic stratification, and the development of novel targeted therapies. The present study aimed at addressing these issues by means of metabolomics, a novel high-throughput approach useful in other liver diseases. Methods: 64 patients with biopsy-proven alcoholic hepatitis were included and compared with 26 patients with decompensated alcoholic cirrhosis without superimposed alcoholic hepatitis, which was ruled out by liver biopsy. Results: The comparison of the metabolic profiles of patients with alcoholic hepatitis and decompensated cirrhosis showed marked differences between both groups. Importantly, metabolic differences were found among alcoholic hepatitis patients when subjects were stratified according to 90-day survival. Based on these findings, two non-invasive signatures were developed. The first one allowed an accurate non-invasive diagnosis of alcoholic hepatitis (AUROC 0.932; 95% CI 0.901-0.963). The second signature showed a good performance in the prognostic stratification of patients with alcoholic hepatitis (AUROC 0.963; 95% CI 0.895-1.000). Conclusions: Signatures based on metabolomics allowed an accurate non-invasive diagnosis and prognostic stratification of alcoholic hepatitis. The differences observed in the metabolic profile of the patients according to the presence and severity of alcoholic hepatitis are related with different mechanisms involved in the pathophysiology of alcoholic hepatitis such as peroxisomal activity, synthesis of inflammatory mediators or oxidation. This information could be useful for the development of novel targeted therapies.

What's in Metabolomics for Alcoholic Liver Disease?

Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD. 30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept cross-sectional study. Baseline assessment consisted in evaluation of Maddrey's Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis. From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV. Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD.

Hospital-Acquired Infection Is the Strongest Predictor of In-hospital Mortality in Patients With Alcoholic Hepatitis

Introduction: Alcoholic hepatitis (AH) is a clinical syndrome associated with high mortality and utilization of resources. We performed this study to evaluate predictors of in-hospital mortality (IHM) among AH patients. Methods: A retrospective chart review was done on patients discharged from our hospital with a diagnosis of AH. Patients who met a well characterized definition of AH (serum bilirubin > 3 mg/dL, AST to ALT ratio of > 1.5, recent heavy alcohol use, and absence of other causes of liver disease) were included in the study. Chi-square and t-tests were used to compare categorical and continuous variables. Multivariate logistic regression was used to evaluate the impact of several variables on IHM. Results: 105 patients with AH (median age 46yrs, 56% male, 74% white, 57% with cirrhosis, MELD score 23) were included in the study. Complications present on admission included acute kidney injury (AKI) (44%), encephalopathy (29%), infection (24%), and gastrointestinal bleeding (17%). Complications that developed during the hospitalization included AKI (48%) with 8% requiring dialysis, infection (15%), encephalopathy (12%), and gastrointestinal bleeding (5%). 67 patients (64%) received treatment for AH including steroids (n=33), pentoxifylline (21), or both (n=13).15 patients (14%) died during hospitalization. Compared to those that survived hospitalization, patients with IHM had a higher incidence of AKI on admission (73 vs. 39%, P=0.013), in-hospital AKI (73 vs. 20%, P < 0.0001), in-hospital encephalopathy(40 vs. 8%, P=0.0005), in-hospital infection (47 vs. 10% P=0.0003), pentoxifylline use (60 vs. 28%, P=0.014), and in-hospital renal replacement therapy (33 vs. 3%, P < 0.0001). They were also more likely to meet SIRS criteria (73 vs. 46%, P=0.046) and have a higher admission MELD score (32 vs. 23, P=0.0003). The use of prophylactic antibiotics was similar among patients with IHM and those who survived hospitalization (33 vs. 29%, P=0.73). On multivariate logistic regression, hospital-acquired infection was the single most important predictor for IHM (OR 15, 2.3-99, P=0.005). Prophylactic antibiotic use (OR 1.04, 0.14-8.1, P=0.96) and admission MELD score (OR 1.07, 0.98-1.17, P=0.13) were not predictive of IHM. Conclusion: Patients with AH have high in-hospital mortality and hospital acquired infection appears to be the strongest predictor of IHM. Prophylactic antibiotic use does not affect IHM and so clinicians should be vigilant to reduce the risk of infection and treat appropriately if there is evidence of an infection.

Alcoholic Hepatitis: A Retrospective Study of Index Hospitalization, Survival, Readmission, Recidivism, Recurrence and Transplant

Introduction: Alcoholic hepatitis (AH) is a clinical syndrome associated with high short term mortality. Data on natural history of AH after initial hospitalization are scanty. Methods: A retrospective chart review was performed on all patients with discharge diagnosis of AH from January 2012 to October 2015. Patients with well characterized AH - heavy alcohol use with last drink within 6 weeks prior to admission, bilirubin >3mg/dL, AST:ALT ratio >1.5 and both transaminases < 400 IU/L, were included in our study. Medical charts were reviewed for demographic characteristics, complications at and during admission, treatment options (corticosteroid, pentoxifylline and LT), antibiotic use, readmission, recidivism and death Results: 105 AH patients (median age 46 years, 56% male, 74% white, 57% with cirrhosis) were included. 49.5% of patients met SIRS criteria at admission. Median laboratory values at admission included WBC 10.7(7.1-15.6), platelets 137(92-188), AST 175(119-242), ALT 54(41-83), bilirubin 14.1(7.9-23.2), sodium 131(126-135), PT 18.9(14.5-23.3) and MELD 23(18-31). Complications at admission included AKI (44%),encephalopathy(30%), gastrointestinal bleeding (GIB) (17%) and infection (24%). During hospitalization, the incidence for these complications were 28%,12%, 5% and 15% respectively. 72% had severe AH with MELD>20 or encephalopathy, of which 64% (n=54) were treated medically with either steroids 32 %( n=33), pentoxifylline 20%(n=21) or both 12% (n=13). Overall, 90 (86%) AH patients survived the index hospitalization. Of the survivors of index hospitalization, 15 were lost to follow up, and 12 of remaining 75 (16%) died within 6 months and 16(21%) within 12 months. 46% patients were readmitted within a year, 33% had recidivism and 21% had recurrent AH. On logistic regression analysis, none of the baseline factors was predictive of recidivism. However recidivism was associated with readmissions (78 vs. 33%, P=0.005). Recurrent AH as cause for readmission was associated with higher 6-month mortality as compared to readmission for cause other than recurrent AH (31 vs. 9%, P=0.043). Among survivors of index hospitalization, only 12% were considered for liver transplant(LT) and only 2 patients got LT. Conclusion: AH is associated with high rate of mortality, with limited survival benefit from corticosteroids or pentoxifylline. LT is not addressed often in these patients with recidivism being one of the major barriers. Recurrent AH is a common cause for readmission and poor long term survival. Large prospective studies are needed to identify factors predictive of recidivism, develop strategies to decrease recidivism, and develop protocols for implementing early LT in patients with severe AH.

Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH and the effect of this variability on the proposed AHHS categories. Hematoxylin-eosin- and trichrome-stained slides from 32 patients diagnosed with AH with liver biopsies within 1month of presentation (2000 to 2015) were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated, and an AHHS category (mild, moderate, severe) was assigned. The Fleiss' kappa coefficient (κ) analysis was performed to determine the interobserver agreement. A slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathologic features of AH with κ value ranging from 0.20 (95% confidence interval (CI): 0.03 to 0.46, megamitochondria) to 0.52 [95% CI: 0.40 to 0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (κ=0.33, 95% CI: 0.20 to 0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a κ value of 0.40 (95% CI: 0.22 to 0.60). In general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice.

Living Donor Liver Transplantation for Severe Alcoholic Hepatitis Not Responding to Medical Management: An Experience of 31 Patients

Background and Aim: There is limited data on outcomes of living donor liver transplantation (LDLT) for alcoholic hepatitis. Methods: The study included LDLT recipients for severe alcoholic hepatitis not responding to medical management (n = 31), diagnosis of alcoholic hepatitis was both clinical and explant based. Immunosuppression protocol consisted of calcineurin inhibitors (mainly tacrolimus), mycophenolate and short-term steroids. The data is shown number, mean (SD) or median (25–75 IQR). Results: All LDLT recipients were males. The disease severity score before LDLT were as follows; Child's 11.1 ± 1, MELD 23.7 ± 4.1, modified Maddrey's discriminant function (mDF) score 54 (33–81). These patients were abstinent for a duration of 3 (2–6) months before LDLT and none had psychiatric contraindication for transplant. The serum biochemistries were as follows; bilirubin 8.7 (6–15) mg/dl, INR 2 ± 0.4, albumin 2.8 ± 0.4 g/dl. All patients underwent LDLT with a Graft to recipient weight ratio (GRWR) of 0.95 ± 0.17. The post-transplant ICU and hospital stay were 5 ± 1 and 16 ± 7 days. A total of seven (22.5%) patients had fungal infections. Biliary complications occurred in 5 patients. A total of five patients (16%) died during a follow up of 19 (11–26) months; causes of death included bacterial sepsis in 4 and colonic mucormycosis in one, the survival curve is shown in Figure 1. Four patients had relapse of alcohol intake (one occasional, two moderate and one heavy amount of alcohol intake). Conclusion: Living donor liver transplantation for severe alcoholic hepatitis not responding to medical management is associated with good survival. The authors have none to declare.

Hepatology Clinical.

Hepatology Clinical.