Berberine with Alfa Lipoic Acid (ALA) in Non Alcoholic Steato-hepatitis (NASH). A randomized double blinded placebo control trial. A Clinical pilot - The BANISH Trial

Objective: NASH is a globally challenging clinical morbidly; causing cirrhosis and liver cancer in due time with formidable cost burden. Therapeutic modalities have not yet been fully established. Anti‐oxidants and insulin sensitizers altering insulin resistance, inhibiting intra hepatic oxidative stress with inhibition of formation of free radicals and blocking inflammatory cytokines to prevent fibrosis. Berberine is a natural substance extracted from plants like Berberis which is found to up‐regulate intra hepatic pathways as insulin sensitizer, via GLP‐1 up regulation and Acyl palmotyl mechanism on fatty acid oxidation, induction of PPAR gama; all that blocks the terminal inflammatory Cytokine release TNF Alfa to prevent fibrosis that will prevent the End stage liver disease (ESLD) and liver cancer. Methods: Hundred and twenty patients (n=120) with NASH were recruited. Mean BMI 29.9% (29% to 32%) with 69 males and 51 females. Hispanic 46, Caucasians 34, Asian Pacific15, Black 11, Asian 14. Mean HbA1C 6.2 (5.9‐ 6.8), Mean HOMA 2.7 (2.1‐3.6), ALT 54 (38‐79), Triglyceride 287 (233‐344), LDL c 163 (129‐176), Leptin 63 (43‐98), Adiponectin 0.9 (0.1‐1.1), RBP 4 of 5.8 (4.0‐6.8), TNF Alfa 3.8 (2.1 4.8), IL 12 of 5.3 (3.9‐7.8), Serum Fibrotic and Steatotic scores were measured at 0 and then at 6 months. Daily allowed caloric content was 2,000 cal/ day, no documented exercise except daily activities at baseline for 6 months. All patients were divided into: Primary endpoints: ALT normalization, near normalization of HOMA Index and lipid panel Secondary endpoints: Normalization of Inflammatory markers eg. Leptin, TNF Alfa, IL 10, and reversal of fibrosis and steatosis score. Exclusion Criteria: Chronic hepatitis B and C, HIV, Other liver diseases, Alcohol consumption more than 30 grams a week, Diabetes, Drugs (Steroids, Tamoxifen) causing fatty liver or any lipodystrophic syndromes. Results:table Conclusion: All the study arms showed statistically significant (p<0.05) post interventional change except for Adiponectin in group A (p=0.09) Results (Table Presented).