Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update

Table 1 Studies evaluating the effect of hypolipidaemic drug treatment on non-alcoholic fatty liver disease or non-alcoholic steatohepatitis

Ref.	Year	n of all	n with NAFLD/NASH	Method of diagnosis of NAFLD/NASH	Drug	Dose/d	Duration of treatment	Results-main findings
Gómez-Domínguez et al[107]	2006	25	22	ALT levels	Atorvastatin	10-80 mg	12 mo	Normalization of ALT and lipid profile
Hyogo et al[108]	2008	31	31	Biopsy-proven NASH	Atorvastatin	10 mg	24 mo	Liver steatosis and NAFLD activity score were significantly improved; in 4 increase in fibrosis stage.
Kimura et al[109]	2010	45	45	Biopsy-proven NASH	Atorvastatin	10 mg	12 mo	The steatosis grade and NAFLD activity score were significantly improved.
Nelson et al[110]	2009	16	10	Biopsy-proven NASH	Simvastatin	20 mg	12 mo	No statistically significant improvement in serum ALT, hepatic steatosis, necroinflammatory activity or stage of fibrosis within or between groups.
Athyros et al[111]	2010	1600	437	ALT levels -ultrasonography	Atorvastatin	24 mg	3 yr	Improved ALT, AST, GGT, AP, and ultrasonography. Reduced cardiovascular events more than those without NAFLD (P = 0.007).
Hyogo et al[112]	2011	20	13	Biopsy-proven NASH	Pitavastatin	2 mg	12 mo	Improved NAFLD activity score and fibrosis stage In 54% and 42%, respectively, improved
								histology, however, 3/13 patients progression of fibrosis.
Hyogo et al[113]	2012	42	42	Biopsy-proven NASH	Atorvastatin	10 mg	12 mo	Improved NAFLD activity score, normalization of liver enzymes and TNF-α, and increased liver to spleen density ratio.
Nakahara et al[114]	2012	19	19	Biopsy-proven NASH	Rosuvastatin	2.5 mg	24 mo	NAFLD activity score and fibrotic stage did not change significantly in all patients, they were improved in 33.3% and 33.3% of patients, and stayed stable in 33.3% and 55.6%, respectively.
Athyros et al[115]	2011	1123	326	ALT levels -ultrasonography	Atorvastatin	20-30 mg	42 mo	Improved ALT, AST, GGT, AP, and ultrasonography. Eradicated cardiovascular events in high dose group.
Tikkanen et al[116]	2013	8863	1081	ALT levels	Atorvastatin	80 mg	5 yr	Normalization of liver enzyme values and greater CVD benefit with atorvastatin in the elevated ALT group.
					Simvastatin	20-40 mg
Kargiotis et al[117]	2014	6	6	Biopsy-proven NASH	Rosuvastatin	10 mg	12 mo	Complete resolution of NASH in 5 patients. Normalization of liver enzyme values in all patients.
					Monotherapy
Park et al[122]	2011	45	45	Biopsy-proven NASH	Ezetimibe	10 mg	24 mo	Steatosis grade, necroinflammatory grade, ballooning, and NAFLD activity score were significantly improved from baseline. Fibrosis stage was not significantly changed.
Zhu et al[124]	2008	72	72	ALT levels -ultrasonography	n-3 PUFA	6 g	6 mo	ALT was reduced but other liver enzymes not. Ultrasonography improved in 53% of patients

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AP: Alkaline phosphatase; CVD: Cardiovascular disease; GGT: Gamma-glutamyltransferase.