The natural history of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease has a variable prognosis which is predictable to an extent based on the presence or absence of histological liver injury. Past studies have determined a number of clinical and laboratory parameters which predict greater severity on the initial biopsy, although all of these measures have limitations and biopsy remains the gold standard at this time. For patients with early stage non-alcoholic steatohepatitis (NASH), about one third will progress to stage 3 or 4 (cirrhosis) over 5-10 years. Thus, early-stage NASH constitutes one of the groups most likely to benefit from treatments now undergoing investigation. Among those who progress to NASH cirrhosis, about 25% will develop major complications of portal hypertension within 3 years. In contrast, non-NASH fatty liver tends to be stable over time, although there appears to be an increased cancer risk in all forms of fatty liver, albeit greater in NASH compared to non-NASH fatty liver. Interestingly, the cause of death among patients with NASH is more often due to cardiovascular disease or non-liver malignancy than cirrhosis. However, the accelerated risk of cirrhosis in this group compared to cardiovascular disease suggests that this picture is likely to change in the foreseeable future. Meanwhile, the relationship between these comorbidities will increasingly lead to patients with both coronary disease or malignancy and NASH-related cirrhosis presenting clinicians with a very challenging set of problems in coming years.