Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Raptis, Dimitrios D.; Mantzoros, Christos S.; Polyzos, Stergios A.

doi:10.2147/tcrm.s352008

Cited by 17 publications

(6 citation statements)

References 94 publications

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“…B1344, an FGF-21 analog, reduced the expression of TNF-α and other cytokines in the liver of mice with diet-induced NASH [ 95 ], corroborating earlier evidence showing FGF-21 analogs to be effective in both animal models and humans with NASH, although their direct effect on TNF-α has not been investigated in human NASH to-date [ 94 ]. As a result, numerous clinical trials with FGF-21 analogs are currently underway [ 94 ].…”

Section: Treatment Considerationssupporting

confidence: 70%

“…Fibroblast growth factor-21 (FGF-21) analogs or mimetics act at the same receptors as the endogenous hepatokine FGF-21, which is regarded as a promising molecule against hepatic steatosis, inflammation and apoptosis [ 94 ]. B1344, an FGF-21 analog, reduced the expression of TNF-α and other cytokines in the liver of mice with diet-induced NASH [ 95 ], corroborating earlier evidence showing FGF-21 analogs to be effective in both animal models and humans with NASH, although their direct effect on TNF-α has not been investigated in human NASH to-date [ 94 ]. As a result, numerous clinical trials with FGF-21 analogs are currently underway [ 94 ].…”

Section: Treatment Considerationsmentioning

confidence: 99%

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The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease

Vachliotis

Polyzos

2023

Curr Obes Rep

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Purpose of Review To summarize experimental and clinical evidence on the association between tumor necrosis factor-α (TNF-α) and nonalcoholic fatty liver disease (NAFLD) and discuss potential treatment considerations. Recent Findings Experimental evidence suggests that TNF-α is a cytokine with a critical role in the pathogenesis of NAFLD. Although, the production of TNF-α may be an early event during the course of nonalcoholic fatty liver (NAFL), TNF-α may play a more substantial role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and NAFLD-associated fibrosis. Moreover, TNF-α may potentiate hepatic insulin resistance, thus interconnecting inflammatory with metabolic signals and possibly contributing to the development of NAFLD-related comorbidities, including cardiovascular disease, hepatocellular carcinoma, and extra-hepatic malignancies. In clinical terms, TNF-α is probably associated with the severity of NAFLD; circulating TNF-α gradually increases from controls to patients with NAFL, and then, to patients with NASH. Given this potential association, various therapeutic interventions (obeticholic acid, peroxisome proliferator-activated receptors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, probiotics, synbiotics, rifaximin, vitamin E, pentoxifylline, ursodeoxycholic acid, fibroblast growth factor-21, n-3 polyunsaturated fatty acids, statins, angiotensin receptor blockers) have been evaluated for their effect on TNF-α and NAFLD. Interestingly, anti-TNF biologics have shown favorable metabolic and hepatic effects, which may open a possible therapeutic window for the management of advanced NAFLD. Summary The potential key pathogenic role of TNF-α in NAFLD warrants further investigation and may have important diagnostic and therapeutic implications.

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Section: Treatment Considerationssupporting

confidence: 70%

Section: Treatment Considerationsmentioning

confidence: 99%

The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease

Vachliotis

Polyzos

2023

Curr Obes Rep

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“…Fibroblast growth factor (FGF) based therapeutics: FGF analogs have been proposed to target steps of disease pathogenesis. FGF-21 treatments are currently in clinical development for the treatment of NASH[ 153 , 154 ] and data suggests that FGF21 is anti-fibrotic and has the potential to improve the metabolic syndrome and is effective in treating NASH. The BALANCED trial (NCT03976401) evaluated the effects of efruxifermin, a long-acting Fc-FGF21 fusion protein[ 155 ].…”

Section: Introductionmentioning

confidence: 99%

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments

Petagine,

Zariwala,

Patel

2023

World J Gastroenterol

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The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts’ opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

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“…[268][269][270] FGF21 is also being proposed as a potential novel therapeutic modality, especially with regard to improving hepatic steatosis. 271,272 Bariatric surgery to date is still the most effective strategy for weight loss and weight loss maintenance. 273 It has also been associated with improvements in cardiometabolic risk factors, improvement or remission of T2 DM, reduction in CVD events, total mortality, and cancer incidence.…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

“…Furthermore, they have a positive impact on body composition through significant improvements in VAT, fat mass index (FMI), epicardial fat and hepatic steatosis, thus making them an appealing drug in the management of different obesity phenotypes 268–270 . FGF21 is also being proposed as a potential novel therapeutic modality, especially with regard to improving hepatic steatosis 271,272 …”

Section: Natural Course and Clinical Implications Of Mho And Muhnwmentioning

confidence: 99%

Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight

Agius,

Pace,

Fava

2023

Diabetes Metabolism Res

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Over the past 4 decades, research has shown that having a normal body weight does not automatically imply preserved metabolic health and a considerable number of lean individuals harbour metabolic abnormalities typically associated with obesity. Conversely, excess adiposity does not always equate with an abnormal metabolic profile. In fact, evidence exists for the presence of a metabolically unhealthy normal weight (MUHNW) and a metabolically healthy obese (MHO) phenotype. It has become increasingly recognised that different fat depots exert different effects on the metabolic profile of each individual by virtue of their location, structure and function, giving rise to these different body composition phenotypes. Furthermore, other factors have been implicated in the aetiopathogenesis of the body composition phenotypes, including genetics, ethnicity, age and lifestyle/behavioural factors. Even though to date both MHO and MUHNW have been widely investigated and documented in the literature, studies report different outcomes on long‐term cardiometabolic morbidity and mortality. Future large‐scale, observational and population‐based studies are required for better profiling of these phenotypes as well as to further elucidate the pathophysiological role of the adipocyte in the onset of metabolic disorders to allow for better risk stratification and a personalised treatment paradigm.

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Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Cited by 17 publications

References 94 publications

The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease

The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments

Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight

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