scholarly journals Emerging medical therapies for severe alcoholic hepatitis

2020 ◽  
Vol 26 (4) ◽  
pp. 686-696
Author(s):  
David Tornai ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Alcoholic Hepatitis ◽  
Intestinal Barrier ◽  
Immune Defense ◽  
Intestinal Barrier Function ◽  
Recommended Treatment ◽  
Severe Alcoholic Hepatitis ◽  
Elevated Bilirubin ◽  
End Stage ◽  
Underlying Inflammation

Severe alcoholic hepatitis (AH) is an acute and often devastating form of alcohol-associated liver disease. Clinically, AH is characterized by elevated bilirubin, model for end stage liver disease scores >20, and nonspecific symptoms that are caused by underlying inflammation, hepatocyte injury, and impaired intestinal barrier function. Compromised immune defense in AH contributes to infections, sepsis and organ failure. To date, corticosteroids are the only recommended treatment for severe AH, however it does not provide survival benefits beyond 1 month. Recent preclinical and early clinical studies in AH aided understanding of the disease and presented opportunities for new therapeutic options targeting inflammation, oxidative stress, liver regeneration and modification of intestinal microbiota. In this comprehensive review, we discuss promising preclinical results and ongoing clinical trials evaluating novel therapeutic agents for the treatment of severe AH.

scholarly journals Markers of Intestinal Permeability Are Rapidly Improved by Alcohol Withdrawal in Patients with Alcohol-Related Liver Disease

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1659
Author(s):  
Finn Jung ◽  
Katharina Burger ◽  
Raphaela Staltner ◽  
Annette Brandt ◽  
Sebastian Mueller ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Damage ◽  
Alcohol Withdrawal ◽  
Barrier Function ◽  
Binding Protein ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fatty Acid Binding ◽  
Liver Health ◽  
Related Liver Disease

Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients.

Fatty liver disease in children

2011 ◽  
Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Liver Injury ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Hepatitis ◽  
Alcoholic Fatty Liver ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Alcoholic Fatty Liver Disease

Demographics 406Pathophysiology 406Differential diagnoses 407Presenting features 407Investigation 408Management 409Fatty liver disease is now increasingly recognized in children, particularly in the setting of obesity.The term non-alcoholic steatohepatitis (NASH) was first coined in 1980 by Ludwig to describe a pattern of liver injury in adults in which the liver histology was consistent with alcoholic hepatitis, but in whom significant alcohol consumption was denied. NASH can be considered as part of a broader spectrum of non-alcoholic fatty liver disease that extends from simple steatosis through steatohepatitis that is characterized by the potential to progress to fibrosis, cirrhosis and subsequent end stage liver disease....

scholarly journals Treatment of Decompensated Alcoholic Liver Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
John Menachery ◽  
Ajay Duseja
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Alcoholic Hepatitis ◽  
Nutritional Therapy ◽  
Decompensated Cirrhosis ◽  
Chimeric Antibody ◽  
Necrosis Factor Alpha ◽  
Therapeutic Goals ◽  
Definitive Therapy ◽  
Severe Alcoholic Hepatitis

Alcoholic liver disease (ALD) is a spectrum ranging from simple hepatic steatosis to alcoholic hepatitis and cirrhosis. Patients with severe alcoholic hepatitis can have clinical presentation almost similar to those with decompensated cirrhosis. Scoring with models like Maddrey discriminant function, a model for end-stage liver disease, Glasgow alcoholic hepatitis score, and Lille model are helpful in prognosticating patients with ALD. One of the first therapeutic goals in ALD is to induce alcohol withdrawal with psychotherapy or drugs. Most studies have shown that nutritional therapy improves liver function and histology in patients with ALD. The rationale for using glucocorticoids is to block cytotoxic and inflammatory pathways in patients with severe alcoholic hepatitis. Pentoxifylline, a tumor necrosis factor alpha (TNFα) suppressor, and infliximab, an anti-TNFαmouse/human chimeric antibody, has been extensively studied in patients with alcoholic hepatitis. Liver transplantation remains the definitive therapy for decompensated cirrhosis/alcoholic hepatitis despite the issues of recidivism, poor compliance with postoperative care, and being a self-inflicted disease.

scholarly journals Mediterranean Diet and NAFLD: What We Know and Questions That Still Need to Be Answered

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2971 ◽  
Author(s):  
Maria Corina Plaz Torres ◽  
Alessio Aghemo ◽  
Ana Lleo ◽  
Giorgia Bodini ◽  
Manuele Furnari ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mediterranean Diet ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
End Stage Liver Disease ◽  
Recommended Treatment ◽  
Clinical Scenarios ◽  
Proven Efficacy ◽  
End Stage ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is expected to become the leading cause of end-stage liver disease worldwide over the next few decades. In fact, NAFLD encompasses different clinical scenarios, from the simple accumulation of fat (steatosis) to steatohepatitis (NASH), NASH-cirrhosis, and cirrhosis complications. In this context, it is fundamental to pursue strategies aimed at both preventing the disease and reducing the progression of liver fibrosis once liver damage is already initiated. As of today, no pharmacological treatment has been approved for NAFLD/NASH, and the only recommended treatment of proven efficacy are life-style modifications, including diet and physical exercise pointing at weight loss of 5%–7%. Different dietetic approaches have been proposed in this setting, and in this review, we will discuss the evidence regarding the efficacy of the Mediterranean Diet as a treatment for NAFLD. In particular, we will report the effects on liver-related outcomes.

scholarly journals Fenretinide Improves Intestinal Barrier Function and Mitigates Alcohol Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Han Tang ◽  
Marta Melis ◽  
Karen Mai ◽  
Lorraine J. Gudas ◽  
Steven E. Trasino
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Intestinal Permeability ◽  
Kupffer Cells ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Protein Levels ◽  
Tnf Α ◽  
Alcohol Liver Disease

Alcohol liver disease (ALD) is a major cause of liver-related mortality globally, yet there remains an unmet demand for approved ALD drugs. The pathogenesis of ALD involves perturbations to the intestinal barrier and subsequent translocation of bacterial endotoxin that, acting through toll-like receptor 4 (TLR4), promotes hepatic inflammation and progression of ALD. In the present study we investigated the ability of fenretinide (Fen) [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid with known anti-cancer and anti-inflammatory properties, to modulate intestinal permeability and clinical hallmarks of ALD in a mouse model of chronic ethanol (EtOH) exposure. Our results show that EtOH-treated mice had reductions in mRNA and protein expression of intestinal tight junction proteins, including claudin one and occludin, and increases in intestinal permeability and endotoxemia compared to pair-fed mice. Also, EtOH-treated mice had marked increases in hepatic steatosis, liver injury, and expression of pro-inflammatory mediators, including TNF-α, and TLR4-positive macrophages, Kupffer cells, and hepatocytes in the intestines and liver, respectively. In contrast, EtOH + Fen-treated mice were resistant to the effects of EtOH on promoting intestinal permeability and had higher intestinal protein levels of claudin one and occludin. Also, EtOH + Fen-treated mice had significantly lower plasma levels of endotoxin, and reductions in expression of TNF-α and TLR4 positive macrophages, Kupffer cells, and hepatocytes in the intestine and liver. Lastly, we found that EtOH + Fen-treated mice exhibited major reductions in hepatic triglycerides, steatosis, and liver injury compared to EtOH-treated mice. Our findings are the first to demonstrate that Fen possesses anti-ALD properties, potentially through modulation of the intestinal barrier function, endotoxemia, and TLR4-mediated inflammation. These data warrant further pre-clinical investigations of Fen as a potential anti-ALD drug.

scholarly journals Alcoholic Hepatitis and Liver Transplantation

2017 ◽  
Vol 1 (1) ◽  
pp. 3-4
Author(s):  
Gianni Testino ◽  
Silvia Leone
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Alcoholic Hepatitis ◽  
Short Term ◽  
Term Survival ◽  
Alcohol Relapse ◽  
Severe Alcoholic Hepatitis ◽  
Long Time ◽  
Short Term Survival

Some authors affirm that early liver transplant (LT) provides excellent short-term survival in patients with severe alcoholic hepatitis (SAH) (1–4) and similar rates of alcohol relapse compared to patients with 6 months of abstinence. We agree with the choice of not excluding patients who manifest their decompensation with bleeding and infections (common complications of SAH) and patients with psychiatric comorbidities. Data from the literature have stated for a long time that the approach to patients with alcoholic liver disease (ALD) should be changed with no ethical or technical preconceptions. The reasons in favor of this change are as follows:

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