Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

Table 1 Prospective and retrospective studies of the risk of cardiovascular mortality in patients with nonalcoholic fatty liver disease diagnosed by liver biopsy and/or by ultrasonography

Ref.	Study design	NAFLD patients	Diagnosis of NAFLD	Mean duration follow-up (yr)	Result
Matteoni et al[26], 1999	Retrospective, Hospital-based	132	Histology	18.0	No adjustment made. Higher all-cause, liver-related mortality but no difference in CVD mortality (NASH vs simple steatosis)
Dam-Larsen et al[21], 2004	Retrospective, Hospital-based	109	Histology	16.7	Analysis performed by gender. No difference in all-cause and liver-related or CVD mortality (simple steatosis vs general population)
Adams et al[20], 2005	Retrospective community-based	420	US and/or histology	7.6	Matched for gender, age and country Higher all-causae, liver-related and CVD mortality (CVD is the second cause of death by frequency) in NAFLD patients (especially cirrhosis)
Targher et al[12], 2005	Prospective case-control, Hospital-based	248/21031	US	5.0	NAFLD was independently associated with increased nonfatal CVD and CVD mortality
Ekstedt et al[5], 2006	Retrospective, Hospital-based	129	Histology	13.7	Matched for gender, age and country Higher all-cause, liver-related and CVD mortality (NASH but no simple steatosis vs general population)
Hamaguchi et al[28], 2007	Prospective, community-based	312/16372	US	5.0	NAFLD was independently associated with increased risk of nonfatal CVD events
Targher et al[27], 2007	Prospective, Hospital-based	1421/21031	US	6.5	NAFLD was independently associated with increased risk of nonfatal CVD events and CVD mortality
Haring et al[29], 2009	Prospective, community-based	2490/41603	US and altered GGT	7.3	NAFLD was independently associated with increased risk of all-cause and CVD mortality in men
Rafiq et al[22], 2009	Retrospective, Hospital-based	173	Histology	13.0	No adjustments made Higher liver-related mortality, but no difference in overall mortality (NASH vs simple steatosis)
Söderberg et al[23], 2010	Retrospective, Hospital-based	118	Histology	18.0	Matched for gender, age and year Higher all-cause, liver-related and CVD mortality (NASH but no simple steatosis vs general population)
Lazo et al[32], 2011	Prospective, population-based (third NHANES study population 1988-1994)	2089/113714	US	14.3	Independent increased risk of CVD but no increased risk in all-cause, liver-related and CVD mortality
Stepanova et al[33], 2012	Prospective, population-based (third NHANES study population 1988-1994)	2492/113714	US	14.3	Independent increased risk of CVD but no increased risk in all-cause, liver-related and CVD mortality
Treeprasertsuk et al[31], 2012	Prospective, community-based	309	US, CT, MRI, and or Histology	11.5	Higher 10-Year CVD risk (NAFLD vs general population)
Kim et al[34], 2013	Prospective, population-based (third NHANES study population 1988-1994)	4083/111544	US and NAFLD Fibrosis Score	14.5	US-Defined NAFLD was not associated with overall mortality. NAFLD with advanced fibrosis was independently associated with overall mortality (majority of deaths were due to CVD)
Stepanova et al[25], 2013	Retrospective, Population-based	289	Histology	6.25	No adjustments made Higher risk of liver-related mortality in NASH than non-NASH. NAFLD and type II diabetes highest risk for overall and liver-related mortality

¹Patients with type 2 diabetes;

²Participants of health checkup program;

³West Pomerania population;

⁴United Stated adult population. US: Ultrasonography; CT: Computed tomography; MRI: Magnetic resonance imaging; CVD: Cardiovascular disease; NAFLD: Nonalcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis.