Search

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients’ management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.

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. [ABSTRACT FROM AUTHOR]

Background: Alcohol-associated liver disease is the leading cause of liver transplantation in the western world. For these patients we calculated life expectancies both at time of transplant and several years later, stratified by key risk factors, and determined if survival has improved in recent years. Methods: Data on 14 962 patients with alcohol-associated liver disease who underwent liver transplantation in the MELD era (2002-2018) from the United States Organ Procurement and Transplantation Network database were analyzed using the Cox proportional hazards regression model and life table methods. Results: Demographic and past medical history factors related to survival were patient age, presence of diabetes or severe hepatic encephalopathy, and length of hospital stay. Survival improved over the study period, at roughly 3% per calendar year during the first 5 years posttransplant and 1% per year thereafter. Conclusions: Life expectancy in transplanted patients with alcohol-associated liver disease was much reduced from normal, and varied according to age, medical risk factors, and functional status. Survival improved modestly over the study period. Information on patient longevity can be helpful in making treatment decisions. [ABSTRACT FROM AUTHOR]

Legionnaires' disease is an atypical pneumonia caused by Legionella pneumophila. Legionella species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols. Patients commonly present with fever, chills, and cough. However, in immunosuppressed patients or severe cases, the disease can lead to multiorgan failure. In recent years, the incidence of Legionnaires' disease has drastically increased and unfortunately is commonly underdiagnosed. Gold-standard diagnosis is made through sputum cultures; however, urine Legionella antigen remains the most common test used for diagnosis. Goal-directed care includes antibiotics and supportive care. This case highlights a rare and unique presentation of Legionnaires' disease presenting with an elevated 2:1 aspartate aminotransferase to alanine transaminase pattern, typically seen with alcoholic hepatitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Eidy et al.)

Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes.

A 69-year-old man was admitted to Hanawa Kousei Hospital with acute hepatitis attributed to alcohol consumption. His condition improved with conservative treatment. Computed tomography (CT) showed localized thickening of the colonic wall at the splenic flexure ; carcinoembryonic antigen level was slightly elevated to 9.7 ng/mL. Colonoscopy (CS) showed an ulcerative lesion in the colonic splenic flexure. Ischemic colitis (IC) and type 4 colon cancer were suspected, but biopsy was not confirmatory. Malignancy could not be ruled out by contrast-enhanced CT ; repeat CS showed circumferential stenosis of the colonic splenic flexure. Ischemic colitis was suspected based on changes between the first and second CS. Biopsy histopathology led us to diagnose stricture- type IC. Constipation, but not intestinal obstruction, occurred. Conservative treatment improved the stenosis. Excessive alcohol consumption may lead to IC ; imaging studies may be useful to distinguish IC from colon cancer. Since most cases of ischemic colitis can be improved with conservative treatment, patients with stricture-type ischemic colitis may also be treated without surgery early on, with follow-up that includes careful, periodic imaging. [ABSTRACT FROM AUTHOR]

Impaired immune responses and increased susceptibility to infection characterize acute inflammatory conditions such as pancreatitis and alcoholic hepatitis and are major causes of morbidity and mortality. However, the mechanisms that drive this apparent immune paresis remain poorly understood. Monocytes mediate host responses to damage and pathogens in health and disease, and three subsets of monocytes have been defined based on CD14 and CD16 expression. We sought to determine the changes in monocyte subsets in acute pancreatitis (AP) and acute alcoholic hepatitis (AAH), together with functional consequences and mechanisms that underlie this change. Peripheral blood mononuclear cells (PBMCs) from patients with AP or AAH were compared with healthy controls. Monocyte subsets were defined by HLA-DR, CD14, and CD16 expression. Changes in surface and intracellular protein expression and phosphorylation were determined by flow cytometry. Phenotype and function were assessed following stimulation with lipopolysaccharide (LPS) or other agonists in the presence of specific inhibitors of TNFα and a disintegrin and metalloproteinase 17 (ADAM17). Patients with AP and AAH had reduced CD14++CD16+ intermediate monocytes compared to controls. Reduction of intermediate monocytes was recapitulated ex vivo by stimulating healthy control PBMCs with Toll-like receptor (TLR) agonists LPS, flagellin or polyinosilic:polycytidylic acid (poly I:C). Stimulation caused shedding of CD14 and CD16, which could be reversed using the ADAM17 inhibitor, TMI005 but not direct inhibitors of TNFα, a known ADAM17-target. Culturing PBMCs from healthy controls resulted in expansion of intermediate monocytes, which did not occur when LPS was in the culture medium. Cultured intermediate monocytes showed reduced expression of CX3CR1, CCR2, TLR4, and TLR5. We found reduced migratory responses, intracellular signaling and pro-inflammatory cytokine production, and increased expression of IL-10. Stimulation with TLR agonists results in ADAM17-mediated shedding of phenotypic markers from CD16+ monocytes, leading to apparent “loss” of intermediate monocytes. Reduction in CD14++CD16− monocytes and increased CD14++CD16+ is associated with altered responses in functional assays ex vivo. Patients with AP and AAH had reduced proportions of CD14++CD16+ monocytes and reduced phosphorylation of NFκB and IL-6 production in response to bacterial LPS. Together, these processes may contribute to the susceptibility to infection observed in AP and AAH.

Impaired immune responses and increased susceptibility to infection characterize acute inflammatory conditions such as pancreatitis and alcoholic hepatitis and are major causes of morbidity and mortality. However, the mechanisms that drive this apparent immune paresis remain poorly understood. Monocytes mediate host responses to damage and pathogens in health and disease, and three subsets of monocytes have been defined based on CD14 and CD16 expression. We sought to determine the changes in monocyte subsets in acute pancreatitis (AP) and acute alcoholic hepatitis (AAH), together with functional consequences and mechanisms that underlie this change. Peripheral blood mononuclear cells (PBMCs) from patients with AP or AAH were compared with healthy controls. Monocyte subsets were defined by HLA-DR, CD14, and CD16 expression. Changes in surface and intracellular protein expression and phosphorylation were determined by flow cytometry. Phenotype and function were assessed following stimulation with lipopolysaccharide (LPS) or other agonists in the presence of specific inhibitors of TNFα and a disintegrin and metalloproteinase 17 (ADAM17). Patients with AP and AAH had reduced CD14++CD16+ intermediate monocytes compared to controls. Reduction of intermediate monocytes was recapitulated ex vivo by stimulating healthy control PBMCs with Toll-like receptor (TLR) agonists LPS, flagellin or polyinosilic:polycytidylic acid (poly I:C). Stimulation caused shedding of CD14 and CD16, which could be reversed using the ADAM17 inhibitor, TMI005 but not direct inhibitors of TNFα, a known ADAM17-target. Culturing PBMCs from healthy controls resulted in expansion of intermediate monocytes, which did not occur when LPS was in the culture medium. Cultured intermediate monocytes showed reduced expression of CX3CR1, CCR2, TLR4, and TLR5. We found reduced migratory responses, intracellular signaling and pro-inflammatory cytokine production, and increased expression of IL-10. Stimulation with TLR agonists results in ADAM17-mediated shedding of phenotypic markers from CD16+ monocytes, leading to apparent "loss" of intermediate monocytes. Reduction in CD14++CD16− monocytes and increased CD14++CD16+ is associated with altered responses in functional assays ex vivo. Patients with AP and AAH had reduced proportions of CD14++CD16+ monocytes and reduced phosphorylation of NFκB and IL-6 production in response to bacterial LPS. Together, these processes may contribute to the susceptibility to infection observed in AP and AAH. [ABSTRACT FROM AUTHOR]

Madelung's disease is a rare condition characterized by symmetric growth of fatty tumors (lipomas) around the neck, shoulders, upper arms, and trunk. It often affects men with a history of alcohol abuse. Here we report a review of the literature about this disease together with the description of a patient affected by Madelung's disease and acute alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Rising mortality in the United States due to alcoholic liver disease (ALD) and the dearth of effective treatments for ALD have led to increased research in this area, particularly in alcoholic hepatitis. To understand the burden of illness and potential economic value of effective treatments, we conducted a health care claims analysis of over 15,000 commercially insured adults who were hospitalized with alcoholic hepatitis (AH) between 2006 and 2013 and followed for up to 5 years. Their average age was 54 years and 68% were male. Over 5 years, about two-thirds of these adults died (44% in the first year), and fewer than 500 received liver transplants. There were nearly 40,000 re-hospitalizations, with over 50% of the survivors re-hospitalized within a year and nearly 75% through the second year. The total costs were nearly $145,000 per patient, with costs decreasing over time from over $50,000 in the first year (including the index hospitalization) to about $10,000 per year in the later years. Total costs for the cohort over 5 years were $2.2 billion. Patients who received a liver transplant averaged about $300,000 in transplant-related costs and over $1,000,000 in total health care costs over 5 years. Average costs in years following the index hospitalization were similar to diabetes. AH has a high mortality and is a high-cost condition. [ABSTRACT FROM AUTHOR]

Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose of Review To briefly summarize topical ethical issues in patients with cirrhosis. Recent Findings The "four quadrants" framework is ideally suited to address ethical issues in patients with cirrhosis. The presence of hepatic encephalopathy complicates any ethical analysis and stresses the importance of advanced directives and end of life planning, both of which appear to be poorly applied. Organ allocation in liver transplantation (LT) based on survival benefit, a "not unreasonable standard" to assess live donor LT (LDLT) in patients removed from the wait list, LT in patients with acute alcoholic hepatitis, and LT in undocumented immigrants are supported by sound ethical principles. Summary Significant ethical issues remain challenging and unresolved for patients with cirrhosis. Further research must be done to assess how frequently ethical problems occur in individual patients. Clear, detailed policies, based on strong ethical platforms, must be developed to further address these significant ethical challenges. [ABSTRACT FROM AUTHOR]

Background/Aim: It has recently been reported that treatment with pentoxifylline, an inhibitor of tumour necrosis factor, improves survival in severe alcoholic hepatitis. The present study was initiated to test the hypothesis that pentoxifylline improves short term survival in patients with acute alcoholic hepatitis in Indian scenario. Materials and Methods: Single center prospective observational study. We evaluated patients diagnosed with alcoholic hepatitis who were admitted to our hospitals from September 2008 to September 2010. Patients with history of chronic alcohol intake or a recent alcoholic binge, Jaundice and one or more of the following clinical and laboratory findings: palpable tender hepatomegaly, Leucocytosis, hepatic encephalopathy and AST:ALT ratio>2 with absolute values of AST < 500 IU/L and ALT < 200 IU/L were included in the study. Patients with gastrointestinal hemorrhage and other possible causes of hepatitis were excluded. Results: Twenty of the 49 patients were treated with pentoxifylline. Pentoxyfylline treatment did not affect mortality significantly (p=0.081). However, treatment with pentoxyfylline in those with severe alcoholic hepatitis with DF≥32, MELD score≥21 and GAHS ≥9 significantly reduced mortality (p=0.037, 0.025, 0.001 respectively). Baseline bilirubin, creatinine, urea, MELD score and GAHS were significantly high among the patients who succumbed to the disease as compared to those who survived. Conclusion: Patients with severe alcoholic hepatitis (Maddrey’s discriminant function ≥32; or MELD score ≥21: or GAHS ≥9), can be treated with pentoxifylline, as it is safe, economical, and appears to be useful in improving short term mortality, especially in the Indian scenario

Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia. Lifestyle contributes to the development and progression of both diseases. Although alcohol abstinence can cause regression of ALD, and weight loss can cause regression of NAFLD, many patients with these diseases develop cirrhosis. ALD and NAFLD account for nearly 30% of liver transplants performed in the United States. Patients receiving liver transplants for ALD or NAFLD have similar survival times as patients receiving transplants for other liver disorders. Although ALD and NAFLD recur frequently after liver transplantation, graft loss from disease recurrence after transplantation is uncommon. Cardiovascular disease and de novo malignancy are leading causes of long-term mortality in liver transplant recipients with ALD or NAFLD. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) represents a reversible syndrome associated with high short-term mortality, characterized by acute decompensation in patients with chronic liver disease and extrahepatic organ failure. Diagnosis and prognosis assessment is based on a newly developed diagnostic score, the Chronic Liver Failure Consortium Organ Failure score. Susceptibility to infections and systemic inflammation are typical triggers. The authors report a case in which a patient with alcohol-related cirrhosis was admitted to the hospital with acute decompensation and developed ACLF during hospitalization. This case led to an evaluation of the underlying process causing ACLF: infection versus acute alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

Background: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH). Methods: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis patients or healthy controls by ExoQuick. The exosomes were characterized by transmission electron microscopy and Western blot and enumerated with a Nanoparticle Tracking Analysis system. Firefly™ microRNA Assay was performed on miRNA extracted from mice sera. TaqMan microRNA assay was used to identify differentially expressed miRNAs in plasma of cohort of patients with AH versus controls followed by construction of receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of the candidates. Results: The total number of circulating EVs was significantly increased in mice after alcohol feeding. Those EVs mainly consisted of exosomes, the smaller size vesicle subpopulation of EVs. By performing microarray screening on exosomes, we found nine inflammatory miRNAs which were deregulated in sera of chronic alcohol-fed mice compared to controls including upregulated miRNAs: miRNA-192, miRNA-122, miRNA-30a, miRNA-744, miRNA-1246, miRNA 30b and miRNA-130a. The ROC analyses indicated excellent diagnostic value of miRNA-192, miRNA-122, and miRNA-30a to identify alcohol-induced liver injury. We further validated findings from our animal model in human samples. Consistent with the animal model, total number of EVs, mostly exosomes, was significantly increased in human subjects with AH. Both miRNA-192 and miRNA-30a were significantly increased in the circulation of subjects with AH. miRNA-192 showed promising value for the diagnosis of AH. Conclusion: Elevated level of EVs/exosomes and exosome-associated miRNA signature could serve as potential diagnostic markers for AH. In addition to the biomarker diagnostic capabilities, these findings may facilitate development of novel strategies for diagnostics, monitoring, and therapeutics of AH. [ABSTRACT FROM AUTHOR]

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

Background Dysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis ( AAH) and determine their utility to predict survival in severe AAH. Methods A prospective, case-control study design was used. Seventy-six patients hospitalized with severe AAH and 25 ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180 days after enrollment to determine the survival. Results AAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose-specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor-1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor- α ( TNF- α), interleukin ( IL)-6, IL-8, and IL-15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180 days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL-6 and TNF- α were associated with 180-day survival, and all 5 markers demonstrated accuracy by area under receiver-operator curve analysis. Serum IL-6 levels ≥38.66 pg/ml most precisely identified deaths in severe AAH. Patients with IL-6 ≥ 38.66 pg/ml had significantly decreased mean survival compared to those with lower levels. Conclusions AAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL-6 may be a useful biomarker to risk stratify severe AAH patients at the highest risk of mortality. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe. Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease. Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft. There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores. Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up. There is conflicting evidence to support a fixed period of pretransplant abstinence, although most units do follow this. Alcoholic hepatitis (AH) continues to be a contraindication for transplantation, however there is a need for further research in this field as a subset of patients with AH who do not respond to medical treatment, have high early mortality and could benefit from transplantation. One year, 3-year, and 5-year survival post-transplant is similar for both ALD and non-ALD recipients. The incidence of post-transplant rejection and retransplantation is also similar to other recipients. ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation. ALD patients are more prone to develop de-novo malignancy; this is attributed to the long term effect of alcohol, tobacco combined with immunosuppression. Post-transplant surveillance is important to detect early relapse to alcoholism, presence of de-novo malignancy and treat the same adequately. [ABSTRACT FROM AUTHOR]

Background & Aims: Adipose tissue is an important source of cytokines. Excess weight is an independent risk factor for steatosis, acute alcoholic hepatitis (AAH), and cirrhosis in patients with alcoholic liver disease (ALD). In this study, we investigated the role of adipose tissue in human ALD. Patients and methods: Fifty patients with ALD underwent liver and abdominal subcutaneous adipose tissue biopsies and supplied blood samples for the investigation of cytokine gene expression and secretion, as well as liver histology. Results: The levels of TNF-α and IL-10 in adipose tissue were higher in patients with AAH. IL-10 level in adipose tissue was also correlated with fibrosis score. TNF-α gene expression in adipose tissue was correlated with Maddrey score, blood C-reactive protein (CRP) concentration and liver IL-6 concentration. IL-6 production levels in the liver were higher in patients with AAH and correlated with AAH score, liver histological lesions, liver TNF-α concentration, Maddrey score, and blood CRP concentration. Plasma concentrations of soluble forms of TNF-receptor were correlated with inflammatory lesions in the liver, Maddrey score and fibrosis score. Conclusion: In patients with ALD, inflammation occurs not only in the liver, but also in the adipose tissue. Adipose tissue inflammation is correlated with the severity of pathological features in the liver. Our findings may account for the harmful interactions between body mass index, AAH, fibrosis, and cirrhosis in alcoholic patients. [Copyright &y& Elsevier]

Background/Aims: Severe alcoholic hepatitis is associated with high morbidity and short-term mortality. Corticosteroids are the only widely used therapy but established contraindications to treatment or the risk of serious side-effects limit their use. The perceived need for alternative treatments together with the theoretical benefits of anti-oxidant therapy triggered the design of a randomised clinical trial comparing these treatment modalities. Methods: One hundred and one patients were randomized into a clinical trial of corticosteroids or a novel antioxidant cocktail with a primary endpoint of 30-day mortality. Results: At 30 days there were 16 deaths (30%) in the corticosteroid treated group compared with 22 deaths (46%) in the antioxidant treated group (P=0.05). The odds of dying by 30 days were 2.4 greater for patients on antioxidants (95% confidence interval 1.0–5.6). A diagnosis of sepsis was made more frequently in the AO group (P=0.05), although microbiologically proven episodes of infection occurred more often in the CS group (P<0.01). The survival advantage for corticosteroid treated patients was lost at 1 year of follow-up (P=0.43). Conclusions: This study has shown that corticosteroids in the form of prednisolone 30mg daily are superior to a broad antioxidant cocktail in the treatment of severe alcoholic hepatitis. [Copyright &y& Elsevier]

A 69-year-old man was admitted to Hanawa Kousei Hospital with acute hepatitis attributed to alcohol consumption. His condition improved with conservative treatment. Computed tomography (CT) showed localized thickening of the colonic wall at the splenic flexure;carcinoembryonic antigen level was slightly elevated to 9.7 ng/mL. Colonoscopy (CS) showed an ulcerative lesion in the colonic splenic flexure. Ischemic colitis (IC) and type 4 colon cancer were suspected, but biopsy was not confirmatory. Malignancy could not be ruled out by contrast-enhanced CT;repeat CS showed circumferential stenosis of the colonic splenic flexure. Ischemic colitis was suspected based on changes between the first and second CS. Biopsy histopathology led us to diagnose stricture-type IC. Constipation, but not intestinal obstruction, occurred. Conservative treatment improved the stenosis. Excessive alcohol consumption may lead to IC;imaging studies may be useful to distinguish IC from colon cancer. Since most cases of ischemic colitis can be improved with conservative treatment, patients with stricture-type ischemic colitis may also be treated without surgery early on, with follow-up that includes careful, periodic imaging.