Epidemiology and Natural History of Non-Alcoholic Steatohepatitis

Argo, Curtis K.; Caldwell, Stephen H.

doi:10.1016/j.cld.2009.07.005

Cited by 356 publications

(277 citation statements)

References 147 publications

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“…In around 47% of the severely obese adults this benign hepatic lipid accumulation evolves into nonalcoholic steatohepatitis (NASH) characterized by inflammatory infiltration of the liver and low‐level fibrosis 32. Between 10 and 29% of the individuals with NASH develop advanced fibrosis, cirrhosis, and ultimately, hepatocellular carcinoma (HCC) 33, 34. This progressive disease development is characterized by increasing severity and predisposition to mortality.…”

Section: Introductionmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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Section: Introductionmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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“…This progression rate may be an overestimate due to selection bias. 40,41 Some 40%-62% of patients with NASH-related cirrhosis develop a complication of cirrhosis, including HCC, after 5-7 years of followup. 42,43 Retrospective data suggest that as many as 4%-27% of cases of NASH transform to HCC after the development of cirrhosis, although the overall occurrence of HCC in the setting of NAFLD remains a rare complication.…”

Section: Natural History Of Nafldmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection

2010

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Hepatocellular carcinoma (HCC) is a common and deadly malignancy that is increasing in incidence in developed countries. The emergence of hepatitis C virus (HCV) accounts for about half of this increase in HCC, although the etiology of HCC in 15%-50% of new HCC cases remains unclear. The most common form of chronic liver disease in developed countries is nonalcoholic fatty liver disease (NAFLD), which encompasses a broad spectrum of histopathology. The prevalence of NAFLD, including the more aggressive nonalcoholic steatohepatitis (NASH), is increasing with the growing epidemics of diabetes and obesity. NASH can progress to cirrhosis and its related complications. Growing evidence suggests that NASH accounts for a large proportion of idiopathic or cryptogenic cirrhosis, which is associated with the typical risk factors for NASH. HCC is a rare, although important complication of NAFLD. Diabetes and obesity have been established as independent risk factors for the development of HCC. New evidence also suggests that hepatic iron deposition increases the risk of HCC in NASH-derived cirrhosis. Multiple case reports and case reviews of HCC in the setting of NASH support the associations of diabetes and obesity with the risk of HCC, as well as suggest age and advanced fibrosis as significant risks. Insulin resistance and its subsequent inflammatory cascade that is associated with the development of NASH appear to play a significant role in the carcinogenesis of HCC. The complications of NASH, including cirrhosis and HCC, are expected to increase with the growing epidemic of diabetes and obesity.

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“…2,3 Importantly up to 25% of NAFLD patients develop NASH, and in approximately one-third of NASH patients there is slowly progressive liver fibrosis leading to cirrhosis. 4,5 In 1998, the 'two hit' theory of disease pathogenesis was proposed in which lipid accumulation and steatosis as first hit sensitizes the liver to a variety of second hits (eg, oxidative stress) that lead to necroinflammation and fibrosis. 6 Recent experimental data suggest, however, that dietary cholesterol intake rather than existing liver steatosis represents a major risk for the development of NASH.…”

mentioning

confidence: 99%

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

Kampschulte

Stöckl

Langheinrich

et al. 2014

Laboratory Investigation

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Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis.Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-kB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.

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Epidemiology and Natural History of Non-Alcoholic Steatohepatitis

Cited by 356 publications

References 147 publications

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

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