Fatty liver medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
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Overview
The treatment of fatty liver depends on what is causing it, and generally, treating the underlying cause will reverse the process of steatosis if implemented at early stage. Recent studies suggest that diet, exercise, and especially antiglycemic drugs may alter the course of the disease. A randomized controlled trial found that pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis.[1]
Elderly may not benefit from treatment[2].
Patients with nonalcoholic steatosis on imaging, but normal liver function tests, may not have increased risk and so not need treatment[3].
Medical Therapy
Clinical practice guidelines
Clinical practice guidelines direct treatment.
Per the American Gastroenterological Association (AGA) in 2021[4], per Figure 3 notes, treatment may include:
- "Patients with T2DM may benefit from some diabetes medications, such as pioglitazone and some GLP-1 RAs that have reported histological improvement in RCTs in patients with NASH, either with or without diabetes. Among GLP-1 RAs, semaglutide has the strongest evidence of liver histological benefit."
- "Vitamin E improves steatohepatitis in patients with NASH without diabetes, with less evidence in patients with T2D."
Per the American Association for the Study of Liver Diseases (AASLD) in 2023[5]:
- "Semaglutide can be considered for its approved indications (T2DM/obesity) in patients with NASH, as it confers a cardiovascular benefit and improves NASH."
- "Pioglitazone improves NASH and can be considered for patients with NASH in the context of patients with T2DM."
- "Vitamin E can be considered in select individuals as it improves NASH in some patients without diabetes."
"Available data on semaglutide, pioglitazone, and vitamin E do not demonstrate an antifibrotic benefit, and none has been carefully studied in patients with cirrhosis."
Systematic reviews
Systematic reviews are available[6].
Original studies
Key trials include:
- Semaglutide[7]
- Pioglitazone and vitamin E for patients without diabetes mellitus[8]
- Pioglitazone[1]
- Obeticholic acid[9]. Obeticholic acid is a farnesoid X receptor (FXR) agonist. FXR is a nuclear receptor in the liver and intestine. "FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes."[10]
- Lanifibranor[11] is a peroxisome proliferator-activated receptor (PPAR) agonist.
- Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analog[12]
References
- ↑ 1.0 1.1 Belfort R, Harrison SA, Brown K; et al. (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis". N. Engl. J. Med. 355 (22): 2297–307. doi:10.1056/NEJMoa060326. PMID 17135584.
- ↑ van Kleef LA, Sonneveld MJ, Kavousi M, Ikram MA, de Man RA, de Knegt RJ (2022). "Fatty liver disease is not associated with increased mortality in the elderly: A prospective cohort study". Hepatology. doi:10.1002/hep.32635. PMID 35753042 Check
|pmid=value (help). - ↑ Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB; et al. (2020). "Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes". Hepatology. 72 (4): 1242–1252. doi:10.1002/hep.31157. PMC 8318072 Check
|pmc=value (help). PMID 32022277 Check|pmid=value (help). - ↑ Kanwal F, Shubrook JH, Adams LA, Pfotenhauer K, Wai-Sun Wong V, Wright E; et al. (2021). "Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease". Gastroenterology. 161 (5): 1657–1669. doi:10.1053/j.gastro.2021.07.049. PMC 8819923 Check
|pmc=value (help). PMID 34602251 Check|pmid=value (help). - ↑ Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D; et al. (2023). "AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease". Hepatology. doi:10.1097/HEP.0000000000000323. PMID 36727674 Check
|pmid=value (help). - ↑ 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). - ↑ 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). - ↑ Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM; et al. (2010). "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis". N Engl J Med. 362 (18): 1675–85. doi:10.1056/NEJMoa0907929. PMC 2928471. PMID 20427778. Review in: Ann Intern Med. 2010 Sep 21;153(6):JC3-12
- ↑ Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF; et al. (2015). "Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial". Lancet. 385 (9972): 956–65. doi:10.1016/S0140-6736(14)61933-4. PMC 4447192. PMID 25468160.
- ↑ HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207999s003lbl.pdf
- ↑ Francque SM, Bedossa P, Ratziu V, Anstee QM, Bugianesi E, Sanyal AJ; et al. (2021). "A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH". N Engl J Med. 385 (17): 1547–1558. doi:10.1056/NEJMoa2036205. PMID 34670042 Check
|pmid=value (help). - ↑ Sanyal A, Charles ED, Neuschwander-Tetri BA, Loomba R, Harrison SA, Abdelmalek MF; et al. (2019). "Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial". Lancet. 392 (10165): 2705–2717. doi:10.1016/S0140-6736(18)31785-9. PMID 30554783.