Jorge L. Gonzalez-Calvin

Bone mineral density and serum levels of soluble tumor necrosis factors, estradiol, and osteoprotegerin in postmenopausal women with cirrhosis after viral hepatitis.

CONTEXT Cirrhosis after viral hepatitis has been identified as a risk factor for osteoporosis in men. However, in postmenopausal women, most studies have evaluated the effect of primary biliary cirrhosis, but little is known about the effect of viral cirrhosis on bone mass [bone mineral density (BMD)] and bone metabolism. OBJECTIVE Our objective was to assess the effect of viral cirrhosis on BMD and bone metabolism in postmenopausal women. DESIGN We conducted a cross-sectional descriptive study. SETTING AND PATIENTS We studied 84 postmenopausal female outpatients with viral cirrhosis and 96 healthy postmenopausal women from the general community. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN). RESULTS The percentage with osteoporosis did not significantly differ between patients (LS, 43.1%; FN, 32.2%) and controls (LS, 41.2%; FN, 29.4%), and there was no difference in BMD (z-score) between groups. Serum concentrations of soluble TNF receptors, estradiol, and osteoprotegerin (OPG) were significantly higher in patients vs. controls (P < 0.001, P < 0.05, and P < 0.05, respectively). No significant difference was observed in urinary deoxypyridinoline. Serum OPG levels were positively correlated with soluble TNF receptors (r = 0.35; P < 0.02) and deoxypyridinoline (r = 0.37; P < 0.05). CONCLUSIONS This study shows that bone mass and bone resorption rates do not differ between postmenopausal women with viral cirrhosis and healthy postmenopausal controls and suggests that viral cirrhosis does not appear to increase the risk of osteoporosis in these women. High serum estradiol and OPG concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.

Bone Mineral Density, Bone Turnover Markers and Cytokines in Alcohol-Induced Cirrhosis

AIMS Liver cirrhosis is a risk factor for osteoporosis. However, the pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis (AC) is not well understood. Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL-2R), activation markers of cellular immunity, correlate with clinical activity and severity of the AC. The aim of this study is to evaluate the association of these soluble markers with the development of osteoporosis in patients with AC. METHODS We studied 33 consecutive patients with AC and 24 healthy volunteers. Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay. Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay. We also determined serum levels of osteocalcin and bone alkaline phosphatase as biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D-Pyr) as marker of bone resorption. RESULTS Patients with AC had reduced BMD (expressed as z-score) in all sites (LS: P < 0.001 and FN: P < 0.05). Serum concentrations of sTNF-R55 were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.001). Serum levels of sTNF-R55 positively correlated with D-Pyr urinary excretion (r = 0.354; P = 0.01). Serum levels of sIL-2R were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.05). CONCLUSIONS There is a relation between activation of the cellular immunity and osteoporosis in AC. Bone mass loss could be related to the increased bone resorption found in these patients.

Sonographic quantification of a hepato-renal index for the assessment of hepatic steatosis in comparison with 3T proton magnetic resonance spectroscopy.

Context Nonalcoholic fatty liver disease is the most frequent hepatic disorder in the developed world. Currently, liver biopsy and proton magnetic resonance spectroscopy (1H-MRS) are considered the gold standard methods for the quantification of liver fat deposits. Objective To determine whether a Sonographic Hepato-Renal Index (SHRI) calculated using a standard workstation, without a specifically designed software, is an adequate alternative to 1H-MRS for the quantification of fat liver content and diagnosis of steatosis in the general population. Methods A total of 121 volunteers (mean age=46 years, range=21–77 years) were recruited at three medical centers in Granada (Southern Spain) from among individuals attending routine general checkups. All participants were examined by ultrasound and by 1H-MRS 3T, which served as a reference for the diagnosis of steatosis. The SHRI was calculated as the ratio between the echogenicity of the liver and that of the right renal parenchyma. The validity of the methodology was assessed by receiver operating characteristic curves and correlation tests. Results The quantitative SHRI showed a strong correlation (Spearman’s coefficient=0.89, P<0.001) with the 1H-MRS 3T. The optimal SHRI cutoff points of 1.21, 1.28, and 2.15 yielded 100% sensitivity for the diagnoses of steatosis greater than 5, 25, and 50%, respectively, with a specificity greater than 70%. Conclusion This study shows that the SHRI is a valid, simple, reliable, and cost-effective screening tool for the identification, assessment, and quantification of hepatic steatosis in the general population.

Diagnostic accuracy of serum alanine aminotransferase as biomarker for nonalcoholic fatty liver disease and insulin resistance in healthy subjects, using 3t Mr spectroscopy

Abstract Recognition of the close relationship of nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus 2, obesity, metabolic syndrome, and cardiovascular disease has stimulated growing interest in NAFLD as a public health problem. Serum alanine aminotransferase (ALT) has been proposed as a marker of NAFLD, but levels are within the range currently considered “normal” in a large proportion of NAFLD subjects. The aim of the study was to determine the diagnostic accuracy of serum ALT for identifying individuals with NAFLD, using 3-Tesla (T) magnetic resonance spectroscopy (1H-MRS). A cross-sectional study was conducted in 129 healthy subjects. Liver triglyceride content was quantified by 1H-MRS. NAFLD was defined as liver triglyceride content greater than 5.56%. Liver triglyceride content was >5.56% in 79 participants (NAFLD) and lower in the remaining 50 (normal). Serum ALT levels correlated positively with liver triglyceride content (r = 0.58, P < .001), Homeostatic Model Assessment for Insulin Resistance (r = 0.32, P < .01), and fasting insulin (r = 0.31, P < .01), and inversely correlated with adiponectin (r = 0.35, P < .01) and high-density lipoprotein cholesterol (r = 0.32, P < .01). Regression analysis showed that serum ALT was the best predictor of NAFLD (P < .01). Optimal serum ALT cut-off to predict NAFLD was 23 IU/L (area under receiver-operating characteristic curve: 0.93; sensitivity: 0.94; specificity: 0.72). This study shows that serum ALT is a sensitive and accurate biomarker of NAFLD if the “normal” ALT value is revised and established at a lower level. An ALT threshold of 23 IU/L identified 94% of individuals with NAFLD in the present series, using 3-T 1H-MRS for liver triglyceride quantification.

Neopterin, soluble receptors for interleukin-2 and tumor necrosis factor in viral cirrhosis and alcoholic cirrhosis

Abstract Alcoholic cirrhosis and viral cirrhosis are associated with alterations of immune system function and cytokine production. Our aim was to investigate whether serum concentrations of soluble receptors for interleukin-2 (sIL- 2 R) and tumor necrosis factor (55kD-type, sTNFR-55), and serum neopterin can be used as markers to establish differences in etiology and severity in liver cirrhosis and to determine whether they correlate with laboratory and clinical parameters. Thirty three patients with alcoholic and 15 with viral cirrhosis (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy controls were studied. Serum concentrations of sIL2-R, sTNFR-55 and neopterin were significantly raised in patients. No significant differences between alcoholic and viral cirrhosis were found. The concentrations of sIL-2 Rand sTNFR-55 were significantly higher in patients with more severe disease. There existed correlations b<!tween sIL-2R and sTNFR-55 (rs = 0.50, P < 0.001) and between both soluble receptors and the Child-Pugh score (sTNF-R55: rs = 0.70, p < 0.001; sIL-2R: rs = 0.33, p < 0.05) and serum albumin. The results are likely to reflect that the monocyte-macrophage and T-cell functions are stimulated in patients with liver cirrhosis independently of the etiology of the disease, and the persistent activation of the immune system occurs in cirrhosis even at the end stage of the disease. Chronic immune activation might have deletereous consequences on the evolution of cirrhosis.

Insulin resistance in lean and overweight non-diabetic Caucasian adults: Study of its relationship with liver triglyceride content, waist circumference and BMI

Aims Insulin resistance is the pathophysiological precursor of type 2 diabetes mellitus (DM-2), and its relationship with non-alcoholic fatty liver disease (NAFLD) has been widely studied in patients with obesity or metabolic syndrome using not only ultrasound but also liver biopsies or proton magnetic resonance spectroscopy (H1-MRS) to assess liver fat content. In contrast, there are no studies on insulin resistance and NAFLD in lean or overweight Caucasian individuals using H1-MRS or liver biopsies for the quantification of hepatic triglyceride content. Our objectives were to study the presence of insulin resistance in lean and overweight Caucasian adults and investigate its possible relationship with liver triglyceride content, waist circumference (as proxy of visceral adiposity), BMI, and cardiometabolic risk factors. Methods A cross-sectional study was conducted in 113 non-obese, non-diabetic individuals classified as overweight (BMI 25–29.9 kg/m2) or lean (BMI 19.5–24.9 kg/m2). Hepatic triglyceride content was quantified by 3T H1-MRS. NAFLD was defined as hepatic triglyceride content >5.56%. Insulin resistance (HOMA-IR), serum adiponectin, and tumor necrosis factor (TNF) were determined. Results HOMA-IR was significantly correlated with hepatic triglyceride content (r:0.76; p<0.0001). The lean-with-NAFLD group had significantly higher HOMA-IR (p<0.001) and lower serum adiponectin (p<0.05) than the overweight-without-NAFLD group. Insulin resistance was independently associated with NAFLD but not with waist circumference or BMI. Regression analysis showed hepatic triglyceride content to be the most important determinant of insulin resistance (p<0.01). Conclusions Our findings suggest that NAFLD, once established, seems to be involved in insulin resistance and cardio-metabolic risk factors above and beyond waist circumference and BMI in non-obese, non-diabetic Caucasian individuals.

Femoral artery ultrasound for improving the detection of atherosclerosis in psoriasis

From the AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, Paris, France; Sorbonne Universit e, Facult e de M edecine Sorbonne Universit e, Paris, France; Assistance Publique Hôpitaux de Paris, Service de Gastro-Ent erologie, Hôpital Saint Antoine, Paris, France; AP-HP, Service de Dermatologie, Hôpital Saint-Louis, Sorbonne, Paris, France; Universit e Paris Diderot, Sorbonne Paris Cit e, Paris, France; APHP, Service d’Anatomo-Pathologie, Hôpital Tenon, F-75020, Paris, France; AP-HP, Service de Gastro-Ent erologie, Hôpital Saint-Louis, Paris, France; AP-HP, Service de Gastro-Ent erologie, Hôpital Henri Mondor, F-9400, Cr eteil, France; EC2M3 EA 7375, Universit e Paris-Est Cr eteil, France; AP-HP, Service de Dermatologie, Hôpital Cochin, Paris, France; and Universit e Paris Descartes, Paris, France