Severe Acute Alcoholic Hepatitis Research Articles

Acute-on-chronic liver failure in severe acute alcoholic hepatitis: impact on management, prognostication, and urgency of liver transplantation

Acute-on-chronic liver failure in severe acute alcoholic hepatitis: impact on management, prognostication, and urgency of liver transplantation

Antibioprophylaxy with amoxicillin-clavulanate do not increase survival of patients with severe acute alcoholic hepatitis

Antibioprophylaxy with amoxicillin-clavulanate do not increase survival of patients with severe acute alcoholic hepatitis

Granulocyte colony stimulating factor in decompensated cirrhosis, acute alcoholic hepatitis, and acute-on-chronic liver failure: A comprehensive meta-analysis of randomized controlled trials.

GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis. Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes. In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p=0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p=0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p=0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90. G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

Alcoholic hepatitis - current and future treatment approaches

Acute severe alcoholic hepatitis is a serious disease with poor prognosis. As a result of an improved understanding of the underlying pathomechanisms, a variety of new, innovative therapeutic modalities are currently being investigated that may help to improve prognosis. New approaches include the application of anti-inflammatory agents (e.g., interleukin-1 inhibitors), modifications of the gut-liver axis via fecal microbiome transfer or the administration of non-absorbable antibiotics (e.g., rifaximin), and drugs to enhance hepatocellular regeneration (e.g., interleukin-22 agonists). This article describes current management concepts of alcoholic hepatitis and provides an overview of new potential treatment approaches.

Correlation Between Computed Tomography Findings and the Laboratory Test-Derived Severity Score in Patients With Severe Acute Alcoholic Hepatitis.

This study aimed to compare computed tomography (CT) findings between patients with severe and nonsevere acute alcoholic hepatitis (AAH). We included 96 patients diagnosed with AAH between January 2011 and October 2021 who underwent 4-phase liver CT and laboratory blood tests. Two radiologists reviewed the initial CT images with respect to distribution and grade of hepatic steatosis; transient parenchymal arterial enhancement (TPAE); and presence of cirrhosis, ascites, and hepatosplenomegaly. A Maddrey discriminant function score (4.6 × [patient's prothrombin time - control] + total bilirubin [mg/mL]) was used as cutoff indicator for severity, with a score of 32 or higher indicating severe disease. The image findings were compared between the severe (n = 24) and nonsevere (n = 72) groups using the χ 2 test or Fisher exact test. After univariate analysis, the most significant factor was identified using a logistic regression analysis. In the univariate analysis, there were significant between-group differences in the TPAE, liver cirrhosis, splenomegaly, and ascites ( P < 0.0001, P < 0.0001, P = 0.0002, and P = 0.0163, respectively). Among them, TPAE was the only significant factor for severe AAH ( P < 0.0001; odds ratio, 48.1; 95% confidence interval, 8.3-280.6). Using this single indicator, the estimated accuracy, positive predictive, and negative predictive values were 86%, 67%, and 97%, respectively. Transient parenchymal arterial enhancement was the only significant CT finding in severe AAH.

An Assessment of the Psychosocial Evaluation for Early Liver Transplantation in Patients With Acute Alcoholic Hepatitis in the Context of Alcohol Use Disorder, a Case-Control Study.

Background:Severe acute alcoholic hepatitis (AAH) has an extremely poor prognosis with a high short term mortality rate. As a result, many centers, including our own, have allowed transplant patients to be listed for transplantation prior to achieving 6-months of sobriety. Several scoring systems, designed to target patients with a minimal period of sobriety, have been proposed to identify patients with alcohol use disorder (AUD), who would be predisposed to relapse after liver transplantation. We investigated whether these scoring systems corroborated the results of the non-structured selection criteria used by our center regarding decision to list for transplant.Methods:We conducted a retrospective case-control study of 11 patients who underwent early liver transplantation for AAH matched with 11 controls who were declined secondary to low insight into AUD. Blinded raters confirmed the severity of the diagnosis of DSM-5 and scored the patients on a variety of structured psychometric scales used to predict alcohol relapse. These included the High Risk for Alcohol Relapse Scale (HRAR), Stanford Integrated Psychosocial Assessment Tool (SIPAT), Alcohol Relapse Risk Assessment (ARRA), Hopkins Psychosocial Scale (HPSS), Michigan Alcoholism Prognosis Score (MAPS), Alcohol Use Disorders Identification Test -Consumption (AUDIT-C), and Sustained Alcohol Use Post-Liver Transplant (SALT) scales. All patients who underwent transplantation were followed for harmful and non-harmful drinking until the end of the study period.Results:The transplant recipients had significantly favorable MAPS, HRAR, SIPAT, ARRA, and HPSS scores with cutoffs that matched their previous research. The SALT and AUDIT-C scores were not predictive of our selection of patients for transplantation. Despite an expedited evaluation and no significant period of sobriety, our case cohort had a 30% relapse to harmful drinking after an average of 6.6 years (5-8.5 years) of follow-up.Discussion:Despite the rapid assessment and the short to no period of sobriety, the patient cohort demonstrated a 30% relapse to harmful drinking, consistent with the 20% to 30% relapse to drinking rate reported after liver transplantation for all forms of alcoholic liver disease. Average scores from MAPS, HRAR, SIPAT, ARRA, and HPSS corroborated our current stratification procedures, with lower mean risk scores found in the transplanted group.Conclusion:Patients with AUD and severe AAH who obtain new insight into their disease and posses other favorable psychosocial factors have low rates of AUD relapse post-liver-transplantation. The psychosocial selection criteria for patients with alcoholic hepatitis in our institution are consistent with 4 of the 5 scoring systems investigated in their prediction of sobriety post-transplant.

Severe acute alcoholic hepatitis: can we offer early liver transplantation?

Alcohol-related liver disease is one of the most prevalent liver diseases worldwide and is the second most common indication for liver transplantation. Most transplant programs require 6 months of abstinence prior to transplantation; commonly referred to as the "six-month rule." According to this rule, the patients admitted for severe acute alcoholic hepatitis are not eligible for liver transplantation in most transplant centers. However, there is increasing evidence that if liver transplantation is performed in selected patients after the first episode of severe decompensation with no response to steroid therapy, it represents an effective treatment. In such selected patients, the post-transplant outcomes are good with survival rates that are significantly higher when compared with patients not responding to medical therapy and not transplanted. A multidisciplinary assessment, involving several stakeholders such as a transplant hepatologist, transplant surgeon, psychologist and psychiatrist is becoming mandatory to properly evaluate the candidate to liver transplantation for alcoholic liver diseases and severe acute alcoholic hepatitis. In the clinical setting of severe acute alcoholic hepatitis, further studies are needed for the identification of accepted selection clinical and psychosocial criteria that can provide the best long-term results. The early liver transplantation option should therefore be explored within strict criteria for this setting.

Severe acute alcoholic hepatitis: can we offer early liver transplantation?

Alcohol-related liver disease is one of the most prevalent liver diseases worldwide and is the second most common indication for liver transplantation. Most transplant programs require 6 months of abstinence prior to transplantation; commonly referred to as the six-month rule. According to this rule, the patients admitted for severe acute alcoholic hepatitis are not eligible for liver transplantation in most transplant centers. However, there is increasing evidence that if liver transplantation is performed in selected patients after the first episode of severe decompensation with no response to steroid therapy, it represents an effective treatment. In such selected patients, the post-transplant outcomes are good with survival rates that are significantly higher when compared with patients not responding to medical therapy and not transplanted. A multidisciplinary assessment, involving several stakeholders such as a transplant hepatologist, transplant surgeon, psychologist and psychiatrist is becoming mandatory to properly evaluate the candidate to liver transplantation for alcoholic liver diseases and severe acute alcoholic hepatitis. In the clinical setting of severe acute alcoholic hepatitis, further studies are needed for the identification of accepted selection clinical and psychosocial criteria that can provide the best long-term results. The early liver transplantation option should therefore be explored within strict criteria for this setting.

Non-invasive diagnosis of severe alcoholic hepatitis: Usefulness of cross-sectional imaging

PurposeTo describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of severe acute alcoholic hepatitis (SAAH) and estimate the capabilities of CT and MRI in differentiating SAAH from alcoholic cirrhosis and non-alcoholic steato-hepatitis (NASH) cirrhosis. Materials and methodsFifty patients with pathologically proven SAAH (SAAH group) who underwent CT or MRI examinations up to 30 days before or 15 days after liver biopsy between January 2008 and June 2018 were retrospectively included. There were 31 men and 29 women with a mean age of 52±9 (SD) years (range: 33–67 years). Imaging features of the SAAH group were compared to those obtained in two control groups including 62 patients with alcoholic cirrhosis without acute alcoholic hepatitis (control group 1) and 19 patients with NASH cirrhosis (control group 2) by two independent radiologists blinded to the final diagnosis. Univariate analyses were performed to compare imaging characteristics between the three groups, followed by diagnostic performance analysis for the diagnosis of SAAH of the main CT features. ResultsHeterogeneous steatosis was significantly more frequent in SAAH group than in the control groups (41/50; 82% vs. 7/62; 10% and 1/19; 5% in control groups 1 and 2, respectively for reader 1 and 34/50; 68% vs. 8/62; 13% and 1/19; 5% in control groups 1 and 2, respectively for reader 2; both P=0.01). Transient perfusion disorders were more frequent in SAAH group than in the control groups (35/50; 70% vs. 12/62; 21% and 5/19; 26% in control groups 1 and 2, respectively for reader 1 and 39/50; 78% vs. 14/62; 23% and 13/19; 6% in control groups 1 and 2, respectively for reader 2; both P=0.01). The combination of these two findings yielded 100% specificity (45/45; 95% CI: 92–100) for readers 1 and 2 for the diagnosis of SAAH vs. alcoholic cirrhosis and NASH cirrhosis. ConclusionThe imaging features of SAAH are specific and mainly associate transient heterogeneous steatosis and liver perfusion disorders. CT/MRI may be useful to differentiate SAAH from alcoholic cirrhosis and NASH cirrhosis.

S2626 Alcoholic Hepatitis and COVID-19: The Question of Steroids

INTRODUCTION: The SARS-CoV-2/Novel Coronavirus-19 (COVID-19) has created new challenges for managing acute alcoholic hepatitis (AH). The decision to initiate steroids in AH is now more difficult, as data suggests worsened outcomes in COVID-19 patients treated with steroids. How patients with AH respond to steroids while also COVID-19 infected is an open question. We present a case of severe AH in a COVID-19 infected patient who received steroids. CASE DESCRIPTION/METHODS: Fifty-seven-year-old man with chronic alcohol abuse and alcoholic cirrhosis with portal hypertension presented with dry cough, fatigue, and melena. He had been drinking 1 pint of vodka daily for 1 week. He had normal hemodynamics and oxygen saturation was 98% on room air. Rectal exam was unremarkable. Laboratory data showed normal BUN/Cr, Hgb/Hct 6.4 g/dL/21.6%, PLT 54 K/mL, total bilirubin/direct bilirubin 10.3 mg/dL/ 6.0 mg/dL, Alk Phos 162 IU/L, AST 260 IU/L, ALT 53, and INR 1.9. Viral hepatitis panel was unremarkable. COVID-19 PCR was positive. Chest x-ray revealed bibasilar opacities. Right upper quadrant ultrasound with doppler revealed liver with cirrhotic morphology and no portal vein thrombosis. MDF was 59.1. MELD score was 22. He was started on an octreotide infusion, IV pantoprazole, and IV ceftriaxone. On hospital day 3, he became encephalopathic and was started on lactulose and rifaximin. He developed hepatorenal syndrome and was treated with albumin. He then had worsening coagulopathy and a rising total bilirubin. MDF increased to 37 and prednisolone 40mg daily was started. Seven days into therapy, total bilirubin down trended and kidney function improved. Lille score was 0.980. Although the Lille score suggested he may be a steroid non-responder, his improved mental status, total bilirubin and kidney function led to the decision to treat for 28 days. DISCUSSION: The COVID-19 pandemic creates a new challenge in treating AH. The recommendation is that steroids should be avoided in viral infections. The decision to initiate steroids in patients with AH is influenced by the MDF. However, steroid initiation based on MDF becomes problematic as hepatic injury is a known consequence of COVID-19. Thus, an elevated score may not solely be related to alcohol-induced inflammation. In our case, risk of mortality appeared to be driven by AH and thus steroids were initiated. Despite being a non-responder per the Lille score, the patient improved. This case reveals that it may be safe to use steroids in patients with severe AH and COVID-19 positivity.

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean=39.4years), had higher MELD scores (mean=36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P<.05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.

Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis

Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify patients with AAH at risk for death within 90 days. We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n = 57, model for end-stage liver disease [MELD] scores above 20) or moderate (n = 27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n = 28) or no liver injury (n = 10); 34 participants had nonalcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum levels of K18 using ELISAs and APOPTOSENSE kits. Serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the ratio of AST:ALT did not correlate with MELD scores. Patients with alcohol use disorder had higher serum levels of ALT than patients with severe AAH. Levels of K18M65 and K18M30 had statistically significant increases as liver disease worsened, as did the degree of necrosis (ratio of K18 M65:M30). The ratio of K18M65:ALT was increased in serum from patients with AAH compared with controls. Serum levels of K18 identified patients who died within 90 days with greater accuracy than commonly used static biomarkers. There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). The ratio of K18M65:M30 might be used as marker of mechanism of hepatocyte death, and the ratio of K18M65:ALT might be used to distinguish patients with AAH from patients with nonalcoholic steatohepatitis. Serum levels of K18 might be used to identify patients with severe AAH at risk for death. ClinicalTrials.gov identifier # NCT01922895 and NCT01809132.

Severe alcoholic hepatitis: current perspectives.

Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options – past, present, and future, in patients with severe alcoholic hepatitis.

Outcomes of Patients Hospitalized for Severe Acute Alcoholic Hepatitis.

Severe acute alcoholic hepatitis is a serious condition in individuals who consume significant quantities of alcohol. We aimed to identify risk factors for short-term mortality with this illness. Patients with severe acute alcoholic hepatitis admitted to our academic medical center from 2010 to 2012 were identified. Demographic features, laboratory values, and patient outcomes were recorded. In-hospital mortality and transfer to inpatient hospice were combined to calculate overall inpatient mortality. A total of 251 hospitalizations of 191 patients were identified. The average age was 43.1 years (standard deviation 9.55). Most patients were men (80.6%). Compared with all adult patients admitted to internal medicine services during the same period, patients self-reporting Native American and Hispanic race/ethnicity were overrepresented (11.1% vs 34.0% and 14.8% vs 27.7%, χ2 P < 0.0001). In-hospital mortality was 20.3%. Another 10% of patients were transferred to inpatient hospice facilities. In the multivariate analysis, higher overall inpatient mortality was associated with an admission bilirubin >20 mg/dL (odds ratio 4.59). Of the patients, 11.9% were readmitted with a complication within 30 days-most commonly septic shock. Of the readmitted patients, the overall inpatient mortality was 86.2%. This study confirms the severity of illness among patients with severe acute alcoholic hepatitis. Patients with the highest total bilirubin levels on admission had the highest overall inpatient mortality. Readmission was a strong predictor of overall in-hospital mortality.

Sa1501 – Novel “Enhanced Corticosteroid” Therapy for Patients with Recurrent/ Refractory Severe Acute Alcoholic Hepatitis Who Had a Prior Course of Conventional Corticosteroid Monotherapy

Sa1501 – Novel “Enhanced Corticosteroid” Therapy for Patients with Recurrent/ Refractory Severe Acute Alcoholic Hepatitis Who Had a Prior Course of Conventional Corticosteroid Monotherapy

Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis.

Bacterial infection is frequently observed in patients with alcoholic liver disease (ALD). We examined a possible role of Porphyromonas gingivalis in the development/progression and severity of disease in patients with acute alcoholic hepatitis (AAH). Plasma specimens from 47 patients with AAH (16 moderate, Model for End‐Stage Liver Disease [MELD] score <20]; 31 severe, MELD score >20) and 22 healthy controls (HCs) were collected. Clinical, drinking history (lifetime drinking history [LTDH]), and demographic data were collected. Antibody tests for immunoglobulin (Ig) G, IgM, and IgA against two P. gingivalis strains were performed. Between‐group comparisons and within‐group association analyses were carried out. Patients with severe AAH showed significantly higher plasma levels of IgG, IgA, and IgM against two P. gingivalis strains (W83 and 33277) compared to HCs. Patients with moderate AAH also had significantly elevated anti‐P. gingivalis IgA concentrations for both strains compared to HCs. Male patients with moderate AAH showed a significant inverse association in LTDH and anti‐P. gingivalis IgM. The aspartate aminotransferase:alanine aminotransferase ratio was positively associated with IgM of both strains in male patients with moderate AAH. Female patients with severe AAH showed a significant association between MELD scores and W83 IgM. Conclusion: Antibody response to P. gingivalis in AAH is elevated. Significantly elevated plasma anti‐P. gingivalis IgG, IgA, and IgM in severe AAH provide preliminary data that P. gingivalis could be a novel risk factor in the development/severity of AAH.

Severe acute alcoholic hepatitis and liver transplant: A never-ending mournful story.

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called “6-month rule.” This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.

Meta-analysis of patient survival and rate of alcohol relapse in liver-transplanted patients for acute alcoholic hepatitis.

This review investigated survival and alcoholic relapse following liver transplantation (LT) in patients with severe acute alcoholic hepatitis (AH) without 6months of alcohol abstinence. All studies comparing acute AH patients undergoing LT with a control group were included. CENTRAL, MEDLINE, and Web of Science databases were searched. Survival benefits or odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using a random effects model. The study was registered in PROSPERO (CRD42017057971). According to the search results, two separate meta-analyses were performed: meta-analysis A compared early LT with medical therapy alone in patients with severe AH that were not responding to medical therapy and meta-analysis B compared LT outcome in patients with AH and chronic alcoholic cirrhosis (AC). The search yielded 2232 articles. Eight studies were included in the two meta-analyses-two studies in meta-analysis A and six studies in meta-analysis B. The two studies (n = 70) included in meta-analysis A revealed that 1-year patient survival was significantly higher in the LT group compared with the medical therapy-alone group (survival benefit, 15.88; 95% CI, 3.98-63.35; p < 0.0001). The six studies in meta-analysis B (including 1091 patients) showed that 1-year (survival benefit, 1.65; 95% CI, 0.95-2.89; p = 0.08), 3-year (survival benefit, 1.31; 95% CI, 0.79-2.18; p = 0.30), and 5-year survival (survival benefit, 1.54; 95% CI, 0.92-2.56; p = 0.10) were not significantly different between AH and AC groups. There was no significant difference in the rate of alcohol relapse between the groups (OR, 1.26; 95% CI, 0.53-2.96; p = 0.60). Early LT is a life-saving treatment for AH patients that do not respond to medical therapy. The chance of alcohol relapse after LT is not increased in selected patients.

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis.

Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 to characterize practice patterns and perceptions of LT for SAH. We obtained responses from 45 (41.3%) of 109 surveyed centers, representing all 11 (100%) United Network for Organ Sharing regions. Half (n = 23; 51.1%) reported performing at least 1 LT for SAH, although most (n = 19; 82.6%) of those had performed ≤5 LTs for that indication. Centers expressed near consensus for selection criteria, requiring strong social support (100%), no prior presentations with SAH (91.3%), absence of a severe coexisting psychiatric disorder (91.3%), and official psychosocial evaluation (87.0%). Reported posttransplant survival of SAH patients was excellent, with 17 (73.9%) centers reporting 1-year posttransplant survival exceeding 90%. Among centers that had not performed LT for SAH, the most commonly cited reason was perceived high risk of alcohol relapse. In conclusion, our data demonstrate that LT is increasingly adopted as a therapeutic intervention for patients with SAH and that careful selection allows for excellent 1-year posttransplant survival. Despite this, nearly half of US centers do not perform LT for this indication due to perceived high risk of alcohol relapse. Our data support the use of LT for well-selected patients with SAH.

Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients.

Alcohol-associated liver disease (ALD) remains a major health concern worldwide. Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD. Elevated acrolein adducts and metabolites are detectable in blood and urine. This study evaluates the major urinary acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with acute alcoholic hepatitis (AAH) and examines its association with disease severity and markers of hepatic inflammation and injury. Urine HPMA was significantly higher in patients with severe [model for end-stage liver disease (MELD) ≥ 20] AAH compared with nonsevere AAH (MELD ≤ 19) or non-alcohol-consuming controls, suggesting that urine HPMA is a novel noninvasive biomarker in severe AAH. The association between HPMA and MELD in patients with AAH was nonlinear. In patients with nonsevere AAH, there was a positive trend, although not significant, whereas in severe AAH the association was negative, indicative of extensive injury and glutathione depletion. Consistent with the multifactorial etiology of ALD, our data identified strong combined effects of HPMA and proinflammatory cytokines on hepatocyte cell death, thereby supporting the pathogenic role of acrolein in liver injury. HPMA, together with IL-1β, showed robust associations with cytokeratin 18 caspase-cleaved fragment (CK18-M30; adjusted R2 = 0.812, P = 0.016) and cytokeratin 18 full-length protein (CK18-M65; adjusted R2 = 0.670, P = 0.048); similarly, HPMA, with IL-8, correlated with CK18-M30 (adjusted R2 = 0.875, P = 0.007) and CK18-M65 (adjusted R2 = 0.831, P = 0.013). The apoptosis index (CK18-M30:CK18-M65 ratio) strongly correlated with HPMA, together with IL-1β (adjusted R2 = 0.777, P = 0.022) or tumor necrosis factor-α (TNFα; adjusted R2 = 0.677, P = 0.046). In patients with severe AAH, IL-1β, IL-8, and TNFα are the predominant proinflammatory cytokines that interact with HPMA and play important mediating roles in influencing the extent/pattern of liver cell death. NEW & NOTEWORTHY This is the first study to examine the urinary acrolein metabolite 3-hydroxypropylmercapturic acid (HPMA) in alcoholic liver disease. HPMA was higher in patients with severe acute alcoholic hepatitis (AAH) compared with controls or nonsevere AAH and may be a novel selective, noninvasive biomarker for severe AAH. Consistent with the multifactorial etiology of alcohol-associated liver disease, we identified strong combined effects of HPMA and proinflammatory cytokines (IL-1β, IL-8, and TNFα) on the extent/pattern of liver cell death, thereby supporting the pathogenic role of acrolein.