Systemic treatment of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally, with 15% of cases arising on a background of non-alcoholic fatty liver disease (NAFLD). NAFLD is a heterogenous condition ranging from fatty liver to cirrhosis and is itself a growing global problem, with estimated worldwide prevalence of 50% in 2040. Pathophysiology of NAFLD-HCC is not well understood, there are no dedicated screening programs, and there have been no clinical studies of anti-cancer treatments in this population specifically. However, the NAFLD-HCC population appears different than other aetiologies - patients tend to be older, diagnosed at more advanced stages, have more comorbidities, and overall worse prognosis. Understanding of best treatment options for this group of patients is an urgent unmet clinical need. This narrative review discusses NAFLD-HCC pathophysiology and systemic treatment, and offers suggestions for future directions in this therapy area.