Precision medicine in nonalcoholic fatty liver disease

Lonardo, Amedeo

doi:10.1111/jgh.15850

Cited by 11 publications

(10 citation statements)

References 70 publications

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“…On the one hand, it may better stratify those at high risk of fibrosing liver disease; on the other hand, it may simultaneously allow the identification of increased CVR. This finding is critical for personalized and precision medicine approaches that are eagerly awaited for metabolic disorders and NAFLD [120][121][122][123] . For example, personalized diagnostic and follow-up schedules might be envisaged for these individuals based on noninvasive fibrosis scores.…”

Section: Discussionmentioning

confidence: 99%

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Ballestri¹,

Mantovani²,

Girolamo³

et al. 2023

Metab Target Organ Damage

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Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic techniques associated with ultrasonography or magnetic resonance. Our literature review identified numerous studies demonstrating that biomarkers of fibrosis (the most common being FIB-4) and elastographic techniques predict overall mortality and major cardiovascular events among NAFLD patients. The mechanisms accounting for this association are briefly reviewed. In addition to assessing hepatic fibrosis at baseline, during follow-up, and after therapeutic interventions in NAFLD patients, noninvasive assessment of hepatic fibrosis may predict cardiovascular events and overall mortality in these patients.

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Section: Discussionmentioning

confidence: 99%

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Ballestri¹,

Mantovani²,

Girolamo³

et al. 2023

Metab Target Organ Damage

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“…However, given that the picture is incomplete, additional prospective studies will have to better define the pathomechanics of this scenario. Such as extensively discussed elsewhere [36][37][38], an improved understanding of this will lead to personalized medicine approaches in prevention, diagnosis, management, prognostication, and individualized follow-up protocols.…”

Section: Abbreviationsmentioning

confidence: 99%

Extra-hepatic cancers in metabolic fatty liver syndromes

Lonardo

2023

Explor Dig Dis

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The liver operates an array of vital digestive, metabolic, immunological, and purificatory physiological functions including synthesis of albumin, regulation of glucose and lipid homeostasis, detoxification of ammonia and xenobiotics, choleresis and production of hepatokines and hormones [1]. However, in healthy states, it is not involved in the storage of fatty substrates and, whenever the normal liver threshold is exceeded, accumulated triglycerides will impair whole-body insulin sensitivity, trigger sterile low-grade hepatic metaflammation, and promote the progression of the fibrosing process that will eventually conduce to cirrhosis in a subset of individuals [2,3]. While the histopathological cascade described above was first recognized in the 1800s by distinguished liver pathologists, such as Addison, Rokitansky, Pepper, and Bartolow, until the years 1958-1971 the debate, with the contributions by Zelman and Thaler, mainly focused on such hepato-histopathological changes being indistinguishable irrespective of the inciting triggers: alcohol, obesity, and diabetes [4]. From the perspective of clinical nosography, this finding eventually led to coining the innovative definitions of "nonalcoholic steatohepatitis (NASH)" and "nonalcoholic fatty liver disease (NAFLD)" in the 1980s. "Nonalcoholic" is a composite word that, at least in the spelling used by Ludwig et al., and by Schaffner and Thaler; does not require any hyphens [4] at variance with the use that is sometimes encountered in contemporary literature ("non-alcoholic").To convert a "negative" definition (i.e., nonalcoholic) into a positive diagnosis highlighting the pathogenic (dysmetabolic) origin, while also avoiding stigmatizing alcohol consumption, a panel of international experts have proposed renaming NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD). Although endorsed to an unprecedented extent [5], MAFLD retains some elements of ambiguity and amplifies NAFLD's heterogeneity, therefore creating major implications for research arena and clinical practice [6,7].Compared to the history of NAFLD briefly summarized above, the notions that NAFLD and NAFLD-related metabolic conditions could also be a risk factor for the development of primary liver cancer (PLC) in a limited proportion of individuals are more recent (Table 1) [8-13].While it is logical and somewhat foreseeable that PLC may eventually develop in some individuals with NAFLD, more recent observations substantiate the probably unexpected theory that, further to PLCs, NAFLD

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“…NAFLD is a heterogenous disease with several determinants, including pathophysiological mechanisms, comorbidities, age, sex, genetic variants, microbiota composition, degree of alcohol consumption, and others. [145][146][147] Recent studies have identified distinct subtypes of NAFLD based on histological and molecular characteristics. Liu et al identified two distinct subtypes of NAFLD based on molecular profiling, one subtype characterized by dysregulated immune and inflammatory pathways and the other by dysregulated lipid metabolic pathways.…”

Section: Disease Heterogeneity and Precision Medicinementioning

confidence: 99%

Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies

Agyapong

Dashti

Banini

2023

Annals of the New York Academy of Sciences

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Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end‐stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra‐hepatic outcomes), diagnosis, and current management strategies.

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Precision medicine in nonalcoholic fatty liver disease

Cited by 11 publications

References 70 publications

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Extra-hepatic cancers in metabolic fatty liver syndromes

Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies

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