A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP

Abstract

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential.

Conflict of interest statement

Disclosure statement:

Teodoro Bottiglieri reports having been the chairman of the advisory board for Methylation Sciences Inc., holding stock options in Methylation Sciences Inc., Scientific Advisor to Gnosis S.p.A. and Nestle Health Sciences, Pamlab Inc. and having received research funding from Nestle Health Sciences, Pamlab Inc., distributor of B vitamins as a medical food.

The Principle Investigator and all other Investigators did not have financial conflicts of interest.

©2015 American Association for Cancer Research.

Figures

Figure 1

Flow chart for patient enrollment, randomization, and completion of the study.

Figure 2

AFP levels between Week 0 and Week 30. Serum alpha-fetoprotein (AFP), as reported by Wako Laboratories, for subjects who had AFP at every time point from baseline (Week 30) to end of follow-up (Week 30). Error bars represent standard errors.

Figure 3

Change in AFP by site and treatment arm. Serum AFP increased between Week 0 and Week 24 among subjects randomized to placebo (control) at all sites. At four of the five sites, serum AFP decreased among subjects randomized to SAMe. However, AFP did not decrease among subjects receiving SAMe at the site with the largest number of subjects enrolled (LBVA).

Figure 4

Serum SAMe. (a) Serum SAMe at all study time points among subjects randomized to SAMe or placebo shows that SAMe increased significantly among subject receiving SAMe, but not among subjects receiving placebo, and that serum SAMe level returned to baseline by Week 30. (b) Serum SAMe levels increased between Week 0 and Week 24 among subject randomized to SAMe at all study sites, but did not increase among subjects randomized to placebo.

Figure 4

Serum SAMe. (a) Serum SAMe at all study time points among subjects randomized to SAMe or placebo shows that SAMe increased significantly among subject receiving SAMe, but not among subjects receiving placebo, and that serum SAMe level returned to baseline by Week 30. (b) Serum SAMe levels increased between Week 0 and Week 24 among subject randomized to SAMe at all study sites, but did not increase among subjects randomized to placebo.