Histopathologic Changes in Alcoholic Liver Disease Patients Treated with S-Adenosyl-L-Methionine: An In-Depth Look at Data from a Double-Blinded, Randomized, Placebo-Controlled Trial
Mary D Le, Elena Enbom, Peter K Traum, Samuel W French, Valentina Medici, Charles H Halsted. Harbor-UCLA Medical Center, Torrance, CA; Univesity of California Davis, Sacramento, CA; University of California Davis, Davis, CA
Background: S-adenosyl-L-methionine (SAMe) is a methyl donor for methyltransferase reactions that regulates the synthesis of glutathione, a main cellular antioxidant. SAMe is also involved in regulation of hepatocyte growth, differentiation, and death. Studies have shown that SAMe prevents alcohol-induced liver injury in rats by reducing liver lipid peroxidation and cell proliferation. We evaluated pre- and post-treatment liver biopsies in patients to assess any changes after SAMe treatment.
Design: Liver biopsies of thirteen randomized patients with ALD (six in the treatment arm and seven in the placebo arm) were evaluated at baseline and at 24 weeks following treatment with SAMe. Patients received 1.2 g of SAMe or placebo by mouth daily. Liver biopsies were histopathologically scored using accepted criteria for the following categories: fat, inflammation, necrosis, fibrosis, percent fibrosis per square field (morphometric fibrosis), tunnel formation, smooth muscle actin, Kupffer cells, polymorphonuclear leukocytes (PMN), lipogranules, lymphocytes, balloon cell formation (ghost cells), Mallory Denk bodies, and duct metaplasia.
Results: Although the treatment and placebo groups started at different baselines in some of the parameters, we observed that there was a statistically significant increase in the histopathologic score of morphometric fibrosis in the SAMe treated group. There was surprisingly a decrease in balloon cells and fibrosis in the placebo group but not the SAMe treated group. The scores of PMN infiltration, inflammation, and lipogranules trended up with treatment with SAMe, and the sores of necrosis, SMA, and Kupffer cells trended down in both the treated and placebo group, however, the p values were greater than 0.05.
Conclusions: In this study the treatment with SAMe caused an increase in morphometric fibrosis, whereas without treatment, the placebo group had a decrease in balloon cell formation and fibrosis. This highlights that stopping consumption of alcohol will also decrease balloon cell formation and fibrosis and differs from the previous human study that showed no significant difference in SAMe treated patients compared to placebo. Our study shows when alcohol consumption is stopped and SAMe is given, there may be a worsening of some liver pathology features.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 153, Tuesday Afternoon