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.

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.

Lipoproteína de alta densidade e hipertensão arterial sistêmica estão associados à atividade necroinflamatória hepática em pacientes com hepatite C crônica / High-density lipoprotein cholesterol and systemic arterial hypertension are associated with hepatic necroinflammatory activity in patients with chronic hepatitis c

ABSTRACT 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.

RESUMO Contexto: Aproximadamente 71 milhões de pessoas estão infectadas pelo vírus da hepatite C em todo o mundo. Um número significativo desses indivíduos desenvolverá cirrose hepática e/ou carcinoma hepatocelular. Além do fígado, há evidências científicas que associam doenças cardiovasculares e hepatite C crônica; no entanto, os mecanismos biológicos implicados na ocorrência dessas condições ainda não foram completamente esclarecidos. Objetivo: Avaliar a associação entre histologia hepática, comorbidades clínicas e perfil lipídico em pacientes com hepatite C crônica. Investigar associações entre histologia hepática e parâmetros demográficos, nutricionais, bioquímicos e virológicos. Métodos: Oitenta e cinco pacientes com hepatite C crônica foram prospectivamente submetidos à biópsia hepática. Biópsias hepáticas foram obtidas de cada paciente por via percutânea com agulha de Menghini. A fibrose foi avaliada de acordo com o sistema de pontuação METAVIR, como segue: F0, sem fibrose; F1, expansão portal fibrosa; F2, alargamento portal fibroso com poucos septos; F3, fibrose em ponte com distorção arquitetônica; e F4, cirrose hepática. A atividade foi classificada com base no grau de infiltração de linfócitos e necrose de hepatócitos, de A0 a A3. O diagnóstico da doença hepática foi baseado em métodos clínicos, bioquímicos, histológicos e radiológicos. Os dados foram analisados por modelos de regressão logística. Resultados: Neste estudo transversal, realizado em um ambulatório do hospital universitário, foram incluídos 85 pacientes que tinham média de idade de 57,2±10,7 anos, sendo 45 (52,9%) do sexo feminino. Havia 10 pacientes com cirrose. Os pacientes com METAVIR F3-F4 eram significativamente mais velhos (P=0,02) e tinham níveis mais elevados de ALT (P=0,0006), AST (P<0,0001), γ-GT (P=0,03) e bilirrubina (P=0,001) e, maior tempo de protrombina do que pacientes com escore F0-F2. Os níveis de albumina (P=0,01) foram significativamente mais baixos naqueles classificados como METAVIR F3-F4. Idade (OR=1,09; IC95%=1,02-1,16; P=0,02), esteatose (OR=4,03; IC95%=1,05-15,45; P=0,04) e HDL-C <60 mg/dL (OR=7,67; 95%IC=1,71-34,49; P=0,008) foram independentemente associados à fibrose. Hipertensão (OR=6,36; IC95%=1,31-30,85; P=0,02) e HDL-C <60 mg/dL (OR=9,85; IC95%=2,35-41,39; P=0,002) foram independentemente associados à atividade necroinflamatória. Hipertensão (OR=6,94; IC 95%=1,92-25,05; P=0,003) e HDL-C <60 mg/dL (OR=3,94; IC95%=1,27-12,3; P=0,02) foram associados à atividade inflamatória de interface. Os triglicerídeos (TG >150 mg/dL) permaneceram associados à atividade inflamatória lobular. Conclusão: Níveis de coleterol HDL <60 mg/dL foram independentemente associados à atividade necroinflamatória na hepatite C crônica. Pacientes com hipertensão têm risco aumentado de desenvolver atividade necroinflamatória.

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.

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.

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.

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.

Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients.

AIMS: To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines. METHODS: A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models. RESULTS: The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082*A, IL10-819*T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms. CONCLUSIONS: This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.

Bioelectrical Impedance Analysis-Derived Measurements in Chronic Hepatitis C: Clinical Relevance of Fat-Free Mass and Phase Angle Evaluation.

OBJECTIVE: Because cirrhotic patients are at high risk of malnutrition and sarcopenia, we evaluated the prevalence of low fat-free mass index (FFMI) and low phase angle (PhA) among patients with chronic hepatitis C (CHC). METHODS: In total, 135 subjects with CHC (50.4% males; mean age, 52.4 ± 11.8 years; 65.9% noncirrhotic and 34.1% compensated cirrhotic patients) were prospectively included and evaluated by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. RESULTS: Low FFMI and low PhA were identified in 21.5% and 23.7% of the patients, respectively. Compensated cirrhotic patients had lower PhA values than those without cirrhosis. Low FFMI was associated with male sex (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.00-7.01; P = .04) and malnutrition (OR, 4.27; 95% CI, 1.42-12.90; P = .01). Low PhA was associated with cirrhosis (OR, 3.92; 95% CI, 1.56-9.86; P = .004), malnutrition (OR, 5.52; 95% CI, 1.73-17.62; P = .004), and current alcohol use (OR, 2.77; 95% CI, 1.01-7.58; P = .05). Reactance (Xc) normalized for height (H), an indicator of muscle strength, was independently associated with male sex, age, hypertension, and serum albumin. CONCLUSION: Host factors, including clinical comorbidities, lifestyle, and nutrition status, are associated with low FFMI and low PhA in noncirrhotic and in compensated cirrhotic patients with CHC. These findings highlight the relevance of evaluating body composition in patients chronically infected by hepatitis C virus independently of the stage of liver disease.