scholarly journals What’s Past Is Prologue: History of Nonalcoholic Fatty Liver Disease

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 397 ◽  
Author(s):  
Giovanni Targher

Since the initial descriptions in the early 1980s by Dr. Ludwig et al. and Drs. Schaffner and Thaler, who firstly coined the terms nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), this liver disease has become a global health problem worldwide, causing considerable liver-related and extra-hepatic morbidity and mortality. Based on pathophysiological insights gained from the past decades, it has been clearly established that NAFLD is a metabolic liver disease whose etiology and pathogenesis extends beyond the liver and that NAFLD has important clinical implications, especially in terms of an increased risk of developing both cardiovascular disease (which represents the leading cause of death in this patient population) and other extra-hepatic manifestations, such as type 2 diabetes mellitus, chronic kidney disease, and some extra-hepatic cancers. The aim of this brief commentary is to discuss a recent review article written by Dr. Lonardo and colleagues, who raised awareness of the history of NAFLD. Since “What’s past is prologue”, I believe that this review article focusing on the history of NAFLD may contribute to better understanding the disease itself, as well as to anticipating the lines of the future clinical and pharmacological research of this common and burdensome liver disease.

2008 ◽  
Vol 19 (8) ◽  
pp. 1564-1570 ◽  
Author(s):  
Giovanni Targher ◽  
Michel Chonchol ◽  
Lorenzo Bertolini ◽  
Stefano Rodella ◽  
Luciano Zenari ◽  
...  

2019 ◽  
Vol 28 (4) ◽  
pp. 433-438 ◽  
Author(s):  
Vera Karamfilova ◽  
Antoaneta Gateva ◽  
Yavor Assyov ◽  
Asen Alexiev ◽  
Alexey Savov ◽  
...  

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. Methods: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. Results: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). Conclusions: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So-Ryoung Lee ◽  
Kyung-Do Han ◽  
Eue-Keun Choi ◽  
Seil Oh ◽  
Gregory Y. H. Lip

AbstractWe evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046–1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106–1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.


JGH Open ◽  
2021 ◽  
Author(s):  
Mohammad Shafi Kuchay ◽  
Narendra Singh Choudhary ◽  
Sunil Kumar Mishra ◽  
Tarannum Bano ◽  
Sakshi Gagneja ◽  
...  

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