Association of Adjuvant S Adenosyl Methionine with Ursodeoxycholic Acid in Alcoholic Hepatitis: An Exploratory Prospective Observational Study
Deepak Chinagi *
Department of General Medicine, BLDE DU Shri B. M. Patil Medical College, Hospital and Research Centre, Vijayapura–586101, India.
Shruti Sheelin
Department of General Surgery, BLDE DU Shri B. M. Patil Medical College, Hospital and Research Centre, Vijayapura–586101, India.
Shashank Jogur
Skan Research Trust, Bengaluru-560027, Karnataka, India.
Nivedita Patil
BLDEA’s SSM College of Pharmacy and Research Centre, Vijayapura-586101, India.
*Author to whom correspondence should be addressed.
Abstract
Background: Alcoholic hepatitis (AH) is a serious medical condition with limited treatment options and significant short-term mortality risk. While S‑adenosyl methionine (SAMe) and ursodeoxycholic acid (UDCA) individually exhibit hepatoprotective properties, their combination remains inadequately evaluated in AH.
Aim: This exploratory study aimed to assess the association of adding SAMe to UDCA on biochemical and clinical outcomes in patients with AH.
Methodology: In this prospective observational cohort study conducted at a tertiary healthcare facility in India, 100 patients with AH (50 per group) were enrolled. Group A received SAMe (800–1200 mg/day) in addition to UDCA (15–20 mg/kg/day), whereas Group B received UDCA alone for 12 weeks. All patients received standard medical care, including corticosteroids when indicated (Maddrey's discriminant function >32) and nutritional support. The primary outcome was biochemical response at week 12, defined as either a ≥50% reduction in serum bilirubin from baseline or a serum bilirubin level <2 mg/dL. Secondary outcomes included MELD score improvement (≥3-point reduction), 90-day mortality, and adverse events.
Findings: Baseline characteristics were balanced between groups. The primary outcome was achieved in 60% of the SAMe + UDCA group versus 40% of the UDCA monotherapy group (absolute difference: 20%, 95% CI: 1–39%; p = 0.045; number needed to treat = 5). MELD score improvement (≥3 points) was observed in 56% versus 36% (p = 0.04; adjusted OR = 2.45, 95% CI: 1.05–5.72). Mean bilirubin reduction was 58.2% versus 41.5% (p = 0.036). Ninety-day mortality was 10% versus 16% (p = 0.38). Adverse event rates were comparable between groups (24% versus 16%; p = 0.31), with no unexpected safety signals.
Summary: The addition of SAMe to UDCA was associated with improved biochemical response and MELD scores in patients with AH, without excess adverse events. However, because of the observational, non-randomised design, these findings should be interpreted with caution, as they are subject to potential confounding and selection bias and do not establish causality. A definitive randomised controlled trial is warranted to confirm these hypothesis-generating results.
Keywords: Alcoholic hepatitis, S-adenosyl methionine, ursodeoxycholic acid, biochemical response, bilirubin, MELD score, adjunctive therapy, hepatoprotection, prospective observational study, liver disease