Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis

Wong, Vincent Wai‐Sun; Singal, Ashwani K.

doi:10.21037/tgh.2019.06.06

Cited by 37 publications

(28 citation statements)

References 90 publications

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“…Many drugs with various targets are currently being evaluated in the field of NAFLD: thyroid hormone receptor-beta agonists, aramchol (a steroyl-CoA desaturase-1 inhibitor), etc. 131 The therapeutic landscape is expected to evolve in the coming years.…”

Section: Medical Treatmentsmentioning

confidence: 99%

Combined alcoholic and non-alcoholic steatohepatitis

2020

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While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.

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Section: Medical Treatmentsmentioning

confidence: 99%

Combined alcoholic and non-alcoholic steatohepatitis

2020

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“…A phase 2 clinical trial of another selective thyromimetic, VK2809, demonstrated similar results. 72 …”

Section: Treatment Implicationsmentioning

confidence: 99%

“…A phase 2 clinical trial of another selective thyromimetic, VK2809, demonstrated similar results. 72 Other thyroid hormone metabolites that could improve NAFLD/NASH treatment are T2 and 3-iodothyronamine (referred to as T1AM). A study performed in rats demonstrated that exogenous T2 could decrease liver fat, TGs and LDL cholesterol; 73 however, small human studies including up to 40 patients with metabolic syndrome treated with T2 showed no effect on lipid profile and insulin resistance.…”

Section: Treatment Implicationsmentioning

confidence: 99%

Hypothyroidism and Nonalcoholic Fatty Liver Disease: Pathophysiological Associations and Therapeutic Implications

Kizivat

Marić

Mudri

et al. 2020

Journal of Clinical and Translational Hepatology

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Nonalcoholic fatty liver disease (NAFLD) is a complex clinical entity which can be secondary to many other diseases including hypothyroidism, characterized by lowering of thyroid hormones and increased thyroid stimulating hormone (TSH). A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity, even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications. In addition, a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment, currently in phase 3 clinical trials. In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment, specifically thyroid hormone receptor (THR) agonist and its metabolites.

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“…Despite NAFL affects around one-third of the Western world with an incidence that continues to grow, no pharmacological drugs have been already approved for the treatment of the disease. Currently, only lifestyle change (diet and physical activity) is suggested to these patients [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

Antonucci¹,

Porcu²,

Timperi

et al. 2020

Journal of Immunology Research

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Neutrophils or PolyMorphonuclear Neutrophils (PMNs) are key effector cells of the innate immune system and thanks to their remarkable plasticity, establish a cross talk with T cells modulating their survival and effector functions. During Nonalcoholic Steatohepatitis (NASH), the advanced form of hepatic steatosis or NAFL, PMNs infiltrate liver tissue, becoming a histological feature of NASH. Our aim was to evaluate the frequency of PMNs in NAFL and NASH patients in order to understand how they modulate the activity of circulating CD4+ and CD8+ T cells. In our cohort of patients, NASH patients displayed a higher frequency of circulating PMNs that was strongly correlated to liver enzymes, grade of steatosis, inflammation and fibrosis, the hepatocellular ballooning, and NAFLD Activity Score (NAS). Furthermore, even if ex vivo, in both groups of patients, PMNs shared the same phenotype of resting cells, after 24 hours of coculture with autologous CD4+ and CD8+ T cells, PMNs of NASH patients acquired a more active phenotype, becoming able to strongly inhibit proliferation and activation of CD4+ and CD8+ T cells. The higher ability of PMNs of NASH patients in suppressing CD4+ and CD8+ T cells, over time, might contribute in reducing the immunological defense of liver tissue against damages thus taking part in the progression of the NAFL disease toward NASH.

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Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis

Cited by 37 publications

References 90 publications

Combined alcoholic and non-alcoholic steatohepatitis

Combined alcoholic and non-alcoholic steatohepatitis

Hypothyroidism and Nonalcoholic Fatty Liver Disease: Pathophysiological Associations and Therapeutic Implications

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

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