Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Background Fibrosis impacts long-term outcomes among patients with nonalcoholic fatty liver disease (NAFLD). Due to well-documented flaws associated with liver biopsy, there has been a recent emphasis on prioritizing noninvasive testing over liver biopsy for the assessment of fibrosis. Methods A comprehensive systematic review and frequentist random effects network meta-analysis was performed among randomized controlled trials reporting pharmacologic intervention in NAFLD. The primary endpoint was the absolute change in liver stiffness measurement (LSM) via elastography. Secondary endpoints included changes in noninvasive serologic tests including APRI, fibrosis-4 index, NAFLD fibrosis score, enhanced liver fibrosis (ELF) and FibroTest (FibroSure in the USA). Results Forty-five randomized controlled trials enrolling 6932 patients were identified for this network meta-analysis. Across the primary endpoint, firsocostat, semaglutide, montelukast, cilofexor plus firsocostat, obeticholic acid and diacerein (change in LSM via vibration controlled transient elastography), in addition to lubiprostone and pemafibrate (change in LSM via magnetic resonance elastography) were found to be the most effective and statistically significant treatment interventions. Similarly, the following interventions were determined to be most effective as compared to placebo among secondary endpoints: saroglitazar, lubiprostone, and obeticholic acid (change in APRI); saroglitazar, semaglutide, firsocostat and cilofexor plus firsocostat (change in ELF); obeticholic acid and belapectin [change in FibroTest/FibroSure]. Conclusion This is the first systematic review and network meta-analysis reporting pharmacologic efficacy in the progression of fibrosis based on noninvasive testing among patients with NAFLD. Semaglutide, obeticholic acid, firsocostat, cilofexor plus firsocostat and lubiprostone were found to be the most effective treatments based on their consistent efficacy reproduced across multiple endpoints, both via elastography and noninvasive blood tests.