Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now ...receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this disease.
Ultrasonography is a widely accessible imaging technique for the detection of fatty liver, but the reported accuracy and reliability have been inconsistent across studies. We aimed to perform a ...systematic review and meta‐analysis of the diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver. We used MEDLINE and Embase from October 1967 to March 2010. Studies that provided cross‐tabulations of ultrasonography versus histology or standard imaging techniques, or that provided reliability data for ultrasonography, were included. Study variables were independently ed by three reviewers and double checked by one reviewer. Forty‐nine (4720 participants) studies were included for the meta‐analysis of diagnostic accuracy. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate‐severe fatty liver, compared to histology (gold standard), were 84.8% (95% confidence interval: 79.5‐88.9), 93.6% (87.2‐97.0), 13.3 (6.4‐27.6), and 0.16 (0.12‐0.22), respectively. The area under the summary receiving operating characteristics curve was 0.93 (0.91‐0.95). Reliability of ultrasound for the detection of fatty liver showed kappa statistics ranging from 0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability. Sensitivity and specificity of ultrasound was similar to that of other imaging techniques (i.e., computed tomography or magnetic resonance imaging). Statistical heterogeneity was present even after stratification for multiple clinically relevant characteristics. Conclusion: Ultrasonography allows for reliable and accurate detection of moderate‐severe fatty liver, compared to histology. Because of its low cost, safety, and accessibility, ultrasound is likely the imaging technique of choice for screening for fatty liver in clinical and population settings. (HEPATOLOGY 2011; 54:1082–1090)
Previous estimates of the prevalence of nonalcoholic fatty liver disease (NAFLD) in the US population relied on measures of liver enzymes, potentially underestimating the burden of this disease. We ...used ultrasonography data from 12,454 adults who participated in the Third National Health and Nutrition Examination Survey, conducted in the United States from 1988 to 1994. We defined NAFLD as the presence of hepatic steatosis on ultrasonography in the absence of elevated alcohol consumption. In the US population, the rates of prevalence of hepatic steatosis and NAFLD were 21.4% and 19.0%, respectively, corresponding to estimates of 32.5 (95% confidence interval: 29.9, 35.0) million adults with hepatic steatosis and 28.8 (95% confidence interval: 26.6, 31.2) million adults with NAFLD nationwide. After adjustment for age, income, education, body mass index (weight (kg)/height (m)²), and diabetes status, NAFLD was more common in Mexican Americans (24.1%) compared with non-Hispanic whites (17.8%) and non-Hispanic blacks (13.5%) (P = 0.001) and in men (20.2%) compared with women (15.8%) (P < 0.001). Hepatic steatosis and NAFLD were also independently associated with diabetes, with insulin resistance among people without diabetes, with dyslipidemia, and with obesity. Our results extend previous national estimates of the prevalence of NAFLD in the US population and highlight the burden of this disease. Men, Mexican Americans, and people with diabetes and obesity are the most affected groups.
We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence ...of cardiovascular disease (CVD) or its risk factors.
This was a cross-sectional study of 4,472 adults aged 20-59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders.
Participants with NAFLD showed lower overall performance on the SDLT (β = 0.726, 95% confidence interval CI 0.105-1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (β = 0.018, 95% CI 0.006-0.030) and aspartate aminotransferase (β = 0.021, 95% CI 0.005-0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (β = 0.002, 95% CI 0.0001-0.004).
NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications.
The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely ...unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women.
A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound.
During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status.
In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD.
Persons with prediabetes and diabetes mellitus are at high risk for cardiovascular events. However, the relationships of prediabetes and diabetes mellitus to the development of subclinical myocardial ...damage are unclear.
We measured cardiac troponin T with a highly sensitive assay (hs-cTnT) at 2 time points, 6 years apart, among 9051 participants of the community-based Atherosclerosis Risk in Communities Study with no diabetes mellitus, or prediabetes, and without cardiovascular disease including silent myocardial infarction by ECG. First, we examined the incidence of elevated hs-cTnT (≥14 ng/L) at 6 years of follow-up. Second, we examined clinical outcomes during the subsequent ≈14 years of follow-up among persons with and without incident elevations in hs-cTnT. Cumulative probabilities of elevated hs-cTnT at 6 years among persons with no diabetes mellitus, prediabetes, and diabetes mellitus were 3.7%, 6.4%, and 10.8%, respectively. Compared with normoglycemic persons, the adjusted relative risks for incident elevated hs-cTnT were 1.40 (95% CI, 1.08-1.80) for prediabetes and 2.47 (95% CI, 1.78-3.43) for diabetes mellitus. Persons with diabetes mellitus and incident elevations in hs-cTnT were at a substantially higher risk of heart failure (hazard ratio, 6.37 95% CI, 4.27-9.51), death (hazard ratio, 4.36 95% CI, 3.14-6.07), and coronary heart disease (hazard ratio, 3.84 95% CI, 2.52-5.84) compared with persons without diabetes mellitus and no incident elevation in hs-cTnT.
Prediabetes and diabetes mellitus were independently associated with the development of subclinical myocardial damage, as assessed by hs-cTnT, and those persons with evidence of subclinical damage were at highest risk for clinical events. These results support a possible deleterious effect of hyperglycemia on the myocardium, possibly reflecting a microvascular cause.
Aims/hypothesis
The aim of this study was to evaluate the prospective association between baseline and 9 year change in alcohol consumption and long-term risk of diabetes and whether these ...associations might be modified by sex and/or BMI.
Methods
We conducted a prospective analysis of 12,042 Atherosclerosis Risk in Communities (ARIC) study participants without prevalent diabetes (55% women, 78% white, mean age 54 years). Alcohol consumption was assessed at visit 1 (1987–1989) and visit 4 (1996–1998). We used Cox models to estimate hazard ratios for diabetes risk by baseline drinking categories and change in alcohol consumption, stratified by sex and obesity status.
Results
During a median follow-up of 21 years, there were 3795 incident cases of diabetes. Among women, consuming 8–14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.75, 95% CI 0.58, 0.96) compared with current drinkers consuming ≤1 drink/week. Among men, consuming 8–14 drinks/week was associated with a borderline significant lower risk of diabetes (HR 0.84, 95% CI 0.70, 1.00) and consuming >14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.81, 95% CI 0.67, 0.97) (
p
interaction
< 0.01 for sex). For both sexes, among current drinkers, there was a significant decreasing trend in diabetes risk as the alcohol consumption increased. The association was modified by BMI (
p
interaction
= 0.042 for women,
p
interaction
< 0.001 for men). In women, the inverse association was only seen among overweight and obese participants. In men, the inverse association was more pronounced among obese participants. On average, drinking status did not change substantially over the 9 year period. For men with alcohol intake ≥7 drinks/week at baseline, decreasing alcohol intake was associated with higher risk of diabetes (HR per daily drink decrease 1.12, 95% CI 1.02, 1.23).
Conclusions/interpretation
In this community-based population, there was an inverse association between alcohol consumption and diabetes risk. The amount of the alcohol consumption associated with lower risk was different in women and men, and the association was more pronounced among participants with higher BMI.
Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, was associated with subclinical atherosclerosis in many cross-sectional studies, but the prospective ...association between NAFLD and the progression of atherosclerosis has not been evaluated. This study was conducted to evaluate the association between NAFLD and the progression of coronary atherosclerosis.
This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD), liver disease or cancer at baseline who participated in a repeated regular health screening examination between 2004 and 2013. Fatty liver was diagnosed by ultrasound based on standard criteria, including parenchymal brightness, liver-to-kidney contrast, deep beam attenuation and bright vessel walls. Progression of coronary artery calcium (CAC) scores was measured using multidetector CT scanners.
The average duration of follow-up was 3.9 years. During follow-up, the annual rate of CAC progression in participants with and without NAFLD were 22% (95% CI 20% to 23%) and 17% (16% to 18%), respectively (p<0.001). The multivariable ratio of progression rates comparing participants with NAFLD with those without NAFLD was 1.04 (1.02 to 1.05; p<0.001). The association between NAFLD and CAC progression was similar in most subgroups analysed, including in participants with CAC 0 and in those with CAC >0 at baseline.
In this large cohort study of adult men and women with no history of CVD, NAFLD was significantly associated with the development of CAC independent of cardiovascular and metabolic risk factors. NAFLD may play a pathophysiological role in atherosclerosis development and may be useful to identify subjects with a higher risk of subclinical disease progression.
Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association ...between circulating sex hormones and liver fat.
We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States.
Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant.
On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.
PDF
