Sex hormones, sex hormone binding globulin, and abdominal aortic calcification in women and men in the multi-ethnic study of atherosclerosis (MESA)

Background

Conflicting findings exist regarding the associations of sex hormones with subclinical atherosclerosis.

Methods

This is a substudy from MESA of 881 postmenopausal women and 978 men who had both abdominal aortic calcification (AAC) quantified by computed tomography and sex hormone levels assessed [Testosterone (T), estradiol (E2), dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG)]. We examined the association of sex hormones with presence and extent of AAC.

Results

For women, SHBG was inversely associated with both AAC presence [OR = 0.62, 95% CI 0.42-0.91 for 1 unit greater log(SHBG) level] and extent [0.29 lower log(AAC) for 1 unit greater log(SHBG) level, β = −0.29 (95% CI −0.57 to −0.006)] adjusting for age, race, hypertension, smoking, diabetes, BMI, physical activity, and other sex hormones. After further adjustment for total and HDL-cholesterol, SHBG was not associated with ACC presence or extent. In men, there was no association between SHBG and AAC. In both men and women, neither T, E2, nor DHEA was associated with AAC presence or extent.

Conclusion

After adjustment for non-lipid cardiovascular risk factors, SHBG levels are inversely associated with both the presence and severity of AAC in women but not in men, which may be accounted for by HDL.     

Plasma cyclic 3',5'-adenosine monophosphate in patients with elevated pulmonary pressure due to left-to-right shunt

Background

Increased pulmonary blood flow in patients with left-to-right shunt has been shown to be associated with alterations in prostacyclin-synthesis. There are limited data with respect to the plasma cAMP in patients with elevated pulmonary artery pressure due to left-to-right shunt. We hypothesized that plasma cAMP might be influenced by pulmonary blood flow or pressure in patients with left-to-right shunt.

Methods

Plasma cAMP from venous blood was measured in 122 healthy controls aged 8.3 (0.2 - 14.9) years (median [range]) and in 130 patients with left-to-right shunt aged 1.4 (0.1 - 19.1) years by radioimmunoassay.

Results

Plasma cAMP in controls and in patients was similar and decreased with age. Healthy infants (n = 42) showed higher plasma cAMP (46 [27-112] nmol/l) than children > 6 years of age (n = 40, 39 [19-73] nmol/l; P < 0.001).

Conclusions

These values should be taken into consideration when reporting plasma values for cAMP in patients with congenital heart disease. The values for healthy children obtained in this study should allow a better interpretation of plasma cAMP levels in various disease conditions such as chronic renal failure, liver chirrhosis, hyperthyreosis, or children with intellectual disability.     

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease

Background and aims

Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.

Methods and results

Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p = 0.048). Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p < 0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p = 0.05).

Conclusion

Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress

Aim

This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.

Methods

Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.

Results

Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.

Conclusions

Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance

Objective

To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients.

Methods

A total of 81 non-diabetic EH patients, including 54 with IR and 27 without IR, were enrolled. After two weeks wash-out, patients with IR were randomly assigned to telmisartan (group T) or amlodipine (group A) for 6 months. Blood samples were taken before and after treatment for measurement of routine biochemical parameters, visfatin and insulin resistance (measured by HOMA-IR).

Results

Visfatin was independently correlated with HOMA-IR (r = 0.845, P = 0.000). After 6 months of treatment, both drugs lowered HOMA-IR, more significantly so in group T than group A (P = 0.010). Serum visfatin levels increased in group T but decreased in group A.

Conclusion

Serum visfatin levels were higher in non-diabetic EH patients with IR compared with those without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin increased with telmisartan yet decreased with amlodipine treatment.     

Serum FGF21 levels are increased in newly diagnosed type 2 diabetes with nonalcoholic fatty liver disease and associated with hsCRP levels independently

Objective

Fibroblast growth factor (FGF21) has beneficial effects on lipolysis. Highly sensitive C-reactive protein (hs-CRP) is a predictor of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the levels of serum FGF21 and hs-CRP in newly diagnosed type 2 diabetes patients with and without NAFLD, and further explored the correlation between FGF21 with hs-CRP in newly diagnosed type 2 DM.

Research design and methods

69 patients with newly diagnosed type 2 DM and 30 normal subjects were included in the study. FGF21 and hs-CRP were measured by ELISA kits. The severity of NAFLD was measured by ultrasound.

Results

Serum FGF21 in newly diagnosed type 2 DM with NAFLD group were significantly increased (p < 0.01). There was no difference for the FGF21 level in normal control group and newly diagnosed type 2 DM without NFALD group. In type 2 DM group, the FGF21 level was positively correlated with hsCRP (r = 0.417, p < 0.001). In multiple stepwise regression models, only hsCRP was a significantly independent determinant for serum FGF21.

Conclusions

Serum levels of FGF21 are closely related to liver steatosis in newly diagnosed type 2 DM patients.     

Insulin resistance index (HOMA-IR) levels in a general adult population: curves percentile by gender and age. The EPIRCE study

Aims

To describe the distribution of HOMA-IR levels in a general nondiabetic population and its relationships with metabolic and lifestyles characteristics.

Methods

Cross-sectional study. Data from 2246 nondiabetic adults in a random Spanish population sample, stratified by age and gender, were analyzed. Assessments included a structured interview, physical examination, and blood sampling. Generalized additive models (GAMs) were used to assess the effect of lifestyle habits and clinical and demographic measurements on HOMA-IR. Multivariate GAMs and quantile regression analyses of HOMA-IR were carried out separately in men and women.

Results

This study shows refined estimations of HOMA-IR levels by age, body mass index, and waist circumference in men and women. HOMA-IR levels were higher in men (2.06) than women (1.95) (P = 0.047). In women, but not men, HOMA-IR and age showed a significant nonlinear association (P = 0.006), with increased levels above fifty years of age. We estimated HOMA-IR curves percentile in men and women.

Conclusions

Age- and gender-adjusted HOMA-IR levels are reported in a representative Spanish adult non-diabetic population. There are gender-specific differences, with increased levels in women over fifty years of age that may be related with changes in body fat distribution after menopause.     

Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study

Background

Low serum estradiol has been more strongly associated with low bone mineral density in elderly men than has testosterone, but its association with incident hip fracture is unknown. We examined whether low estradiol increases the risk for future hip fracture among men and explored whether testosterone levels influence this risk.

Methods

We examined 793 men (mean age = 71 years) evaluated between 1981 and 1983, who had estradiol measures and no history of hip fracture, and followed until the end of 1999. Total estradiol and testosterone were measured between 1981 and 1983. Hip fractures were identified and confirmed through medical records review through the end of 1999. We created 3 groups of men based on estradiol levels and performed a Cox-proportional hazards model to examine the risk for incident hip fracture, adjusted for age, body mass index, height, and smoking status. We performed similar analyses based on testosterone levels, and then based on both estradiol and testosterone levels together.

Results

There were 39 men who sustained an atraumatic hip fracture over follow-up. Incidence rates for hip fracture (per 1000 person-years) were 11.0, 3.4, and 3.9 for the low (2.0-18.1 pg/mL [7-67 pmol/L]), middle (18.2-34.2 pg/mL [67-125 pmol/L]), and high (≥34.3 pg/mL [≥126 pmol/L]) estradiol groups, respectively. With adjustment for age, body mass index, height, and smoking status, the adjusted hazard ratios for men in the low and middle estradiol groups, relative to the high group, were 3.1 (95% confidence interval [CI], 1.4-6.9) and 0.9 (95% CI, 0.4-2.0), respectively. In similar adjusted analyses evaluating men by their testosterone levels, we found no significant increased risk for hip fracture. However, in analyses in which we grouped men by both estradiol and testosterone levels, we found that men with both low estradiol and low testosterone levels had the greatest risk for hip fracture (adjusted hazard ratio: 6.5, 95% CI, 2.9-14.3).

Conclusion

Men with low estradiol levels are at an increased risk for future hip fracture. Men with both low estradiol and low testosterone levels seem to be at greatest risk for hip fracture.     

Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in Children with Nonalcoholic Fatty Liver Disease

Objective:

To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease (NAFLD).

Methods:

One hundred and eight obese (body mass index (BMI) >95th percentile for age and sex) adolescents with NAFLD were included in the study. Mean age of the subjects was 13.8±3.9 years (9-17 yrs). The diagnosis of NAFLD was based on the presence of liver steatosis with high transaminases. The subjects were randomly divided into two groups. Group 1 (PUFA group, n=52) received a 1000 mg dose of PUFA once daily for 12 months and lifestyle intervention. Group 2 (placebo group, n=56) received a recommended diet plus placebo and lifestyle intervention for 12 months. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from fasting samples.

Results:

BMI, fasting insulin levels and HOMA-IR values in both groups decreased significantly at the end of the study. In group 1, 67.8% of the patients had a decrease from baseline in the prevalence of steatosis (p<0.001). Frequency of elevated alanine aminotransferase (ALT) levels (39.2% to 14.2%; p<0.01) and elevated aspartate aminotransferase (AST) levels (25% to 17.8%; p=0.01) decreased significantly in the PUFA group. Following a 12-month diet plus placebo and lifestyle intervention treatment, 40.3% (21) of the patients in the placebo group also showed a decrease in frequency of steatosis (p=0.04) and slight decreases in frequency of elevated ALT levels (38.4% to 28.8%; p=0.01) and AST levels (30.7% to 28.8%; p>0.05).

Conclusion:

Our results indicated that n-3 PUFA treatment is safe and efficacious in obese children with NAFLD and can improve ultrasonographic findings and the elevated transaminase levels.     

The Effect of Helicobacter Pylori Eradication on Liver Fat Content in Subjects With Non-Alcoholic Fatty Liver Disease: A Randomized Open-Label Clinical Trial

Background

The role of Helicobacter pylori (HP) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is unclear.

Objectives

The aim of this study was to evaluate the effect of HP eradication on liver fat content (LFC), liver function tests (LFT), lipid profile, and homeostasis model assessment-IR (HOMA-IR) index in NAFLD.

Patients and Methods

Dyspeptic patients with increased serum aminotransferase levels were enrolled in the study. The exclusion criteria were factors affecting serum aminotransferase or HP treatment strategy. Participants with persistent elevated serum aminotransferase level and ultrasound criteria for identification of fatty liver were presumed to have NAFLD. “NAFLD liver fat score” was used to classify NAFLD. Those with “NAFLD liver fat score” greater than -0.64 and positive results for urea breath test (UBT), were included. Lifestyle modification was provided to all participants. HP eradication was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein (HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of eight weeks and twenty four weeks.

Results

One hundred (49 males) patients with the mean age of 43.46 (± 11.52) were studied. Repeated measure ANOVA showed a significant reduction in LFC, anthropometric measurements, and laboratory parameters (except for HDL) in the both groups during the study; however, no significant difference was observed between the groups.

Conclusions

It seems that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin resistance in dyspeptic NAFLD patients.     

The Effect of Pioglitazone and Metformin on Liver Function Tests,Insulin Resistance,and Liver Fat Content in Nonalcoholic Fatty Liver Disease: A Randomized Double Blinded Clinical Trial

Background

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of insulin resistance (IR) syndrome. The effect of insulin sensitizers on liver function tests and metabolic indices in NAFLD patients is a matter of debate.

Objectives

The aim of study was to compare the effects of two different insulin sensitizers, pioglitazone, and metformin, on liver function tests (LFT), lipid profile, homeostasis model assessment-IR (HOMA-IR) index, and liver fat content (LFC) in NAFLD patients.

Materials and Methods

This double blind clinical trial was performed on patients who were referred to a gastroenterology clinic with evidence of fatty liver in ultrasonography. After excluding other causes, participants with persistent elevated alanine aminotransferase (ALT) levels and “NAFLD liver fat score” greater than -0.64 were presumed to have NAFLD and were enrolled. They were randomly assigned to take metformin (1 g/day) or pioglitazone (30 mg/day) for four months. Fasting serum glucose (FSG), ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, cholesterol (CHOL), high and low density lipoprotein (HDL, LDL), HOMA-IR, and LFC were checked at the baseline, two and four months post-treatment. LFC was measured by a validated formula.

Results

Eighty patients (68 males) with mean age of 35.27 (± 7.98) were included. After 2 months, LFT was improved significantly in the pioglitazone group and did not change in the metformin group. After four months, both medications significantly decreased serum levels of LFT, FSG, CHOL, LDL, HOMA-IR, and LFC, and increased serum level of HDL. No statistically significant differences were seen between the two treatment groups with regard to the changes of laboratory parameters and LFC from baseline to four months post-treatment.

Conclusions

During the four months, the use of metformin (1 g/day) and pioglitazone (30 mg/day) were safe and might have equally affected LFT, HOMA-IR, lipid profile, and LFC in NAFLD patients.     

Prevalence and Factors Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Korean Population

Background/Aims

Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in Asia, but little is known about the disease in the nonobese population. The aims of this study were to investigate the prevalence of NAFLD and the factors associated with it in a nonobese Korean population and to compare the clinical characteristics of nonobese and obese subjects with NAFLD.

Methods

This cross-sectional study used data from 2,058 subjects who participated in a medical checkup program.

Results

The prevalence of NAFLD was 12.4% (213/1,711) in the nonobese population. A higher body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) values, higher alanine aminotransferase (ALT) levels, triglyceride concentrations 150 mg/dL, and hyperuricemia were independently associated with the presence of NAFLD in the nonobese subjects. Compared with the obese subjects with NAFLD, the nonobese subjects with NAFLD were composed of a higher proportion of females and had lower BMIs, smaller waist circumferences, lower HOMA-IR values, and fewer metabolic irregularities.

Conclusions

Higher BMIs, HOMA-IR values, ALT levels, hypertriglyceridemia, and hyperuricemia were associated with NAFLD in the nonobese subjects. Clinicians should be particularly aware of the possibility of NAFLD in nonobese Asian people.     

Hepato-systemic gradient of carbon monoxide in cirrhosis

Background and aims

Experimental data suggest that in liver cirrhosis splanchnic and systemic vasculature exhibit marked endothelial Carbon monoxide (CO) overproduction, while recent data demonstrated heme oxygenase (HO) hyperactivity in the liver of rats with cirrhosis. No data are so far available on CO levels in the hepatic veins of cirrhotic patients. We aimed at evaluating whether plasma CO levels differ between systemic (peripheral vein) and hepatic (hepatic vein) circulation in patients with viral cirrhosis with and without ascites.

Methods

We enrolled 31 consecutive non-smoking in- or outpatients with liver cirrhosis. We measured wedge (occluded, WHVP) and free hepatic venous pressures (FHVP) and hepatic-vein pressure gradient (HVPG) was the calculated. Plasma level of NO and plasma CO concentration were determined both in peripheral vein and in the hepatic vein in cirrhotics.

Results

In cirrhotic patients plasma CO levels were significantly higher in the hepatic vein (16.66 ± 10.71 p.p.m.) than in the peripheral vein (11.71 ± 7.00 p.p.m). Plasma NO levels were significantly higher in peripheral vein (97.02 ± 21.11 μmol/ml) than in the hepatic vein (60.76 ± 22.93 μmol/ml).

Conclusions

In patients with liver cirrhosis we documented a hepato-systemic CO gradient as inferred by the higher CO values in the hepatic vein than in the peripheral vein. In cirrhotic patients, CO and NO exhibit opposite behavior in the liver, while both molecules show increased values in the systemic circulation. It can be speculated that increased intra-hepatic CO levels might represent a counterbalancing response to reduced NO intra-hepatic levels in human liver cirrhosis.     

Does testosterone have a role in erectile function?

Purpose

Despite the well-established role of testosterone in enhancing libido, its exact contribution to erections in men remains unclear. The main objectives of this review are to clarify the role of testosterone in erectile function and evaluate its therapeutic value in men with erectile dysfunction (ED).

Methods

Review of the relevant literature (English, French, and Spanish) from 1939 to June 2005 was conducted using data sources from MEDLINE, endocrinology text books, and hand searching of cross-references from original articles and reviews. Clinical trials, animal studies, case reports, reviews, and guidelines of major associations were included.

Results

Animal and preliminary human studies suggest that testosterone may facilitate erection by acting as vasodilator of the penile arterioles and cavernous sinusoids. Following castration, most, but not all, men had partial or complete loss of erection. Hypogonadism is not a common finding in ED, occurring in about 5% of cases, and in general, there is lack of association between serum testosterone levels, when present in normal or moderately low levels, and erectile function. Most trials using testosterone for treatment of ED in hypogonadal men suffer from methodological problems and report inconsistent results, but overall, suggest that testosterone may be superior to placebo. Erectile function is more likely to improve with testosterone therapy in patients with severe degrees of hypogonadism. Testosterone treatment may ameliorate the response to the phosphodiesterase 5 (PDE5) inhibitors in hypogonadal men and men with low-normal serum testosterone. Repeated measurement of morning serum total testosterone is a fairly accurate and easy method to evaluate androgenecity, but measurement of free or bioavailable testosterone is recommended in conditions that alter the levels of sex-hormone-binding globulin (SHBG), such as in the elderly and in obesity.

Conclusions

Available data suggest that in most men circulating levels of testosterone, well below the normal range, are essential for normal erection and that higher levels of serum testosterone may not have major impact on erectile function. Screening for hypogonadism in all men with ED is necessary to identify cases of severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment.     

Which metabolic syndrome criteria best predict the presence of non-alcoholic fatty liver disease?

Aims

To know which MS criteria best predict the presence of NAFLD and the prevalences of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) diagnosed ultrasonographically among pre-diabetic and diabetic subjects based on three different MS criteria (IDF, ATP III, WHO).

Methods

Subjects were screened and those with a fasting serum glucose level ≥100 mg/dL were further tested with a 75 g oral glucose tolerance test. And those who were newly diagnosed as having pre-diabetes or diabetes were evaluated for MS and NAFLD. We compared the risk ratios of NAFLD among three MS criteria using multivariate and multiple logistic regression analyses.

Results

A total of 1365 subjects (977 males, mean age 48.4 ± 9.5 years) were analyzed. The WHO criteria produced the highest prevalence of MS in both the pre-diabetic (49.8%) and diabetic (58.9%) groups. The IDF criteria produced the highest odds ratio for NAFLD in both pre-diabetic (3.89 [95% CI 2.75-5.51]) and diabetic (5.53 [95% CI 3.21-9.52]) groups.

Conclusions

The prevalence of MS depends on the set of diagnostic criteria used. IDF criteria best predicts the presence of NAFLD. The presence of NAFLD should be considered as a component of the diagnostic criteria for MS.     

Adalimumab is effective in long-term real life clinical practice in both luminal and perianal Crohn's disease. The Madrid experience

Objective

To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.

Methods

Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed.

Results

174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to everyweek. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them.

Conclusions

Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.     

Serum TGF-��, Serum MMP-1, and HOMA-IR as Non-Invasive Predictors of Fibrosis in Egyptian Patients with NAFLD

Background/Aim:

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent cause of chronic liver disease worldwide. A number of these patients progress to nonalcoholic steatohepatitis (NASH) which carries significant morbidity and mortality. The aim of this study is to evaluate the diagnostic value of serum levels of transforming growth factor beta-1 (TGF-β1) matrix metalloproteinase-1 (MMP-1), and insulin resistance as predictors of fibrosis in Egyptian NAFLD patients.

Patients and Methods:

Fifty patients with NAFLD and different stages of fibrosis were studied. Serum levels of TGF-β1, MMP-1, and fasting serum insulin were measured; calculation of the homeostasis model assessment for insulin resistance (HOMA-IR) was done.

Results:

TGF-β1 gives a sensitivity of 100% and specificity of 94.4% for stage 1 fibrosis, 100% and 93.9%, respectively, for stage 2 fibrosis, and 97.7% and 100%, respectively, for stage 3 fibrosis. MMP-1 showed sensitivity and specificity of 88% and 81.8%, respectively, for stage 2 fibrosis, 90.9% and 55.56%, respectively, for stage 3 fibrosis, but it is of no diagnostic value in stage 1 fibrosis.

Conclusion:

Serum TGF-β1, MMP-1, and insulin resistance (HOMA-IR) proved to be potentially useful noninvasive markers in predicting fibrosis in NASH patients.     

Comparison of portal vein doppler indices and hepatic vein doppler waveform in patients with nonalcoholic fatty liver disease with healthy control

Background

The purpose of the present study is to investigate the association of nonalcoholic fatty liver disease (NAFLD) with the doppler waveform pattern of hepatic veins and portal vein doppler indices.

Objectives

This assay may be useful in evaluating the natural course of NAFLD and monitor treatment efficacy on follow-up.

Patients and Methods

This case control study was performed in 31 patients with NAFLD and 31 normal healthy adults who served as the control group. The patients presented with elevated liver enzymes levels (ALT/AST) and hyperechogenic livers in the B-mode ultrasonography examination. Eleven patients had a liver biopsy. After an 8-hour fast,B-mode and duplex doppler ultrasonography were performed, and the waveform patterns of the right hepatic vein, portal vein diameter, grade of fatty liver, portal vein pulsatility index (VPI), and mean flow velocity (MFV) were measured.

Results

VPI and MFV values were 0.42 ± 0.92 and 17.27 ± 5.34 cm/second, respectively, in the control group and 0.25 ± 0.50 and 12.82 ± 4.32 cm/second in patients with NAFLD (P< 0.01). The frequency of abnormal hepatic vein doppler waveform patterns (biphasic or monophasic) was significantly higher in patients with NAFLD (55.2%) versus control subjects (3.2%) (P < 0.001). There was no correlation between the degree of fat infiltration and VPI (P = 0.714), MFV (P = 0.911), or hepatic vein waveform pattern (P = 0.197). We found no correlation between liver enzyme levels and MFV or VPI. However, the rate of abnormal hepatic vein was higher in patients with enzyme levels that exceeded twice the normal value (P = 0.05).

Conclusions

Patients with NAFLD have a high rate of abnormal hepatic vein doppler waveform patterns, and decreased VPI and MFV are suggestive of reduced vascular compliance in the liver. Elevated liver enzymes levels do not influence VPI or MFV, but patients with abnormal enzymes have higher rates of abnormal hepatic vein doppler waveform patterns.     

High FVIII level is associated with idiopathic portal vein thrombosis in South India

Background

In the majority of the cases of portal vein thrombosis in India, the etiology cannot be determined. A high level of factor VIII (FVIII) is a risk factor for venous thromboembolism.

Methods

In this study from South India, FVIII was estimated in 32 patients with idiopathic portal vein thrombosis (PVT), 12 healthy controls and 12 disease controls with chronic liver disease.

Results

Eighty-four percent of the patients with portal vein thrombosis (27/32) vs 17% of healthy controls (2/12) had high factor VIII levels (P <.0001). FVIII levels were significantly different between the subset of PVT patients with normal liver function compared with healthy controls (P <.001) and also between the subset of PVT patients with abnormal liver function compared with disease controls (P <.05).

Conclusions

A high factor VIII level seems to contribute to the development of portal vein thrombosis in India.     

Depression and perceptions about heart failure predict quality of life in patients with advanced heart failure

Background

Mood is an independent predictor of mortality and quality of life (QoL) for people with heart failure. However, the underlying belief systems involved in mood are unknown.

Objective

We sought to identify psychological and clinical variables predicting mood and QoL for people diagnosed with heart failure (HF).

Methods

One hundred and forty-six HF patients were assessed with standardized measures, to determine their beliefs about HF, coping styles, mood, and QoL.

Results

Patients with more negative beliefs about the consequences of HF and with less perceived control over symptoms showed maladaptive coping styles such as denial and behavioral disengagement, and more severe levels of depression and anxiety. Depression also independently predicted QoL outcomes.

Conclusions

Anxious and depressed patients have more negative beliefs about HF, leading to negative coping behaviors and poor QoL. Our evidence suggests that changing negative beliefs may improve the psychological well-being and QoL of patients, irrespective of disease severity.