Muriel Webb

Role of leisure-time physical activity in nonalcoholic fatty liver disease: A population-based study†

Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross‐sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty‐nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P ≤ 0.03). The SteatoTest was significantly lower among subjects engaging in any PA or resistance PA at least once a week (P ≤ 0.01). PA at least once a week in all categories was associated with a reduced risk for abdominal obesity. Adjusting for sex, engaging in any kind of sports (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.44‐0.96 per 1 standard deviation increment in PA score) and resistance exercise (OR 0.61, 95% CI 0.38‐0.85) were inversely associated with NAFLD. These associations remained unchanged after adjusting for homeostasis model assessment, most nutritional factors, adiponectin, and resistin. Only the association with resistance PA remained significant with further adjustment for body mass index (OR 0.61, 95% CI 0.44‐0.85). Adding leptin or waist circumference to the model eliminated the statistical significance. Conclusion: Habitual leisure‐time PA, especially anaerobic, may play a protective role in NAFLD. This association appears to be mediated by a reduced rate of abdominal obesity. (HEPATOLOGY 2008;48:1791‐1798.)

Diagnostic Value of a Computerized Hepatorenal Index for Sonographic Quantification of Liver Steatosis

OBJECTIVE Quantification of liver steatosis is clinically relevant in various liver diseases but cannot be done by conventional sonography, which only provides a qualitative assessment with significant observer variability. The aim of this study was to assess sonography as an objective tool for the quantification of liver steatosis. MATERIALS AND METHODS Files of 111 patients with chronic liver disease who were referred for sonographically guided liver biopsy were collected. A hepatorenal sonographic index was calculated on the basis of the ratio between the echogenicity of the liver and that of the right kidney cortex using histogram echo intensity. Liver steatosis was graded by histology. RESULTS A significant correlation was found between histologic steatosis and the hepatorenal sonographic index (r = 0.82, p < 0.001). The validity of the hepatorenal sonographic index for the diagnosis of fatty liver was compared with liver biopsies with a steatosis level > 5%. The area under the receiver operating characteristic curve was 99.2% (95% CI, 98-100%). The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis > 5% was 1.49, with sensitivity of 100% and specificity of 91%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 25% was 1.86, with sensitivity of 90% and specificity of 90%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 60% was 2.23, with sensitivity of 90% and specificity of 93%. CONCLUSION The hepatorenal sonographic index is a sensitive noninvasive method for steatosis quantification. It can diagnose small amounts of liver fat that would be missed by conventional sonography. It is reproducible and operator independent and can serve as an efficient tool to follow patients with steatosis and evaluate the efficacy of new treatment techniques.

Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up

BACKGROUND & AIMS Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLDs epidemiology in prospective follow-up of individuals sampled from the general population. METHODS Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. RESULTS Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. CONCLUSIONS Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

AIM To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease (NAFLD). METHODS Cross-sectional study of subjects from the general population, a subgroup from the First Israeli National Health Survey, without excessive alcohol consumption or viral hepatitis. All subjects underwent anthropometric measurements and fasting blood tests. Evaluation of liver fat was performed using four noninvasive methods: the SteatoTest; the fatty liver index (FLI); regular abdominal ultrasound (AUS); and the hepatorenal ultrasound index (HRI). Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods: the HRI, the ratio between the median brightness level of the liver and right kidney cortex; and the SteatoTest, a biochemical surrogate marker of liver steatosis. The FLI is calculated by an algorithm based on triglycerides, body mass index, γ-glutamyl-transpeptidase and waist circumference, that has been validated only vs AUS. FLI < 30 rules out and FLI ≥ 60 rules in fatty liver. RESULTS Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests. The prevalence rate of NAFLD was 31.1% according to AUS. The FLI was very strongly correlated with SteatoTest (r = 0.91, P < 0.001) and to a lesser but significant degree with HRI (r = 0.55, P < 0.001). HRI and SteatoTest were significantly correlated (r = 0.52, P < 0.001). The κ between diagnosis of fatty liver by SteatoTest (≥ S2) and by FLI (≥ 60) was 0.74, which represented good agreement. The sensitivity of FLI vs SteatoTest was 85.5%, specificity 92.6%, positive predictive value (PPV) 74.7%, and negative predictive value (NPV) 96.1%. Most subjects (84.2%) with FLI < 60 had S0 and none had S3-S4. The κ between diagnosis of fatty liver by HRI (≥ 1.5) and by FLI (≥ 60) was 0.43, which represented only moderate agreement. The sensitivity of FLI vs HRI was 56.3%, specificity 86.5%, PPV 57.0%, and NPV 86.1%. The diagnostic accuracy of FLI for steatosis > 5%, as predicted by SteatoTest, yielded an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI: 0.95-0.98). The diagnostic accuracy of FLI for steatosis > 5%, as predicted by HRI, yielded an AUROC of 0.82 (95% CI: 0.77-0.87). The κ between diagnosis of fatty liver by AUS and by FLI (≥ 60) was 0.48 for the entire sample. However, after exclusion of all subjects with an intermediate FLI score of 30-60, the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65, representing good agreement. Excluding all the subjects with an intermediate FLI score, the sensitivity of FLI was 80.3% and the specificity 87.3%. Only 8.5% of those with FLI < 30 had fatty liver on AUS, but 27.8% of those with FLI ≥ 60 had normal liver on AUS. CONCLUSION FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI. However, if intermediate values are excluded FLI has high diagnostic value vs AUS.

Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up

Non‐alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre‐DM in a 7‐year prospective follow‐up of healthy volunteers.

Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial

AIM To evaluate the effect of resistance training (RT) on non alcoholic liver disease (NAFLD) patients. METHODS A randomized clinical trial enrolling NAFLD patients without secondary liver disease (e.g., without hepatitis B virus, hepatitis C virus or excessive alcohol consumption). Patients were randomly allocated either to RT, three times weekly, for 3 mo or a control arm consisting of home stretching. The RT included leg press, chest press, seated rowing, latissimus pull down etc. with 8-12 repetitions, 3 sets for each exercise, for a total duration of 40 min. Hepatic ultrasound, fasting blood tests, anthropometrics and body composition by dual energy X-ray absorptiometry were assessed. At baseline and follow-up, patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake. Steatosis was quantified by the hepatorenal-ultrasound index (HRI) representing the ratio between the brightness level of the liver and the right kidney. The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy. RESULTS Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching. After dropout or exclusion from analysis because of protocol violation (weight change > 3 kg), thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol. All baseline characteristics were similar for the two treatment groups with respect to demographics, anthropometrics and body composition, blood tests and liver steatosis on imaging. HRI score was reduced significantly in the RT arm as compared to the stretching arm (-0.25 ± 0.37 vs -0.05 ± 0.28, P = 0.017). The RT arm had a significantly higher reduction in total, trunk and android fat with increase in lean body mass. There was no correlation between the reduction in HRI in the RT arm and weight change during the study, but it was positively correlated with the change in trunk fat (r = 0.37, P = 0.048). The RT arm had a significant reduction in serum ferritin and total cholesterol. There was no significant difference between arms in dietary changes and these did not correlate with HRI change. CONCLUSION Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin. RT may serve as a complement to treatment of NAFLD.

Coffee consumption and nonalcoholic fatty liver onset: a prospective study in the general population

Retrospective studies suggest that coffee consumption may exert beneficial effects in patients with nonalcoholic fatty liver; however, prospective data supporting a protective role on liver steatosis development are lacking. In this study, we aimed to evaluate the association between coffee consumption and fatty liver onset in the general population. The analysis was performed both in a cross-sectional cohort (n = 347) and, prospectively, in a subcohort of patients without fatty liver at baseline and followed-up for 7 years (n = 147). Fatty liver was diagnosed with abdominal ultrasound and liver steatosis was quantified noninvasively by hepatorenal index (HRI) and SteatoTest, whereas FibroTest was used to assess fibrosis degree. A structured questionnaire on coffee consumption was administrated during a face-to-face interview. Neither the incidence nor the prevalence of fatty liver according to ultrasonography, SteatoTest, and the HRI was associated with coffee consumption. In the cross-sectional study, high coffee consumption was associated with a lower proportion of clinically significant fibrosis ≥ F2 (8.8% vs 16.3%; P = 0.038); consistently, in multivariate logistic regression analysis, high coffee consumption was associated with lower odds for significant fibrosis (odds ratio = 0.49, 95% confidence interval, 0.25-0.97; P = 0.041) and was the strongest predictor for significant fibrosis. No association was demonstrated between coffee consumption and the new onset of nonalcoholic fatty liver, but coffee intake may exert beneficial effects on fibrosis progression.

Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion – Preliminary report

BACKGROUND There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. OBJECTIVE To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. SUBJECTS We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. METHODS Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. RESULTS Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). CONCLUSION NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

Non‐high‐density lipoprotein cholesterol independently predicts new onset of non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk. Non‐high‐density lipoprotein cholesterol (non‐HDL‐C), i.e. total cholesterol minus HDL, is a well‐established risk factor for CVD; however, its association with NAFLD development has not been established. Our aim was to test whether non‐HDL‐C is an independent predictor of new onset of NAFLD.

Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease

To evaluate the association between circulating levels of endocannabinoids (eCBs) and non‐alcoholic fatty liver disease (NAFLD).