|
| Treatment strategy | Medication/intervention | Comment |
|
| Lifestyle modification | Weight loss | 5–10% weight loss can lead to biochemical and histological improvement [24, 25] |
| Hypocaloric diet alone | Better response when combined with exercise and reduced carbohydrate and fat [54, 55] |
| Dietary composition | Diet should include addition of PUFA and decreased saturated and transfatty acids [40–42]. Mediterranean diet has shown improvement in ALT, insulin levels, and histological markers [59, 60] |
| Exercise alone | Effective even without weight loss [38, 61] |
| Diet plus exercise | Greatest beneficial effect [24, 64, 65] |
| Bariatric surgery | Could be beneficial in reversing NASH [22, 66]; some studies show worsening fibrosis [67, 68] |
| Orlistat | Not enough evidence to support or oppose its use |
| Sibutramine | FDA withdrew sibutramine from market due to cardiovascular events |
|
| Insulin sensitivity | Thiazolidinediones | For patients with NASH, they improve insulin resistance, biomarkers, steatosis, and inflammation [69, 70]; caution should be taken in regard to cardiovascular risks |
| Metformin | It offers no additional biochemical or histological benefits |
| Meglitinides and incretin mimetics | GLP-1 analog has shown histological improvement in phase 2 trial [71] |
|
| Antilipidemic | Statins | Decrease in transaminases, possible role in delaying progression from NAFL to NASH; safe to use in patients with NAFL and NASH |
| Fenofibrate | Possible increased mortality risk in NAFLD patients |
| Niacin | May be hepatotoxic |
| NPC1L1 inhibitor | Not enough evidence to support or oppose its use |
| n-3 polyunsaturated fatty acids | May help reverse NAFLD according to some studies [72, 73] |
|
| Antioxidants | Vitamin E | Improves histological markers in nondiabetic NASH [70]; may have greater benefit when combined with other agents [74–76]; may be associated with increased risk for cardiovascular events and prostate cancer |
| SAM, NAC, and betaine | Not enough evidence to support or oppose its use |
|
| Anti-inflammatory | Pentoxifylline | May improve liver enzymes and histology [77] |
|
| Probiotics | | May improve liver enzymes, insulin resistance, and anti-inflammatory markers [78, 79] |
|
| Cytoprotective and antiapoptotic agents | Ursodeoxycholic acid | May improve liver enzymes and histology, but further well-designed studies are needed |
|
| Other | RAAS | Small studies show improvement in liver enzymes and histology, but larger randomized controlled studies are warranted |
| Coffee | Coffee is associated with decreased prevalence of NAFLD and may have a role in delaying progression of fibrosis [80] |
| Vitamin D | Replacement does not show improvement [81] |
| Phlebotomy | Not enough evidence to support or oppose its therapeutic use |
|
| Herbal | Milk thistle | May improve liver chemistry and histology especially in combination with other agents such as vitamin E and phospholipids [82, 83] |
|
