Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy

Bellentani, Stefano; Saccoccio, Gioconda; Masutti, Flora; Crocè, Lory Saveria; Brandi, Giovanni; Sasso, Franco; Cristanini, Giovanni; Tiribelli, Claudio

doi:10.7326/0003-4819-132-2-200001180-00004

Cited by 1,126 publications

(799 citation statements)

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“…Our finding of a positive relation between obesity and noncancer liver disease mortality accords with those from other population-based studies in which cirrhosis-related deaths (in prospective analyses) 15 or fatty liver disease (in cross sectional analyses) 13,14 were the outcomes of interest. The elevated risk of liver cancer mortality in obese men apparent herein also supports the findings of a recent meta-analysis of 10 published studies.…”

Section: Discussionsupporting

confidence: 88%

“…[8][9][10][11][12] In the few general population-based surveys conducted, the prevalence of liver disease, particularly hepatic steatosis (fatty liver disease), also appears to be higher in heavier people. 13,14 However, as has been highlighted, 15 interpretation of these findings is complicated by the issue of reverse causality. Thus, while it may be that obesity is indeed a risk factor for liver disease, it is equally plausible that liver disease may lead to weight reduction (through, for instance, the loss of muscle mass), thereby resulting in an underestimation of the importance of obesity as a risk factor, or weight gain (through, for instance, peripheral oedema), thereby leading to an overestimation of its role.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, while it may be that obesity is indeed a risk factor for liver disease, it is equally plausible that liver disease may lead to weight reduction (through, for instance, the loss of muscle mass), thereby resulting in an underestimation of the importance of obesity as a risk factor, or weight gain (through, for instance, peripheral oedema), thereby leading to an overestimation of its role. Furthermore, with few exceptions, 13,14 these studies are based on clinical samples without normal weight comparison groups. Hence, it is less clear what influence, if any, obesity may have on liver disease in population-based studies of individuals who are initially free of the condition.…”

Section: Introductionmentioning

confidence: 99%

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Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

et al. 2008

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Obesity has been implicated in the aetiology of liver disease. However, to date, evidence is largely drawn from cross-sectional studies, where interpretation is hampered by reverse causality, and from studies on clinical populations that have limited generalisability. In this prospective cohort study, data on body mass index (BMI) and covariates were collected at baseline on 18 863 male government employees (aged 40-69 years). Respondents were then followed up for a maximum of 38 years of age. Mortality surveillance gave rise to 13 129 deaths, 122 of which were due to liver disease (57 cancers; 65 non-cancers). In ageadjusted analyses, BMI was positively related to total liver disease mortality (hazards ratio per 1 s.d. increase in BMI; 95% confidence interval (CI): 1.36; 1.14, 1.62) in a graded fashion across the weight categories (P-value for trend: 0.01). The magnitude of this association was somewhat stronger for non-cancer liver disease deaths (1.47; 1.16, 1.86) than for cancer liver disease deaths (1.25; 0.96, 1.62). Excluding deaths in the first 10 years of follow-up somewhat strengthened the BMIFnoncancer liver disease association. Adjustment for socioeconomic position, other candidate confounders and mediating factors led to the modest attenuation of these associations. Further investigation in prospective cohort studies with more detailed data on liver disease, for instance using biochemical tests of liver function or hepatic ultrasonography, is warranted.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

et al. 2008

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“…A hyperechogenic liver ultrasound was defined as the presence of an ultrasound pattern of a bright liver, with evident density differences between hepatic and renal parenchyma. 26 In SHIP, ultrasound examinations and readings underlie strict quality standards. [27][28][29][30] For the laboratory examinations, nonfasting blood samples were drawn from the cubital vein in the supine position.…”

Section: Methodsmentioning

confidence: 99%

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels

et al. 2009

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The aim of the present study was to investigate the association of serum gamma-glutamyltransferase (GGT) levels with all-cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population-based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis. GGT was divided into age-and sex-dependent quintiles to calculate overall and sex-specific crude incidence mortality rates. Hepatic steatosis was defined by elevated GGT levels (>80%) and the presence of hyperechogenic liver ultrasound. We used multiple-adjusted Cox proportional hazards regression models, first, to assess the direct effect of GGT on all-cause mortality, second, to stratify according to the ultrasonographic finding, and third, to investigate potential mediating effects of cardiometabolic risk factors. During 29,810 person-years (7.3 years, median) of follow-up, 307 individuals (7.5%) died, resulting in a death rate of 0.86 deaths per 1000 person-years. Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.08-2.05), but not in women (HR 1.30; 95% CI, 0.80-2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21-3.27). Cause-specific mortality analysis by cardiovascular disease deaths confirmed the sex-specific association. Adjustment for cardiometabolic risk factors did not affect the estimates. Conclusion: In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification.

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“…However moderate amounts of alcohol (30-50 g/day) in patients exposed to metabolic risk factors are frequent and have a much lower impact than overweight in inducing steatosis. 63 New drugs, especially antiinflammatory and antifibrotics, should be tested in this group of patients as well. Patients with cirrhosis are also excluded from most trials.…”

Section: Special Populations For Nashmentioning

confidence: 99%

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

2010

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Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges for trial design and proposes endpoints for future proof of principle, registrational, and postmarketing trials. (HEPATOLOGY 2010;52:2206-2215 N onalcoholic steatohepatitis (NASH) is emerging as the next big therapeutic challenge in hepatology. 1 Currently the top cause of newly identified chronic liver diseases, NASH has potential for fibrosis, cirrhosis decompensation, and hepatocellular carcinoma. Not all individuals with metabolic risk factors will experience these adverse outcomes and identifying those at risk is critical. Prognostic markers for progression have mostly been derived from histological studies. Compared to steatosis alone or to steatosis and minimal inflammation, the coexistence of inflammation, cell injury (ballooning), and steatosis, a pathological aggregate labeled steatohepatitis, is associated with a significant increase in overall mortality and in liver-related mortality. The degree of inflammation is the best predictor of fibrosis progression, 2 a widely accepted surrogate for hard endpoints such as cirrhosis, endstage liver disease, and possibly hepatocellular carcinoma.Insulin resistance (IR) is consistently found in patients with NASH in both cross-sectional and longitudinal studies. Moreover, there is a stepwise increase in the severity of IR and its phenotypic complications (clustered as elements of the metabolic syndrome) between normal liver, isolated steatosis, and steatohepatitis that has prompted speculation that IR might contribute to liver damage. Logically, most therapeutic trials focused on insulin sensitizers (IS) as candidate therapies.The aim of this report is to critically review the results of trials of metformin and glitazones for NASH. We highlight methodological challenges for trial design and propose endpoints for future proof of principle, registrational, and postmarketing trials.

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Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy

Cited by 1,126 publications

References 20 publications

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

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