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Author

Paul Angulo

Other affiliations: Mayo Clinic, Durham University
Bio: Paul Angulo is an academic researcher from University of Kentucky. The author has contributed to research in topics: Nonalcoholic fatty liver disease & Primary sclerosing cholangitis. The author has an hindex of 77, co-authored 191 publications receiving 32339 citations. Previous affiliations of Paul Angulo include Mayo Clinic & Durham University.


Papers
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Journal ArticleDOI
Paul Angulo1
TL;DR: Nonalcoholic fatty liver disease is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

4,705 citations

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TL;DR: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis, although the absolute risk is low.

2,681 citations

Journal ArticleDOI
TL;DR: A simple scoring system accurately separates patients with nonalcoholic fatty liver disease with and without advanced fibrosis, rendering liver biopsy for identification ofAdvanced fibrosis unnecessary in a substantial proportion of patients.

2,387 citations

Journal ArticleDOI
TL;DR: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.

2,061 citations

Journal ArticleDOI
TL;DR: The etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management are discussed in this paper, where the authors discuss the etiology and pathogenesis of NFLD.
Abstract: NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management.

1,566 citations


Cited by
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Journal ArticleDOI
TL;DR: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.

6,746 citations

Journal ArticleDOI
TL;DR: A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve current concepts for screening and treatment of this disease.

4,768 citations

Journal ArticleDOI
Paul Angulo1
TL;DR: Nonalcoholic fatty liver disease is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

4,705 citations

Journal ArticleDOI
TL;DR: The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review.
Abstract: Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element–binding proteins (SREBPs). SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1–4). In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles. The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice. These studies form the subject of this review.

4,406 citations