Mechanisms of NAFLD development and therapeutic strategies

Nature Medicine, Journal Year: 2018, Volume and Issue: 24(7), P. 908 - 922

Published: June 29, 2018

Language: Английский

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Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

Hepatology, Journal Year: 2017, Volume and Issue: 67(1), P. 123 - 133

Published: Aug. 12, 2017

Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they a growing cause of cirrhosis hepatocellular carcinoma (HCC) increasingly an indicator for transplantation. A Markov model was used to forecast NAFLD progression. Incidence based on historical projected changes adult prevalence obesity type 2 diabetes mellitus (DM). Assumptions were derived from published literature available validated using national surveillance data incidence NAFLD‐related HCC. Projected cirrhosis, advanced disease, liver‐related mortality quantified through 2030. Prevalent cases forecasted increase 21%, 83.1 million (2015) 100.9 (2030), while NASH will 63% 16.52 27.00 cases. Overall among population (aged ≥15 years) is at 33.5% 2030, median age 50 55 years during 2015‐2030. In 2015, approximately 20% classified as NASH, increasing 27% by reflection both progression aging population. decompensated 168% 105,430 HCC 137% 12,240 Liver deaths 178% estimated 78,300 During 2015‐2030, there be nearly 800,000 excess deaths. Conclusion: With continued high rates DM along with population, States. Strategies slow growth therapeutic options necessary mitigate burden. (H epatology 2018;67:123‐133).

Language: Английский

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Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030

Journal of Hepatology, Journal Year: 2018, Volume and Issue: 69(4), P. 896 - 904

Published: June 7, 2018

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis hepatocellular carcinoma globally. This burden is expected to increase as epidemics obesity, diabetes metabolic syndrome continue grow. The goal this analysis was use Markov model forecast NAFLD using currently available data.A used estimate NASH progression in eight countries based on data for adult prevalence obesity type 2 mellitus (DM). Published estimates expert consensus were build validate the projections.If DM level off future, we project modest growth total cases (0-30%), between 2016-2030, with highest China result urbanization lowest Japan shrinking population. However, at same time, will 15-56%, while mortality advanced more than double an aging/increasing population.NAFLD represent large growing public health problem efforts understand epidemic mitigate needed. If current historical rates, both increase. Since reversible, campaigns awareness diagnosis, promote diet exercise can help manage future burden.Non-alcoholic lead disease. Both conditions becoming prevalent A mathematical built how associated change over time. Results suggest increasing liver-related coming years.

Language: Английский

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Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

Hepatology, Journal Year: 2017, Volume and Issue: 65(5), P. 1557 - 1565

Published: Jan. 28, 2017

Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk by stage has not been systematically evaluated. We aimed to quantify stage–specific all‐cause and liver‐related NAFLD. Through a systematic review meta‐analysis, we identified five adult NAFLD cohort studies reporting (0‐4). Using 0 as reference population, rate ratios (MRRs) with 95% confidence intervals (CIs) for were estimated. The study reported according Preferred Reporting Items Systematic Reviews Meta‐Analyses statement. Included 1,495 patients 17,452 patient years follow‐up. Compared no (stage 0), at an increased mortality, this increases fibrosis: 1, MRR = 1.58 (95% CI 1.19‐2.11); 2, 2.52 1.85‐3.42); 3, 3.48 2.51‐4.83); 4, 6.40 4.11‐9.95). results more pronounced exponentially each increase 1.41 0.17‐11.95); 9.57 1.67‐54.93); 16.69 2.92‐95.36); 42.30 3.51‐510.34). Limitations include inability adjust comorbid conditions or demographics known impact progression inclusion simple steatosis steatohepatitis without comparison group. Conclusion: stage; these data have implications assessing utility benefits regression from one another. (H epatology 2017;65:1557‐1565).

Language: Английский

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The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe

Hepatology, Journal Year: 2016, Volume and Issue: 64(5), P. 1577 - 1586

Published: Aug. 20, 2016

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic disease. There uncertainty around the economic burden NAFLD. We constructed steady-state prevalence model to quantify this in United States and Europe. Five models were estimate NAFLD four European countries. Models built using series interlinked Markov chains, each representing age increments general populations. Incidence remission rates calculated by calibrating against real-world rates. The data validated computerized called DisMod II. patients transitioned between nine health states (nonalcoholic liver, nonalcoholic steatohepatitis [NASH], NASH-fibrosis, NASH-compensated cirrhosis, NASH-decompensated hepatocellular carcinoma, transplantation, post-liver transplant, death). Transition probabilities sourced from literature calibrated data. Utilities obtained Short Form-6D. Costs local fee schedules. In States, over 64 million people are projected have NAFLD, with annual direct medical costs about $103 billion ($1,613 per patient). Europe-4 countries (Germany, France, Italy, Kingdom), there ∼52 an cost €35 (from €354 €1,163 highest aged 45-65. significantly higher when societal included.The analysis quantifies enormity clinical burdens which will likely increase as incidence continues rise. (Hepatology 2016;64:1577-1586).

Language: Английский

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Nonalcoholic Fatty Liver Disease 2020: The State of the Disease

Gastroenterology, Journal Year: 2020, Volume and Issue: 158(7), P. 1851 - 1864

Published: Feb. 13, 2020

Language: Английский

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Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

Gut, Journal Year: 2017, Volume and Issue: 66(6), P. 1138 - 1153

Published: March 17, 2017

Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in setting non-alcoholic fatty liver disease (NAFLD) may be associated with a systemic inflammatory 'milieu' initiated part by liver-secreted cytokines molecules. Consequently, pathophysiological effects NAFLD extend beyond large body clinical evidence demonstrating to independently both prevalent incident cardiovascular (CVD), chronic kidney (CKD) type 2 diabetes mellitus (T2DM). The magnitude risk developing these extrahepatic diseases parallels underlying severity NAFLD, such that patients steatohepatitis (NASH) appear at greater CVD, CKD T2DM than those simple steatosis. Other modifiers include genetic variants (eg, patatin-like phospholipase domain-containing 3 trans-membrane 6 superfamily member polymorphisms), visceral adipose tissue accumulation, dietary intake gut microbiome. Emerging data also suggest factor for colonic neoplasia reduced bone mineral density, especially among men. Importantly, improvement/resolution is incidence improved function, adding weight causality suggesting focused treatments reduce complications. Awareness associations important clinicians CVD management, screening are routine management NAFLD.

Language: Английский

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The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease

Hepatology International, Journal Year: 2020, Volume and Issue: 14(6), P. 889 - 919

Published: Oct. 1, 2020

Language: Английский

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Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?

Journal of Hepatology, Journal Year: 2017, Volume and Issue: 68(2), P. 335 - 352

Published: Nov. 6, 2017

Language: Английский

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NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Gut, Journal Year: 2020, Volume and Issue: 69(9), P. 1691 - 1705

Published: April 22, 2020

Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to third of the world's adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) associated with higher risk all-cause mortality and leading causes death among patients are cardiovascular diseases (CVDs), followed by extrahepatic malignancies liver-related complications. A growing body evidence also indicates strongly an increased major CVD events other cardiac complications (ie, cardiomyopathy, valvular calcification arrhythmias), independently traditional factors. This narrative review provides overview literature on: (1) for association between cardiovascular, arrhythmic complications, (2) putative pathophysiological mechanisms linking (3) current pharmacological treatments might benefit or adversely affect CVD.

Language: Английский

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