Natural History of Non-Alcoholic Fatty Liver Disease: A Study With Paired Liver Biopsies

Reddy, Yala Kirthi; Marella, Hemnishil K.; Jiang, Yu; Ganguli, Surosree; Snell, Peter D.; Podila, Pradeep; Maliakkal, Benedict

doi:10.1016/j.jceh.2019.07.002

Cited by 31 publications

(32 citation statements)

References 29 publications

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“…ranging from simple steatosis [nonalcoholic fatty liver (NAFL)] to steatohepatitis (NASH) with or without liver fibrosis or cirrhosis. The natural history of disease progression is complex, supported by findings of rapid fibrosis progression on one hand and spontaneous disease regression on the other hand (3,4). Unfortunately, we do not have a pathophysiology-driven explanation for the observed phenotypic variability of this liver disease.…”

mentioning

confidence: 83%

Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition

Kakiyama

Marques

Martin

et al. 2020

Journal of Lipid Research

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Nonalcoholic fatty liver disease (NAFLD) is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in mice to elucidate a plausible mechanistic pathway for promoting the transition from NAFL to NASH. We show that oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the “acidic/alternative” pathway of cholesterol metabolism. Specifically, we report data showing that an inability to up-regulate CYP7B1, in the setting of insulin resistance, results in the accumulation of toxic intracellular cholesterol metabolites that promote inflammation and hepatocyte injury. This metabolic pathway, initiated and exacerbated by insulin resistance, offers insight into approaches for the treatment of NAFLD.

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mentioning

confidence: 83%

Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition

Kakiyama

Marques

Martin

et al. 2020

Journal of Lipid Research

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“…In India, obesity is taking a big leap and hence proportionately there is a rise in NAFLD as well [3][4][5]. NAFLD increases risk of liver-related morbidity and mortality because of development of non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma [6][7][8]. There is bidirectional association between NAFLD and metabolic syndrome; cardiovascular disease is the leading cause of mortality in NAFLD [3,8,9].…”

Section: Introductionmentioning

confidence: 99%

Endoscopic sleeve gastroplasty — minimally invasive treatment for non-alcoholic fatty liver disease and obesity

Jagtap

Kalapala

Katakwar

et al. 2021

Indian J Gastroenterol

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Introduction Adequate weight loss can lead to reduction in steatosis, inflammation, and fibrosis in patients with obesity and nonalcoholic fatty liver disease (NAFLD). We evaluated the role of endoscopic sleeve gastroplasty (ESG) in patients with obesity and NAFLD. Methods In this single-center prospective study, consecutive adult patients with NAFLD who underwent ESG between November 2018 and May 2019 were included. The primary outcome was the impact of ESG on hepatic parameters: change in alanine aminotransferase (ALT), hepatic steatosis index (HSI), NAFLD fibrosis score (NFS), fibrosis-4 index (FIB-4), and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) from baseline to 6 and 12 months. Secondary outcomes included change in glycated hemoglobin (HbA1c), percentage weight loss, and safety. Analysis of variance with repeated measures was used for statistical analysis. Results A total of 26 patients (mean age [SD] 41.5 [9.58] years; 16 females) with mean (SD) weight of 99.43 (21.89) kg at baseline were included. There was significant improvement in ALT (mean ± SD) from baseline of 59.54 ± 17.02 IU/L to 49.50 ± 11.72 IU/L and 48.42 ± 13.22 IU/L at 6 and 12 months (p = 0.001). Mean (SD) NFS was significantly improved from 0.228 (1.00) at baseline to −0.202 (1.16) and −0.552 (1.08) at 6 and 12 months (p 0.001). Mean (SD) HSI, FIB-4, and APRI scores significantly reduced from baseline to 6 and 12 months (p = 0.001). There was 18.07% total body weight loss at 12 months, with significant improvement in HbA1c. There were no major adverse events. Conclusion ESG is a safe and effective treatment option for patients with NAFLD and obesity causing significant weight loss. Rigorous randomized trials are required to incorporate ESG in NAFLD treatment algorithm.

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“…Importantly, they identified a subgroup of ‘rapid progressors’, with one in five progressors advancing from no fibrosis at baseline to advanced fibrosis or cirrhosis over a mean 5.9 years [ 7 ]. More recent studies have also demonstrated progression to advanced fibrosis or cirrhosis in around 20% of patients with baseline steatosis without evidence of NASH, over an average follow up of 4 to 8 years [ 22 , 23 ]. Overall, 34% of patients have progressive disease, 43% have stable disease and 22% will regress [ 7 ].…”

Section: Disease Progressionmentioning

confidence: 99%

“…HCC typically arises on a background of cirrhosis, but in NAFLD it can also occur precirrhosis. NAFLD, non-alcoholic fatty liver diseases; NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma baseline steatosis without evidence of NASH, over an average follow up of 4 to 8 years [22,23]. Overall, 34% of patients have progressive disease, 43% have stable disease and 22% will regress [7].…”

Section: Disease Progressionmentioning

confidence: 99%

Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications

et al. 2021

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Purpose of Review Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification. Recent Findings PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. Summary It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.

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Natural History of Non-Alcoholic Fatty Liver Disease: A Study With Paired Liver Biopsies

Cited by 31 publications

References 29 publications

Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition

Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition

Endoscopic sleeve gastroplasty — minimally invasive treatment for non-alcoholic fatty liver disease and obesity

Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications

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