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Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.

ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury.To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy.The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ?40 U/L and by ?30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis.ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (?2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (?2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E.Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss.NCT00063622.

SUBMITTER: Hoofnagle JH

PROVIDER: S-EPMC3775262 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.

Hoofnagle J H JH Van Natta M L ML Kleiner D E DE Clark J M JM Kowdley K V KV Loomba R R Neuschwander-Tetri B A BA Sanyal A J AJ Tonascia J J

Alimentary pharmacology & therapeutics 20130529 2

<h4>Background</h4>Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury.<h4>Aim</h4>To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy.<h4>Methods</h4>The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reass ...[more]

PMID: 23718573

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Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

Project description:The extent to which vitamin E (alpha-tocopherol) intake early in childhood is associated with alanine aminotransferase (ALT) level later in childhood is unknown. The objective of this research is to test the hypothesis that higher alpha-tocopherol intake during early childhood is associated with lower odds of elevated ALT levels during mid-childhood and to examine how body mass index (BMI) influences these relationships. We studied 528 children in Project Viva. Mothers reported child dietary intake at early childhood visits (median 3.1 years) using a validated food frequency questionnaire. At mid-childhood (median 7.6 years), we collected child blood and anthropometric data. The main outcome was elevated sex-specific mid-childhood ALT level (?22.1 U/L for female children and ?25.8 U/L for male children). In multivariable logistic regression models, we assessed the association of energy-adjusted alpha-tocopherol intake with ALT levels, adjusting for child age, sex, race/ethnicity, diet, and age-adjusted sex-specific BMI z-score at mid-childhood. Among children in this study, 48% were female, 63% were non-Hispanic white, 19% were non-Hispanic black, and 4% were Hispanic/Latino. Mean alpha-tocopherol intake was 3.7 ± 1.0 mg/day (range, 1.4-9.2) at early childhood. At mid-childhood, mean BMI z-score was 0.41 ± 1.0 units and 22% had an elevated ALT level. In multivariable-adjusted logistic regression models, children with higher early childhood vitamin E intake had lower odds of elevated mid-childhood ALT (adjusted odds ratio [AOR], 0.62; 95% confidence interval [CI], 0.39, 0.99) for quartiles 2-4 compared with the lowest quartile of intake. Findings persisted after accounting for early childhood diet (AOR, 0.62; 95% CI, 0.36, 1.08) and were strengthened after additionally accounting for mid-childhood BMI z-score (AOR, 0.56; 95% CI, 0.32, 0.99). CONCLUSION:In this cohort, higher early childhood intake of alpha-tocopherol was associated with lower odds of elevated mid-childhood ALT level. (Hepatology 2018;67:1339-1347).

Dataset Information

Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.

Publications

Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.

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