(31) Effect of Obeticholic Acid in Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) Patients: A Systematic Review and Meta-Analysis
Background: The prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is high and it has become the fast emerging global public health issue. As there is no approved pharmacological treatment for NAFLD/NASH, we evaluated the effect of obeticholic acid (OCA) in NAFLD/NASH patients which is an approved drug for treating other liver disease (i.e primary biliary cholangitis).
Objectives: To investigate the efficacy and safety of OCA in NAFLD and NASH patients.
Methods: We have included patients aged >18 years, irrespective of gender and diagnosed with NAFLD/ NASH. We excluded observational and non-randomized studies; case reports; case series; reviews; animal studies; in vitro studies; abstracts and book chapters. The primary outcome was to evaluate the effect of OCA on liver enzymes, lipoproteins, liver histology and body weight. The secondary outcome was to evaluate the adverse events occured due to OCA therapy in NAFLD and NASH patients. Subgroup analysis was also performed based on the dose to check the better therapeutic dose of OCA. Statistical analysis Meta-analysis was performed using Review manager software. The data obtained were expressed as standardized mean difference (SMD) for continuous data and risk ratio (RR) along with 95%CI for binary outcomes. Heterogeneity was assessed using Chi- square (I2) statistical test.
Results: ALT and AST were significantly improved in OCA treatment group when compared with placebo group [SMD = -0.29, 95% CI: (-0.38 to -0.19); p < 0.00001; I2=15%] and [SMD = -0.22, 95% CI: (-0.32 to -0.13); p < 0.00001; I2=48%] respectively. ALP levels were significantly elevated in OCA treatment group [SMD = 0.66, 95% CI: (0.48 to 0.85); p < 0.00001; I2=37%]. The overall outcome of total cholesterol was found to be significantly elevated in OCA treatment group when compared with the placebo group [SMD = 0.52, 95% CI: (0.09 to 0.94); p = 0.02; I2=75%]. Triglyceride levels and LDL levels have shown non-significant changes in the patients who received OCA when compared with those who did not receive OCA treatment [SMD = -0.12, 95% CI: (-0.30 to 0.06); p = 0.20; I2=0%] and [SMD= 1.60, 95% CI: (-0.12 to 3.32); p = 0.07; I2=99%]. Furthermore, HDL levels were significantly reduced in OCA treatment group when compared with the placebo group [SMD = -0.49, 95% CI: (-0.89 to -0.08); p =0.02; I2=72%]. Improvement in steatosis, hepatocellular ballooning, lobular inflammation and fibrosis was significantly higher in the patients who received OCA when compared with those who did not receive OCA [RR: 1.25, 95% CI: (1.03 to 1.52); p = 0.02; I2=53%], [RR: 1.39, 95% CI: (1.17 to 1.64); p = 0.0001; I2=0%], [RR: 1.23, 95% CI: (1.07 to 1.40); p = 0.002; I2=29%] and [RR: 1.85, 95% CI: (1.44 to 2.38); p < 0.00001; I2=0%] respectively. A significant reduction in body weight was observed in OCA treatment group when compared with the placebo group [SMD = -0.23, 95% CI: (-0.33 to -0.12); p < 0.0001; I2=0%] .
Conclusions: This study signifies that OCA is preferable in showing favorable outcomes related to liver biochemistry, liver histology in NASH/NAFLD patients and concluded that 25 mg dose of OCA was found to be more potential in terms of the better therapeutic response. However, it has also shown some adverse events. Further research investigating the long-term effect of different doses of OCA in a large sample size is requisite.
