# S-adenosylmethionine treatment in alcoholic cirrhosis

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $365,634

## Abstract

Project Summary
Alcoholic cirrhosis is a leading cause of morbidity and mortality in the US. One of the key drivers in its
pathogenesis is the reduction in hepatic methionine adenosyltransferase 1A (MAT1A) expression resulting in
the reduction in hepatic S-adenosylmethionine (SAMe) levels. The reduction in SAMe level leads to several
adverse intracellular consequences, which include promoting the inflammatory cascades in immune cells such
as macrophages by lipopolysaccharides (LPS), oxidative stress and endoplasmic reticulum (ER) stress. There
is extensive preclinical evidence that support the use of SAMe in alcoholic liver disease but human trials using
SAMe in alcoholic cirrhosis have not provided clear evidence of efficacy. One large trial conducted in Spain by
one of the co-investigators (Dr. José Mato) showed SAMe treatment (1200 mg in divided doses for two years)
reduced the mortality of less advanced alcoholic cirrhotics but this was done as a post-hoc analysis and no
mechanism was investigated. A shorter (six months) trial done in the U.S. was negative but the dropout rate
was very high and abstinence was required to stay in the trial, which may have obscured the SAMe effect
since placebo group had marked improvement likely due to abstinence. This application involves two
academic centers in the United States (Cedars-Sinai Medical Center in Los Angeles and Indiana University
Hospital), a research institute in Spain (CIC bioGUNE), and NIAAA intramural liver research scientist (Dr. Bin
Gao) to examine SAMe in humans with alcoholic cirrhosis. We propose a randomized double-blind placebo
controlled trial to determine the efficacy of SAMe and its mechanistic effects in patients with alcoholic cirrhosis
in the real world setting by encouraging but not requiring abstinence. In addition, we aim to investigate the
underlying mechanism(s) of SAMe and use novel metabolomics to follow response to treatment and examine if
baseline metabolomics profiles correlate with response to SAMe. Two specific aims are proposed: Aim 1: we
will perform a randomized double-blind placebo controlled study between SAMe (1,200 mg/day given in two
divided dose) and placebo, in patients with alcoholic cirrhosis (Child class A and B) for 24 months. The
primary endpoint will be the mortality of any causes between groups. The key secondary endpoints are the
changes in intestinal permeability, serum endotoxin, markers of immune cell activations, and liver-specific
mortality. Complementary metabolomics using liquid-chromatography-mass spectrometry (LC-MS) and NMR
spectroscopy at baseline and NMR at the end of the trial will assess response to treatment and whether certain
profiles predict response to SAMe. Aim 2: we will determine the effect of SAMe treatment on oxidative stress,
and ER-stress induced mitochondrial DNA and cytochrome P450 2E1 enriched microparticles. Our application
is novel and relevant to an un-met need area of research where no proven effective treatments a...

## Key facts

- **NIH application ID:** 10022083
- **Project number:** 5U01AA026817-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Suthat Liangpunsakul
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,634
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022083

## Citation

> US National Institutes of Health, RePORTER application 10022083, S-adenosylmethionine treatment in alcoholic cirrhosis (5U01AA026817-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022083. Licensed CC0.

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