Hypothetical treatment of patients with non-alcoholic steatohepatitis: Potential impact on important clinical outcomes

Background & Aims Currently, standard of care (SOC) treatment for NASH is limited to lifestyle modifications. Drug regimens are being evaluated currently. We assessed the impact of a short-term hypothetical treatment on clinical outcomes of NASH. Methods Markov models estimated differences in outcomes between SOC and 2 hypothetical NASH treatments (A and B). We modelled 10 000 50-year-old biopsy-proven NASH patients over lifetime horizon. Health states included NASH with fibrosis (F1-F3), cirrhosis, hepatocellular carcinoma, liver transplant and mortality. Fibrosis Regression Factor (FRF) variable modelled the probability of 1-3 stage fibrosis improvement with treatment. Annual probability of treatment (ATP) ranged from 10%-70%. Treatment success was defined as regression to fibrosis, whereas failure was defined as progression to stages beyond cirrhosis. In treatment-A, successful treatment was followed by a maintenance regimen which stopped disease progression. After a successful treatment-B, patients remained at risk of disease progression. Differences in outcomes were calculated between both treatments and SOC models. We conducted a probabilistic sensitivity analysis. Results At 10% to 70% ATP, treatment-A averts 353 to 782 liver transplants and 1277 to 2381 liver-related deaths relative to SOC. Treatment-B averts 129 to 437 liver transplants and 386 to 1043 liver-related deaths. Sensitivity analysis shows our model is robust in estimating liver-related mortality and LTs averted, but is sensitive when estimating QALYs gained. Conclusions With a small annual probability of treatment and FRF = 1, a 2-year treatment followed by maintenance of histologic improvement for patients would be highly beneficial relative to short-term treatment alone.