Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning?

Table 1 Common causes of secondary liver steatosis

Macrovesicular steatosis	Microvesicular steatosis
Alcohol consumption	Reye’s syndrome
Parenteral nutrition	Acute fatty liver of pregnancy
Hepatitis C	HELLP syndrome
Starvation/Malnutrition	Genetic metabolic diseases (e.g., LCAT deficiency, cholesterol ester storage disease)
Abetalipoproteinemia	Heat stroke
Lipodystrophy	Drugs (valproate, anti-retroviral drugs)
Celiac disease
Wilson’s disease
Drugs (e.g., corticosteroids, tamoxifen, amiodarone)

HELLP syndrome: Hemolysis, elevated liver enzymes and low platelets syndrome; LCAT: Lecithin-cholesterol-acyltransferase.

Table 2 International diabetes federation definition of the metabolic syndrome

Increased waist circumference [≥ 94 cm (men) or ≥ 80 cm (women)], with ethnic-specific waist circumference1 cut-points; plus any two of the following:

Triglycerides > 150 mg/dL (1.7 mmol/L) or treatment for elevated triglycerides

HDL cholesterol < 40 mg/dL (1.03 mmol/L) in men or < 50 mg/dL (1.29 mmol/L) in women, or treatment for low HDL

Systolic blood pressure > 130, diastolic blood pressure > 85 mmHg, or treatment for hypertension

Fasting plasma glucose > 100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes; an oral glucose tolerance test is recommended for patients with an elevated fasting plasma glucose, but not required

¹For South Asia and Chinese patients, waist ≥ 90 cm (men) or ≥ 80 cm (women); for Japanese patients, waist ≥ 90 cm (men) or ≥ 80 cm (women). HDL: High density lipoprotein.

Table 3 Summary of treatment options in patients with non-alcoholic steatohepatitis

Intervention	Recommendation	Notes
Weight loss	Highly recommended	Diet and exercise should target significant weight loss
		5% weight loss reduces hepatic steatosis
		Greater weight loss may be needed to improve hepatic inflammation
Metformin	Not recommended	Not recommended for specific therapy of NASH
		Should be used when indicated for treatment of type 2 diabetes mellitus
Thiazolidinediones	Recommended in selected patients	There is evidence for pioglitazone usage in non-diabetic patients with biopsy-proven NASH
		There are questions regarding long-term safety
RAAS inhibition (ACE-I/ARBs)	Not recommended	Not recommended for specific therapy of NASH
		Can be used when indicated for treatment of hypertension
Incretin mimetics	Not recommended	Not recommended for specific therapy of NASH
		Can be used when indicated for type 2 diabetes mellitus
Vitamin E	Recommended in selected patients	Vitamin E 800 IU/d
		Evidence in non-diabetic biopsy-proven NASH
		There is evidence regarding increased all-cause mortality associated with vitamin E usage
Statins	Not recommended	Not recommended for specific therapy of NASH
		Can be used safely when indicated for dyslipidemia
Ursodeoxycholic acid	Not recommended	A RCT showed no benefit of UDCA
Orlistat	Not recommended	Can be used as an adjunct for weight loss in selected cases
Omega-3 fatty acids	Not recommended	Can be used to treat hypertriglyceridemia
Pentoxifylline	Not recommended	Inconclusive evidence
		May warrant further investigation

NASH: Non-alcoholic steatohepatitis; ACE-I: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blocker; UDCA: Ursodeoxycholic acid; RCT: Randomized-controlled trial.