Comparison of the severity of metabolic, liver and cardiovascular damage in NAFLD patients attending the hepatology clinic over the last three decades

Lombardi, Rosa; Colavolpe, Lucia; Alletto, Francesca; Cespiati, Annalisa; Fatta, E.; Bertelli, C.; Cinque, Felice; Pisano, Giuseppina; Pulixi, E.A.; Francione, Paolo; Maffi, Gabriele; Iuculano, F.; Dongiovanni, Paola; Burdick, L.; Bignamini, Daniela; Maggioni, Marco; Valenti, L.; Fracanzani, Anna Ludovica

doi:10.1016/j.dld.2023.07.009

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…In this study, markers of glucose metabolism (fasting blood glucose, TYG index, glucose intolerance and metabolic syndrome) and liver enzymes, mainly ALT, were predictors of incident diabetes in non-diabetic obese subjects receiving routine medical treatment over a mean follow-up of about 14 years. Raised liver enzymes, ALT and AST could be signs of MAFLD (NAFLD) [ 15 ] [ 16 – 19 ], and liver steatosis is a component of metabolic syndrome X/insulin resistance syndrome [ 18 – 22 ]. Therefore, it is not surprising that increased ALT levels were associated with incident diabetes in obese subjects receiving routine medical treatment.…”

Section: Discussionmentioning

confidence: 99%

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

Folli,

Pontiroli,

Zakaria

et al. 2023

Acta Diabetol

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Aims The role of liver steatosis and increased liver enzymes (ALT) in increasing incident type 2 diabetes mellitus (T2DM) is debated, because of their differential effects on different ethnicities and populations. The aim of this study was to evaluate the role of elevated ALT in the development of T2DM in non-diabetic obese subjects receiving routine medical treatment. Methods A total of 1005 subjects [296 men and 709 women, aged 45.7 ± 13.12 years, body mass index (BMI) 39.5 ± 4.86 kg/m2] were followed for a mean period of 14.3 ± 4.44 years. Subjects were evaluated for several metabolic variables, including the triglyceride-glucose index and the presence of metabolic syndrome (IDF 2005 definition), and were subdivided into ALT quartiles. Results T2DM developed in 136 subjects, and the difference was significant between the first and the fourth ALT quartile (p = 0.048). Both at univariate analysis and at stepwise regression, ALT quartiles were associated with incident T2DM. Traditional risk factors for T2DM coexisted, with a somehow greater predictive value, such as triglyceride-glucose index, age, arterial hypertension, LDL-cholesterol, and metabolic syndrome. Conclusions These data suggest an association between elevated ALT levels and the risk of incident T2DM in obesity.

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Section: Discussionmentioning

confidence: 99%

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

Folli,

Pontiroli,

Zakaria

et al. 2023

Acta Diabetol

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“…Although the prevalence of obesity in the USA is expected to reach a plateau, the global prevalence of NASH is predicted to keep rising until 2030, owing to the ongoing contribution of T2D in increasing the ratio of NASH to isolated steatosis within the next decade [ 29 ]. Worryingly, compared with previous decades, patients with NAFLD have arrived for medical observation with more severe liver disease and higher subclinical atherosclerosis burden [ 30 ]. This finding accounts for NASH being the most frequent indication for liver transplantation among elderly individuals [ 31 ].…”

Section: Definitions Burden and Methodsmentioning

confidence: 99%

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Lonardo,

Ballestri,

Mantovani

et al. 2024

Metabolites

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This narrative review aims to illustrate the notion that nonalcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH), is a systemic metabolic disorder featuring both adverse hepatic and extrahepatic outcomes. In recent years, several NASH trials have failed to identify effective pharmacological treatments and, therefore, lifestyle changes are the cornerstone of therapy for NASH. with this context, we analyze the epidemiological burden of NASH and the possible pathogenetic factors involved. These include genetic factors, insulin resistance, lipotoxicity, immuno-thrombosis, oxidative stress, reprogramming of hepatic metabolism, and hypoxia, all of which eventually culminate in low-grade chronic inflammation and increased risk of fibrosis progression. The possible explanations underlying the failure of NASH trials are also accurately examined. We conclude that the high heterogeneity of NASH, resulting from variable genetic backgrounds, exposure, and responses to different metabolic stresses, susceptibility to hepatocyte lipotoxicity, and differences in repair-response, calls for personalized medicine approaches involving research on noninvasive biomarkers. Future NASH trials should aim at achieving a complete assessment of systemic determinants, modifiers, and correlates of NASH, thus adopting a more holistic and unbiased approach, notably including cardiovascular–kidney–metabolic outcomes, without restricting therapeutic perspectives to histological surrogates of liver-related outcomes alone.

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Comparison of the severity of metabolic, liver and cardiovascular damage in NAFLD patients attending the hepatology clinic over the last three decades

Cited by 2 publications

References 31 publications

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

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