[Elsevier] New Approach Combination-Dosed Therapy for Nonalcoholic Steatohepatitis Versus Vitamin E: A Randomized Controlled Trial Copy

Purpose: There is currently no US Food and Drug Administration-approved remedy for nonalcoholic steatohepatitis (NASH). The present study evaluated the efficacy of N-acetyl cysteine (NAC) and rosuvastatin (RSV) compared with conventional vitamin E in patients with NASH.

Methods: This study was designed as a parallel, double-blinded, randomized controlled trial. Ninety patients who met the eligibility criteria were enrolled in this study. Subsequently, 45 patients were allocated to each group as follows: group 1 reported consistent administration of vitamin E 400 IUⓇ (PHARCO-Pharmaceuticals) twice daily over a duration of 6 months. Group 2 included patients with NASH who received NAC, Gemacysteine 300 mgⓇ (GEMA-Pharma) at 1200 mg twice daily, along with RSV, Crestor 20 mgⓇ (AstraZeneca). To achieve the study's objective, FibroScanⓇ examination of liver tissue and fibrosis scores, as well as tests for liver aminotransferases, lipid profile, glycemic parameters, and hepatic and renal functions, besides health-related quality of life using the Short-Form 36 were evaluated before and after 6 months of treatment.

Findings: In group 1, a statistically significant decrease in the mean value of steatosis was observed after 6 months by 6.05% (P = 0.017), whereas treated group 2 exhibited a reduction of 16.49% (P = 0.001). Group 2 reported a statistically significant decrease in the mean fibrosis value of approximately 19.5% (P = 0.001). Fibrosis-4 Index score's significance stated a reduction in the mean values within treatment group 2, with decreases of 51.70%. MACK-3 score which is a combination of homeostatic model assessment, aspartate aminotransferase, and cytokeratin-18, exhibited a notable reduction in mean values within treatment group 2 by 25.06% (P = 0.001). Concerning biological markers, malondialdehyde, both groups reported significant reductions in mean values of 11.90% (P = 0.006) and 27.43% (P = 0.001), respectively. Group 2 exhibited substantial reductions in mean levels of all biological markers: NOD-like receptor-associated protein 3 inflammasome decreased by 24.40%, tumor necrosis factor-α by 9.64%, tissue inhibitor of metalloproteinases 1 by 10.28%, N-terminal propeptide of procollagen type III by 14.58%, cytokeratin-18 by 23.44%, and fibroblast growth factor-21 by 15.08% (P < 0.05), whereas group 1 did not demonstrate significant differences. Group 2 has substantial improvement in various metabolic parameters and health-related quality of life with accepted safety profile parameters.

Implications: Patients in group 2 treated with the combination of NAC/RSV exhibited tolerability and efficacy in improving liver steatosis and fibrosis, besides metabolic parameters, indicating a new combination approach to the management of NASH.

Clinicaltrials: gov identifier: NCT06105060.