Objective:To determine if race-ethnicity is correlated with case-fatality rates among low-income patients hospitalized for COVID-19. Research Design:Observational cohort study using electronic health record data. Patients:All patients assessed for COVID-19 from March 2020 to January 2021 at one safety net health system. Measures:Patient demographic and clinical characteristics, and hospital care processes and outcomes. Results:Among 25,253 patients assessed for COVID-19, 6,357 (25.2%) were COVID-19 positive: 1,480 (23.3%) hospitalized; 334 (22.6%) required intensive care; and 106 (7.3%) died. More Hispanic patients tested positive (51.8%) than non-Hispanic Black (31.4%) and White patients (16.7%, P<.001]. Hospitalized Hispanic patients were younger, more often uninsured, and less likely to have comorbid conditions. Non-Hispanic Black patients had significantly more diabetes, hypertension, obesity, chronic kidney disease, and asthma (P<.05). Non-Hispanic White patients were older and had more cigarette smoking history, COPD, and cancer. Non-Hispanic White patients were more likely to receive intensive care (29.6% vs 21.1% vs 20.8%, P=.007) and more likely to die (12% vs 7.3% vs 3.5%, P<.001) compared with non-Hispanic Black and Hispanic patients, respectively. Length of stay was similar for all groups. In logistic regression models, Medicaid insurance status independently correlated with hospitalization (OR 3.67, P<.001) while only age (OR 1.076, P<.001) and cerebrovascular disease independently correlated with in-hospital mortality (OR 2.887, P=.002). Conclusions:Observed COVID-19 in-hospital mortality rate was lower than most published rates. Age, but not race-ethnicity, was independently correlated with in-hospital mortality. Safety net health systems are foundational in the care of vulnerable patients suffering from COVID-19, including patients from under-represented and low-income groups.

BACKGROUND:Malnutrition is a commonly encountered issue in patients with alcohol-associated liver disease. The role of nutritional supplementation in the management of alcohol-associated liver disease is integral to patient outcomes-it has been shown to decrease rates of hepatic encephalopathy, improve outcomes post-liver transplant, reduce 90-day hospital readmissions and lower mortality. Despite these benefits, many studies have shown nutritional support to be an underutilised tool in the care of patients with alcohol-associated liver disease.AIMS:To review the epidemiology, pathophysiology, recommendations for nutritional assessment and supplementation, as well as future directions for research of the relationship between nutrition and alcohol-associated liver disease.METHODS:A literature search was conducted via PubMed using MeSH terms to inform this narrative review.RESULTS:Decreased dietary intake, socioeconomic status, impaired absorption of nutrients and increased free radical species are implicated in the pathophysiology of malnutrition in alcohol-associated liver disease.CONCLUSIONS:Malnutrition is common in alcohol-associated liver disease, and physicians should be aware of its association with poor clinical outcomes. Routine nutritional assessment, involvement of a dietician and nutritional supplementation are recommended to improve clinical outcomes in patients with alcohol-associated liver disease.

The previous American Association for the Study of Liver Diseases (AASLD) practice guideline on 'alcoholic liver disease' published in 2010, has been an undoubted success (1). According to Google Scholar on June 14, 2019, it has received more than 1,400 citations. In 2018, the AASLD Practice Guideline Committee decided that the field was ready for a new guideline, now called 'a guidance'. This article is protected by copyright. All rights reserved.

OBJECTIVES: Alcoholic hepatitis (AH) develops in approximately 30% of chronic heavy drinkers. The immune system of patients with AH is hyperactivated, yet ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are highly enriched in liver, mucosa, and peripheral blood and contribute to antimicrobial immunity. We aimed to determine whether MAIT cells were dysregulated in heavy drinkers with and without AH and the effects of alcohol abstinence on MAIT cell recovery. METHODS: MR1 tetramers loaded with a potent MAIT cell ligand 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil were used in multiparameter flow cytometry to analyze peripheral blood MAIT cells in 59 healthy controls (HC), 56 patients with AH, and 45 heavy drinkers without overt liver disease (HDC) at baseline and 6- and 12-month follow-ups. Multiplex immunoassays were used to quantify plasma levels of cytokines related to MAIT cell activation. Kinetic Turbidimetric Limulus Amebocyte Lysate Assay and ELISA were performed to measure circulating levels of 2 surrogate markers for bacterial translocation (lipopolysaccharide and CD14), respectively. RESULTS: At baseline, patients with AH had a significantly lower frequency of MAIT cells than HDC and HC. HDC also had less MAIT cells than HC (median 0.16% in AH, 0.56% in HDC, and 1.25% in HC). Further, the residual MAIT cells in patients with AH expressed higher levels of activation markers (CD69, CD38, and human leukocyte antigen [HLA]-DR), the effector molecule granzyme B, and the immune exhaustion molecule PD-1. Plasma levels of lipopolysaccharide and CD14 and several cytokines related to MAIT cell activation were elevated in patients with AH (interferon [IFN]-α, interleukin [IL]-7, IL-15, IL-17, IL-18, IL-23, IFN-γ, and tumor necrosis factor α). Decreased MAIT cell frequency and upregulated CD38, CD69, and HLA-DR correlated negatively and positively, respectively, with aspartate aminotransferase level. MAIT cell frequency negatively correlated with IL-18. HLA-DR and CD38 levels correlated with several cytokines. At follow-ups, abstinent patients with AH had increased MAIT cell frequency and decreased MAIT cell activation. However, MAIT cell frequency was not fully normalized in patients with AH (median 0.31%). DISCUSSION: We showed that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of blood MAIT cells and the residual cells were highly activated. Alcohol abstinence partially reversed those abnormalities.

Previous studies have identified drug and alcohol use as risk factors for readmission using claims data, but not by using substance use screening scores. This preliminary study tested the hypothesis that prevalence of 30-day readmission would be higher among patients screening positive on the 10-item Alcohol Use Disorders Identification Test (AUDIT-10) or the 10-item Drug Abuse Screening Test (DAST-10) tools at intake than among the general patient population. Social workers screened 4708 adult inpatients using prescreening questions followed by the AUDIT-10 and/or DAST-10. Patients with positive screens were followed for readmissions within 30 days of discharge. A positive screening score on the AUDIT-10 or DAST-10 instrument at intake was associated with higher risk of readmission to the general medicine wards within 30 days; this relationship appears complex and subject to mediation. Post hoc chart review found that the majority of readmissions among patients with positive screens were not immediately attributable to substance use. Further study is needed to verify these preliminary findings.

Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P < 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR] = 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR = 0.13, 95% CI: 0.07-0.24). Conclusion: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.

BACKGROUND:Despite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the United States.METHODS:We utilized a single-level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n = 74,972) compared to those with chronic liver diseases not caused by alcohol (n = 350,140) and those without underlying liver diseases (n = 1,447,063).RESULTS:The prevalence of adjustment disorder, anxiety disorder, posttraumatic stress disorder, and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p-values <0.05). Younger age, female gender, and White race were the independent predictors of psychiatric/substance use disorders among hospitalized patients with ALD.CONCLUSIONS:Hospitalized patients with ALD have significantly high prevalence of concomitant psychiatric and substance abuse disorders when compared to those with chronic liver diseases not caused by alcohol and those without underlying liver diseases. Screening and appropriate intervention should be implemented as part of routine clinical care for these patients.

BACKGROUND:Lifetime prevalence of posttraumatic stress disorder (PTSD) in the general population is reported to be 6.8%. Individuals with alcohol dependence and substance abuse have high prevalence of PTSD. However, the prevalence of PTSD in heavy drinkers with alcoholic hepatitis (AH) is not known.The study's aim was to determine the prevalence of PTSD in heavy drinkers with and without AH.METHODS:We screened for PTSD using the Primary Care-PTSD questionnaire among heavy drinkers with (n = 115) and without (n = 64) AH participating in a multicenter observational study in which participants were followed up to 12 months following their enrollment.RESULTS:The prevalence of PTSD in heavy drinkers with AH was 34% and was not different from heavy drinking controls without liver disease (34%). In the entire group screened for PTSD, the presence of PTSD was associated with higher alcohol consumption as reported by average drinks per last 30 days and average grams of alcohol consumed per day (p = 0.047 for both tests), but not associated with relapse of heavy drinking or mortality. Similarly, patients with AH and PTSD did not have higher relapse rate or higher mortality compared to patients with AH but no PTSD.CONCLUSIONS:Compared to previously reported prevalence in general population, heavy drinking individuals with or without AH have significantly higher prevalence of PTSD. However, PTSD was not associated with higher relapse rate or higher mortality in this population.

Intestinal dysbiosis is implicated in alcoholic hepatitis (AH). However, changes in the circulating microbiome, its association with the presence and severity of AH, and its functional relevance in AH is unknown. Qualitative and quantitative assessment of changes in the circulating microbiome were performed by sequencing bacterial DNA in subjects with moderate AH (MAH) (n = 18) or severe AH (SAH) (n = 19). These data were compared with heavy drinking controls (HDCs) without obvious liver disease (n = 19) and non-alcohol-consuming controls (NACs, n = 20). The data were related to endotoxin levels and markers of monocyte activation. Linear discriminant analysis effect size (LEfSe) analysis, inferred metagenomics, and predictive functional analysis using PICRUSt were performed. There was a significant increase in 16S copies/ng DNA both in MAH (P < 0.01) and SAH (P < 0.001) subjects. Compared with NACs, the relative abundance of phylum Bacteroidetes was significantly decreased in HDCs, MAH, and SAH (P < 0.001). In contrast, all alcohol-consuming groups had enrichment with Fusobacteria; this was greatest for HDCs and decreased progressively in MAH and SAH. Subjects with SAH had significantly higher endotoxemia (P = 0.01). Compared with alcohol-consuming groups, predictive functional metagenomics indicated an enrichment of bacteria with genes related to methanogenesis and denitrification. Furthermore, both HDCs and SAH showed activation of a type III secretion system that has been linked to gram-negative bacterial virulence. Metagenomics in SAH versus NACs predicted increased isoprenoid synthesis via mevalonate and anthranilate degradation, known modulators of gram-positive bacterial growth and biofilm production, respectively. Conclusion: Heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions. (Hepatology 2018;67:1284-1302).

Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P o 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR]1⁄4 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR 1⁄4 0.13, 95% CI: 0.07-0.24). Conclusions: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses. Key Indexing Terms: Aldehyde dehydrogenase; Gene polymorphism; Alcoholic liver disease; Risk. [Am J Med Sci 2018;] (]):]]]–]]].] INTRODUCTION Excessive alcohol drinking is one of the most significant risk factors for health problems such as injuries, liver diseases and cancer. Drinking becomes excessive when it causes or elevates the risk for alcohol-related problems or complicates the management of other health problems. According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), excessive drinking is defined as men who drink thern Society for Clinical Investigation. Published by Els www.ssciweb.org more than 4 standard drinks in a day (or more than 14 per week) and women who drink more than 3 drinks in a day (or more than 7 per week). Alcoholic liver disease (ALD) is a major adverse health event resulting from excessive drinking. Its pathogenesis is a multistep process consisting of a series of histopathologic changes. More than 90% of drinkers develop alcoholic steatosis which is reversible upon abstinence. However, if excessive alcohol use continues, the disease evier Inc. All rights reserved. 1

Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits' expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring.

The TREAT Consortium has carried out clinical studies on alcoholic hepatitis (AH) for over 4 years. We encountered problems with participant recruitment, retention, and eligibility for specific protocols. To improve our ability to carry out such trials, we reviewed recruitment screening logs, end of study logs, and surveyed study coordinators to learn the reasons for missing patients, why patients declined enrollment, and the number of patients eligible for treatment trials. Associations of the recruited subjects' demographics with their adherence to follow-up appointments were examined. Three hundred eight-seven patients (AH and heavy drinking controls) were enrolled in the observational study, and 55 AH patients were recruited into treatment trials. About half of patients identified with AH could not be recruited; no specific reason could be determined for about two-thirds of these. Among the patients who gave a reason for not participating, the most common reasons were feeling too sick to participate, desire to concentrate on abstinence, and lack of interest in research. Approximately a quarter of the AH patients met eligibility criteria for treatment trials for moderate or severe AH and we were able to recruit half to two-thirds of those eligible. Approximately 35% of participants in the observational study returned for both 6- and 12-month follow-up visits. We did not identify biopsychosocial or demographic correlates of retention in the study. This analysis revealed that attempts at recruitment into trials for AH miss some subjects because of structural issues surrounding their hospital admission, and encounter a high rate of patient refusal to participate. Nonetheless, more than half of the patients who met the eligibility criteria for moderate or severe AH were entered into clinical trials. Retention rates for the observational study are relatively low. These findings need to be accounted for in clinical trial design and power analysis.

Alcoholic hepatitis (AH) develops in only a small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty‐eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls were enrolled and followed up to 12 months. At baseline, HDC and healthy controls had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (tumor necrosis factor alpha, interleukin 6 [IL‐6], IL‐8, interferon gamma–induced protein 10, IL‐4, IL‐9, IL‐10, fibroblast growth factor 2, IL‐7, IL‐15, and transforming growth factor alpha) but lower levels of the anti‐inflammatory macrophage‐derived chemokine. AH patients also had more activated yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of cluster of differentiation 38 (CD38) and CD69 but low levels of human leukocyte antigen DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less interferon‐gamma in response to T‐cell stimulation. Up‐regulated IL‐6, IL‐8, CD38, and CD69 and down‐regulated macrophage‐derived chemokine, human leukocyte antigen DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL‐6, IL‐8, CD38, and CD69 were reduced, whereas levels of macrophage‐derived chemokine, human leukocyte antigen DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of tumor necrosis factor alpha, IL‐8, IL‐10, fibroblast growth factor 2, and IL‐7 remained higher. Conclusion: AH patients were in a highly immune‐dysregulated state, whereas HDC showed little evidence of immune activation; alcohol abstinence reversed most, but not all, of the immunological abnormalities. (Hepatology 2017;66:575–590).

It is with profound sadness that we note the loss of Dr Lawrence Lumeng who passed away on June 21, 2017, at age 77, following a long battle against progressive pulmonary fibrosis that was triggered by a viral lung infection in 2004. As a founding member of the Indiana Alcohol Center he made numerous seminal contributions to the field of alcoholism, alcohol metabolism, and alcoholic liver disease. Dr Lumeng was born on August 19, 1939 in Manila, Philippines; one of six children to the late Ming Lu and Lucia Lin who were Chinese immigrants. He moved to the United States as a teenager and lived in Indianapolis most of his life. He graduated from Indiana University School of Medicine (IUSM) in 1964, interned at the University of Chicago, and returned to Indiana University Medical Center for Internal Medicine residency and fellowship training in Gastroenterology. From 1969 to 1971 he served in the United States Army as a major and a research internist stationed at the Walter Reed Army Medical Center. He was appointed Assistant Professor of Medicine and Biochemistry in 1971, advanced to Associate Professor in 1974, and then promoted to Full Professor in 1979. From 1984 to 2007, he served as the Chief of the Division of Gastroenterology and Hepatology at IUSM. Together with his colleagues, he successfully built one of the foremost academic GI divisions in the country that continually ranked in the top 15 from 1993 until recently. As a physician-scientist, Dr Lumeng was funded continuously by either the VA or NIAAA (NIH) from 1971 until his retirement in 2013. Early on, he identified the malate-aspartate shuttle as the major pathway that inhibits citric-acid cycle flux and beta-oxidation in the mitochondrion during ethanol oxidation (an underlying mechanism of alcoholic fatty liver). He delineated how acetaldehyde can adversely affect vitamin B6 metabolism, and he identified several protein-acetaldehyde adducts that are produced in erythrocytes and the liver with chronic alcohol exposure. In the realm of genetics, his research accomplishments include the following: (1) Jointly with Drs Ting-Kai Li and Nick Grahame, he successfully raised, by selective breeding, several rodent lines that exhibit contrasting alcohol drinking preferences, ie, P/NP rat lines in the 1970’s, the HAD1-2/LAD1-2 rat lines in the 80’s, and the HAP1-2/LAP1-2 murine lines in the 90’s; (2) Jointly with Drs Ting-Kai Li and William McBride, he demonstrated that P and HAD1-2 selected rats are the best validated rodent models of alcoholism and also excellent models to recapitulate binge drinking, “relapse and loss of control” drinking, adolescent alcohol misuse, and compulsive drinking. Additionally, they clearly demonstrated that the corticomesolimbic dopamine pathway is the key brain reward pathway for alcohol-seeking behavior; and (3) Jointly with Drs Ting-Kai Li, Lucinda Carr, and Tiebing Liang, he established Npy, Snca, and Crfr2 as the top candidate genes that contribute to various CNS aspects of alcoholism. Because embryonic stem cells commonly used in mice to knockout genes cannot be deployed in the rat, Drs Lumeng and Tiebing Liang recently utilized the zinc finger nuclease technology to create Npy KO rats using NP rats as the background. The results clearly showed that NPY in concert with a host of other neuropeptides controls voluntary alcohol drinking (alcohol use vs abuse). Larry published more than 300 full-length scientific papers, reviews, and book chapters. He was the recipient of the VA High Priority Research Program on Alcoholism (1979); elected to the American Society for Clinical Investigation (1980); recipient of Annual Award for Scientific Excellence, RSA (1991); elected to the American Association of Physicians (1995); appointed to the Council of the Sagamores of the Wabash by Governor Frank O’Bannon, State of Indiana (2004) and was the recipient of two IU Trustee Teaching Awards (2004, 2008). Dr Lumeng was also a busy clinical hepatologist for nearly 25 years at Indiana University Medical Center. He was the founding medical director of IU’s liver transplantation program which now ranks among the top 5 adult liver transplant programs in the United States. He cared for thousands of patients with liver disease both at Indiana University Medical Center as well as the Veterans Administration Hospital in Indianapolis. He was a gifted educator and taught hepatology to a generation of medical students, residents, and fellows who are practicing all over the United States. He was a terrific mentor who shaped the careers of numerous faculty members. Some of his mentees include Dr David W. Crabb (former Chair of Medicine at IUSM), Dr Douglas K. Rex (Distinguished Professor and Chief of Endoscopy at IUSM), Dr Robert Hawes (former President of the ASGE and highly renowned advanced endoscopist), Dr Stuart Sherman (Clinical Director of GI and highly renowned advanced endoscopist), Dr Won Cho (Chief of GI at Medstar Washington Hospital Center), Dr Frank Gress (Chief of Endoscopy at Columbia), Dr Suthat Liangpunsakul (Chief of Hepatology at Indianapolis VA) and Dr Naga Chalasani (Chief of Gastroenterology and Hepatology at IUSM). The faculty and friends of the Division of Gastroenterology and Hepatology established an endowed, annual Lawrence Lumeng Lectureship with Dr Anil Rustgi as the inaugural speaker in 2008. Other recipients of this lectureship are Drs Scott Friedman (2009), Robert Hawes (2010), Michael Camilleri (2011), Gail Hecht (2012), Arun Sanyal (2013), M. Bishr Omary (2014), Richard Peek (2015), Hashem El-Serag (2016), and Carol Burke (2017). In 2016, the GI Division established the Lawrence Lumeng Endowed Professorship in Gastroenterology and Hepatology with Dr Thomas F. Imperiale as the inaugural holder of this endowed professorship. On a personal level, Dr Lumeng was loved and admired by a generation of fellows and faculty members. He expected results from his team and he reveled in recounting the successes of his faculty and fellows. He became one of Indiana University basketball’s most devoted fans almost immediately on his arrival in Indianapolis and never allowed a negative comment about Bobby Knight in his presence. He could always find the best Chinese food around and many of those who worked in his program got their introduction to authentic Chinese cuisine under his tutelage. Larry was devoted to his wife of 50 years, Pauline, whom Larry characterized as his best friend, soul mate, conscience, and pilot. He adored his children: Carey, now a pediatric pulmonologist at the University of Michigan, and Emily, a research epidemiologist/scientist employed by the New York City Department of Health. Larry was a beloved grandfather to 6 grandchildren. Larry played an enormous and pivotal role in building a premier GI division at Indiana University. He leaves a legacy of excellence in scholarship, patient care and teaching.

OBJECTIVE:To examine the natural history of acute alcoholic hepatitis (AH) and identify predictors of mortality for AH using data from a prospective multicenter observational study.PARTICIPANTS AND METHODS:We analyzed data from 164 patients with AH and 131 heavy-drinking controls with no liver disease. Participants underwent clinical/laboratory assessment at baseline and 6 and 12 months after enrollment. Multivariable analyses were conducted to identify variables associated with mortality and examine the association between coffee drinking and risk of AH.RESULTS:Thirty-six patients with AH died during follow-up, with estimated 30-day, 90-day, 180-day, and 1-year survival of 0.91 (95% CI, 0.87-0.96), 0.85 (95% CI, 0.80-0.91), 0.80 (95% CI, 0.74-0.87), and 0.75 (95% CI, 0.68-0.83), respectively. In the multivariable analysis, higher serum bilirubin level (hazard ratio [HR]=1.059; 95% CI, 1.022-1.089), lower hemoglobin level (HR=1.263; 95% CI, 1.012-1.575), and lower platelet count (HR=1.006; 95% CI, 1.001-1.012) were independently associated with mortality in AH. Compared with controls, fewer patients with AH regularly consumed coffee (20% vs 44%; P<.001), and this association between regular coffee drinking and lower risk of AH persisted after controlling for relevant covariates (odds ratio=0.26; 95% CI, 0.15-0.46). Time-dependent receiver operating characteristic curve analysis revealed that Model for End-Stage Liver Disease; Maddrey Discriminant Function; age, serum bilirubin, international normalized ratio, and serum creatinine; and Child-Pugh scores all provided similar discrimination performance at 30 days (area under the curve=0.73-0.77).CONCLUSION:Alcoholic hepatitis remains highly fatal, with 1-year mortality of 25%. Regular coffee consumption was associated with lower risk of AH in heavy drinkers.

Abstract Objectives: To elucidate the genetic variability between heavy drinkers with and without alcoholic hepatitis (AH). Materials and methods: An exploratory genome-wide association study (GWAS; NCT02172898) was conducted comparing 90 AH cases with 93 heavy drinking matched controls without liver disease in order to identify variants or genes associated with risk for AH. Individuals were genotyped using the multi-ethnic genotyping array, after which the data underwent conventional quality control. Using bioinformatics tools, pathways associated with AH were explored on the basis of individual variants, and based on genes with a higher ’burden’ of functional variation. Results: Although no single variant reached genome-wide significance, an association signal was observed for PNPLA3 rs738409 (p = .01, OR 1.9, 95% CI 1.1–3.1), a common single nucleotide polymorphism that has been associated with a variety of liver-related pathologies including alcoholic cirrhosis. Using the improved gene set enrichment analysis for GWAS tool, it was shown that, based on the single variants’ trait-association p-values, multiple pathways were associated with risk for AH with high confidence (false discovery rate [FDR] < 0.05), including several pathways involved in lymphocyte activation and chemokine signaling, which coincides with findings from other research groups. Several Tox Functions and Canonical Pathways were highlighted using Ingenuity Pathway Analysis, with an especially conspicuous role for pathways related to ethanol degradation, which is not surprising considering the phenotype of the genotyped individuals. Conclusion: This preliminary analysis suggests a role for PNPLA3 variation and several gene sets/pathways that may influence risk for AH among heavy drinkers.