Influence of lifestyle‐related diseases and age on the development and progression of non‐alcoholic fatty liver disease

Shima, Toshihide; Seki, Kazuhiko; Umemura, Atsushi; Ogawa, Rie; Horimoto, Ryuji; Oya, Hirohisa; Sendo, Rei; Mizuno, Masayuki; Okanoue, Takeshi

doi:10.1111/hepr.12384

Cited by 32 publications

(24 citation statements)

References 33 publications

(69 reference statements)

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“…In our results, age was also a risk factor in the progression of fibrosis. Similarly in agreement with other published data involving older groups of Japanese 39 , age is strongly associated with the development and progression of NASH 33 . However, this agreement does not preclude the observation that in children with NAFLD, steatosis is associated with advanced fibrosis as indicated in the latest published report 40 .…”

Section: Discussionsupporting

confidence: 93%

“…Although non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, the clinical association between non-alcoholic steatohepatitis (NASH), the severe version of NAFLD, and lifestyle-related diseases such as obesity, type 2 diabetes mellitus (T2DM), hypertension (HTN) and dyslipidemia has not been clarified 20 . Ethnicity and BMI were associated with the progression of fibrosis and the presence of cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

et al. 2017

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Background & Aim Several factors involved in the development of liver fibrosis in African American patients with chronic hepatitis C (CHC) have not been well-studied. We aimed to evaluate some of these risk factors. Methods We reviewed pathology and medical records of 603 African Americans with chronic hepatitis C virus (HCV) infection at Howard University Hospital from Jan. 2004 to Dec. 2013. Among the clinical and pathological data collected were HIV (human immunodeficiency virus), HCV genotype, Hepatitis B virus (HBV), diabetes mellitus (DM), hypertension (HTN), body mass index (BMI), and hepatic steatosis. Results The frequency of DM, HTN, HIV and HBV were 22%, 16%, 11%, and 4%, respectively. Median BMI was 27.3 kg/m2. The frequency of fibrosis stages 0, 1, 2, 3 and 4 were 2%, 48%, 28%, 11% and 11%, respectively. In multivariate logistic regression, we found a significant association between liver fibrosis stage (3–4 vs. 0–2) and HIV infection (OR=2.4, P = 0.026), hypertension (OR=3.0, P = 0.001), age (OR=2.6 for every 10 years, P<0.001), weight (OR = 1.1 for every 10 pound increase, P = 0.002) and steatosis grade (OR = 1.6, P = 0.002). The frequency of liver steatosis was 73%. In an ordinal logistic regression, significant risk factors for steatosis were female gender (OR = 1.5, P = 0.034) and inflammation grade (P=0.001). Conclusion This study shows that steatosis is independently associated with fibrosis in African American patients with HCV infection. Female patients were at higher risk for steatosis.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

et al. 2017

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“…Sustained lifestyle changes need integrated multidisciplinary approaches, which provide behavioural support for weight loss and healthier lifestyle habits in patients with NAFLD . Age is strongly associated with the development and progression of liver steatosis so that early and timely articulated medical and behavioural approaches in youngsters might imply a more comprehensive understanding of information and factors involved in the onset and continuation of fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%

Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion

Trovato

Martines

Brischetto

et al. 2015

Liver International

139

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“…A genetic predisposition and metabolic factors are believed to be important in NASH pathogenesis [4]. It has been found that approximately 70% of diabetic people have some form of NAFLD, and that approximately 5% to 20% of people with diabetes have cirrhosis due to NASH, while the five-year HCC rate in NASH patients is 0%–15% [3,5,6]. While liver cirrhosis secondary to hepatitis C infection is still the main cause of liver cancer and the most common indication for liver transplantation in the world, the prevalence of NAFLD and NASH-related cirrhosis and HCC will become an increasingly major health care problem in the future.…”

Section: Introductionmentioning

confidence: 99%

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

Kakehashi

Стефанов

Ishii

et al. 2017

IJMS

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To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

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Influence of lifestyle‐related diseases and age on the development and progression of non‐alcoholic fatty liver disease

Abstract: Age is strongly associated with the development and progression of NASH. Type 2 DM may play the most crucial role among lifestyle-related diseases in the development and progression of NASH.

Cited by 32 publications

References 33 publications

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

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