Table 3.
The effect of therapeutic interventions on TNF-α in patients with NAFLD as derived from clinical trials.*,a
| Intervention (reference) | Category or action | Dosage | Type of study | Population (n) | Control | Duration | TNF-α measurement | TNF-α change | |
|---|---|---|---|---|---|---|---|---|---|
| Pioglitazone [66] | PPAR-γ agonist | 30 mg od | Prospective cohort study | Biopsy-defined NASH (18) | - | 12 months | Circulating TNF-α | ↔ | |
| Liraglutide [82] | GLP-1RA | 1.8 mg od | RCT | T2DM + US-defined NAFLD (30) | Metformin | 12 weeks | Circulating TNF-α | ↓ | |
| Probiotics [83] | Living microorganisms | Various | Meta-analysis of 21 RCTs | Biopsy- or MRS- or US-defined NAFLD (1037) | Placebo | NA | Circulating TNF-α | ↔ | |
| Synbiotics [84] | Synbiotics (Probiotics + Prebiotics) | Various | Meta-analysis of 7 RCTs | NAFLD (419) | Placebo | NA | Circulating TNF-α | ↓ | |
| Rifaximin [87] | Antibiotic | 550 mg bid | RCT | Biopsy-defined NASH (50) | Placebo | 6 months | Circulating TNF-α | ↓ | |
| Vitamin E [89] | Antioxidant | 300 mg bid δ-tocotrienol | RCT | US-defined NAFLD (100) | α-tocopherol | 12 months | Circulating TNF-α | ↓ | |
| Pentoxifylline [90] | Phosphodiesterase inhibitor | Various | Meta-analysis of 3 RCTs and 2 prospective cohorts | Biopsy- or US-defined NAFLD (147) | Placebo, UDCA | Various | Circulating TNF-α | ↓ | |
| Pentoxifylline [91] | Phosphodiesterase inhibitor | Various | Meta-analysis of 5 RCTs | Biopsy- or US-defined NAFLD (157) | Placebo | 3–12 months | Circulating TNF-α | ↔ | |
| UDCA + Vitamin E [93] | Bile acid + Antioxidant | 12–15 mg/kg/day + 400 IU bid | RCT | Biopsy-defined NASH (41) | UDCA + placebo, placebo + placebo | 24 months | Circulating TNF-α | ↔ | |
| Atorvastatin [97] | Statin | 10 mg od | Prospective cohort study | Biopsy-defined NASH + dyslipidemia (42) | - | 12 months | Circulating TNF-α | ↓ | |
| EPA [100] | n-3 PUFA | 2700 mg od | Prospective cohort study | Biopsy-defined NASH (23) | - | 12 months | Circulating TNF-α R | ↓ | |
| ALA/ EPA/ DHA + Diet [101] | n-3 PUFA + Diet | 2 gr od + 30% caloric restriction | RCT | US-defined NAFLD (36) | Diet (30% caloric restriction) | 6 months | Circulating TNF-α | ↓ | |
Abbreviations: ↓, decrease; ↔ , no change, compared to control
ALA alpha-linolenic acid, bid twice daily, CFU colony-forming unit, DHA docosahexaenoic acid, EPA eicosapentaenoic acid, GLP-1RA glucagon-like peptide-1 receptor agonist, MRS magnetic resonance spectroscopy, NA not available, NAFLD nonalcoholic fatty liver disease, NASH nonalcoholic steatohepatitis, n-3 PUFA n-3 polyunsaturated fatty acids, od once daily, PPAR peroxisome proliferator-activated receptor, R receptor, RCT randomized-controlled trial, T2DM type 2 diabetes mellitus, TNF-α tumor necrosis factor-α, tid three times a day, UDCA ursodeoxycholic acid, US ultrasound
*The table includes selected meta-analyses, RCTs and prospective observational studies, considered to be the best available evidence to-date, according to the principles of evidence-based medicine
a References are sorted according to the order mentioned in the text