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A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the West. Non-alcoholic steatohepatitis (NASH) is the progressive form of NAFLD and can lead to cirrhosis, hepatocellular carcinoma, and is associated with increased cardiovascular risks. Multiple components and risk factors are thought to be involved in the pathogenesis of NAFLD and NASH. Optimal therapy has not yet been found, but many advances have been made with the discovery of potential therapeutic options. In this paper, we aim to provide a comprehensive review of approved, studied, and upcoming treatment options for NAFLD and NASH. Non-pharmacologic therapy (lifestyle modifications and bariatric surgery) and pharmacologic therapy are both reviewed. Pharmacologic therapy target components thought to be involved in the pathogenesis of this disease process including insulin resistance, oxidative stress, inflammation, lipid metabolism, and fibrosis are reviewed in this paper. Results of the emerging treatment targets in phase 2 and 3 clinical trials are also included.

SUBMITTER: Ganguli S

PROVIDER: S-EPMC6863115 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis.

Ganguli Surosree S DeLeeuw Peter P Satapathy Sanjaya K SK

Hepatic medicine : evidence and research 20191115

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the West. Non-alcoholic steatohepatitis (NASH) is the progressive form of NAFLD and can lead to cirrhosis, hepatocellular carcinoma, and is associated with increased cardiovascular risks. Multiple components and risk factors are thought to be involved in the pathogenesis of NAFLD and NASH. Optimal therapy has not yet been found, but many advances have been made with the discovery of potential therapeut ...[more]

PMID: 31814783

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Project description:Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver disease, including non-alcoholic fatty liver (NAFL) and its more progressive form, non-alcoholic steatohepatitis (NASH). The prevalence of NAFLD/NASH along with type 2 diabetes and obesity is rising worldwide. In those who develop NASH, unlike those with bland steatosis (NAFL), lipotoxic lipids drive hepatocyte injury, inflammation and stellate cell activation leading to progressive accumulation of collagen or fibrosis, ultimately leading to cirrhosis and increased risk of hepatocellular carcinoma. Hypothyroidism is associated with NAFLD/NASH; specifically, intrahepatic hypothyroidism drives lipotoxicty in preclinical models. Agonists of thyroid hormone receptor (THR)-β, which is primarily found in the liver, can promote lipophagy, mitochondrial biogenesis and mitophagy, stimulating increased hepatic fatty acid β-oxidation, and thereby decreasing the burden of lipotoxic lipids, while promoting low-density lipoprotein (LDL) uptake and favourable effects on lipid profiles. A number of THR-β agonists are currently being investigated for NASH. This review focuses on resmetirom, an orally administered, once-daily, small-molecule, liver-directed, ß-selective THR agonist, as it is furthest along in development. Data from completed clincal studies outlined in this review demonstrate that resmetirom is effective in reducing hepatic fat content as measured by magnetic resonance imaging-derived proton density fat fraction, reduces liver enzymes, improves non-i nvasive markers of liver fibrogenesis and decreases liver stiffness, while eliciting a favourable cardiovascular profile with a reduction in serum lipids, including LDL cholesterol. Topline phase III biopsy data showed resolution of NASH and/or fibrosis improvement after 52 weeks of treatment, with more detailed peer-reviewed findings anticipated in order to certify these findings. Longer term clinical outcomes from both MAESTRO-NASH and MAESTRO-NASH OUTCOMES will be a pivotal juncture in the drug's road towards being approved as a NASH therapeutic.

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A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis.

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A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis.

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