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Can we reliably predict response to corticosteroid treatment in severe alcoholichepatitis? 29881814 2018 11 14 2471-254X 2 6 2018 Jun Hepatology communications Hepatol Commun Can we reliably predict response to corticosteroid treatment in severe alcoholichepatitis? 625-627 10.1002/hep4.1191 Chokshi Shilpa S Chief Scientific Officer Institute of Hepatology Foundation for Liver Research London United Kingdom. eng Editorial 2018 04 27 United States Hepatol Commun 101695860 2471-254X 2018 03 29
Baseline urine metabolic phenotype in patients with severe alcoholichepatitis and its association with outcome Severe alcoholichepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra-high performance liquid
AlcoholicHepatitis: Lost in Translation Alcoholichepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholichepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable (...) advances have been made in this area recently, with the goal of generating a mouse model of alcoholichepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholichepatitis. In addition, we will review the basic mechanisms of alcoholichepatitis
Prediction of histologic alcoholichepatitis based on clinical presentation limits the need for liver biopsy The clinical presentation of alcoholichepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte (...) characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070-1084).
Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK. This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcoholdependence, damage (...) to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot
Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease The aim of this study was to investigate the role of osteopontin (OPN) in hematopoietic stem cell (HPSC) mobilization to the liver and its contribution to alcoholic liver disease (ALD). We analyzed young (14-16 weeks) and old (>1.5 years) wild-type (WT) littermates and global Opn knockout (Opn-/- ) mice for HPSC mobilization to the liver. In addition (...) , WT and Opn-/- mice were chronically fed the Lieber-DeCarli diet for 7 weeks. Bone marrow (BM), blood, spleen, and liver were analyzed by flow cytometry for HPSC progenitors and polymorphonuclear neutrophils (PMNs). Chemokines, growth factors, and cytokines were measured in serum and liver. Prussian blue staining for iron deposits and naphthol AS-D chloroacetate esterase staining for PMNs were performed on liver sections. Hematopoietic progenitors were lower in liver and BM of young compared
Interaction between the patatinâ€like phospholipase domainâ€containing protein 3 genotype and coffee drinking and the risk for acute alcoholichepatitis Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated (...) with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholichepatitis (AH) in a well-characterized cohort of subjects from the Translational Research and Evolving AlcoholicHepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee
Severe AlcoholicHepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase Alcoholichepatitis (AH) is an acute inflammatory liver disease with poor prognosis. Infections in AH are difficult to detect and contribute to short-term mortality. Intrahepatic cholestasis and elevated alkaline phosphatase levels are also associated with worse outcomes. This report describes an uncommon presentation of severe AH.
Role of gp91phox in hepatic macrophage programming and alcoholic liver disease Hepatic macrophages (MΦs) are important in the development and progression of alcoholic liver disease (ALD). This study investigates the role of gp91phox (nicotinamide adenine dinucleotide phosphate oxidase 2) in the severity of ALD and specifically in regulating hepatic MΦ efferocytic capability and the subsequent reprogramming associated with resolution of inflammation. After 4 weeks of ethanol feeding, more severe (...) ALD developed in gp91phox-/- mice than in wild-type (WT) C57Bl/6J mice, evidenced by increased liver injury and inflammation. This phenomenon was not sex dependent, and thus the majority of experiments were performed with female mice. While total hepatic MΦ numbers did not differ between genotypes, hepatic infiltrating MΦs (IMs) were slightly more numerous in gp91phox-/- mice, and both IMs and resident Kupffer cells displayed enhanced proinflammatory and reduced tissue-restorative programming
In Patients With Severe AlcoholicHepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA Infections are common in patients with severe alcoholichepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection
Current Management of AlcoholicHepatitis and Future Therapies Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholichepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End (...) -stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have
Intensive Enteral Nutrition Is Ineffective for Patients With Severe AlcoholicHepatitis Treated With Corticosteroids Severe alcoholichepatitis (AH) is a life-threatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH.We enrolled 136 heavy consumers of alcohol
Combining Data From Liver Disease Scoring Systems Better Predicts Outcomes of Patients With AlcoholicHepatitis Several models have been used to determine prognoses of patients with alcoholichepatitis. These include static systems (the Maddrey discriminant function; age, bilirubin, international normalized ratio, creatinine [ABIC] score; and model for end-stage liver disease [MELD] score) and dynamic models (the Lille model). We aimed to combine features of all of these models to develop (...) a better method to predict outcomes of patients with alcoholic hepatitis.We collected data from several databases of patients with severe alcoholichepatitis treated with corticosteroids in France and the United Kingdom to create a model to predict patient survival (derivation cohort, n = 538 patients). We compared the performances of 3 joint-effect models (Maddrey+Lille, MELD+Lille, and ABIC+Lille) to determine which combination had the best prognostic value, based on known patient outcomes. The model
Prednisolone or pentoxifylline for alcoholichepatitis. Alcoholichepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholichepatitis, but uncertainty about their benefit persists.We conducted a multicenter, double-blind, randomized trial (...) with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholichepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone
Acute alcoholichepatitis and cellular Th1 immune responses to alcohol dehydrogenase. Alcoholichepatitis is characterised by florid hepatic inflammation, liver failure, and death within 28 days in 35% of patients. We recently showed proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T-helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH-specific cellular (...) immunity is present in alcoholic hepatitis.PBMCs were collected from 15 patients with alcoholichepatitis (modified Maddrey's discriminant function >32), nine with alcohol-related cirrhosis (long-term alcohol abstinence), and three healthy controls. 25 overlapping peptides, spanning the human ADH β1 subunit, were constructed. Proliferation to ADH peptides (1 × 10(5) cells per well, cultured with 10 mM peptides for 7 days) was assessed by (3)H-thymidine incorporation. A stimulation index (SI) of 2·5
Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease. The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic fibrosis in people with liver diseases. Transient elastography is a non-invasive method (...) for assessing and staging hepatic fibrosis.To determine the diagnostic accuracy of transient elastography for diagnosis and staging hepatic fibrosis in people with alcoholic liver disease when compared with liver biopsy. To identify the optimal cut-off values for differentiating the five stages of hepatic fibrosis.The Cochrane Hepato-Biliary Group Controlled and Diagnostic Test Accuracy Studies Registers, The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded (last
A histologic scoring system for prognosis of patients with alcoholichepatitis There is no histologic classification system to determine prognoses of patients with alcoholichepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality.We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH (...) and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the AlcoholicHepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis.The degree of fibrosis, degree of neutrophil
groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07).In patients with alcoholichepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been (...) Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholichepatitis: a randomized clinical trial. Prednisolone or pentoxifylline is recommended for severe alcoholichepatitis, a life-threatening disease. The benefit of their combination is unknown.To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1
Is There Really Any Role For Steroids In Acute AlcoholicHepatitis? Is There Really Any Role For Steroids In Acute AlcoholicHepatitis? – Clinical Correlations Search Is There Really Any Role For Steroids In Acute AlcoholicHepatitis? December 8, 2011 7 min read By Keri Herzog, MD Faculty Peer Reviewed The patient is a 48-year-old male with a history of heavy alcohol use (he drinks about 1 pint of vodka daily) who presented to the hospital when he noticed that he had become increasingly (...) ? Alcoholichepatitis (AH) was a term that was first used in 1961, however there were many antecedent descriptions in the medical literature of patients who . Evidence exists suggesting that an increased risk of cirrhosis and AH is due, not only to daily ingestion of large amounts of alcohol (greater than 10-20g/day for women and 20-40g/day for men) , but with contributions from genetic and environmental factors. Chronicalcohol consumption has been demonstrated to cause hepatocyte dysfunction