Efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis: a systematic review and meta-analysis

Malik, Adnan; Nadeem, Mahum; Malik, Muhammad Imran

doi:10.1007/s12328-021-01491-7

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…In addition, an experimental compound, elafibranor (a PPARα/δ dual agonist) specifically designed for cardiometabolic diseases, has been tested in clinical trials in patients with NAFLD/NASH. Elafibranor exhibited hepatoprotective properties by reducing hepatic fat storage and enzyme activity 40 . Here, we attempted to reproduce these clinical trial outcomes using the HepG2 steatosis OOC system.…”

Section: Resultsmentioning

confidence: 99%

A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip

Wiriyakulsit,

Keawsomnuk,

Thongin

et al. 2023

Sci Rep

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Nonalcoholic fatty liver disease (NAFLD) begins with benign steatosis caused by ectopic storage of triacylglycerols in the liver. Persistent steatosis, in combination with other genetic and environmental factors, leads to nonalcoholic steatohepatitis (NASH) characterized by functional impairment, inflammation, and fibrosis. However, it remains unclear how persistent steatosis directly contributes to the progression of NAFLD, which may represent a therapeutic target. The organ-on-a-chip (OOC) has emerged as a new culture platform to recapitulate human pathological conditions under which drug candidates can be screened. Here, we developed a simple OOC steatosis model using the Mimetas OrganoPlate with a human liver cell line, HepG2. Treating the HepG2 OOCs with fatty acid overload induced steatosis within 24 h. Moreover, persistent steatosis for 6 days impaired OOC viability and hepatic function, as measured by a WST-8 assay and albumin production, respectively. Lastly, the HepG2 OOCs were exposed to drugs being tested in clinical trials for NAFLD/NASH during the 6-day period. Pioglitazone improved the OOC viability while elafibranor reduced the steatosis in association with reduced viability and albumin production. In conclusion, we show that the HepG2 steatosis OOC model is a useful tool on which the efficacy and toxicity of various therapeutic candidates can be tested.

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Section: Resultsmentioning

confidence: 99%

A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip

Wiriyakulsit,

Keawsomnuk,

Thongin

et al. 2023

Sci Rep

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“…Elafibranor reached phase III studies, discontinued early due to unproven efficacy of the drug after 72 weeks of treatment [ 97 ].…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications

Boccatonda¹,

Andreetto

D’Ardes

et al. 2023

Biomedicines

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Non-alcoholic fatty liver disease (NAFLD) is defined as a chronic liver disease characterized by excessive fat accumulation in the liver without another obvious cause (no excessive alcohol consumption, hepatotoxic medications, toxins, viral infections, genetic hepatic diseases), therefore it is an exclusion diagnosis. The term NAFLD literally refers to non-alcohol related hepatopathy and does not adequately correlate with metabolic dysfunction and related cardiovascular risks. Therefore, researchers and scientific societies have moved towards changing the terminology. The novel nomenclature for a metabolic-associated fatty liver disease (MAFLD) has been proposed in 2020 by a group of experts to overcome the issues related to the old terminology. The diagnosis of MAFLD is based on the presence of hepatic steatosis and at least one between these three conditions: type 2 diabetes mellitus (T2DM), obesity or metabolic dysregulation. MAFLD has been shown to be an independent risk factor for cardiovascular diseases and atherosclerosis. It is better related to the main risk factors for atherosclerosis and cardiovascular diseases than NAFLD, such as dyslipidemia, T2DM and hypertension. The aim of this review is to highlight the reasons why the term NAFLD is moving to the term MAFLD, what are the conceptual basis of this choice and its clinical implications, particularly in the cardiovascular field.

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“…Interventions addressing GGT outcomes in the setting of various treatment options in patients with NAFLD and NASH are summarized in Table 2 [80][81][82][83][84][85] .…”

Section: Effects Of Treatment On Ggt Valuesmentioning

confidence: 99%

Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk

Lonardo¹,

Ndrepepa²

2022

Metab Target Organ Damage

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This concise review article critically examines the recent medical literature regarding gamma glutamyl transferase (GGT) with a special emphasis on newly proposed indications for GGT use, including cardiovascular risk assessment. GGT is a ubiquitous glycosylated protein embedded in the outer surface of cell membranes, which catalyzes the transfer of glutamyl groups from various substrates and plays a key role in the antioxidant/pro-oxidant balance. In the past, the enzyme was considered a non-specific liver test. Current evidence supports the role of GGT in the assessment of portal hypertension in cystic fibrosis, porto-sinusoidal vascular disease, malignant mesothelioma, and incident type 2 diabetes and as a biomarker of cardiometabolic risk and cardiovascular disease. Several specific points including the use of GGT in hepatology as a sensitive but poorly specific test and the association of GGT with metabolic syndrome, nonalcoholic fatty liver disease and its fibrotic stages, cardiometabolic risk, chronic kidney disease, neurodegenerative disorders and dementia, idiopathic pulmonary arterial hypertension, and Corona Virus Disease 2019 (COVID-19) are addressed based on the most recent research in these fields. Putative mechanisms linking GGT with increased metabolic stress and the effects of various therapeutic interventions on GGT values are also discussed. We conclude that GGT has evolved from an indiscriminate liver test and an index of alcohol consumption to a biomarker of cardiometabolic health. The proper interpretation of GGT values (i.e., of hepatic vs. extrahepatic origin) is deeply affected by the clinical and epidemiological context. We propose that GGT may be utilized in public health campaigns, in the research arena, and in clinical practice to identify those individuals who can benefit most from the proactive preventive and therapeutic approaches, given that they are at high cardiometabolic risk.

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Efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis: a systematic review and meta-analysis

Cited by 13 publications

References 30 publications

A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip

A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip

From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications

Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk

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