Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease.

OBJECTIVE: The evaluation of serum sex steroids and sex hormone-binding globulin (SHBG) levels in postmenopausal women with nonalcoholic fatty liver disease (NAFLD) and their association to the disease severity. DESIGN: Twenty-two postmenopausal women with biopsy-proven NAFLD and 18 matched controls were recruited. Blood samples for serum SHBG, total testosterone, estradiol levels and standard biochemical tests were obtained after overnight fasting. Free androgen index (FAI), calculated free (cFT) and bioavailable testosterone were estimated by standard formulas. RESULTS: The NAFLD group had lower serum SHBG levels and higher values of cFT, bioavailable testosterone and FAI, despite exhibiting similar to controls levels of serum total testosterone and estradiol. Serum SHBG levels (adjusted odds ratio [aOR]=0.912; 95% CI 0.854-0.973), bioavailable testosterone (aOR=1.254; 95% CI 1.010-1.556) and FAI (aOR=2.567; 95% CI 1.153-5.716), but not cFT, were associated with NAFLD independently of age, body mass index (BMI) and waist circumference. Serum estradiol levels were associated with the presence of nonalcoholic steatohepatitis (NASH) independently of age, BMI and waist circumference (aOR=0.727; 95% CI 0.537-0.985). CONCLUSIONS: Low SHBG levels and high metabolically active testosterone fractions were independently associated with NAFLD. Among NAFLD patients, serum estradiol levels were independently associated with NASH. However, these results need further validation from large-scale studies.

A novel noninvasive index for nonalcoholic steatohepatitis: a pilot study.

OBJECTIVE: The potential development of a noninvasive marker predicting nonalcoholic steatohepatitis (NASH). METHODS: Thirty patients with biopsy-proven nonalcoholic fatty liver disease were evaluated by numerous anthropometric, clinical and biochemical parameters. RESULTS: Serum glutamic oxaloacetic transaminase (SGOT; p = 0.027), log (erythrocyte sedimentation rate) (ESR; p = 0.034) and homocysteine (p = 0.041) were associated with NASH independently from gender, age and body mass index. When combined, the regression model provided R(2) = 0.563 (p = 0.001) and area under the ROC curve = 0.873 ± 0.066 (p < 0.001). CONCLUSION: This noninvasive marker, named HSENSI (acronym of homocysteine, SGOT, ESR, Nonalcoholic Steatohepatitis Index), consists of three low cost, easily measurable parameters and may accurately predict NASH.

Adipocytokines and cytokeratin-18 in patients with nonalcoholic fatty liver disease: Introduction of CHA index.

BACKGROUND AND RATIONALE: Insulin resistance (IR), adipocytokines, oxidative stress and hepatic apoptosis play a pathogenetic role in nonalcoholic fatty liver disease (NAFLD). AIMS: The evaluation of specific adipocytokines and markers of IR, oxidative stress and apoptosis in NAFLD patients; the introduction of a combined non-invasive index for nonalcoholic steatohepatitis (NASH). MATERIAL AND METHODS: Thirty patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 15 with NASH) and 24 controls were recruited. Blood samples for total and high molecular weight (HMW) adiponectin, visfatin and tumor necrosis factor (TNF)-α, the apoptotic by-product cytokeratin (CK)-18, the reactive oxygen metabolites (ROMs) and standard biochemical tests were measured. Homeostatic model of assessment - insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. MAIN RESULTS: Total and HMW adiponectin were significantly lower and TNF-α higher in either NAFL or NASH group compared to control group; CK-18 was significantly higher in NASH compared to either NAFL or control group. CHAI (an acronym of CK-18, HOMA-IR, AST Index) was calculated as the product of parameters being significantly different between NAFL and NASH groups. CHAI was significantly higher in NASH (24.2 [15.1-214.0]) compared to either NAFL (15.7 [6.8-22.7]) or control (5.1 [2.4-7.6]) group (p < 0.001) and significantly higher as the severity of steatosis, fibrosis, ballooning, lobular and portal inflammation advanced. CONCLUSION: CHAI was escalating from controls to NAFL and NASH and was higher by increasing the severity of all the main histological lesions. However, a validation study is needed before introducing CHAI in clinical practice.

Helicobacter pylori infection in patients with nonalcoholic fatty liver disease.

OBJECTIVE: Clinical data regarding Helicobacter pylori (Hp) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was the evaluation of Hp infection in patients with NAFLD and its association with disease severity. METHODS: 28 patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 13 with nonalcoholic steatohepatitis [NASH]) and 25 matched healthy controls were recruited. Blood samples for anti-Hp Immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting, and (13)C urea breath test was performed before liver biopsy in NAFLD group. RESULTS: Higher rates of anti-Hp IgG (P=.038) were observed in NAFLD compared to control group. Only two NAFLD patients neither were Hp IgG seropositive nor did they have a history of eradication treatment compared to 11 control subjects (P=.002). Both Hp infection (assessed by history of Hp eradication treatment and/or Hp IgG seropositivity) (P=.034) and log(HOMA-IR) (P=.007) could independently predict NAFLD in logistic regression analysis. There were similar rates of Hp IgG seropositivity or positivity in (13)C urea breath test or their combination between NAFL and NASH patients. There were no significant differences in steatosis grade, fibrosis stage, lobular or portal inflammation, or ballooning, when NAFLD patients were divided according to Hp IgG seropositivity or (13)C urea breath test positivity. CONCLUSIONS: Hp infection may represent one more hit contributing to the pathogenesis of NAFL, though not to the progression from NAFL to NASH. These results warrant further validation. If confirmed, eradicating Hp infection may have certain therapeutic perspectives in NAFLD treatment.

Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease.

The aim of the study was the evaluation of serum vitamin B12 and folate levels in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and their association with the disease severity. Thirty patients with biopsy-proven NAFLD and 24 healthy controls matched for gender, age, body mass index and waist circumference were recruited. Blood samples for vitamin B12, folate, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance was calculated. There was no difference in serum vitamin B12 and folate levels between groups. Neither vitamin B12 nor folate levels were significantly different within any histological category, including steatosis grade, fibrosis stage, lobular inflammation, portal inflammation and ballooning. In conclusion, similar vitamin B12 and folate levels were observed in non-alcoholic steatohepatitis and non-alcoholic fatty liver patients, and controls. Furthermore, vitamin B12 and folate levels were not associated with either insulin resistance or the severity of liver disease.

Serum homocysteine levels in patients with nonalcoholic fatty liver disease.

Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.

Effect of spironolactone and vitamin E on serum metabolic parameters and insulin resistance in patients with nonalcoholic fatty liver disease.

AIM: The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of insulin resistance and nonalcoholic fatty liver disease (NAFLD). The beneficial effect of spironolactone in a mouse model with diabetes and NAFLD has recently been reported. The main aim was assessment of the effect of spironolactone on serum metabolic parameters and insulin resistance in patients with NAFLD. METHODS: This study includes preliminary results of a single-centre randomised controlled trial of treatment with vitamin E (group 1, 10 patients) versus spironolactone plus vitamin E (group 2, 10 patients) in biopsy-proven NAFLD. Serum transaminases, lipids, potassium, sodium, glucose and insulin were measured, and homeostatic model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated before and 8( )weeks after baseline assessment. RESULTS: Insulin was decreased within group 2 (15.3 ± 2.7 at baseline vs. 10.3 ± 5.0 at week 8, p = 0.013). Although no difference in glucose was observed, HOMA-IR significantly decreased (4.4 ± 0.9 vs. 2.8 ± 0.5, respectively, p = 0.047). QUICKI was increased, but not statistically significantly. CONCLUSIONS: Spironolactone and vitamin E combined therapy seems to exhibit a favourable effect on serum insulin and HOMA-IR in patients with NAFLD. If validated in a large-scale clinical trial, it may prove an inexpensive therapeutic approach for the management of NAFLD patients.

Dual-energy X-ray absorptiometry and quantitative ultrasound in patients with Paget's disease of bone before and after treatment with zoledronic acid: association with serum bone markers and Dickkopf-1.

The main aim of this study was to determine the effect of zoledronic acid (ZOL) on parameters of dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) in unaffected bones of patients with Paget's disease of bone (PDB). The secondary aim was the association of bone markers and Dickkopf (DKK)-1 with parameters of DXA and QUS. Ten consecutive patients with polyostotic PDB (median age: 63 yr) received a single 5-mg ZOL infusion. The patients were subjected to calcaneal QUS and DXA of both lumbar spine (LS) and femoral neck (FN). Blood samples for serum bone markers and DKK-1 were serially obtained for 12 mo. There was a significant increase in LS (p=0.005) and FN bone mineral density (BMD) (p=0.021) 12 mo after ZOL infusion. QUS parameters remained unaffected throughout the study. A significant correlation between broadband ultrasound attenuation and DKK-1 (p<0.001) and between speed of sound and DKK-1 (p=0.033) at baseline was found, which remained significant after adjustment for gender, age, and body mass index. Our data suggest that a single ZOL infusion significantly increases nonpagetic BMD 12 mo after treatment but has no effect on QUS parameters or DKK-1. Significant correlations were observed between QUS parameters and DKK-1 at baseline.

Serum homocysteine, folate and vitamin B12 in patients with Paget's disease of bone: the effect of zoledronic acid.

High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin B(12) stimulate bone resorption and adversely affect collagen cross-linking. The aim of this study was the evaluation of serum levels of HCY, folate and vitamin B(12) in patients with Paget's disease of bone (PDB) and the effect of zoledronic acid (ZOL) on their serum levels. Nine consecutive patients with polyostotic PDB (median age 66 years) received a single 5-mg ZOL infusion. Blood samples for HCY, folate, vitamin B(12), 25-hydroxyvitamin D (25-OH-D), total serum alkaline phosphatase (TSAP), bone-specific serum alkaline phosphatase (BSAP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were obtained at baseline and 3, 6 and 12 months after ZOL infusion. Twelve age-, gender- and BMI-matched healthy individuals were recruited for the control group at baseline assessment. Patients with PDB had significantly higher serum HCY (p = 0.028), folate (p < 0.001) and bone markers [TSAP (p < 0.001), BSAP (p < 0.001) and CTX (p < 0.001)] compared with the control group at baseline. In the pagetic group, serum HCY significantly decreased 3 months after ZOL infusion and remained essentially unchanged up to the end of the study (p = 0.005). Serum vitamin B(12) and folate remained unaffected throughout the study. Our data suggest that serum HCY levels are increased in patients with PDB. A single ZOL infusion results in a decrease in HCY levels that might represent another mechanism for the reduction of the activity of PDB achieved by ZOL.