Any treatment for NASH should aim at improving NASH-related mortality and reducing progression to cirrhosis or HCC. Currently, only lifestyles interventions are recommended for the treatment of NASH, since no drugs have yet been tested in phase III trials and approved by regulatory authorities.
1) Lifestyle interventions
The close relationship between unhealthy lifestyle and NAFLD makes lifestyle correction mandatory in all patients, with the potential not only to improve liver disease, but also hyperglycaemia, atherogenic dyslipidaemia and high blood pressure. Relatively small amounts of weight loss reduce liver fat and improve hepatic insulin resistance.
2) Bariatric surgery
Bariatric surgery is an efficient method to achieve significant weight loss, reverse insulin resistance, and reduce cardiovascular risk and long-term mortality. A meta-analysis on the effect of bariatric surgery in NAFLD revealed that the pooled proportion of patients with improvement or resolution was 91.6% for steatosis, 81.3% for steatohepatitis, 65.5% for fibrosis, and that 69.5% of patients experienced complete resolution of NASH. Nevertheless, the AASLD practice guidance states that while bariatric surgery can be considered in otherwise eligible patients with NAFLD or NASH, it is premature to consider it as an established option for the treatment of NASH.
3) Pharmacotherapy: lack of approved therapies
European and U.S. guidelines recommend that pharmacotherapy should be reserved for patients with biopsy-proven NASH, particularly those with significant fibrosis (stage F2 and higher), but also those with early-stage NASH who are at high risk of disease progression. As yet, no drugs have been approved for treatment of NASH and thus any recommendation for pharmacological therapy is off-label. However, the EASL-EASD-EASO guideline states that pioglitazone or vitamin E or their combination may be used for NASH.