Active clinical trials for "Hepatitis, Alcoholic"

The pathogenesis of the alcoholic liver disease (ALD) is a complex interplay of various etiopathological factors other than direct alcohol toxicity. These factors include inflammation & oxidative stress, dysbiosis, intestinal hyperpermeability, and endotoxemia. Dietary fats not only improve nutritional status in ALD but specific properties of saturated fats (SF) have the potential to favourably modulate these causative factors. This project has two parts, in the animal study 10 groups of murine model of alcoholic hepatitis (AH) would be given SF in the form of Desi Ghee and in the human study patients with AH would be randomized into two groups, one with SF ( Desi Ghee) and the other with usual unsaturated fat (cooking oil). In all effect of SF on gut microbiota, hepatic steatosis, TLR-4 expression, serum adiponectin, endotoxin levels, intestinal tight junction proteins and inflammatory markers in murine models of AH, along with hepatic morbidity & lipid profile, in patients with ALD would be studied.

Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of S-adenosylmethionine (SAMe) levels, which can affect numerous important cellular processes. SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear. A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2-year survival in those with less advanced liver disease. However, important changes in methionine metabolism and histological changes were not included in the study. Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease.

35% of Acute Alcoholic Hepatitis patients (AAH) do not respond to corticoids and died after 6 months. Chronic alcohol abuse depletes glutathione in the hepatocytes and makes the latter more sensitive to excessive TNFα levels. Re-establishment of a stock of antioxidants by administration of a precursor (N-acetyl cysteine, NAC) in combination with corticoids (C) could make the hepatocytes more resistant and improve survival. The investigators' study's primary endpoint was improvement of survival at 6 months. The secondary endpoints were survival at 1 and 3 months, tolerance of NAC and a drop in blood bilirubin levels at D7

In Mexico, alcoholic liver disease is the fourth cause of mortality (INEGI). Patients with severe alcoholic hepatitis have a high mortality at 28 days and 6 months, patients receiving standard therapy with prednisone that are non responders (Lille> 0.45) have a survival of 53.3 ± 5.1 % to 28 days. At present, there is not a completely effective treatment for non responders patients, with a high mortality, so it is necessary to look for other therapeutic strategies. The omega-5 fatty acid (punicic acid) has been considered a powerful antioxidant, it is an agonist of PPAR gamma, has been shown to reduce lipid peroxidation, and restore levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. It has also been shown to inhibit the expression of proinflammatory cytokines (such as IL6, IL8, IL23, IL12 and TNFalpha) through PPAR and modulation delta. The objective of this study is to evaluate the effect of Omega 5 fatty acid on inflammatory markers and antioxidant-oxidant balance markers in patients with severe alcoholic hepatitis treated with prednisone. HYPOTHESIS. Omega 5 fatty acid being a PPARgamma agonist reduces lipid peroxidation and protein damage, restoring reduced glutathione levels, as well as decreasing proinflammatory cytokines, in patients with Severe Alcoholic Hepatitis treated with prednisone and supplementation with fatty acid Omega 5.

Alcoholic hepatitis is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol. The pathogenesis is not completely understood. Patients who are severely affected present with subacute onset of fever, hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal hemorrhage). However, milder forms of alcoholic hepatitis often do not cause any symptoms. Alcoholic hepatitis usually persists and progresses to cirrhosis if heavy alcohol use continues. If alcohol use ceases, alcoholic hepatitis resolves slowly over weeks to months, sometimes without permanent sequelae but often with residual cirrhosis. F-652 is a recombinant fusion protein containing human interleukin 22 (IL-22) and human Immunoglobulin G2 (IgG2)-Fc produced in CHO cells in serum-free culture. F-652 under development is intended to treat patients with graft vs host disease (GvHD) after bone marrow transplantation, and acute alcoholic hepatitis (AAH), a severe form of alcoholic liver disease (ALD). Both GvHD and AAH are diseases with unmet medical need. The current investigational new drug (IND) application is to conduct a phase Ia clinical study in GvHD patients to evaluate the safety and pharmacokinetic profile, and biomarkers of F-652 treatment by intravenous infusion (IV). IL-22 is a member of the IL-10 family of cytokines which control bacterial infection, homeostasis, and tissue repair. IL-22 may be used to treat patients with ALD because of its antioxidant, anti-apoptotic, anti-steatotic, anti-microbial, and proliferative effect that have been demonstrated in various experimental systems.

Severe Alcoholic hepatitis (SAH), defined by modified Maddrey's Discriminant Function (DF) ≥32, is associated with significant morbidity and mortality. Of the various treatment modalities evaluated for treatment of SAH, corticosteroids have been the most extensively studied. Five out of 13 RCTs, and four out of 5 meta-analysis have shown a survival benefit with corticosteroids, especially in patients with DF ≥32 and/ or encephalopathy.However, the role of corticosteroids in SAH still remains somewhat controversial. Corticosteroid therapy is not considered the ideal option by all authors because their beneficial effect seems to be confined to a highly selected minority group in which the inhibitory effect of corticosteroids on liver inflammation is not outweighed by side effects such as weakened defence against infections, anti-anabolic effects, and possible ulcer promoting effects. Also corticosteroids are contraindicated in patients with renal failure, gastro-intestinal (GI) bleed, pancreatitis and active sepsis. Therefore, there have been constant efforts to evaluate new therapies for SAH. In a recent trial, combination of glucocorticoids plus N-acetylcysteine was found to improve one month survival in patients with SAH, compared with glucocorticoids alone. However the 6 month survival was not different in both groups. Human Colostrum (HC) and Bovine Colostrum (BC) are rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that colostrum components, Lactroferrin, immunoglobulin and growth factor benefits physically active person and in treatment of autoimmune disorders. It is used for the treatment of a wide variety of gastrointestinal conditions, including non-steroidal anti-inflammatory drug-induced gut injury, H pylori infection, immune deficiency related diarrhea as well as infective diarrhea. The guidelines by American College of Gastroenterology and other authors have suggested that a combination of CS and other drugs, which have different mechanisms of action, may be more beneficial for reducing mortality in SAH. Hence, we plan to conduct this pilot study to investigate the efficacy of a novel combination of corticosteroids, and Bovine colostrum in the treatment of SAH.

Hypothesis: Oral administration of hyperimmune bovine colostrum enriched with anti-LPS antibodies will reduce endotoxemia, and improve pathophysiological and clinical parameters related to severe alcoholic hepatitis (SAH). IMM 124-E is safe in subjects with severe alcoholic hepatitis being treated with steroids. Aim: To perform a phase 2a "proof of concept" placebo-controlled, dose-ranging study of Imm 124-E (hyperimmune bovine colostrum enriched with IgG anti-LPS) in subjects with severe AH on steroids.

The primary objective of this study is to evaluate the safety and tolerability of selonsertib (GS-4997) in combination with prednisolone versus prednisolone alone in participants with severe alcoholic hepatitis (AH).

Acute alcoholic hepatitis (AAH) is the most severe form of alcoholic liver disease (ALD) and is associated with a high risk of dying in the short term. Corticosteroids are generally recommended in patients with severe AAH, but its use is still controverted and contraindicated in case of active infection or gastrointestinal bleeding. Therefore, alternative therapeutic options are needed.Ethanol consumption results in the depletion of endogenous antioxidant capabilities and patients with ALD have evidence of antioxidant deficiencies.Due to its effects on glutathion stores restoration and as such the limitation of the oxidative stress and its good tolerance and safety profile, N-acetylcysteine (NAC) is an attractive agent for the treatment of AAH.In this context, we hypothesized that NAC might be beneficial in severe AAH.

The treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge for clinicians involved in the management of severe alcoholic liver disease. In patients with Maddrey function higher than 32, compelling evidence from data has shown that corticosteroids improve short-term survival. However, novel strategies or molecules are required in light of the fact that approximately 40 % of patients continue to die at 6 months. A double-blinded randomized controlled trial of 101 patients has showed that Pentoxifylline improves survival of patients with severe AH, as compared to placebo. In terms of mechanisms, the effect of pentoxifylline is related to prevention of hepatorenal function whereas corticosteroids induce an early improvement in liver function. When considering these differences of mechanisms, many clinicians suggest that the addition of pentoxyfilline to corticosteroids is an attractive option that needs to be tested in patients with severe AH.