Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis.

BACKGROUND: Malnutrition is common in patients with alcohol-related liver disease and is associated with outcome in patients with alcoholic hepatitis. Trace elements (cobalt, copper, iron, selenium and zinc) are micronutrients essential for many cellular processes including antioxidant pathways. The prevalence and relevance of trace element deficiency is unknown in alcoholic hepatitis. AIM: To determine the prevalence of trace element deficiency and its association with clinical outcomes in patients with alcoholic hepatitis. METHODS: Serum was obtained from patients with alcoholic hepatitis, alcohol-related cirrhosis and healthy volunteers as part of clinical trials, cohort studies and a biobank. Trace element concentration was measured by inductively coupled plasma mass spectrometry. Association of trace element levels with development of infection within 90 days and mortality within 28 and 90 days was evaluated by multivariate logistic regression. RESULTS: Sera from 302 patients with alcoholic hepatitis, 46 with alcohol-related cirrhosis and 15 healthy controls were analysed for trace element concentration. The prevalence of zinc deficiency (85%) and selenium deficiency (67%) in alcoholic hepatitis was higher than in alcohol-related cirrhosis (72% [p=0.04] and 37% [p<0.001], respectively). Zinc, selenium, copper and chromium were significantly different between groups. Iron deficiency was a predictor of development of infection within 90 days. Zinc deficiency was a predictor of mortality within 28 and 90 days. CONCLUSION: Trace element deficiency in patients with alcoholic hepatitis is highly prevalent and associated with infection and mortality. Supplementation with selected trace elements may improve clinical outcomes in this patient group but further insight is required of their biological and clinical effects.

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.

Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in the treatment of alcoholic hepatitis: randomized-controlled multicenter study.

BACKGROUND: Probiotics might reduce gut-derived microbial lipopolysaccharide (LPS) by restoring bowel flora in patients with alcoholic hepatitis (AH). We evaluated the therapeutic effects of probiotics in patients with AH. PATIENTS AND METHODS: Between September 2010 and April 2012, 117 patients (probiotics 60 and placebo 57) were prospectively randomized to receive the 7 days of cultured Lactobacillus subtilis/Streptococcus faecium (1500 mg/day) or placebo. All patients were hospitalized and were not permitted to consume alcohol for the 7 days of the study. Liver function test, proinflammatory cytokines, LPS, and colony-forming units by stool culture were examined and compared after therapy. RESULTS: In both groups, the mean levels of aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin, and prothrombin time were significantly improved after 7 days of abstinence. In the probiotics group (baseline and after), albumin (3.5 ± 0.7 and 3.7 ± 0.6 g/dl, P=0.038) and tumor necrosis factor-α (121 ± 244 and 71 ± 123 pg/ml, P=0.047) showed differences. In addition, the number of colony-forming units of Escherichia coli was significantly reduced (435 ± 287 and 168 ± 210, P=0.002). In the placebo group, the level of LPS (1.7 ± 2.8 and 2.0 ± 2.7 EU/ml) was significantly increased. In the intergroup comparison, significant differences in the levels of tumor necrosis factor-α (P=0.042) and LPS (P=0.028) were observed between the groups. CONCLUSION: Immediate abstinence is the most important treatment for patients with AH. In addition, 7 days of oral supplementation with cultured L. subtilis/S. faecium was associated with restoration of bowel flora and improvement of LPS in patients with AH.

Anti-inflammatory function of ginsenoside Rg1 on alcoholic hepatitis through glucocorticoid receptor related nuclear factor-kappa B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is the dried root of Panax ginseng C.A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Pharmacological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rg1 is the most pharmacological active one. AIM OF THE STUDY: Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms. MATERIALS AND METHODS: C57BL/6 mice were given oral consumption of 6g/kg alcohol 1h after treated with Rg1 (10, 20 and 40mg/kg) or dexamethasone (1mg/kg) for 9 consecutive days. Biochemical analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. RESULTS: According to our data, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in alcohol-intoxicated mouse livers. In addition, changes of GR related NF-κB pathway, including phospho-IκB-α, were also modulated to normal levels. CONCLUSION: This study demonstrates that Rg1 might promote GR mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis.

Relative and combined effects of chronic alcohol consumption and HCV infection on serum zinc, copper, and selenium.

In alcoholic hepatitis, Kupffer cells are activated by intestinal gram-bacteria, leading to cytokine production and free radicals release, which, enhancing cytokine secretion, create a positive feedback loop which contributes to liver inflammation. Free radicals also damage the liver in chronic hepatitis C virus (HCV) infection, a condition frequently associated to alcohol consumption. In both situations, activity of antioxidant enzymes and of its cofactors zinc (Zn), selenium (Se), and copper (Cu) is important. This study was performed to assess the relative and combined effects of chronic alcoholism and HCV infection on serum Se, Zn, and Cu, and its relation with serum malondialdehyde (MDA) and tumor necrosis factor-α, interferon-γ, and interleukins (IL) 4, 6, and 8, in 19 HCV- alcoholic patients, 12 HCV+ alcoholic patients, nine HCV+ non-alcoholic patients, and 20 controls. Serum Zn and Se were lower in both HCV+ and HCV- alcoholic patients, whereas serum Cu was lower in HCV+ individuals. Serum Zn and Se were related to liver function derangement. MDA levels were higher in alcoholics, but no relation was observed between trace elements and MDA or cytokines, so that our results do not support a relevant role of the analyzed trace elements in the pathogenesis of chronic liver disease.

[Effect of the phytohepatoprotective agent maxar on the hepatic morphofunctional status in patients with chronic hepatitis]. / Vliianie fitogepatoprotektora maksara na morfofunktsional'noe sostoianie pecheni u bol'nykh khronicheskim gepatitom.

The paper provides evidence for that as compared with the well-known drug carsil, the new Russian phytohepatoprotective agent maxar has a therapeutic efficiency in patients with mild and moderate chronic hepatitis (CH) of viral and alcoholic etiology. Maxar has been found to produce a more pronounced hepatoprotective effect, to a greater extent, in CH of alcoholic etiology.

[The efficacy of vitogepat and sirepar in combination with karsil in chronic liver lesions]. / Effektivnost' vitogepata i sirepara v sochetanii s karsilom pri khronicheskom porazhenii pecheni.

It has been shown in experiments on white rats that chronic (for one month) intoxication with CCl4 and C2H5OH results in liver injury. It manifests by activation of aminotransferases (ALT, AST) and alkaline phosphatase in blood serum, initiation of lipid peroxidation, depletion of the liver pool of reduced glutathione, and suppression of bile production. The liver preparations (sirepar and vitohepat) reduce hepatotoxicity of the poisons in question. The use of vitohepat and sirepar in combination with carsil potentiated hepatoprotective and antioxidative activity of the liver preparations.

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition.

Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis.