1. Understand the pathogenesis of NASH based on the substrate overload lipotoxic liver injury (SOLLI) paradigm and how it predicts points of intervention.
2. Understand how lifestyle modification and drugs currently in clinical trials fit into this paradigm.
3. Understand that NASH is likely multifactorial in its underlying causes and these causes may differ in different patients.
There are currently no approved treatments for NASH. Lifestyle modification with a focus on healthy eating habits, weight loss when appropriate and regular exercise the mainstays of treatment but these are difficult for many patient to achieve and even more difficult to sustain. Bariatric surgery is effective for some patients but is not universally appropriate or accessible. Pharmacological treatment is currently being evaluated in clinical trials. Potential treatments can be broadly categorized into modulators of energy intake and disposal, modulators of adipose tissue inflammation and lipolysis, inhibitors of hepatic fatty acid synthesis (de novo lipogenesis), modulators of hepatocellular injury, inflammation, repair and cell death, and finally, modulators of fibrogenesis. Many of the treatments under evaluation focus on the downstream events, but effective modulation of energy intake (eg, modulators of satiety and eating behaviors) and modulators of energy efficiency and disposal may have the added benefit of addressing obesity and the other components of the metabolic syndrome. Effective treatment of NASH in the future will likely rely on a personalized approach based on our understanding of the underlying genetic, epigenetic and environmental contributors in each patient. For now, lifestyle modification plus an empiric approach to new therapies as they become available will likely be the general approach until we get smart enough to know who will respond to which therapies.
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