Non-alcoholic fatty liver disease medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
Clinical practice guidelines from NICE[1] and the American Association for the Study of Liver Diseases (AASLD)[2] direct management. The available guidelines have been compared and summarized[3].
Weight loss, withdrawal of hepatotoxic agents, and management of underlying insulin resistance/metabolic syndrome is the mainstay of treatment in non-alcoholic fatty liver disease (NAFLD).
Medical Therapy
There is no FDA approved specific treatment for NAFLD. Weight loss, withdrawal of hepatotoxic agents, and management of underlying insulin resistance/metabolic syndrome is the mainstay of treatment in non-alcoholic fatty liver disease (NAFLD).
Systematic reviews, using network analyses, by the Cochrane Collaboreation[4] made no conclusion, whereas a non-Cochrane review[5] made the following conclusions:
- ≥1 stage of fibrosis improvement: "Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively.
- NASH resolution: "semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively."
The combination of vitamin E (400 IU b.i.d.) and pioglitazone has been studies in one trial[6].
Glucagon-like Peptide-1 Receptor Agonists (GLP1-RA)
Randomized controlled trials have been executed of:
- Semaglutide[7]:
- "An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P=0.48)" over 6 years of treatment.
Weight management
- Lifestyle modifications to achieve weight loss is a central aspect of management of NAFLD in obese patients.
- Weight management includes caloric restriction, reduction in saturated fat intake, and regular exercise.
- At present time there is no pharmacological agent that produces safe weight loss resulting in regression of steato-hepatitis and fibrosis. However, orlistat is an FDA approved drug regimen for safe weight loss.
- Weight reduction can help to reduce levels of liver enzymes, insulin.
- Preferred regimen: Orlistat 120 mg PO q8h.
Management of hyperlipidemia
- The direct effect of anti-lipid agents on NAFLD and liver histology has not been clearly understood; however, trials suggest no harm[8] and observational studies suggest benefit[9].
- Statins are the drugs of choice, however statins should not be administered as primary treatment of NAFLD, but rather as treatment of hyperlipidemia.
- The goal is to get the LDL down to < 100 mg/dl.
- Preferred regimen: Atorvastatin 40 mg PO q24h.
Management of Insulin resistance
- Rosiglitazone is recommended among all patients who develop NAFLD.
- Long term treatment with rosiglitazone in patients with NAFLD shows significant improvement.
- Preferred regimen: Rosiglitazone 4 mg PO/OD q24h .[10]
- Alternative regimen: Pioglitazone 4mg PO/OD.[11]
- Alternative regimen: Liraglutide 1.2 mg PO/OD.
Anti-oxidants
- Antioxidants offer hepatocyte protection from free radical damage.
- Patients with NAFLD are recommended to use ursodeoxycholic acid (UDCA) in combination with vitamin E.[12]
- Vitamin E alone or in combination with vitamin C is also recommended in patients without any side effects in fibrosis score.[13]
The combination of vitamin E (400 IU b.i.d.) and pioglitazone has been studies in one trial[6].
Miscellaneous
- Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa, the leaves of these plant have been studied extensively and it has shown to be beneficial in NAFLD and in prevention and alleviation of NAFLD.[15]
References
- ↑ NICE (2016). Non-alcoholic fatty liver disease (NAFLD): assessment and management. Available at https://www.nice.org.uk/guidance/ng49
- ↑ Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M; et al. (2018). "The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases". Hepatology. 67 (1): 328–357. doi:10.1002/hep.29367. PMID 28714183.
- ↑ Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L (2018). "Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis". World J Gastroenterol. 24 (30): 3361–3373. doi:10.3748/wjg.v24.i30.3361. PMC 6092580. PMID 30122876.
- ↑ Lombardi R, Onali S, Thorburn D, Davidson BR, Gurusamy KS, Tsochatzis E (2017). "Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD): an attempted network meta-analysis". Cochrane Database Syst Rev. 3: CD011640. doi:10.1002/14651858.CD011640.pub2. PMC 6464620. PMID 28358980.
- ↑ Majzoub AM, Nayfeh T, Barnard A, Munaganuru N, Dave S, Singh S; et al. (2021). "Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH". Aliment Pharmacol Ther. 54 (7): 880–889. doi:10.1111/apt.16583. PMC 8711247 Check
|pmc=value (help). PMID 34435378 Check|pmid=value (help). - ↑ 6.0 6.1 Bril F, Biernacki DM, Kalavalapalli S, Lomonaco R, Subbarayan SK, Lai J; et al. (2019). "Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial". Diabetes Care. 42 (8): 1481–1488. doi:10.2337/dc19-0167. PMID 31332029.
- ↑ Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V; et al. (2021). "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis". N Engl J Med. 384 (12): 1113–1124. doi:10.1056/NEJMoa2028395. PMID 33185364 Check
|pmid=value (help). - ↑ Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K; et al. (2010). "Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis". Lancet. 376 (9756): 1916–22. doi:10.1016/S0140-6736(10)61272-X. PMID 21109302. Review in: J Fam Pract. 2011 Sep;60(9):536-8
- ↑ Kamal S, Khan MA, Seth A, Cholankeril G, Gupta D, Singh U; et al. (2017). "Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis". Am J Gastroenterol. 112 (10): 1495–1505. doi:10.1038/ajg.2017.170. PMID 28585556.
- ↑ Saryusz-Wolska M, Szymańska-Garbacz E, Jabłkowski M, Białkowska J, Pawłowski M, Kwiecińska E, Omulecka A, Borkowska A, Ignaczak A, Loba J, Czupryniak L (2011). "Rosiglitazone treatment in nondiabetic subjects with nonalcoholic fatty liver disease". Pol. Arch. Med. Wewn. 121 (3): 61–6. PMID 21430606.
- ↑ Bril F, Kalavalapalli S, Clark VC, Lomonaco R, Soldevila-Pico C, Liu IC, Orsak B, Tio F, Cusi K (2017). "Response to Pioglitazone in Patients With Nonalcoholic Steatohepatitis With vs Without Type 2 Diabetes". Clin. Gastroenterol. Hepatol. doi:10.1016/j.cgh.2017.12.001. PMID 29223443.
- ↑ Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, Zala JF, Helbling B, Steuerwald M, Zimmermann A (2006). "Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis". Clin. Gastroenterol. Hepatol. 4 (12): 1537–43. doi:10.1016/j.cgh.2006.09.025. PMID 17162245.
- ↑ Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S (2003). "Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis". Am. J. Gastroenterol. 98 (11): 2485–90. doi:10.1111/j.1572-0241.2003.08699.x. PMID 14638353.
- ↑ Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682.
- ↑ Vergara-Jimenez M, Almatrafi MM, Fernandez ML (2017). "Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease". Antioxidants (Basel). 6 (4). doi:10.3390/antiox6040091. PMID 29144438.