Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain) have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.
Citations
Citations to this article as recorded by
Liver metabolism in human MASLD: A review of recent advancements using human tissue metabolomics Emily Flam, Joel T. Haas, Bart Staels Atherosclerosis.2025; 400: 119054. CrossRef
Multifaceted Interactions Between Bile Acids, Their Receptors, and MASH: From Molecular Mechanisms to Clinical Therapeutics Xuan Tang, Yuanjiao Zhou, Li Xia, Xiulian Lin, Yao Zhu, Menghan Chen, Jiayao Wang, Yamei Li Molecules.2025; 30(15): 3066. CrossRef
Dietary Omega-3 Fatty Acids from Fish and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Mediterranean Population: Findings from the NUTRIHEP Cohort Rossella Tatoli, Bonfiglio Caterina, Rossella Donghia, Pasqua Letizia Pesole, Luigi Fontana, Gianluigi Giannelli Nutrients.2025; 17(21): 3372. CrossRef
Unlocking the Therapeutic Potential of Ellagic Acid for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis Tharani Senavirathna, Armaghan Shafaei, Ricky Lareu, Lois Balmer Antioxidants.2024; 13(4): 485. CrossRef
Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study Seul Ki Han, Myung Jae Seo, Taesic Lee, Moon Young Kim, Anna Di Sessa PLOS ONE.2024; 19(5): e0303333. CrossRef
Influence of Lipid Class Used for Omega-3 Fatty Acid Supplementation on Liver Fat Accumulation in MASLD I Sabinari, O Horakova, T Cajka, V Kleinova, MR Wieckowski, M Rossmeisl Physiological Research.2024; (Suppl 1): S295. CrossRef
Statins for the Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis Weiwei Dai, Baohong Xu, Peng Li, Junhua Weng American Journal of Therapeutics.2023; 30(1): e17. CrossRef
Hepatitis C and Nonalcoholic Steatohepatitis in the 21st Century: Impact on Liver Disease and Liver Transplantation Sonia Samuel, Ahmad Abulawi, Raza Malik Gastroenterology Insights.2023; 14(3): 249. CrossRef
Omega‐3 phospholipids and obesity‐associated NAFLD: Potential mechanisms and therapeutic perspectives Marko Mitrovic, Gabriella Sistilli, Olga Horakova, Martin Rossmeisl European Journal of Clinical Investigation.2022;[Epub] CrossRef
Enfermedad hepática grasa relacionada a trastornos metabólicos A. Fabrizzio Bardales Silva Revista Médica Basadrina.2022; 15(4): 85. CrossRef
Lower serum copper concentrations are associated with higher prevalence of nonalcoholic steatohepatitis: a matched case–control study Huai Zhang, Kenneth I. Zheng, Pei-Wu Zhu, Sui-Dan Chen, Gang Li, Hong-Lei Ma, Liang-Jie Tang, Ou-Yang Huang, Christopher D. Byrne, Giovanni Targher, Xiao-Dong Wang, Ming-Hua Zheng European Journal of Gastroenterology & Hepatology.2022; 34(8): 838. CrossRef
Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease Raghu Ramanathan, Ahmad Hassan Ali, Jamal A. Ibdah International Journal of Molecular Sciences.2022; 23(13): 7280. CrossRef
Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism Hongmei Yan, Weiyun Wu, Xinxia Chang, Mingfeng Xia, Sicheng Ma, Liu Wang, Jian Gao Biology of Sex Differences.2021;[Epub] CrossRef
Fructose intake is not associated to the risk of hepatic fibrosis in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) Vittoria Zambon Azevedo, Valesca Dall’Alba Clinical Nutrition.2021; 40(6): 4275. CrossRef
Effect of Coffee Consumption on Non-Alcoholic Fatty Liver Disease Incidence, Prevalence and Risk of Significant Liver Fibrosis: Systematic Review with Meta-Analysis of Observational Studies Maryam Ebadi, Stephen Ip, Rahima A. Bhanji, Aldo J. Montano-Loza Nutrients.2021; 13(9): 3042. CrossRef
Association between the Severity of Nonalcoholic Fatty Liver Disease and the Risk of Coronary Artery Calcification Chien-Chih Chen, Wei-Chien Hsu, Han-Ming Wu, Jiun-Yi Wang, Pei-Yu Yang, I-Ching Lin Medicina.2021; 57(8): 807. CrossRef
Statins in Non-alcoholic Steatohepatitis Jose D. Torres-Peña, Laura Martín-Piedra, Francisco Fuentes-Jiménez Frontiers in Cardiovascular Medicine.2021;[Epub] CrossRef
Real-world Comorbidity Burden, Health Care Utilization, and Costs of Nonalcoholic Steatohepatitis Patients With Advanced Liver Diseases Robert J. Wong, Nandita Kachru, Diane J. Martinez, Meghan Moynihan, A. Burak Ozbay, Stuart C. Gordon Journal of Clinical Gastroenterology.2021; 55(10): 891. CrossRef
iTRAQ‑based quantitative proteomics analysis of the hepatoprotective effect of melatonin on ANIT‑induced cholestasis in rats Dingnan Wang, Han Yu, Yunzhou Li, Zongying Xu, Shaohua Shi, Dou Dou, Lili Sun, Zhili Zheng, Xinghua Shi, Xiulan Deng, Xianggen Zhong Experimental and Therapeutic Medicine.2021;[Epub] CrossRef
Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine Tingting Shi, Li Wu, Wenjun Ma, Liping Ju, Minghui Bai, Xiaowei Chen, Shourong Liu, Xingxin Yang, Junping Shi, Svein Haavik Evidence-Based Complementary and Alternative Medicine.2020;[Epub] CrossRef
Gut microbial fatty acid metabolites (KetoA and KetoC) affect the progression of nonalcoholic steatohepatitis and reverse cholesterol transport metabolism in mouse model Neng Tanty Sofyana, Jiawen Zheng, Yuki Manabe, Yuta Yamamoto, Shigenobu Kishino, Jun Ogawa, Tatsuya Sugawara Lipids.2020; 55(2): 151. CrossRef
Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View Rodrigo Valenzuela, Luis A. Videla Nutrients.2020; 12(2): 499. CrossRef
Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy Salvatore Petta, Jie Ting, Stefania Saragoni, Luca Degli Esposti, Sanatan Shreay, Maria Letizia Petroni, Giulio Marchesini Nutrition, Metabolism and Cardiovascular Diseases.2020; 30(6): 1014. CrossRef
Hospitalization costs and risk of mortality in adults with nonalcoholic steatohepatitis: Analysis of a French national hospital database Jérôme Boursier, Sanatan Shreay, Cecile Fabron, Elodie Torreton, Jeremy Fraysse EClinicalMedicine.2020; 25: 100445. CrossRef
Ethyl Acetate Fraction of Amomum xanthioides Ameliorates Nonalcoholic Fatty Liver Disease in a High-Fat Diet Mouse Model Hwi-Jin Im, Seung-Ju Hwang, Jin-Seok Lee, Sung-Bae Lee, Ji-Yun Kang, Chang-Gue Son Nutrients.2020; 12(8): 2433. CrossRef
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming Soung Won Jeong Diabetes & Metabolism Journal.2020; 44(5): 640. CrossRef
Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: Current Issues and Future Perspectives in Preclinical and Clinical Research Clarissa Berardo, Laura Giuseppina Di Pasqua, Marta Cagna, Plinio Richelmi, Mariapia Vairetti, Andrea Ferrigno International Journal of Molecular Sciences.2020; 21(24): 9646. CrossRef
A round trip from nonalcoholic fatty liver disease to diabetes: molecular targets to the rescue? Amedeo Lonardo, Simonetta Lugari, Stefano Ballestri, Fabio Nascimbeni, Enrica Baldelli, Mauro Maurantonio Acta Diabetologica.2019; 56(4): 385. CrossRef
Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures Stefania Lama, Daniela Vanacore, Nadia Diano, Carla Nicolucci, Sonia Errico, Marcello Dallio, Alessandro Federico, Carmelina Loguercio, Paola Stiuso Scientific Reports.2019;[Epub] CrossRef
Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach Sandra A. Soto‐Alarcón, Macarena Ortiz, Paula Orellana, Francisca Echeverría, Andrés Bustamante, Alejandra Espinosa, Paola Illesca, Daniel Gonzalez‐Mañán, Rodrigo Valenzuela, Luis A. Videla BioFactors.2019; 45(6): 930. CrossRef
The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis Yan-Xiao Ji, Zan Huang, Xia Yang, Xiaozhan Wang, Ling-Ping Zhao, Pi-Xiao Wang, Xiao-Jing Zhang, Michele Alves-Bezerra, Lin Cai, Peng Zhang, Yue-Xin Lu, Lan Bai, Mao-Mao Gao, Huan Zhao, Song Tian, Yong Wang, Zhi-Xiang Huang, Xue-Yong Zhu, Yan Zhang, Jun Go Nature Medicine.2018; 24(2): 213. CrossRef
Prevention and management of gastroesophageal varices Yeon Seok Seo Clinical and Molecular Hepatology.2018; 24(1): 20. CrossRef
Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action Eleonora Scorletti, Christopher D. Byrne Molecular Aspects of Medicine.2018; 64: 135. CrossRef
NAFLD and HIV: Do Sex, Race, and Ethnicity Explain HIV-Related Risk? Subada Soti, Kathleen E. Corey, Jordan E. Lake, Kristine M. Erlandson Current HIV/AIDS Reports.2018; 15(3): 212. CrossRef
Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction Lucienne Juillerat-Jeanneret, John-David Aubert, Josip Mikulic, Dela Golshayan Journal of Medicinal Chemistry.2018; 61(22): 9811. CrossRef
Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases Francesca Bonomini, Elisa Borsani, Gaia Favero, Luigi F. Rodella, Rita Rezzani Nutrients.2018; 10(9): 1135. CrossRef
First
Prev
