Treatment of non-alcoholic fatty liver disease

Figures & data

Table 1 Causes of non-alcoholic fatty liver disease

Nutritional	Drugs
Starvation	Glucocorticoids
Obesity*	Tamoxifen
Bariatric surgery	Amiodarone
Parenteral nutrition	Valproic acid
Celiac disease	Zidovudine
Metabolic	Didanosine
Insulin resistance*	Other
Dyslipidemia*	Inflammatory bowel disease
Fatty liver of pregnancy	Halogenated hydrocarbons
	Toxic mushrooms

* Most common causes.

Figure 1 The natural history of non-alcoholic fatty liver disease.

Figure 2 Unifying concept of the pathogenesis of NAFLD. ROS = reactive oxygen species, TG = triglycerides, VLDL = very low density lipoprotein, CYP = cytochrome P450.

Table 2 Types of NAFLD by histology and outcome

Category	Histology	Outcome
Type 1	steatosis only	non-progressive
Type 2	steatosis plus lobular inflammation	benign course
Type 3	steatosis, lobular inflammation and ballooning degeneration	NASH without fibrosis, may progress to cirrhosis
Type 4	steatosis, ballooning degeneration with Mallory bodies and/or fibrosis	NASH, may progress to cirrhosis

Table 3 Summary of interventions in NAFLD

Treatment	Ref	N	Study Design	ALT/AST	Histology		US/MRI
					Steatosis	Inflammation/fibrosis
Steatosis/Insulin Resistance
Weight loss	Huang et al 2005	23	CS	U	U	U	ND
Weight loss	Suzuki et al 2005	348	CS	I	ND	ND	ND
Weight loss	Petersen et al 2005	8	C	ND	I	ND	I
Bariatric surgery	Barker et al 2006	19	CS	ND	I	I	ND
Bariatric surgery	Mattar et al 2005	70	CS	ND	I	I	ND
Bariatric surgery	Dixon et al 2004	36	CS	ND	I	I	ND
Bariatric surgery	Clark et al 2005	16	CS	ND	I	I	ND
Bariatric surgery	Klein et al 2006	7	CS	U	I	U	U
Bariatric surgery	Mathurin et al 2006	185	CS	I	I	I	ND
Orlistat	Harrison et al 2004	10	CS	I	U	U	ND
Orlistat	Zelber-Sagi et al 2006	52	R, DB, PC	ND	ND	ND	I
Orlistat	Sabuncu et al 2003	12	CS	I	ND	ND	I
Sibutramine	Sabuncu et al 2003	13	CS	I	ND	ND	I
Pioglitazone	Promrat et al 2004	18	CS	I	I	I	I
Pioglitazone	Sanyal et al 2004	10	R, C	U	U	I	ND
Pioglitazone	Belfort et al 2006	55	R, B, PC	I	I	I	I
Rosiglitazone	Neuschwander-Tetri et al 2003	30	CS	I	I	I	I
Rosiglitazone	Ratziu et al 2006	63	R, DB, PC	I	ND	I	ND
Metformin	Marchesini et al 2001	14	C	I	ND	ND	ND
Metformin	Uygun et al 2004	17	R, C	I	U	U	I
Metformin	Schwimmer et al 2005	10	CS	I	ND	ND	ND
Atorvastatin	Horlander et al 2001	7	CS	U	U	I	ND
Atorvastatin	Kiyici et al 2003	27	CS	I	I	ND	I
Pravastatin	Rallidis et al 2004	5	CS	I	ND	I	ND
Rosuvastatin	Antonopoulos et al 2006	23	CS	I	ND	ND	ND
Gemfibrozil	Basaranoglu, Acbay et al 1999	23	R, C	I	ND	ND	ND
Apoptosis
Ursodiol	Laurin et al 1996	24	R, C	I	I	U	ND
Ursodiol	Kiyici et al 2003	27	CS	I	I	U	U
Ursodiol	Lindor et al 2004	80	R, B, PC	U	U	U	ND
Oxidative Stress/Inflammation: Antioxidants
Vitamin E	Lavine 2000	11	CS	I	ND	ND	ND
Vitamin E & C	Harrison et al 2003	23	R, DB, PC	U	ND	U	ND
Vitamin E	Bugianesi et al 2005	28	R, C	I	ND	ND	ND
Oxidative Stress/Inflammation: Pro-biotics/Pre-biotics
VSL#3	Loguercio et al 2005	22	CS	I	ND	ND	ND
Oxidative Stress/Inflammation: Anti-cytokines
Pentoxifylline	Adams et al 2004	20	CS	I	ND	ND	ND
Pentoxifylline	Satapathy et al 2004	18	CS	I	ND	ND	ND
Pentoxifylline	Lee et al 2006	11	R, DB, PC	U	ND	ND	ND
Oxidative Stress/Inflammation: Glutathione recursors
Betaine	Abdelmalek et al 2001	10	CS	I	U	I	ND
Betaine	Abdelmalek et al 2006	55	R, PC	U	ND	U	ND
Fibrosis
Losartan	Yokohama et al 2004, ^Citation2006	7	CS	I	U	I	ND

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; B, blinded; C, controlled; CS, case series; DB, double-blinded; I, improved; MRI, magnetic resonance imaging; ND, no data; PC, placebo-controlled; R, randomized; U, unchanged; US, ultrasound.

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