The Prevalence and Clinical Correlates of Nonalcoholic Fatty Liver Disease (NAFLD) in African Americans: The Multiethnic Study of Atherosclerosis (MESA)

Background and Aims

Nonalcoholic fatty liver disease (NAFLD) is the number one cause of liver disease in the United States. The prevalence rates in African Americans (AA), while significantly lower than other ethnic groups with similar known risk factors, have been quoted as high as 24 %. We aim to determine if the presence of NAFLD in African Americans is associated with lower triglyceride and/or higher HDL-c levels and if NAFLD risk factors in African Americans differ from other ethnic groups.

Methods

A total of 3,056 participants of the Multi Ethnic Study of Atherosclerosis were included in this study. We utilized the baseline serum, anthropometric and radiographic measurements obtained between 2000 and 2002. NAFLD was defined as liver spleen ratio <1 from CT measurements.

Results

The prevalence of NAFLD was and 11 % in AA. We found that age, education, triglyceride levels, HDL-c levels, waist circumference and HOMA-IR were independent correlates of NAFLD in this population. Among those with NAFLD, AA had significantly lower triglyceride levels than Hispanics [125 mg/dl (95 % CI 107–143) versus 192 mg/dl (95 % CI 169–215), p < 0.001] and Caucasians [185 mg/dl (95 % CI 161–209), p = 0.001]. Serum HDL-c was significantly higher in AA with NAFLD (47 mg/dl; 95 % CI 45–50) when compared to Hispanics (44 mg/dl; 95 % CI 43–66, p = 0.02) and Caucasians (44 mg/dl; 95 % CI 42–46, p = 0.02) with NAFLD.

Conclusions

This study demonstrated that the clinical correlates of NAFLD in African Americans are similar to the correlates of NAFLD in other ethnic groups. Our data also suggests that when evaluating African Americans for NAFLD risk, lower cutoff values should be used to define abnormal triglyceride levels.     

Increased H-FABP concentrations in nonalcoholic fatty liver disease

Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis.

Patients and methods

A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima–media thickness (CIMT) which was measured by high resolution B mode ultrasonography.

Results

H-FABP levels were elevated in patients with NAFLD (16.3?±?4.0 ng/ml) when compared with healthy controls (13.8?±?2.1 ng/ml; p??<?0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64?±?0.17 mm vs. 0.43?±?0.14 mm, p?=?0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r?=?0.255, p?=?0.042), fasting blood glucose level (r?=?0.300, p?=?0.013), CIMT (r?=?0.335, p?=?0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r?=?0.156, p?=?0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p?=?0.04)

Conclusion

Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.     

Homeostasis model assessment of insulin resistance and the risk of cardiovascular events in middle-aged non-diabetic Japanese men

Aims/hypothesis

Little is known about the relationship between the HOMA of insulin resistance (HOMA-IR) and the risk of cardiovascular events in Asian populations, which have lower levels of HOMA-IR than Western populations. Accordingly, we determined the predictive value of HOMA-IR for cardiovascular risk in a Japanese population that was apparently free of diabetes, addressing whether insulin resistance itself increases cardiovascular risk independently of other relevant metabolic disorders.

Methods

We followed 2,548 non-diabetic men aged 35 to 59 years for 11 years. The hazard ratios for the incidence of cardiovascular events due to increased HOMA-IR were estimated using a Cox proportional hazards model that was adjusted for potential confounding factors.

Results

The multivariate-adjusted hazard ratio for cardiovascular events compared with the first quartile of HOMA-IR (≤0.66) was 1.07 (95% CI 0.44–2.64) for the second (HOMA-IR 0.67–1.01), 1.36 (0.56–3.28) for the third (HOMA-IR 1.02–1.51) and 2.50 (1.02–6.10) for the fourth quartile (HOMA-IR ≥1.52). The hazard ratio associated with a one SD (0.61) increment in log-transformed HOMA-IR was 1.51 (1.13–2.02). A similar positive relationship was observed for coronary events and stroke. In addition, the relationship between HOMA-IR and cardiovascular risk was broadly similar in participants with and without hypertension, dyslipidaemia (elevated triacylglycerol and/or reduced HDL-cholesterol), abdominal obesity and current smoking.

Conclusions/interpretation

Increased HOMA-IR predicted subsequent cardiovascular events in non-diabetic Japanese men. The association was independent of traditional cardiovascular risk factors and other relevant metabolic disorders.     

Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety

Background and purpose

Nonalcoholic fatty liver disease (NAFLD) is one of the causes of a fatty liver, occurring when fat is deposited (steatosis) in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome. The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid (ALA) and ursodeoxycholic acid (UDCA) on NAFLD.

Methods

Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day (ALAUDCA) was investigated in patients over a period of 12 months using a randomized, placebo (PLA)-controlled study with four parallel groups. Serum concentration of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and platelets (PLT) were measured at the beginning and at the end of the treatment. Moreover, the AST/ALT ratio and the NAFLD fibrosis score were examined.

Results

A total of 120 patients were randomly assigned to the four groups. ALA and UDCA were safe and well tolerated in the oral daily administration only. AST, ALT, GGT (p < 0.001) showed a significant difference between ALAUDCA and other three groups. Besides, NAFLD fibrosis score underlined a significant reduction (p < 0.04) in the ALAUDCA group, while AST/ALT ratio presented a moderate decline (p > 0.05).

Conclusion

ALAUDCA therapy reduced AST, ALT, GGT values and improved NAFLD fibrosis score and AST/ALT ratio, especially in patients who were on a hypocaloric diet. These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies.     

Assessment of safety in hepatic resection for hepatocellular carcinoma focusing on indirect hyperbilirubinemia

Background/purpose

The indications for hepatic resection for hepatocellular carcinoma (HCC) patients with total bilirubin (T-Bil) equal to or higher than 1.2 mg/dl remain controversial. The aim of this study was to investigate the safety of hepatic resection for HCC patients who showed high T-Bil (≥1.2 mg/dl) with low direct bilirubin (D-Bil ≤ 0.5 mg/dl).

Methods

Thirty-four HCC patients showing high T-Bil with low D-Bil were treated with mono- to tri-segmentectomy between January 2000 and December 2010. The perioperative clinical parameters and prognosis of the high T-Bil/low D-Bil patients were compared with those of 253 HCC patients showing normal T-Bil. In addition, complication rates of the patients with high T-Bil/high D-Bil (n = 4) were analyzed.

Results

The prothrombin time activity, indocyanine green clearance test, asialo-scintigraphy, and platelet count were similar in the two groups. The mean serum albumin in high T-Bil/low D-Bil patients was significantly higher than that of normal T-Bil patients (4.2 ± 0.5 vs. 4.0 ± 0.4 g/dl, P = 0.004). There were no significant differences in operation time, intraoperative bleeding, red cell concentrate transfusion rate, postoperative complication rate, and disease-free and overall survivals between the two groups. Postoperative hyperbilirubinemia (T-Bil >5 mg/dl) with ascites was observed in one of four high T-Bil/high D-Bil patients (25 %).

Conclusions

Mono- to tri-segmentectomy can be performed in patients with low D-Bil (≤0.5 mg/dl) similarly to patients with low T-Bil (<1.2 mg/dl), even in HCC patients showing high T-Bil (≥1.2 mg/dl).     

Serum hs-CRP was correlated with treatment response to pegylated interferon and ribavirin combination therapy in chronic hepatitis C patients

Background/aims

Serum high sensitivity C-reactive protein (hs-CRP) is a surrogate marker for cardiovascular disease risks and related mortality. However, the features of hs-CRP in chronic HCV infection (CHC) patients have not been fully addressed. This study aimed to elucidate the characteristics of hs-CRP and its correlation with clinical profiles in CHC patients.

Methods

Ninety-five CHC patients and 95 age- and sex-matched healthy controls were enrolled for serum hs-CRP level, biochemical, and metabolic profiles examinations. Sequential changes of hs-CRP levels in CHC patients receiving peginterferon/ribavirin combination therapy were also evaluated.

Results

The mean hs-CRP level of CHC patients was significantly higher than that of healthy controls (0.97 ± 0.11 vs. 0.24 ± 0.07 mg/L, P < 0.001). There was no significant correlation between hs-CRP and both virological and histological factors. CHC patients with a high LDL-C level had significantly higher mean hs-CRP (1.38 ± 0.20 mg/L) than that of patients without (0.59 ± 0.06 mg/L) (P < 0.001). Hs-CRP level was significantly decreased in 83 patients after peginterferon/ribavirin combination therapy (0.24 vs. 0.62 mg/L, P < 0.001), particularly in 68 patients achieving a sustained virological response (0.25 vs. 0.64 mg/L, P < 0.001).

Conclusion

CHC patients had a higher hs-CRP level than healthy controls which could be ameliorated after peginterferon/ribavirin combination therapy.     

The effect of etanercept on hepatic fibrosis risk in patients with non-alcoholic fatty liver disease, metabolic syndrome, and psoriasis

Background

Patients with psoriasis show a greater prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than their counterparts with NAFLD and without psoriasis. The link between these three pathological conditions is a chronic low-grade inflammatory status. In this study, we aimed to evaluate the effect of etanercept versus psoralen and UVA (PUVA) therapy on the hepatic fibrosis risk in patients with psoriasis, metabolic syndrome, and NAFLD (with NAFLD diagnosed by ultrasonography).

Methods

Eighty-nine patients with chronic moderate-to-severe plaque-type psoriasis, metabolic syndrome, and NAFLD received etanercept or PUVA treatment. The two groups of patients were compared for anthropometric variables (body mass index and waist/hip ratio), lipid profile, glucose homeostasis, inflammatory status, risk of hepatic fibrosis, and ultrasonographic aspect of the liver, both at baseline (time [T] 0) and after 24 weeks of treatment (T24).

Results

After 24 weeks of treatment, only in the group receiving etanercept, we detected significant reductions (p < 0.05) in the aspartate transaminase (AST)/alanine transaminase (ALT) ratio, C-reactive protein (CRP) serum levels, fasting insulin levels, and homeostasis model assessment (HOMA) index, and a significant increase in the Quantitative Insulin-Sensitivity Check Index (QUICKI) (p < 0.05).

Conclusions

In patients with psoriasis, metabolic syndrome, and NAFLD, the risk of the development of hepatic fibrosis seems to be directly correlated with insulin resistance. Etanercept could be more efficacious to reduce the risk of developing hepatic fibrosis than PUVA therapy, and this preventive effect could be related to its anti-inflammatory and glucose homeostatic properties. We note that a limitation of the study was that the diagnosis of NAFLD was conducted by ultrasonography.     

The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease

Background

It is suggested that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), can be associated with insomnia and gastro-esophageal reflux disease (GERD). The relationship between GERD and insomnia in subjects with biopsy-proven NAFLD was investigated.

Methods

This study enrolled 123 patients with biopsy-proven NAFLD. Insomnia was assessed by the Athens Insomnia Scale (AIS), a self-assessment psychometric instrument designed to quantify sleep difficulty based on ICD-10 criteria; AIS scores ≥ 6 were considered positive for insomnia. GERD symptoms were evaluated using a frequency scale for the symptoms of GERD (FSSG); FSSG scores ≥ 8 were considered positive. Logistic regression models were used to evaluate the association of insomnia with GERD, after adjusting for potential confounders. Thirteen patients with GERD were treated with the proton pump inhibitor rabeprazole (RPZ; 10 mg/day), for 12 weeks.

Results

Of the 123 patients, 76 (62 %) were female and 87 (71 %) were obese, with 34 (28 %) having AIS scores ≥ 6 and 31 (25 %) having FSSG scores ≥ 8. Liver biopsy revealed that 40 patients (33 %) had NAFL and 83 (67 %) had NASH. FSSG and AIS scores were similar in the two groups. HOMA-IR, FSSG scores and γGT (GGT) concentrations were significantly higher in insomniacs than in non-insomniacs. Logistic regression analysis demonstrated that FSSG score and GGT concentration were independently associated with insomnia. RPZ treatment resulted in significantly reductions in both AIS and FSSG scores.

Conclusions

Nearly 30 % of patients with biopsy-proven NAFLD had insomnia, which was related to GGT and GERD and could be relieved by RPZ treatment.     

Nonalcoholic Fatty Liver Disease Increases Risk for Gastroesophageal Reflux Symptoms

Background

Nonalcoholic fatty liver disease (NAFLD) is now recognized as a leading cause of liver dysfunction. Gastroesophageal reflux disease (GERD) is a common disorder causing symptoms that often impair patients’ quality of life. In recent years, the prevalence of both these diseases has increased, partially overlapping the rise of metabolic disorders.

Aims

We investigated whether a relation does exist between NAFLD and GERD symptoms.

Methods

Cross-sectional study among 206 outpatients diagnosed with NAFLD and 183 controls. We collected clinical and laboratory data, assessed severity and frequency of GERD symptoms and the esophageal endoscopic pattern.

Results

The prevalence of GERD symptoms was higher in NAFLD patients than controls (61.2 vs. 27.9 %, p < 0.001). We found a positive association between NAFLD and the experiencing of heartburn, regurgitation and belching. GERD symptoms were related to body mass index (BMI) and metabolic syndrome (MetS); a strong association persisted after adjustment for all the covariates (adjusted OR 3.49, 95 CI % 2.24–5.44, p < 0.001).

Conclusions

Our data show that the prevalence of GERD typical symptoms is higher in patients with NAFLD. GERD was associated with higher BMI and MetS, but not with age and diabetes type 2. NAFLD remained strongly associated with GERD, independently of a coexisting MetS status. Consistent with these findings, MetS can be considered a shared background, but cannot completely explain this correlation. We suggest NAFLD as an independent risk factor for GERD symptoms.     

Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study

Aims/hypothesis

Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR.

Methods

We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n = 5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n = 2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat ≥5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy (¹H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories.

Results

The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n = 1167) and FIN-D2D (n = 459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cut-off for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (<5.56% on ¹H-MRS) in linear regression analysis. The 2.0 HOMA-IR measured in Helsinki corresponded to 1.3, 1.6, 1.8, 1.8, 2.0 and 2.1 in six other laboratories. The inter-laboratory CV% of HOMA-IR was 25% due to inter-assay variation in insulin (25%) rather than glucose (5%) measurements.

Conclusions/interpretation

The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.

     

Serum biomarkers and the prognosis of AMI patients

Background

It has been proven that serum lactate dehydrogenase (LDH) and total bilirubin (TB) increase during acute myocardial infarction (AMI). However, how they influence the prognosis of AMI patients is still not completely known.

Methods

A total of 239 patients diagnosed with AMI and admitted to the Fourth Clinical Hospital of Harbin Medical University, between 2007 and 2008, were enrolled in this study. All the patients had not undergone primary percutaneous coronary intervention (PCI) because the time window (24 h) was missed. They all underwent PCI 1 week after the onset of symptoms. Serum high-sensitivity C-reactive protein (hs-CRP), TB, LDH, and other biomarkers were determined between 24 and 48 h of symptom onset. All of the patients were followed up for an average of 3.2±0.4 years for occurrence of major adverse cardiac events (MACE).

Results

Patients with MACE had significantly higher levels of hs-CRP, LDH, cystatin C, uric acid, a higher ratio of LDH and TB (LDH/TB), and a lower level of TB: 8.48±3.84 vs. 2.13±1.32 μmol/l, p<0.01; 1,355.8±654.3 vs. 1,151.7±415.4 U/l, p<0.01; 1.69±0.76 vs. 1.00±0.46 mg/l, p<0.01; 419.6±109.2 vs. 343.2±108.2 μmol/l, p<0.01 and 141.1±46.2 vs. 61.2±26.5, p<0.01; 18.3±6.7 vs. 14.8±6.6 mg/l, p<0.01, respectively. In the multivariate COX analysis, LDH, cystatin C, and LDH/TB were significantly associated with the prognosis of these patients.

Conclusions

Patients under higher oxidative stress tend to have more MACE. LDH, cystatin C, and LDH/TB are strongly related to the prognosis of AMI patients undergoing elective PCI.     

Fatty Liver Disease Index: A Simple Screening Tool to Facilitate Diagnosis of Nonalcoholic Fatty Liver Disease in the Chinese Population

Background and Objectives

A simple screening tool is needed as an aid to optimize management of nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to design a simple index that could be used to predict the presence of NAFLD.

Methods

A cross-sectional case–control study design was used for this study with 6,926 subjects who had received health assessments.

Results

Multivariate analysis indicated that body mass index (BMI), triglyceride (TG), alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio (ALT/AST ratio), and hyperglycemia (HG) were independent risk factors for NAFLD. These variables were used to construct a fatty liver disease (FLD) index: FLD index = BMI + TG + 3 × (ALT/AST ratio) + 2 × HG (presence of HG, HG = 1; absence of HG, HG = 0). The FLD index had an area under the receiver-operating characteristic (AUROC) curve of 0.819 in the training set and 0.817 in the validation set. Values of the FLD index <28.0 or >37.0 excluded the possibility of NAFLD with sensitivity of 94.9 % or detected NAFLD with specificity of 96.0 %, respectively.

Conclusions

The FLD index is a simple, efficient NAFLD screening tool for the Chinese population that may be used to select people for further analysis and/or treatment, and/or for lifestyle modification.     

Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease

Background/aims

The magnitude of antigen-specific immunity was assessed in a murine model of nonalcoholic fatty liver diseases (NAFLD). Because antigen-specific immunity was diminished in NAFLD mice, the underlying mechanisms were evaluated through analysis of the functions of antigen-presenting dendritic cells (DC) and other immunocytes.

Methods

For 12 weeks, NAFLD mice received a high-fat (60%) and high-calorie (520 kcal/100 g) diet. C57BL/6 mice (controls) received a standard diet. NAFLD mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). Antibody to HBsAg (anti-HBs), HBsAg and HBcAg-specific cellular immune response and functions of whole spleen cells, T lymphocytes, B lymphocytes and spleen DCs of NAFLD and control mice were assessed in vitro.

Results

Levels of anti-HBs and the magnitude of proliferation of HBsAg and HBcAg-specific lymphocytes were significantly lower in NAFLD mice than control mice (P < 0.05). The spleen cells of NAFLD mice produced significantly higher levels of inflammatory cytokines (P < 0.05) and exhibited significantly increased T cell proliferation compared with control mice (P < 0.05). However, the antigen processing and presenting capacities of spleen DCs were significantly decreased in NAFLD mice compared with control mice (P < 0.05). Palmitic acid, a saturated fatty acid, caused diminished antigen processing and presenting capacity of both murine and human DCs.

Conclusions

Nonalcoholic fatty liver disease mice exhibit decreased magnitudes of antigen-specific humoral and cellular immune responses. This effect is mainly, if not solely, due to impaired antigen processing and presentation capacities of DC.     

Anthropometric and Clinical Factors Associated with Mortality in Subjects with Nonalcoholic Fatty Liver Disease

Aim

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and may be associated with increased mortality. Our aim was to determine whether anthropometric measures are independently associated with mortality in NAFLD.

Methods

The third National Health and Nutrition Examination Surveys (1988–1994) data was used. Extensive radiologic, serologic and clinical data were available. NAFLD was defined as moderate-to-severe hepatic steatosis on the hepatic ultrasound in the absence of any cause of chronic liver disease (e.g. hepatitis C virus RNA negative, hepatitis B-surface antigen negative, normal transferrin saturation and alcohol consumption <20 gram/day). Anthropometric measures [body mass index (kg/m²), waist, hip, arm, and thigh circumferences (cm), waist-to-hip ratio, percentage of body fat, and sum of skinfolds (mm)], laboratory measures and clinico-demographic data were analyzed. Statistical analyses were conducted with SUDAAN 10.0.

Results

A total of 10,565 adult participants were included [2,510 (weighted 21 %) with NAFLD and 8,055 non-NAFLD controls]. In multivariate analysis, NAFLD was independently associated with being Mexican-American (including Hispanic or other ethnicity), larger waist circumference (cm), type-2 diabetes, insulin resistance and hypertension. After about 14 years (median) of follow up, liver-specific mortality was independently associated with NAFLD and being White.

Conclusions

Components of metabolic syndrome, and Mexican-American ethnicity are independently associated with NAFLD. Furthermore, NAFLD is an independent predictors of liver-specific mortality in men and Whites.     

Heterogeneous Postprandial Lipoprotein Responses in the Metabolic Syndrome, and Response to Fenofibrate Therapy

Background

Hypertriglyceridemia subjects with metabolic syndrome exhibit variable postprandial triglyceride responses. We investigate the effects of fenofibrate therapy on postprandial triglyceride-containing lipoproteins in subjects with early (3.5 h) versus late (8 h) postprandial triglyceride responses.

Methods

Fifty-five subjects with fasting hypertriglyceridemia (≥1.7 mmol/L (150 mg/ dL) and <5.8 mmol/L (500 mg/dL)) and ≥2 Adult Treatment Panel III criteria of the metabolic syndrome were randomized to daily fenofibrate (160 mg/d) or placebo for 12 weeks in a double-blind controlled clinical trial. A standardized fat load (50 g/m²) was given orally after a 12 h fast. Blood specimens were obtained at 0 h (fasting), 3.5 h, and 8 h after the test meal. Analysis is confined to the 53 subjects with clearly identifiable early or late triglyceride peaks prior to therapy.

Results

Fenofibrate was more effective in late peakers (n?=?8) when compared to early peakers (n?=?15) with respect to reducing postprandial triglyceride concentrations (?67% vs. ?34%, p?=?0.0024) and large VLDL (?76% vs. ?31%, p?=?0.0016), and increasing total HDL particles (20% vs. 11%, p?=?0.008) and large HDL particles (185% vs. 88%, p?=?0.003). On fenofibrate therapy, 100% of those initially designated as late peakers were reclassified as early peakers; 47% of late peakers assigned to placebo were reclassified as early peakers.

Conclusions

Late postprandial triglyceride responders have attenuated clearance of large VLDL particles, but they were more responsive to fenofibrate.     

Identifying Practice Gaps to Optimize Medical Care for Patients with Nonalcoholic Fatty Liver Disease

Background

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Primary care providers (PCPs), in contrast to gastroenterology/hepatology (GI/Hep) providers, are the first medical contact for the majority of patients with, or at risk for, NAFLD. PCP awareness of and facility with NAFLD is critical for management of these patients.

Aim

The purpose of this study was to assess understanding and practice patterns of PCPs and non-GI/Hep subspecialty providers with respect to the diagnosis and management of NAFLD.

Methods

We administered an online, 61-question survey to 479 providers in internal medicine, family medicine, endocrinology, cardiology, and obstetrics and gynecology (ObGyn) across three health systems: academic medical center, safety-net health system and managed care health system.

Results

There were 246 respondents (51 %), with the majority (87 %) being PCPs (internal medicine, family medicine, ObGyn). Only 31 % of providers identified NAFLD as a clinically important diagnosis in their practice. Although 65 % of providers reported some degree of facility in diagnosing NAFLD, less than half (47 %) were comfortable managing NAFLD. Only 33 % refer patients with suspected NAFLD to GI/Hep. Subspecialists in endocrinology and cardiology reported greater clinical concern over NAFLD and were more likely (67 %) to refer patients with suspected NAFLD to GI/Hep.

Conclusions

The majority of providers do not identify NAFLD as a clinically important diagnosis and do not refer to GI/Hep. However, 83 % expressed a need for education on NAFLD. Our data reveal practice gaps within NAFLD care and identify opportunities for targeted education to guide PCPs in the evaluation and management of NAFLD.     

Serum uric Acid as a predictor for the development of nonalcoholic Fatty liver disease in apparently healthy subjects: a 5-year retrospective cohort study

Background/Aims

This study evaluated the relationship between hyperuricemia and nonalcoholic fatty liver disease (NAFLD) by comparing the incidence rates of NAFLD in relation to serum uric acid levels in apparently healthy subjects during a 5-year period.

Methods

Among 15,638 healthy Korean subjects who participated in a health-screening program in 2003 and 2008, respectively, 4954 subjects without other risk factors were enrolled in this study. We compared the incidence rates of NAFLD in 2008 with respect to baseline uric acid levels.

Results

In 2003, serum uric acid levels were categorized into the following quartiles: 0.6-3.9, 3.9-4.8, 4.8-5.9, and 5.9-12.6 mg/dL. The incidence of NAFLD in 2008 increased with the level of baseline uric acid (5.6%, 9.8%, 16.2%, and 20.9%, respectively; p<0.05). Multiple logistic regression analysis demonstrated that hyperuricemia was associated with the development of NAFLD. When compared to the subjects in quartile 1, the odds ratio (OR) for the incidence of NAFLD for quartiles 2, 3, and 4 were 1.53 (95% confidence interval [CI], 1.09-2.16; p=0.014], 1.69 (95% CI, 1.17-2.44; p=0.005), and 1.84 (95% CI, 1.25-2.71; p=0.002), respectively.

Conclusions

High serum uric acid levels appear to be associated with an increased risk of the development of NAFLD.     

Body mass index is the most useful predictive factor for the onset of nonalcoholic fatty liver disease: a community-based retrospective longitudinal cohort study

Background

Nonalcoholic fatty liver disease (NAFLD) can progress to advanced liver disease and non-liver-related diseases. To prevent NAFLD onset, clinicians must be able to easily identify high-risk NAFLD patients so that intervention can begin at an earlier stage. We sought to identify the predictive factors for NAFLD onset.

Methods

In a community-based, longitudinal design, the records of 6,403 Japanese subjects were reviewed to identify those meeting the criteria for NAFLD onset. Univariate and multivariate logistic regression analyses were used to identify predictive factors for NAFLD onset. The accuracy of different models was evaluated according to their areas under the receiver operating characteristic curves. Comparative risk analysis was performed using the Kaplan–Meier method.

Results

Multivariate analysis of 400 subjects who met the criteria for the onset of NAFLD during the observation period confirmed that body mass index (BMI) at baseline was the most useful predictive factor for NAFLD onset in both sexes. Cutoff levels of BMI for NAFLD onset were estimated at 23 kg/m² for men and 22.2 kg/m² for women. The cumulative onset rate of NAFLD was significantly higher in the high BMI group than in the low BMI group in both sexes (P < 0.001).

Conclusion

BMI was confirmed as the most useful predictive factor for NAFLD onset in both sexes; its cutoff levels were similar to those recommended by the World Health Organization for helping to prevent metabolic disease. An accurate BMI cutoff level will enable clinicians to identify subjects at risk for NAFLD onset.     

Oxidative stress is closely associated with insulin resistance in genotypes 1 and 3 chronic hepatitis C

Background

Chronic hepatitis C (CHC) infection is associated with insulin resistance and with oxidative stress, but the relationship between the two has not been thoroughly examined.

Purpose

To evaluate the association between insulin resistance and oxidative stress in CHC patients.

Method

In 115 CHC patients (68 with genotype 1 and 47 with genotype 3), the relationship between the serum concentration of malondialdehyde (MDA), a marker of oxidative stress and insulin resistance as defined by the homeostasis model (HOMA-IR) was examined.

Results

There was no significant difference in MDA levels between genotype 1- and genotype 3-infected subjects (12.882 vs. 12.426 ng/mL, p = 0.2). By univariate analysis, factors associated with HOMA-IR in both genotypes were oxidative stress as measured by MDA (p = 0.002), body mass index (BMI), portal activity, and fibrosis. Genotype-specific differences in HOMA-IR association were steatosis and triglycerides (TG) for genotype 1, and age and glutathione (GSH) for genotype 3. In a stepwise multiple linear regression analysis in both genotypes, MDA was a significant and independent predictor of HOMA-IR (p = 0.04). As expected, BMI and fibrosis were likewise independently correlated to HOMA-IR. In addition, MDA levels were higher (p < 0.001) and GSH levels were lower (p = 0.023) in insulin-resistant subjects compared to their insulin-sensitive counterparts.

Conclusions

It is concluded that in CHC, oxidative stress is an independent predictor of HOMA-IR, irrespective of virus genotype. Further studies on the role of oxidative stress in the development of insulin resistance in CHC are warranted.     

A pilot trial of body weight reduction for nonalcoholic fatty liver disease with a home-based lifestyle modification intervention delivered in collaboration with interdisciplinary medical staff

Background

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome. The aim of this study was to evaluate a 6-month home-based lifestyle modification intervention delivered in collaboration with physicians, hygienists, registered dietitians, and nurses.

Methods

Outpatients with NAFLD diagnosed by abdominal ultrasonography were eligible for this study. Abdominal computed tomography (CT) scan evaluated liver fat deposition by the liver–spleen ratio (L/S ratio) and visceral fat accumulation as the visceral fat area (VFA; cm²). During the 6-month home-based lifestyle modification intervention, each patient was examined by physicians, nurses, hygienists, and registered dietitians, who provided individualized advice to the patients. Patients recorded their daily weight for self-control of weight with recommended diet and exercise regimens.

Results

Sixty-seven NAFLD patients were enrolled in this study and 22 patients (32.8%) completed the 6-month intervention. Nineteen of the 22 patients achieved significant improvements in body weight, body mass index (BMI), waist circumference, VFA, L/S ratio, and systolic blood pressure, with improved laboratory data. Overall, 39 patients withdrew from the intervention. The mean age of the patients who withdrew was 50.0 ± 11.0 years, which was significantly younger than that of the patients who were followed up (60.1 ± 10.1 years; P < 0.01).

Conclusions

The reduction in body weight achieved by NAFLD patients during the 6-month intervention was associated with improved fat deposition and liver function. This intervention offers a practical approach for treating a large number of NAFLD patients with lifestyle modification therapy.