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Gastroenterology Jul 2015
Topics: Hepatitis, Alcoholic; Humans; Research
PubMed: 26008859
DOI: 10.1053/j.gastro.2015.05.015 -
Revista de Gastroenterologia de Mexico... 2020Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response,...
Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.
Topics: Hepatitis, Alcoholic; Humans; Mexico
PubMed: 32532534
DOI: 10.1016/j.rgmx.2020.04.002 -
Turkish Journal of Medical Sciences Nov 2020Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well... (Review)
Review
Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well as for certain early-stage liver tumors. Currently, the greatest challenge facing LT is the simple fact that there are not enough adequate livers for all the potential patients that could benefit from LT. Despite efforts to expand the donor pool to include living and deceased donors, organ shortage is still a major problem in many countries. To solve this problem, the use of marginal liver grafts has become an inevitable choice. Although the definition of marginal grafts or criteria for expanded donor selection has not been clarified yet, they are usually defined as grafts that may potentially cause primary nonfunction, impaired function, or late loss of function. These include steatotic livers, older donors, donors with positive viral serology, split livers, and donation after cardiac death (DCD). Therefore, to get the best outcome from these liver grafts, donor-recipient selection should be vigilant. Alcohol- related liver disease (ALD) is one of the most common indications for LT in Europe and North America. Traditionally, LT for alcoholic liver disease was kept limited for patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Besides, the initial results of early liver transplantation (ELT) without waiting for 6 months of abstinence period are satisfactory in severe alcoholic hepatitis (SAH). It will be important to take care of these patients from a newer perspective.
Topics: Age Factors; End Stage Liver Disease; HIV Infections; Hepatitis, Alcoholic; Humans; Liver Transplantation; Obesity; Tissue Donors; Tissue and Organ Procurement
PubMed: 32222125
DOI: 10.3906/sag-2002-17 -
Gastroenterology Apr 2021We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly...
BACKGROUND & AIMS
We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism.
METHODS
We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells.
RESULTS
Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes.
CONCLUSIONS
Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.
Topics: Acute Kidney Injury; Adaptation, Physiological; Animals; Cell Dedifferentiation; Energy Metabolism; Europe; Female; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Glucose; Glucose-6-Phosphate; Glycogen; Hep G2 Cells; Hepatitis, Alcoholic; Hepatocytes; Hexokinase; Humans; Liver; Male; Metabolome; Metabolomics; Middle Aged; Rats, Wistar; Transcriptome; United States; Rats
PubMed: 33309778
DOI: 10.1053/j.gastro.2020.12.008 -
Journal of Medicine and Life Jun 2013Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less...
Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey's Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT.
Topics: Female; Glucocorticoids; Hepatitis, Alcoholic; Humans; Liver Diseases, Alcoholic; Liver Transplantation; Male
PubMed: 23904876
DOI: No ID Found -
Clinical and Molecular Hepatology Dec 2018Severe 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... (Review)
Review
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.
Topics: Alcohol Dehydrogenase; Alcoholism; Hepatitis, Alcoholic; Humans; Liver Transplantation; Pentoxifylline; Phosphodiesterase Inhibitors; Severity of Illness Index
PubMed: 30360030
DOI: 10.3350/cmh.2018.0044 -
Cells Feb 2020Alcohol use disorder is associated with a wide array of hepatic pathologies ranging from steatosis to alcoholic-related cirrhosis (AC), alcoholic hepatitis (AH), or... (Review)
Review
Alcohol use disorder is associated with a wide array of hepatic pathologies ranging from steatosis to alcoholic-related cirrhosis (AC), alcoholic hepatitis (AH), or hepatocellular carcinoma (HCC). Biomarkers are categorized into two main categories: biomarkers associated with alcohol consumption and biomarkers of alcoholic liver disease (ALD). No ideal biomarker has been identified to quantify the degree of hepatocyte death or severity of AH, even though numerous biomarkers have been associated with AH. This review provides information of some of the novel and latest biomarkers that are being investigated and have shown a substantial association with the degree and severity of liver injury and inflammation. Importantly, they can be measured noninvasively. In this manuscript, we consolidate the present understanding and prospects of these biomarkers; and their application in assessing the severity and progression of the alcoholic liver disease (ALD). We also review current and upcoming management options for AH.
Topics: Animals; Biomarkers; Female; Hepatitis, Alcoholic; Humans; Male
PubMed: 32106390
DOI: 10.3390/cells9030524 -
Alimentary Pharmacology & Therapeutics Nov 2018Intestinal microbiota plays an important role in bile acid homeostasis.
BACKGROUND
Intestinal microbiota plays an important role in bile acid homeostasis.
AIM
To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease.
METHODS
In this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed.
RESULTS
Plasma levels of total bile acids (84.6 vs 6.8 μmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 μmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were lower. Cir_sAH patients had a different microbiota than Cir_noAH patients: at the phyla level, the abundance of Actinobacteria (9 vs 1%, P = 0.01) was higher and that of Bacteroidetes was lower (25 vs 40%, P = 0.04). Moreover, the microbiota of Cir_sAH patients showed changes in the abundance of genes involved in 15 metabolic pathways, including upregulation of glutathione metabolism, and downregulation of biotin metabolism.
CONCLUSIONS
Patients with Cir_sAH show specific changes of the bile acid pool with a shift towards more hydrophobic and toxic species that may be responsible for the specific microbiota changes. Conversely, the microbiota may also alter the bile acid pool by transforming primary to secondary bile acids, leading to a vicious cycle.
Topics: Adult; Aged; Bile Acids and Salts; Diarrhea; Dysbiosis; Feces; Female; France; Gastrointestinal Microbiome; Hepatitis, Alcoholic; Homeostasis; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Prospective Studies
PubMed: 30144108
DOI: 10.1111/apt.14949 -
Toxins Feb 2021Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further...
Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between and , meanwhile negative association was found between and in alcoholic hepatitis patients.
Topics: Adult; Aged; Bacteria; Case-Control Studies; Dysbiosis; Feces; Female; Fungi; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Fungal; Hepatitis, Alcoholic; Humans; Intestines; Male; Metagenome; Metagenomics; Middle Aged; Ribotyping
PubMed: 33672887
DOI: 10.3390/toxins13020143 -
Clinics in Liver Disease Aug 2016Alcoholic hepatitis is an acute form of alcoholic liver disease with variable severity that develops in patients who usually have a history of prolonged and recent... (Review)
Review
Alcoholic hepatitis is an acute form of alcoholic liver disease with variable severity that develops in patients who usually have a history of prolonged and recent alcohol abuse. The diagnosis is clinical and depends on history, physical examination, and laboratory derangements. Liver biopsy is diagnostic but not universally performed, and noninvasive diagnostic modalities are under development. Scoring systems are used to assess severity of disease, predict mortality, and guide decisions for initiation of specific therapies. The natural history and long-term outcomes of alcoholic hepatitis, including recurrence, progression to cirrhosis, and mortality, vary and depend partly on abstinence from alcohol use.
Topics: Alcohol Abstinence; Biopsy; Disease Progression; Female; Hepatitis, Alcoholic; Humans; Male; Models, Biological; Prognosis; Recurrence; Risk Factors; Severity of Illness Index
PubMed: 27373612
DOI: 10.1016/j.cld.2016.02.008