Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

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Management of Metabolic-Associated Fatty Liver Disease/Metabolic Dysfunction-Associated Steatotic Liver Disease: From Medication Therapy to Nutritional Interventions

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2220 - 2220

Published: July 11, 2024

Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting that affects millions of people around the world. It best identified with hepatic fat build-up ultimately leads to inflammation and damage. The classification nomenclature NAFLD have long been controversial topic, until 2020 when group international experts recommended substituting MAFLD (metabolic dysfunction-associated FLD). was then terminologically complemented in 2023 by altering it MASLD, i.e., metabolic steatotic (MASLD). Both MASLD terminologies comprise element disorder, as they offer diagnostic benchmarks are embedded risk factors underlie disease. (as multisystemic disease) provides comprehensive definition includes larger population patients who at morbidity mortality, well adverse cardiovascular diabetes outcomes. highlights risks lean or normal weight individuals, factor has not accentuated discussed previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, exercise therapies extensively studied MASLD. Nutrition plays vital role managing both conditions, where centralizing on diet rich whole vegetables, fruits, foods, healthy fats, proteins, specific nutrients (e.g., omega-3 acids fibers) can improve insulin resistance reduce inflammation. Thus, essential understand nutrition these conditions work develop an individualized plan for optimal health. This review discusses prevention strategies NAFLD/MAFLD/MASLD management, particular attention correction.

Language: Английский

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Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Screening, Diagnosis, and Treatment

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(17), P. 5597 - 5597

Published: Aug. 27, 2023

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic (MASLD) affects ~70% of patients with type 2 diabetes (T2D), ~20% showing signs advanced fibrosis. Patients T2D are at an increased risk developing cirrhosis, failure, and hepatocellular carcinoma their liver-related mortality is doubled compared non-diabetic individuals. Nonetheless, the condition frequently overlooked awareness limited both among physicians. Given recent epidemiological evidence, clinical practice guidelines recommend screening for NAFLD/MASLD fibrosis in T2D. While many drugs currently being tested treatment NAFLD/MASLD, none them have yet received formal approval from regulatory agencies. However, several classes antidiabetic (namely pioglitazone, sodium-glucose transporter inhibitors, glucagon-like peptide 1 receptor agonists, multi-agonists) shown favorable effects terms enzymes, fat content and, some occasions, on histologic features such as inflammation Therefore, diabetologists opportunity to actively treat a concrete possibility changing natural history disease. In present narrative review, we summarize evidence recommendations NAFLD/MAFLD setting T2D, well effect available glucose-lowering hepatic endpoints.

Language: Английский

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The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

Medicina, Journal Year: 2023, Volume and Issue: 59(6), P. 1136 - 1136

Published: June 12, 2023

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome share multiple causal associations. Both conditions have an alarmingly increasing incidence lead to complications, which impact on a variety organs systems, such as the kidneys, eyes, nervous cardiovascular or may cause disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), antidiabetic class with well-established benefits, its members also been studied for their presumed effects steatosis fibrosis improvement in patients NAFLD steatohepatitis (NASH). The MEDLINE Cochrane databases were searched randomized controlled trials examining efficacy SGLT2-i treatment NAFLD/NASH T2DM. Of originally identified 179 articles, 21 articles included final data analysis. Dapagliflozin, empagliflozin, canagliflozin some most used agents proven treating by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat glucotoxicity, lipotoxicity even chronic inflammation. Despite considerable variability study duration, sample size, diagnostic method, resulted improvements non-invasive markers This systematic review offers encouraging results that place at top therapeutic arsenal diagnosed T2DM NAFLD/NASH.

Language: Английский

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Vascular complications of diabetes: A narrative review

Medicine, Journal Year: 2023, Volume and Issue: 102(40), P. e35285 - e35285

Published: Oct. 6, 2023

Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such eyes, kidneys, heart, brain, lead increased patient mortality. major global health issue, its incidence prevalence significantly in recent years. Moreover, expected continue rise more people adopt Western lifestyle diet. Thus, it essential understand epidemiology, pathogenesis, risk factors, treatment of vascular aid patients managing effectively. This paper provides comprehensive review literature clarify above content. Furthermore, this also delves into correlation between novel long noncoding RNAs, gut microbiota, nonalcoholic fatty liver disease, with diabetic

Language: Английский

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Non-alcoholic fatty liver disease: relation to juvenile obesity, lipid profile, and hepatic enzymes

Journal of Medicine and Life, Journal Year: 2023, Volume and Issue: 16(1), P. 42 - 47

Published: Jan. 1, 2023

The prevalence of juvenile obesity is increasing, reaching epidemic proportions, presenting a link not only to NAFLD (non-alcoholic fatty liver disease) but abnormal lipid profiles and enzyme abnormalities. Liver ultrasonography sensitive specific tool for the recognition NAFLD. This study aims assess association between determine other related changes in set indicators, including profile abnormalities serum transaminases. sample included 470 obese 210 non-obese individuals aged 6-16. Anthropometric measures were assessed, with transaminases, abdominal was used detect Fatty found 38% subjects none subjects. Within subjects, mean body mass index (BMI) waist circumference increased significantly patients compared those without liver. Moreover, LDL (low-density lipoprotein), CHOL (cholesterol), enzymes higher presence In conclusion, commonly associates obesity, relating (including elevated LDL) among people, reflecting which increase risk cirrhosis.

Language: Английский

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The Janus of a disease: Diabetes and metabolic dysfunction-associated fatty liver disease

Annals of Hepatology, Journal Year: 2024, Volume and Issue: 29(4), P. 101501 - 101501

Published: April 15, 2024

Metabolic Dysfunction-Associated Fatty Liver Disease and Diabetes Mellitus are two prevalent metabolic disorders that often coexist synergistically contribute to the progression of each other. Several pathophysiological pathways involved in association, including insulin resistance, inflammation, lipotoxicity, providing a foundation for understanding complex interrelationships between these conditions. The presence MASLD has significant impact on diabetes risk development microvascular macrovascular complications, significantly contributes an increased liver fibrosis hepatocellular carcinoma. Moreover, both pathologies have synergistic effect cardiovascular events mortality. Therapeutic interventions targeting discussed, considering lifestyle modifications, pharmacological agents, emerging treatment modalities. review also addresses challenges managing comorbidities, such as need personalized approaches potential health. insights gleaned from this analysis can inform clinicians, researchers, policymakers developing integrated strategies preventing, diagnosing, disorders.

Language: Английский

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From adiposity to steatosis: metabolic dysfunction-associated steatotic liver disease, a hepatic expression of metabolic syndrome – current insights and future directions

Clinical Diabetes and Endocrinology, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 2, 2024

Language: Английский

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Atherogenic index of plasma is an independent predictor of metabolic-associated fatty liver disease in patients with type 2 diabetes

European journal of medical research, Journal Year: 2022, Volume and Issue: 27(1)

Published: July 11, 2022

Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic disease, is the leading cause of that can ultimately lead to cirrhosis. Identifying a screening marker for early diagnosis MAFLD in patients with type 2 diabetes (T2D) reduce risk morbidity and mortality. This study investigated association between atherogenic index plasma (AIP) T2D.A retrospective case-control was conducted medical records T2D were assessed. The baseline characteristics, anthropometric indices, laboratory measurements including functions tests, fasting blood sugar, HbA1C, lipid profile documented.Out 2547 T2D, 824 (32.4%) had MAFLD. multivariate logistic regression analysis showed significant difference female-to-male ratio (1.11 vs. 1.33, OR = 0.347, P-value < 0.001), ALT (42.5 ± 28.1 22.4 11.1, 1.057, AIP (0.6 0.3 0.5 0.3, 5.057, 0.001) non-MAFLD groups, respectively. According quartile, prevalence increased significantly higher quartiles (P-value 0.001). Also, we found cut-off 0.54 predicting (sensitivity 57.8%, specificity 54.4%).In this study, good independent predictor which could help physicians follow-up T2D.

Language: Английский

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Gender difference in the association between serum uric acid and metabolic dysfunction-associated steatotic liver disease in patients with newly diagnosed type 2 diabetes

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 30, 2025

To investigate the relationship between serum uric acid (SUA) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) in newly diagnosed type 2 diabetic patients. We performed this retrospective research among 1087 inpatients with new-onset diabetes millitus (T2DM). Data were analyzed according to gender. Then, populations stratified their body mass index (BMI) men women, respectively. The physical biochemical indicators measured recorded. SUA MASLD was estimated using logistic regression analysis, unadjusted adjusted odds ratios (ORs) calculated. After adjusting for age, BMI, other components of syndrome, independently associated only men, but not women. In addition, both non-overweight/obesity overweight/obesity group. However, related There no association women overweight/obesity. patients, elevated is an independent predictor risk males. females, may depend on significance non-overweight/obese individuals.

Language: Английский

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