Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults

Marengo, Arianna; Jouness, R. Ibrahim Kamal; Bugianesi, Elisabetta

doi:10.1016/j.cld.2015.10.010

Cited by 120 publications

(103 citation statements)

References 49 publications

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“…For example, steatosis has been associated with the metabolic syndrome and insulin resistance, although the cause-effect relationship of this association is not clear424344. Patients with steatosis are also at greater risk for the development of steatohepatitis and hepatic fibrosis, including cirrhosis45. The cause of NAFLD appears to be multifactorial46, although lifestyle (i.e., over-nutrition) plays a significant role by contributing to the development of obesity47.…”

Section: Discussionmentioning

confidence: 99%

A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains

Wood¹,

Chu²,

Argyropoulos

et al. 2017

Sci Rep

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Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy. Using a 443 patient training set, protein biomarker discovery was performed using the highly multiplexed SOMAscan® proteomic assay, a set of 19 clinical variables, and the steatosis predisposing PNPLA3 rs738409 single nucleotide polymorphism genotype status. The most stable markers were selected using a stability selection algorithm with a L1-regularized logistic regression kernel and were then fitted with logistic regression models to classify steatosis, that were then tested against a 133 sample blinded verification set. The highest area under the ROC curve (AUC) for steatosis of PNPLA3 rs738409 genotype, 8 proteins, or 19 phenotypic variables was 0.913, whereas the final classifier that included variables from all three domains had an AUC of 0.935. These data indicate that multi-domain modeling has better predictive power than comprehensive analysis of variables from a single domain.

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Section: Discussionmentioning

confidence: 99%

A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains

Wood¹,

Chu²,

Argyropoulos

et al. 2017

Sci Rep

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“…The prevalence of CHB is approximately 0.5% in the United States, 7% in China, and 10% in African countries [1]. The prevalence of NAFLD varies from 20% to 51%, depending on the study population [3]. The increasing prevalence of NAFLD has resulted in the increased coexistence of CHB and NAFLD.…”

Section: Introductionmentioning

confidence: 99%

The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease

et al. 2017

Oncotarget

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Background/AimThe gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a novel serum model, which was reported more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD).ResultsOf 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GPR was higher than that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89 vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p = 0.104).Materials and Methods131 patients with CHB-NAFLD were included, and the diagnostic performances of GPR, APRI and FIB-4 were compared by receiver operating characteristic (ROC) curves and the area under ROC curves (AUROCs).ConclusionsThe GPR could be used as a non-invasive marker to predict liver fibrosis and cirrhosis in CHB-NAFLD individuals.

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“…NAFLD includes a wide spectrum of disorders associated with fat deposition in the liver that spans from isolated steatosis to nonalcoholic steatohepatitis (NASH) characterized by steatosis with hepatocellular injury, and inflammatory changes with or without fibrosis to NASH with advanced fibrosis and cirrhosis [3,4]. Natural history studies suggest that, although some patients with isolated steatosis may develop significant fibrosis, the majority of individuals in this group appear to have a benign non-progressive clinical course while those with NASH undisputedly may progress to cirrhosis [2,5]. Among the latter group of patients, those with liver fibrosis (stage 2 or higher) appear to be the ones at higher risk of overall and liver-related morbidity and mortality [6].…”

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confidence: 99%

Innate Immunity and Inflammation in NAFLD/NASH

et al. 2016

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Inflammation and hepatocyte injury and death are the hallmarks of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), which is a currently burgeoning public health problem. Innate immune activation is a key factor in triggering and amplifying hepatic inflammation in NAFLD/NASH. Thus, identification of the underlying mechanisms by which immune cells in the liver recognize cell damage signals or the presence of pathogens or pathogen-derived factors that activate them is relevant from a therapeutic perspective. In this review, we present new insights into the factors promoting the inflammatory response in NASH including sterile cell death processes resulting from lipotoxicity in hepatocytes as well as into the altered gut-liver axis function, which involves translocation of bacterial products into portal circulation as a result of gut leakiness. We further delineate the key immune cell types involved and how they recognize both damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs) through binding of surface-expressed pattern recognition receptors (PRRs), which initiate signaling cascades leading to injury amplification. The relevance of modulating these inflammatory signaling pathways as potential novel therapeutic strategies for the treatment of NASH is summarized.

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Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults

Cited by 120 publications

References 49 publications

A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains

A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains

The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease

Innate Immunity and Inflammation in NAFLD/NASH

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