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.

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.

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.

The Lived Experience of Patients Utilizing Second-Generation Direct-Acting Antiviral for Treatment of Chronic Hepatitis C Virus Infection: A Phenomenological Analysis.

Hepatitis C is a global public health problem, and the aim of this study was to understand the experiences of patients with hepatitis C using second-generation antivirals. In-depth interviews were conducted with ten outpatients, cognitively capable of reporting their experience, followed up at a university clinic. Field diaries kept during the interviews were also used. The researchers carried out a thematic analysis to identify the ways in which individuals experienced their medication; then, these ways were reorganized to encompass the essential structures of the experience. The patients experienced the use of DAAs as providing resolution and it was permeated by: the experience of time-stagnant time, waiting for medication and the cure; the experience of spaces, understood as necessary and imposed spaces; the experience of relationships with others, personified by the support provided by healthcare professionals; the experience of sexuality, when patients developed several coping strategies to deal with the challenges imposed by the treatment. To conclude, increasing the knowledge about the patients' experiences can contribute to improve the healthcare model for hepatitis C, since several patients have severe hepatic impairment, and the eradication of the virus is only one of the stages of patients' treatments.

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.

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.

O transtorno depressivo maior está associado ao diabetes mellitus tipo 2 em pacientes com hepatite C crônica / Major depressive disorder is associated with type 2 diabetes in patients with chronic hepatitis c infection

ABSTRACT 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.

RESUMO CONTEXTO: O transtorno depressivo maior (TDM) é comumente detectado em pacientes com hepatite C crônica. Entretanto, fatores potencialmente associados à coocorrência destas condições não são completamente conhecidos. OBJETIVO: Avaliar a frequência de transtornos mentais em pacientes com hepatite C crônica e investigar variáveis associadas ao TDM. MÉTODOS: Pacientes com hepatite C crônica (n=151) atendidos em um centro de referência para hepatite foram avaliados usando o Mini-International Neuropsychiatry Interview e o questionário Cut-Annoyed-Guilty-Eye (CAGE). Análise multivariada foi usada para avaliar as covariáveis independentes associadas ao TDM atual. RESULTADOS: Setenta e seis (50,3%) pacientes apresentaram pelo menos um diagnóstico psiquiátrico atual; dentre eles destaca-se o TDM (33,1%). TDM atual foi independentemente associado à idade (≤50 anos) (OR=2,57; IC95% = 1,25-5,29; P=0,01) e diabetes mellitus tipo 2 (OR=2,80, IC95% = 1,17-6,70; P=0,02). Cirrose foi associada ao diabetes mellitus tipo 2 (OR=5,09; IC95% = 1,73-15,04; P=0,03) e abuso/dependência de álcool atual (OR=2,54; IC95% = 1,04-6,22; P=0,04). DISCUSSÃO: TDM está associado a diabetes tipo 2 em pacientes com hepatite C crônica. Em vigência da era dos antivirais de ação direta, caracterizada por grandes perspectivas para a primeira cura ampla de uma infecção viral crônica, devemos assegurar que a triagem dos transtornos psiquiátricos ocorra durante o atendimento clínico de rotina de pacientes com infecção crônica pelo vírus da hepatite C.

Remodeling of immunological biomarkers in patients with chronic hepatitis C treated with direct-acting antiviral therapy.

The HCV treatment with DAAs has offered a unique opportunity to analyze the changes in the immune system caused by the rapid inhibition of viral replication. We sought to analyze the kinetics profiles of serum biomarkers (LuminexTM) in fifty patients with chronic hepatitis C enrolled in a longitudinal investigation carried out before (baseline), during (W2-4 and W8-12 weeks) and post-treatment (W12-24 weeks) with sofosbuvir plus daclatasvir or simeprevir. The results demonstrated a clear biomarker overproduction in HCV patients at baseline. The kinetics timeline of baseline fold changes upon DAAs treatment revealed an early decline of CXCL8, CCL4, IL-6, IL-15, IL-17, IL-9, GM-CSF and IL-7 at W8-12 and a late shift towards lower levels of CCL3, CCL2, CCL5, IL1ß, TNF-α, IL-12, IFN-γ, IL1-Ra, IL-4, IL-10, IL-13, PDGF, VEGF, G-CSF at W12-24. Our data demonstrated that HCV treatment with DAAs resulted in a clear change of the serum biomarker overproduction, hallmark of untreated HCV patients. High ALT (>69U/L), low platelet (≤150,000/mm3) and cirrhosis status at baseline were factors related to delayed immune response shift, as well as, in the kinetics of baseline fold changes in serum biomarkers. These findings added novel evidences for the immunological restoration process triggered by DAAs.

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.

Experiences with the daily use of medications among chronic hepatitis C patients.

BACKGROUND: Subjective experiences with medication use are individual experiences that can impact health outcomes by contributing to problems related to such use. OBJETIVES: The aim of the present study was to understand the experiences of chronic hepatitis C patients who were taking chronic medications, based on the phenomenology proposed by Merleau-Ponty and connection among this experience with the essential structures of the experience. METHODS: Data were gathered from interviews conducted with ten individuals taking long-term medications at the Viral Hepatitis Outpatient Clinic of the Alfa Gastroenterology Institute of the Hospital das Clínicas, Federal University of Minas Gerais, Brazil. The content of field diaries kept during the interviews were also used. Thematic analysis was employed, enabling the identification of the ways in which individuals experienced their medication routines, which were then reorganized to encompass the essential structures of the experience. RESULTS: The researchers identified four ways patients experience daily medication use, all anchored in corporeality: resolution, adversity, ambiguity, and irrelevance. The first three were based on the perspective that daily medication use is more than a mere mechanical action, involving changes in the phenomenal body, relieving, eliminating or causing symptoms in the physical body, normalizing life and symbolizing the disease. FINAL CONSIDERATIONS: The present study allowed the researchers to infer that the same individual can even simultaneously experience daily medication use in different ways, depending on the disease and the medication in question. It also allowed for the understanding of the cyclical nature of experience with daily medication use, being that the introduction of a new medication can give rise to a new experience. The results point to the complexity of this experience, which requires formal education and places health professionals as responsible for this aspect of care.

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.

Impacto da "Disciplina Relação Médico-Paciente" sobre Atitudes Centradas no Paciente / The Impact of a "Doctor-Patient Relationship" Discipline on Patient-Centred Attitudes

RESUMO Vários estudos têm demonstrado que as atitudes centradas no paciente entre os estudantes de Medicina decaem ao longo do curso de graduação. A relação médico-paciente sofre influência profunda da contemporaneidade, e, cada vez mais, comunicar-se na prática clínica torna-se um desafio. O processo de educar em medicina deve encorajar os estudantes a compartilhar o processo de tomada de decisão com seus pacientes. Os estudantes devem compreender não somente o que preocupa seus pacientes, mas também o que os motiva no cuidado em saúde. No processo ensino-aprendizagem, a adoção de medidas eficazes direcionadas ao aprimoramento da escuta e das habilidades de comunicação torna-se a pedra angular na construção da relação médico-paciente de alta qualidade. O objetivo deste estudo foi avaliar o impacto da disciplina "relação médico-paciente" nas atitudes centradas no paciente entre os estudantes de Medicina. Também foi avaliada a influência de variáveis demográficas e do período do curso de Medicina nessas atitudes. Metodologia Foram incluídos 279 estudantes de Medicina que responderam ao questionário Patient-Practitioner Orientation Scale (PPOS): 128 (45,9%) estudantes matriculados na disciplina "Relação médico-paciente" e 151 (54,1%) estudantes voluntários, que não cursaram a disciplina, pareados por sexo e idade aos que frequentaram a disciplina. Os dados foram analisados no software SPSS 17.0 (SPSS Inc., Chicago IL, EUA). Regressão linear múltipla foi realizada para determinar se variáveis demográficas e o período do curso de Medicina estavam independentemente associados aos escores do PPOS (escore total; dimensões sharing e caring). Modelos logísticos foram criados para avaliar associação entre a disciplina "Relação médico-paciente" e os escores das subescalas do PPOS. Resultados Na análise de regressão linear, sexo feminino (p ≤ 0,01), idade mais avançada (p ≤ 0,02) e estar cursando os primeiros anos da faculdade de Medicina (p ≤ 0,02) estavam significativamente associados às atitudes mais centradas no paciente. Maior pontuação na subescala sharing estava independentemente associada à participação na disciplina "Relação médico-paciente" (4,50 ± 0,65 para aqueles que frequentaram vs. 4,33 ± 0,65 para aqueles não matriculados na disciplina, p = 0,03) em modelo logístico ajustado por sexo, idade e período do curso de Medicina. Educadores da área da saúde devem buscar estratégias inovadoras que estimulem atitudes humanísticas, melhorem as habilidades de comunicação e influenciem de forma decisiva as atitudes adotadas pelos estudantes de Medicina, que devem estar focadas no cuidado centrado no paciente/pessoa.

ABSTRACT Several studies have demonstrated that medical students' attitudes toward patient-centred care tend to decline throughout undergraduate education. At present, the adequate translation of the communication skills among medical students into clinical practice remains a challenge. Regardless of the increased efforts of educators to improve the provision of patient care, learning to communicate as a professional physician remains a complex process. Objectives To evaluate the impact of the "doctor-patient relationship" discipline on medical students' attitudes towards patient-centred care, and to examine whether variables related to demographic characteristics and different stages of education are associated to medical student's patient-centred attitudes. Methods Two-hundred and seventy nine medical students who responded a Patient-Practitioner Orientation Scale (PPOS), a validated instrument exploring attitudes towards the doctor-patient relationship were enrolled: 128 (45.9%) who attended the "Doctor-Patient Relationship" discipline and 151 (54.1%) volunteer students, matched by sex and age, who have not taken the discipline. Multiple linear regression analyses were used to quantify the independent association between PPOS scores (overall PPOS, 'sharing' and 'caring' dimensions), demographic variables and year of medical school. Logistic models were created to quantify the independent association between the "doctor-patient relationship" discipline and PPOS and the sub-scales scores. Results In the linear regression analysis, female gender (p ≤ 0.01), older age (p ≤ 0.02) and earliest years of medical school (p ≤ 0.02) were significantly associated with more patient-centred attitudes. Higher score on the 'sharing' sub-scale was independently associated with attending the "doctor-patient relationship" discipline (4.50 ± 0.65 for those who have studied the discipline vs. 4.33 ± 0.65 for those who have not studied the discipline, p = 0.03) after adjustment, in logistic models, for student's age, gender and years on the medical course. Medical educators should be focused on innovative strategies that stimulate humanistic attitudes, improve communication skills and truly change medical students' behaviour towards patient-centred care.

Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in HCV patients as a prototype to monitor immunotherapy of infectious diseases.

In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.

The phenomenology of Merleau-Ponty in investigations about medication use: constructing a methodological cascade.

Merleau-Ponty innovated when giving primacy to the body and perception in his philosophical proposal. Within the field of health, his thinking gives us access to the knowledge gained from the corporeality of individuals with chronic diseases. The objective of this study was to expand the understanding of phenomena associated with the daily use of medication, which includes increasingly complex drug regimes, through the lens of Merleau-Ponty. To this end, we described the research steps anchored in his phenomenological philosophy and structured them in the form of a cascade, beginning with the definition of phenomenology as a new form of epistemology, existence as a paradigm, and the body as a theory. Furthermore, the methodology included the use of existential structures, namely, time, space, relationships with others, and sexuality, connected through the intentional arc to reach an understanding of the phenomenon of medication use.