Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation.

BACKGROUND: Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B12, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B12 adjuvant therapy were assessed in an infant rat model of BM. METHODS: Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with B12 or placebo, and, 24 h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription, and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA followed by Bonferroni post hoc test. Correlations were tested with Spearman's test. RESULTS: B12 attenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P < 0.05). BM caused global DNA hypomethylation; however, B12 restored this parameter. Accordingly, B12 increased the methylation capacity of hippocampal cells from infected animals, as inferred from the ratio S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) in infected animals. BM upregulated selected pro-inflammatory genes, and this effect was counteracted by B12, which also increased methylation of CpGs at the promoter of Ccl3 of infected animals. CONCLUSION: Hcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B12 shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.

oipA "on" status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil.

BACKGROUND: Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA "on" status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer. METHODS: We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR. RESULTS: Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA "on" status (OR = 9.20; 95%CI = 1.45-58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03-1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA "on" status (OR = 14.75; 95%CI: 2.53-86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA "on" status did not differ between children and adults (P = 0.87). The oipA "on" status was significantly correlated with the presence of cagA and vacA s1 m1. CONCLUSION: oipA "on" status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.

The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients. METHODS: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations. RESULTS: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype. CONCLUSION: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients.

Porcine stomachs with and without gastric ulcer differ in Lactobacillus load and strain characteristics.

Although Lactobacillus species are recognized as normal inhabitants of porcine gastric mucosa, the association of these bacteria with health status or gastric ulcer disease has never been considered. We investigated the bacterial load of Lactobacillus isolated from the antrum, corpus, and pars esophagea of stomachs with (n = 13) and without (n = 10) ulcer of the pars esophagea of slaughtered pigs. We also evaluated in vitro antagonistic properties against typical pathogens of strains isolated from stomachs without ulcer. To quantify Lactobacillus, gastric mucosa samples obtained with 5 mm biopsy punches were smeared on MRS agar and colonies were counted after 48 h of incubation under anaerobic conditions. The score of Lactobacillus was significantly greater in the antrum and corpus of stomachs without ulcer (P < 0.001 for both) when compared with stomachs with ulcer. Fingerprint profiles, obtained by repetitive sequence-based PCR using (GTG)5 primers, showed that the isolates were highly diverse. The reduction of Lactobacillus load in porcine stomachs may be a contributing factor for gastric ulcer. Strains isolated from healthy stomachs, which showed a wide spectrum of antagonistic activity against pathogens, may be viewed as an untapped source of bacteria with potential beneficial properties that deserve to be further investigated.

Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns.

To compare children and adults in respect to the effect of H. pylori infection on the gastric concentrations of cytokines linked to innate and Th1 immune response, as well as to investigate the changes in the gastric concentrations of the studied cytokines according to the age. We studied 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The gastric concentrations of cytokines representative of the innate and Th1 response were higher in the H. pylori-positive than in the -negative children and adults. The gastric concentrations of IL-1α and TNF-α were significantly higher, while those of IL-2, IL-12p70 and IFN-γ were lower in the infected children than in the infected adults. In the infected children, the gastric concentration of IL-1α, IL-2, IL-12p70 and IFN-γ increased, whereas in adults, the gastric concentrations of IFN-γ and IL-12p70 decreased with the aging. Increased gastric concentration of Th1 associated cytokines correlated with increased degree of gastritis that is the background lesion for the development of the H. pylori associated severe diseases. Concluding, Th1 response to H. pylori infection varies according to the age and seems to have determinant implication in the H. pylori infection outcomes.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Agreement and diagnostic differences among three definitions of sarcopenia in patients with chronic hepatitis C.

BACKGROUND: There is neither a gold standard definition nor a universal consensus to diagnose sarcopenia in patients with chronic hepatitis C. Thus, we aimed to compare the prevalence of sarcopenia and the agreement and discrepancies between European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, and Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project (FNIH) definitions in chronic hepatitis C. METHODS: Dual-energy x-ray absorptiometry was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for squared height (ALM/ht2) or for body mass index (ALMBMI). Muscle function was evaluated by handgrip strength. Subjective Global Assessment was used to assess the nutrition status. RESULTS: This cross-sectional study included 103 outpatients (mean age, 50.6 ± 11.3 years; 33.0% with compensated cirrhosis). Sarcopenia prevalence was 8.7%, 9.7%, and 9.7%, according to EWGSOP1, EWGSOP2, and FNIH definitions, respectively. There was neither a sex- nor a liver disease severity-specific difference in the prevalence of sarcopenia between the criteria applied. Sixteen (15.5%) patients fulfilled at least one of these criteria, and 3 out of 16 (18.8%) simultaneously had sarcopenia by consensus of the three criteria. Sarcopenic obesity was identified in 9 out of 16 (56.3%) patients, and 6 out of 9 (66.7%) of these only met FNIH consensus. CONCLUSIONS: In patients without cirrhosis or with compensated cirrhosis, and with chronic hepatitis C, the agreement between EWGSOP1 and EWGSOP2 classifications was substantial for sarcopenia diagnosis. Concerning EWGSOP and FNIH criteria, a fair agreement and limited overlap were found in these patients.

Helicobacter pylori infection in infants and toddlers in South America: concordance between [13C]urea breath test and monoclonal H. pylori stool antigen test.

Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [(13)C]urea breath test ([(13)C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [(13)C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [(13)C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.

HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND SYSTEMIC ARTERIAL HYPERTENSION ARE ASSOCIATED WITH HEPATIC NECROINFLAMMATORY ACTIVITY IN PATIENTS WITH CHRONIC HEPATITIS C.

•HDL cholesterol levels <60 mg/dL were independently associated with necroinflammatory activity in chronic hepatitis C (CHC). •CHC patients with hypertension are at an increased risk of developing necroinflammatory activity. •In patients with CHC, liver fibrosis was independently associated with old age, steatosis, and HDL-C <60 mg/dL. •Triglycerides levels ≥150 mg/dL were associated with lobular inflammatory activity in patients with CHC. Background - Approximately 71 million people are chronically infected with hepatitis C virus (HCV) worldwide. A significant number of these individuals will develop liver cirrhosis and/or hepatocellular carcinoma. Beyond the liver, there is a sizeable body of scientific evidence linking cardiovascular disease and chronic hepatitis C (CHC); however, the biological mechanisms behind the concurrence of these conditions have not been completely clarified yet. Objective - To evaluate associations between hepatic histology, clinical comorbidities and lipid profile in patients with CHC. To investigate associations between liver histology and demographic, nutritional, biochemical and virological parameters. Methods - Eight-five patients with CHC prospectively underwent hepatic biopsy. Liver fragments were obtained from each patient by percutaneous route using a Menghini needle. Fibrosis was evaluated according to the METAVIR scoring system, as follows: F0, no fibrosis; F1, fibrous portal expansion; F2, fibrous portal widening with few septa; F3, bridging fibrosis with architectural distortion; and F4, liver cirrhosis. The activity was classified based on the degree of lymphocyte infiltration and hepatocyte necrosis, from A0 to A3. The diagnosis of liver disease was based on clinical, biochemical, histological, and radiological methods. The data were analyzed by logistic regression models. Results - This cross-sectional study included 85 outpatients followed at the tertiary care ambulatory centre with a mean age of 57.2±10.7 years and 45 (52.9%) were females. There were 10 patients with cirrhosis. Patients with a METAVIR F3-F4 were significantly older (P=0.02) and had higher levels of ALT (P=0.0006), AST (P<0.0001), γ-GT (P=0.03) and bilirubin (P=0.001) and higher prothrombin time than patients with F0-F2 score. Albumin levels (P=0.01) were significantly lower in METAVIR F3-F4. Age (OR=1.09; 95%CI=1.02-1.16; P=0.02), steatosis (OR=4.03; 95%CI=1.05-15.45; P=0.04) and high-density lipoprotein cholesterol (HDL-C) <60 mg/dL (OR=7.67; 95%CI=1.71-34.49; P=0.008) were independently associated with fibrosis. Hypertension (OR=6.36; 95%CI=1.31-30.85; P=0.02) and HDL-C <60 mg/dL (OR=9.85; 95%CI=2.35-41.39; P=0.002) were independently associated with necroinflammatory activity. Hypertension (OR=6.94; 95%CI=1.92-25.05; P=0.003) and HDL-C <60 mg/dL (OR=3.94; 95%CI=1.27-12.3; P=0.02) were associated with interface inflammatory activity. Triglycerides (TG ≥150 mg/dL) remained associated with lobular inflammatory activity. Conclusion - cholesterol levels <60 mg/dL were independently associated with necroinflammatory activity in chronic hepatitis C. Patients with hypertension are at an increased risk of developing necroinflammatory activity.

Sarcopenia in chronic viral hepatitis: From concept to clinical relevance.

Although the frequency of metabolic risk factors for cirrhosis and hepatocellular carcinoma (HCC) is increasing, chronic hepatitis B (CHB) and chronic hepatitis C (CHC) remain the most relevant risk factors for advanced liver disease worldwide. In addition to liver damage, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with a myriad of extrahepatic manifestations including mixed cryoglobulinaemia, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production. Recently, the list has grown to include sarcopenia. Loss of muscle mass or muscle function is a critical feature of malnutrition in cirrhotic patients and has been found in approximately 23.0%-60.0% of patients with advanced liver disease. Nonetheless, among published studies, there is significant heterogeneity in the aetiologies of hepatic diseases and measurement methods used to determine sarcopenia. In particular, the interaction between sarcopenia, CHB and CHC has not been completely clarified in a real-world setting. Sarcopenia can result from a complex and multifaceted virus-host-environment interplay in individuals chronically infected with HBV or HCV. Thus, in the present review, we provide an overview of the concept, prevalence, clinical relevance, and potential mechanisms of sarcopenia in patients with chronic viral hepatitis, with an emphasis on clinical outcomes, which have been associated with skeletal muscle loss in these patients. A comprehensive overview of sarcopenia in individuals chronically infected with HBV or HCV, independent of the stage of the liver disease, will reinforce the necessity of an integrated medical/nutritional/physical education approach in the daily clinical care of patients with CHB and CHC.

Correction to "Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis: An experimental study in Brazil".

[This corrects the article on p. 100 in vol. 12, PMID: 36196438.].

Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B.

BACKGROUND: Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded. AIM: To evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients. METHODS: Dual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively. RESULTS: This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS. CONCLUSION: MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia.

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-ß were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient.

The hypothesis that Helicobactermight be a risk factor for human liver diseases has arisen after the detection of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases. Nevertheless, no explanation that justifies the presence of the bacterium in the human liver has been proposed. We evaluated the presence of Helicobacterin the liver of patients with hepatic diseases of different aetiologies. We prospectively evaluated 147 patients (106 with primary hepatic diseases and 41 with hepatic metastatic tumours) and 20 liver donors as controls. Helicobacter species were investigated in the liver by culture and specific 16S rDNA nested-polymerase chain reaction followed by sequencing. Serum and hepatic levels of representative cytokines of T regulatory cell, T helper (Th)1 and Th17 cell lineages were determined using enzyme linked immunosorbent assay. The data were evaluated using logistic models. Detection of Helicobacter pylori DNA in the liver was independently associated with hepatitis B virus/hepatitis C virus, pancreatic carcinoma and a cytokine pattern characterised by high interleukin (IL)-10, low/absent interferon-γ and decreased IL-17A concentrations (p < 10(-3)). The bacterial DNA was never detected in the liver of patients with alcoholic cirrhosis and autoimmune hepatitis that are associated with Th1/Th17 polarisation. H. pylori may be observed in the liver of patients with certain hepatic and pancreatic diseases, but this might depend on the patient cytokine profile.

MAJOR DEPRESSIVE DISORDER IS ASSOCIATED WITH TYPE 2 DIABETES IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION.

BACKGROUND: Major depressive disorder (MDD) is commonly reported in patients with chronic hepatitis C (CHC); however, the factors behind the co-occurrence of these conditions have not been completely clarified yet. OBJECTIVE: We aimed to evaluate the frequency of mental disorders in CHC patients and to investigate variables associated with MDD. METHODS: CHC patients (n=151) attending a referral Centre for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview and the Cut-Annoyed-Guilty-Eye (CAGE) Questionnaire. Multivariate analysis was used to evaluate independent covariates associated with current MDD. RESULTS: Seventy-six (50.3%) patients had, at least, one current psychiatric diagnosis with MDD (33.1%) being the most common. Current MDD was independently associated with age (≤50 yr.) (OR=2.57; 95%CI=1.25-5.29; P=0.01) and type 2 diabetes mellitus (OR=2.80, 95%CI=1.17-6.70; P=0.02). Cirrhosis was associated with type 2 diabetes mellitus (OR=5.09; 95%CI=1.73-15.04; P=0.03) and current alcohol abuse/dependence (OR=2.54; 95%CI=1.04-6.22; P=0.04). DISCUSSION: MDD is associated with type 2 diabetes in CHC patients. Even in the direct-acting antivirals (DAAs) era, characterized by great perspectives for the first ample cure of a chronic viral infection, we should ensure that the screening for psychiatric disorders takes place in the course of routine clinical care of patients chronically infected with hepatitis C virus.

Derivation and validation of a simple anthropometric equation to predict fat-free mass in patients with chronic hepatitis C.

BACKGROUND: Loss of skeletal muscle mass is very common in chronic liver diseases and affects 30.0-70.0% of the patients with cirrhosis. Given the relevance of muscle wasting in hepatic diseases, a practical screening tool for earlier detection of skeletal muscle mass loss is of utmost significance. AIMS: To develop and validate a simple anthropometric prediction equation for fat-free mass estimation by using Bioelectrical Impedance Analysis (BIA) as a reference method in patients with chronic hepatitis C (CHC). METHODS: We prospectively, included 209 CHC patients, randomly allocated into two groups, 158 patients in a development model (derivation sample) and 51 patients in a validation group (validation sample). Predictive equations were developed using backward stepwise multiple regression and the most adequate and simplest derived predictive equation was further explored for agreement and bias in the validation sample. The accuracy of the predictive equation was evaluated using the coefficient of determination (R2). RESULTS: The predictive equation with an optimal R2 was Fat-Free Mass (Kg) = Sex × 0.17 + Height (m) × 16.83 + Weight (Kg) × 0.62 + Waist Circumference (cm) × (-0.15) + Weight (Kg) × Sex × (-0.30) + Sex × Waist Circumference (cm) × 0.14-6.23; where sex = 1 for female and 0 for male. R2 = 0.93, standard error of the estimate = 2.6 Kg and coefficient of variation = 20.0%, p < 0.001. CONCLUSIONS: Our developed and cross-validated anthropometric prediction equation for fat-free mass estimation by using BIA attained a high coefficient of determination, a low standard error of the estimate, and lowermost coefficient of variation. This study indicates that predictive equations may be reliable and useful alternative methods for clinical evaluation of fat-free mass in patients with CHC.

IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia.

Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1ß were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.

Skeletal muscle mass index and phase angle are decreased in individuals with dependence on alcohol and other substances.

OBJECTIVE: The aim of this study was to evaluate whether low skeletal muscle mass index (SMI) and low phase angle (PhA) are associated with demographic, clinical, lifestyle, and nutritional status in patients dependent on alcohol and other substances. METHODS: We prospectively included 63 individuals dependent on alcohol and other substances and 71 age- and sex-matched healthy controls. Body composition was assessed by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. All included participants underwent a psychiatric evaluation, including the administration of the Mini-International Neuropsychiatric Interview. Univariate and multivariate analysis were performed to evaluate associations between low skeletal muscle mass index (SMI) and low phase angle (PhA) and nutritional, lifestyle, and alcohol use and cocaine/crack use variables, controlling for sex and age. RESULTS: Low SMI and low PhA were identified in 11.1% and 44.5% of the substance dependents, respectively. Low midarm muscle circumference (r = 0.58; P < 0.001), low midarm muscle area (r = 051; P < 0.001), and reduced PhA (r = 0.59; P < 0.001) were positively correlated with low SMI. Multivariate analysis showed that heavy alcohol consumption (≥80 g·d· ≥5 y-1; odds ratio [OR], 2.33; 95% confidence interval [CI], 1.12-4.84; P = 0.02) and sedentary lifestyle (OR, 4.39; 95% CI, 1.29-14.89; P = 0.02) were independently associated with reduced SMI. Low PhA was independently associated with heavy alcohol consumption (OR, 3.64; 95% CI, 1.62-8.15; P = 0.002) and cocaine or crack use (OR, 3.97; 95% CI, 1.05-15.11; P = 0.04) in multivariate analysis. CONCLUSIONS: Low SMI and low PhA are independently associated with heavy alcohol consumption. Low PhA is independently associated with cocaine or crack use.

Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus.

BACKGROUND: Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection. AIM: To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients. METHODS: Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models. RESULTS: Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001). CONCLUSION: This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.