Table 2.

Evidence in favor of the poor prognosis of NAFL patients (5 out of 6 with paired liver biopsies).

Paired Liver Biopsy	# of Patients	Endpoints	Type of Study	Observations	Reference #
yes	52	disease progression	prospective longitudinal study	20–30% of patients with simple steatosis had fibrosis progression; patients received lifestyle advice and metabolic monitoring	[31]
yes	108	factors predicting progression on liver biopsy		progression to NASH in 44% of patients with baseline NAFL	[32]
yes	70	progression of simple steatosis and mild inflammation to NASH and fibrosis	retrospective	ballooning in 16 of the 25 patients with simple steatosis, and bridging fibrosis in 6	[16]
no	1515 (liver biopsy cohort)	hepatic fat accumulation has a causal role in determining liver damage and insulin resistance	mendelian randomization approach	long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease	[33]
yes	411 NAFLD - 150 NAFL - 261 NASH	clinical risk factors associated with progression	systematic review and meta-analysis	Liver fibrosis progresses in NAFL and NASH	[34]
yes	103	histological course of patients with sequential liver biopsies	retrospective	2 out of 3 patients with steatosis develop NASH; 4 out of 4 patients with steatosis and mild inflammation develop NASH; low number of patients	[35]
no	10,568	mortality in NAFLD	retrospective matched cohort study	increased risk of mortality for all histological stages 1.71-times increased risk in NAFL	[36]

Abbreviations: NAFLD, non-alcoholic fatty liver disease; NAFL, non-alcoholic fatty liver; NASH, non-alcoholic steatohepatitis.