How are HCV-infected patients being identified in Brazil: a multicenter study

ABSTRACT Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 ± 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.

Hepatite C no sistema público de saúde brasileiro: impacto da doença / Hepatitis c in the brazilian public health care system: burden of disease

ABSTRACT BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é uma das principais causas de hepatite C crônica e provoca implicações graves para pacientes, familiares e sistema de saúde. OBJETIVO: Os objetivos deste estudo foram: analisar a gravidade da fibrose hepática, comorbidades e complicações da hepatite C; examinar a qualidade de vida relacionada à saúde (QVRS), a perda de produtividade e o uso de recursos e custos no sistema público por pacientes brasileiros com hepatite C crônica, genótipo tipo 1. MÉTODOS: Foi realizado um estudo transversal, multicêntrico em pacientes com hepatite C crônica genótipo-1 para avaliar a carga da doença no sistema público de saúde brasileiro entre novembro de 2014 e março de 2015. Os pacientes foram submetidos a uma elastografia hepática transitória (FibroScan) para avaliar a fibrose e a uma entrevista composta por um questionário desenvolvido para o estudo e cinco questionários padronizados: EQ-5D-3L, HCV-PRO, e WPAI:HepC. RESULTADOS: Foram recrutados 313 pacientes. A amostra foi composta predominantemente por mulheres (50,8%), caucasianos/brancos (55,9%) e indivíduos empregados (39,9%). A média de idade foi 56 (DP=10,4) anos. Em média, os pacientes com HCV esperaram 40,6 (DP=49,6) meses entre o diagnóstico e o primeiro tratamento. Ademais, 42,8% dos pacientes que realizaram o FibroScan tinham cirrose; a comorbidade mais frequente foi doença cardiovascular (62,6%) e a complicação mais comum as varizes esofágicas (54,5%). Os resultados também mostraram que "dor e desconforto" foi a dimensão de QVRS mais afetada (55,0% dos pacientes relataram alguns problemas) e que a média do escore do HCV-PRO foi 69,1 (DP=24,2). Em relação à perda de produtividade, o componente do WPAI:HepC mais afetado foi atividade diária (23,5%) e entre os pacientes empregados, presenteísmo foi mais frequente do que absenteísmo (18,5% vs 6,5%). Os custos diretos médicos totais com essa amostra foi de 12.305,72USD por paciente em um período de dois anos; o tratamento medicamentoso representou 95% desse total. CONCLUSÃO Esse estudo mostrou a maioria dos pacientes possui cirrose, apresenta alta prevalência de doenças cardiometabolicas e varizes esofágicas, QVRS reduzida principalmente em termos de dor/desconforto e dano na produtividade, especialmente presenteísmo. Adicionalmente, nós demonstramos que o HCV impõe uma carga econômica no sistema de saúde brasileiro e que os medicamentos correspondem à maioria dos custos.

Tratamento cirúrgico de lesões císticas do pâncreas: uma experiência unicêntrica / Surgical management of cystic lesions of the pancreas: a single-centre experience

ABSTRACT BACKGROUND: Cystic lesions of the pancreas represent a group of pancreatic diseases with great histological heterogeneity, varying from benign lesions, some of them with malignant potential, to overt malignant lesions. OBJECTIVE: To describe the cases of cystic lesions of the pancreas which underwent surgical intervention at a tertiary university hospital. METHODS: This is a retrospective population-based study (historical cohort) which was carried out enrolling individuals attended at the Outpatient service of Pancreas Surgery of the Hospital de Clínicas of Unicamp. The individuals underwent surgical procedures performed from January 2012 through December 2016. RESULTS: In the period evaluated, 39 cases of cystic lesions of the pancreas which underwent surgery were identified, 26 (66.6%) of which were female. The average age at diagnosis was 47.4±16.4 years (range, 18-73). In regards to symptoms, 35 (89.7%) were symptomatic. The average length of hospital stay was 10 days (range 4-76). Surgeries performed to treat the lesions depended on the localization and type of the lesions: cystojejunostomy (41%), distal pancreatectomy (36%), pancreaticoduodenectomy (15.4%), drainage of ruptured and/or infected pseudocyst (5.2%) and central pancreatectomy (2.6%). CONCLUSION: Cystic lesions of the pancreas are a group of lesions with a highly varying presentation and diagnostic approach and may require an also highly variable surgical treatment. An appropriate preoperative imaging diagnosis is essential for their management.

RESUMO CONTEXTO: As lesões císticas do pâncreas representam um grupo de doenças pancreáticas com grande heterogeneidade histológica, variando desde lesões benignas, algumas com potencial pré-maligno, até outras degeneradas para formas malignas. OBJETIVO: Descrever os casos de LCPs submetidos à intervenção cirúrgica em um hospital universitário terciário. MÉTODOS: Trata-se de um estudo retrospectivo populacional (coorte histórica) realizado com a participação de indivíduos atendidos no Ambulatório de Cirurgia do Pâncreas do Hospital de Clínicas da Unicamp. Os indivíduos foram submetidos a procedimentos cirúrgicos realizados no período de janeiro de 2012 a dezembro de 2016. RESULTADOS: No período avaliado, foram identificados 39 casos de lesões císticas do pâncreas operados, sendo 26 (66,6%) do sexo feminino. A idade média no diagnóstico foi de 47,4±16,4 anos. Em relação aos sintomas, 35 (89,7%) eram sintomáticos. O tempo médio de internação foi de 10 dias (variação de 4-76). As cirurgias realizadas para o tratamento das lesões dependeram da localização e do tipo das lesões: derivação pseudocisto-jejunal (41%), pancreatectomia distal (36%), pancreaticoduodenectomia (15,4%), drenagem de pseudocistos rotos e/ou infectados (5,2%) e pancreatectomia central (2,6%). CONCLUSÃO: As lesões císticas do pâncreas são um grupo de lesões cuja apresentação e abordagem diagnóstica são altamente heterogêneas e que podem requerer um tratamento cirúrgico altamente complexo e variável. Um diagnóstico pré-operatório adequado é essencial para definir o seu tratamento.

Crioglobulinemia: relação entre hepatite C e glomerulonefrite / Cryoglobulinemia: link between hepatitis C and glomerulonephritis

A Hepatite C é um problema de saúde mundial. Uma associação entre infecção pelo vírus da hepatite C (HCV) e crioglobulinemia mista com doença renal tem sido descrita, sendo a glomerulonefrite membranopoliferativa (GNMP) tipo I o acometimento renal mais comum. A GNMP é frequentemente associada com a crioglobulinemia mista tipo II. Esse relato de caso objetiva descrever fatores clínicos dos pacientes com crioglobulinemia mista, a qual é uma manifestação extra-hepática da infecção por HCV, assim como discutir a sua fisiopatologia e tratamento, baseado no relato de caso. (AU)

Hepatitis C is a public health concern worldwide. An association of hepatitis C virus (HCV) infection with mixed cryoglobulinemia and renal disease has been described, and type I membranoproliferative glomerulonephritis (MPGN) is the most common. MPGN is often associated with type II mixed cryoglobulinemia. This case report aimed to describe the clinical features of patients with mixed cryoglobulinemia, a major extrahepatic manifestation of HCV infection, and to discuss its pathophysiology and treatment of HCV infection based on the case report. (AU)

Porfiria cutánea tarda como manifestación extrahepática de hepatitis C crónica: reporte de un caso / Porphyria cutanea tarda as extrahepatic manifestation of chronic hepatitis C: a case report

Se presenta el caso de un paciente varón de 56 años quien es evaluado por presentar a nivel del dorso de ambas manos cicatrices hiperpigmentadas e hipopigmentadas, asociadas a quistes de milia. Se le realizó estudios del metabolismo de las porfirinas y biopsia cutánea de las lesiones los cuales resultaron compatibles con porfiria cutánea tarda. En el laboratorio inicial se encontró elevación de los valores de transaminasas, identificándose posteriormente infección crónica por virus de hepatitis C. Con la finalidad de tratar la infección viral y resolver el compromiso dérmico, considerado como manifestación extrahepática del virus hepatitis C, se inició tratamiento con interferón pegilado y ribavirina evolucionando favorablemente con respuesta viral rápida, carga viral no detectable hasta la actualidad (36 semanas de tratamiento), disminución del nivel de transaminasas séricas y mejoría de las lesiones dérmicas.

The present case is a 56 year old male who present hyperpigmented and hypopigmented scars in both hands, associated with the presence of milia cysts. It was studied the metabolism of porphyrins and skin biopsy of the lesions which were compatible with porphyria cutanea tarda. In the initial laboratory, elevated transaminases values were found and subsequently identified chronic infection of hepatitis C virus. In order to treat viral infection and resolve the dermal commitment; considered extrahepatic manifestation of hepatitis C virus, treatment was started with pegylated interferon and ribavirin, with favorably development and rapid viral response, with undetectable viral load until now (24 weeks of treatment), decreased level of serum transaminases and improvement of skin lesions.

Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy

ABSTRACT Introduction. Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. Material and methods. Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population. The multi-DAA regimen of simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen consisting of peginterferon and ribavirin, with either boceprevir or telaprevir (TT). Sustained-virologic response (SVR) rates, total costs per treatment and adverse events were recorded. Total cost per SVR were compared for the two treatments, controlling for patient demographics and clinical characteristics. Results. One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n = 113). Patients receiving SMV/SOF were older, more treatment experienced, and had a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per patient were $152,775 and $95,943, and average total costs per SVR were $178,237 vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs accounted for 98% of SMV/SOF and 85% of TT treatment costs. Conclusion. The high cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs, such that the cost per cure from TT to multi-DAA therapy has been relatively constant. In order to cure more patients, either additional financial resources will need to be allocated to the treatment of HCV or drug costs will need to be reduced.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Evaluation de la prise en charge de l'hépatite C chronique à Pointe-Noire en 2015

Introduction : La prise ne charge de l'hépatite virale C a connu un tournant décisif depuis la découverte des antiviraux directs. Sa prévalence au Congo-Brazzaville est estimée à 10% avec prédominance du génotype 4 et son traitement se heurte à plusieurs écueils notamment l'accessibilité au traitement. Nous avons réalisé une étude dont l'objectif a été d'évaluer les possibilités de diagnostic et de prise en charge thérapeutique des malades infectés par le virus de l'hépatite C à Pointe-Noire.Méthodes: Il s'est agi d'une étude expérimentale, prospective, descriptive et analytique réalisée dans le service de Gastroentérologie de l'hôpital général de Loandjili de Pointe-Noire.Résultats: Au total notre file active comptaient 81 dossiers des cas d'hépatite C et 34 (41,9%) cas traités ont été inclus. Il s'agissait de 21(61,76%) hommes et de 13(38,24%) femmes d'âge médian 50ans. Il y avait 15 (44,1%) patients alcooliques; 4 (11,8%) patients fumeurs; 15 (44,1%) patients sans intoxication. L'hépatite C était découverte lors d'un dépistage chez 19(55,8%) patients et suite aux symptômes chez 15 (44,1%) patients. Parmi ces 34 malades; 6 (17,6%) étaient du génotype 1 et 23 (67,6%) étaient du génotype 4; chez 5 (14,7%) patients le génotype était inconnue. Le financement du traitement était assuré par l'assurance maladie pour 5 (14,7%) patients; l'employeur pour 13 (38,2%); l'argent personnel pour 12 (35,3%); l'aide des parents pour 3 (8,8%) patients; non identifié chez 1 (2,9%) patient. Sur 34 patients traités par bithérapie pégylée 13(38,2%) étaient guéris et 21(61,7%) n'étaient pas guéris. Il restait 21 patients non guéris dont 2 patients traités par sofosbuvir + ribavirine (24 semaines) et 2 malades traités par sofosbuvir +daclastavir (12 semaines); tous ces 4 malades étaient guéris. Il restait 17 patients non guéris et non traités par les antiviraux directs faute de financement. En analyse uni et multivariée la charge virale était un facteur influençant l'efficacité du traitement.Conclusion : La prise en charge optimale de l'hépatite C chronique est possible au Congo-Brazzaville. Cependant la non disponibilité des médicaments, le prix exorbitants des antiviraux et le manque de couverture sociale, constituent des freins exposant les malades aux complications mortelles. Ainsi la création du programme national de lutte contre les hépatites virales au Congo Brazzaville pourrait lever ces obstacles inadmissibles en 2016

Cribado, diagnóstico y tratamiento de la hepatitis por virus C en la práctica clínica / Screening, diagnosis and treatment of chronic hepatitis C in clinical practice

La hepatitis crónica por el virus de la hepatitis C (HCV) es un problema de salud mundial. En el mundo, 170 millones de personas están infectadas. En Latinoamérica la prevalencia se estima entre 1.0 y 2.3% y en Argentina es en promedio 1.0 a 1.5%. La eficacia del tratamiento de esta enfermedad ha mejorado sustancialmente en los últimos 2 a 3 años. Con los nuevos antivirales de acción directa (AAD) disponibles actualmente, pueden lograrse tasas de respuesta viral sostenida (RVS) mayores al 90-95% prácticamente con pocos efectos adversos. Para poder acceder a estos tratamientos con una alta tasa de curación, y así lograr reducir la carga de la enfermedad en la salud pública, es necesario aumentar el número de pacientes diagnosticados y que estos accedan a un cuidado adecuado. El rol de los médicos de atención primaria es fundamental: deben sospechar la infección, diagnosticarla y complementar su atención con la derivación al especialista. El trabajo conjunto de generalistas y especialistas optimizará el manejo de los recursos disponibles, permitiendo que cada vez más personas infectadas con el HCV sean diagnosticadas y tratadas adecuadamente.

Chronic hepatitis C (HCV) is a global health problem. Worldwide, 170 million people are chronically infected. In Latin America its prevalence is estimated between 1.0 and 2.3%, and in Argentina between 1.0 and 1.5%. Treatment efficacy has considerably improved in the last 2 or 3 years. Sustained virological response (SVR) rates around 90-95% can be achieved with the new direct acting antiviral agents (DAAs) currently available, with few side effects. It is necessary to increase the number of diagnosed patients, linking them to adequate management and treatment. Raising treatment rates will increase the percentage of cured patients, reducing the burden of disease. Primary care physicians´ role is essential to achieve this goal. They must identify persons at risk, diagnose them and work with specialists to continue their medical care. Team working of generalists and specialists will permit that more HCV infected people can access to adequate care and treatment.

Anti-C1q antibody as a predictor of chronic HCV genotype 4 response to treatment in Egyptian children

Background: Hepatitis C virus [HCV] infection has been reported to be the most common blood born pathogen all over the world. The prevalence of HCV in children in developed countries ranges between 0.1 and 0.4%, and is generally lower than in adults. Combinedpegylated interferon and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response [SVR] rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment

Objective: To evaluate anti-C1q antibody as a predictor of chronic HCV response to treatment with combined pegylated interferon alpha-2b and ribavirin in Egyptian children

Methodology: This study was conducted on forty-four chronic HCV-infected children [Male/Female: 30/14; aged 12.02 +/- 3.1 years] from the outpatient clinic, Pediatric Hepatology Department, National Liver Institute, Menoufiya University. They were given combined pegylated interferon alpha-2b [Peg-IFN-alpha-2b] and ribavirin [RBV] for 48 weeks and a quantitative polymerase chain reaction [PCR] for hepatitis C virus Ribonucleic acid was performed at 12, 24, 48 weeks during treatment and after another 24 weeks post-treatment. Anti-HCV antibody and Real-time PCR for HCV-RNA was performed [the detection limit was 15 IU/mL]. Anti-C1q antibodies were performed by enzyme-linked immunosorbent assay [ELISA]

Results: Serum levels of Anti-C1q antibodies were significantly higher [P = 0.001] in the Non-responders group [mean = 14.61 +/- 6.749ng/ml] compared to the SVR one [mean = 2.27 +/- 3.77ng/ml]. No statistically significant difference [P > 0.05] had been found between SVR and Non-responders regarding the age, ALT, viral load, or hepatic necroinflammatory activity and liver fibrosis. Anti-C1q at a cutoff value of 9.05 ng/ml, had sensitivity and specificity of 84.6% and 75% respectively and 92% positive predictive value. No significant correlation between the serum level of anti-C1q antibodies and the age, sex or HCV viral load, liver enzymes, and the degree of fibrosis and necroinflammatory activity was found [P> 0.05] for all parameters

Conclusion: Anti-C1q could be a good predictor for HCV treatment and should be included in pretreatment laboratory assessment for proper choice of chronic HCV children patients who will benefit from combination therapy

Assessment of serum hydroxyproline and osteopontin as noninvasive markers of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

Background: Hepatitis C virus [HCV] infection is a progressive disease that may result in chronic hepatitis, cirrhosis and hepatocellular carcinoma [HCC]. Liver fibrosis is an essential factor that must be considered in the management of patients with HCV. Although liver biopsy represents the gold standard for evaluating the presence, type and stage of liver fibrosis, this technique remains a costly and invasive procedure. Therefore, several diagnostic methods for determining liver fibrosis, such as the detection of serum biomarkers, have been used

Objective: To evaluate the use of serum hydroxyproline [HYP] and osteopontin [OPN] as non invasive direct markers to assess the degree of hepatic fibrosis in Egyptian patients with chronic HCV infection in comparison to indirect markers such as aspartate aminotransferase platelet ratio index [APRI] and to determine the most diagnostically accurate non invasive marker of hepatic fibrosis, hoping to replace liver biopsy in the next few years

Methodology: This study was carried out on 48 patients with chronic HCV infection who had undergone liver biopsy and scored as mild fibrosis [F1], moderate fibrosis [F2], sever fibrosis [F3] and liver cirrhosis [F4] based on Metavir scoring system, and 12 age and sex matched controls. The serum levels of HYP and OPN were measured by enzyme linked immunosorbent assay [ELISA]

Results: There was a highly significant increase in HYP, OPN and APRI in all patients groups in comparison to control group and their increase was significantly associated with the degree of hepatic fibrosis. Furthermore, HYP, OPN and APRI values showed highly significant increase in significant hepatic fibrosis [F2-F4] in comparison to mild fibrosis [F1], and in hepatic cirrhosis [F4] in comparison to hepatic fibrosis [F1-F3]. There was a highly significant positive correlation between serum HYP level, OPN and APRI. The receiver operating characteristic [ROC] curve analysis revealed that OPN has the highest area under the curve [AUC] value for discriminating fibrosis stages, followed by HYP and lastly APRI

Conclusion: This study demonstrated that OPN was the most diagnostically accurate marker for assessing the severity of hepatic fibrosis and served as a prognostic index towards the progression of hepatic fibrosis to cirrhosis in patients with chronic HCV infection, followed by HYP and lastly APRI. These findings indicated that OPN and HYP could be used as non invasive markers of hepatic fibrosis and cirrhosis which would help to reduce the need for liver biopsy in chronic HCV infection

Prevalence, Risk Factors and Clinical Characteristics in Patients with Genotype 6 Chronic Hepatitis C: A Single Institute Experience / 대한소화기학회지

BACKGROUND/AIMS: Hepatitis C genotypes 1 and 2 are widely distributed globally. In contrast, genotype 6 is found mainly in Southeast Asia, while genotype 6 is rare in Korea. This study aims to investigate the prevalence, risk factors and clinical characteristics of patients with genotype 6 chronic hepatitis C. METHODS: We retrospectively identified 133 HCV-infected patients who underwent HCV genotype analysis between January 2012 and December 2012, and analyzed the prevalence, risk factors and clinical characteristics of patients diagnosed with genotype 6 chronic hepatitis C. RESULTS: Among 133 patients, 53 patients (39.8%) were infected with genotype 1, 62 patients (46.6%) with genotype 2, 2 patients (1.5%) with genotype 3, 14 patients (10.5%) with genotype 6, and 2 patients (1.5%) with mixed genotypes (genotype 1 and 6). The risk factors associated with genotype 6 were acupuncture (n=4, 28.6%), intravenous drug use (n=3, 21.4%), tattoo (n=2, 14.3%), and transfusion (n=2, 14.3%). Of the 14 patients with genotype 6, 6 patients were treated with pegylated interferon and ribavirin. Five patients had reached the end of treatment. All patients reaching end of treatment for genotype 6 showed early virological response and sustained virological response. CONCLUSIONS: The prevalence of genotype 6 is 10.5% and mixed infections of genotype 1 and 6 are 1.5% in patients with chronic hepatitis C. A major potential risk factor is intravenous drug use and the treatment response rate to pegylated interferon plus ribavirin is high in patients with genotype 6 chronic hepatitis C. Large scale multicenter studies are needed.

Incidence of and risk factors for thyroid dysfunction during peginterferon alpha and ribavirin treatment in patients with chronic hepatitis C

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.

Association between age at diagnosis and degree of liver injury in hepatitis C

Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p < 0.001). The degree of fibrosis increased with advancing age. Only age at diagnosis and fasting blood glucose were independently associated with disease stage. Those patients with subtype 1a had higher prevalence of F2–F4 than those with subtype 1b. Conclusion: In Brazil, diagnosis of hepatitis C is more commonly established in older patients (age 45–60 years) with more advanced disease. Reassessment of strategies ...

Risk factors for hepatitis C virus transmission in the municipality of Catanduva, State of São Paulo: a case-control study

Introduction Hepatitis C virus (HCV) is primarily transmitted via contact with the blood of infected patients, although the form of contact has not been identified for a significant percentage of carriers. The present study evaluated possible risk factors for HCV transmission in a medium-sized town located in the northwest region of the State of São Paulo. Methods This was a case-control study, with the case group consisting of 190 chronic HCV carriers older than 18 years residing in the municipality of Catanduva. The control group also consisted of 190 individuals with HCV-negative serology. The groups were paired (1:1) for gender, age range (± five years), and place of residence. The same structured questionnaire was applied to all subjects, who gave written informed consent to participate in the study. The data were statistically analyzed using crude and adjusted logistic regression, and the results were expressed as odds ratios with a 95% confidence interval. Results The demographic profiles of the groups indicated a predominance of males (68.9%) and mean ages of 47.1 years (case group) and 47.3 years (control group). After adjusting for conditional regression, the following factors were found to represent risks for HCV: history of sexually transmitted disease (STD) and blood transfusion; accidents with syringes and/or needles; tattoos; and the use of non-injectable drugs and injectable medications. Conclusions The transmission of HCV via the blood route has been well characterized. Other forms of contact with human blood and/or secretions are likely to transmit the virus, although with a lower frequency of occurrence. .

Health-related quality of life in patients with hepatitis C virus infection in Brazil / Calidad de vida relacionada con la salud en pacientes infectados por el virus de la hepatitis C en el Brasil

OBJECTIVE: To quantify the health-related quality of life (HRQoL) burden of hepatitis C virus (HCV) infection among a broad sample of adults in Brazil, particularly among those 40 years of age and older. METHODS: This was a retrospective observational study of data from the 2011 Brazil National Health and Wellness Survey, a large (n = 12 000) cross-sectional survey that includes information on medical conditions and health outcomes, including the Medical Outcomes Study Short-form 12 health questionnaire, version 2 (SF-12v2). Respondents who reported a physician diagnosis of HCV infection were compared with those who reported never experiencing HCV on the Mental (MCS) and Physical (PCS) Component Summary scores and SF-6D health utility scores. Unadjusted comparisons were conducted with chi-square tests for categorical variables and t-tests for continuous variables. Regression was used to adjust outcomes for potential confounds. Subgroup analyses were conducted on those 40 years of age and older. RESULTS: Unadjusted comparisons between respondents infected with HCV (n = 100) and controls (n = 11 694) revealed similar MCS and PCS scores, but HCV patients had lower SF-6D utility scores (0.70 vs. 0.73, P < 0.05). Regressions adjusting for demographic and health characteristics provided similar results to unadjusted comparisons. Subgroup analyses of respondents 40 years of age and older revealed decrements in both MCS (45.95 vs. 49.72, P < 0.05) and SF-6D (0.71 vs. 0.76, P < 0.05). PCS scores were comparable in HCV patients and controls. CONCLUSIONS: HCV infection in Brazil causes significant HRQoL burden, especially among the older population. Prevention measures to curtail the spread of the virus in Brazil should provide societal benefits in terms of quality of life, in addition to preventing morbidity and mortality from chronic infection.

OBJETIVO: Cuantificar la carga de la infección por el virus de la hepatitis C (VHC) en cuanto a calidad de vida relacionada con la salud (CVRS) en una amplia muestra de adultos del Brasil, particularmente en los de 40 años de edad o mayores. MÉTODOS: Se llevó a cabo un estudio retrospectivo y de observación de los datos de la Encuesta Nacional de Salud y Bienestar del Brasil del 2011, una amplia encuesta transversal (n = 12 000) que aporta información sobre trastornos médicos y resultados en materia de salud, e incluye el cuestionario de salud denominado Estudio de los Resultados Médicos, en la versión 2 de su forma abreviada de 12 ítems (SF-12v2). Los entrevistados que notificaron un diagnóstico médico de infección por el VHC se compararon con los que afirmaron que nunca habían padecido esta infección en cuanto a las puntuaciones resumen de las componentes mental (MCS) y física (PCS) y las puntuaciones de utilidad en salud del SF-6D. Se llevaron a cabo comparaciones no ajustadas mediante pruebas de ji al cuadrado para las variables categóricas y pruebas t para las variables continuas. Se empleó un modelo de regresión para ajustar los resultados en cuanto a confusiones potenciales. Se realizaron análisis del subgrupo de adultos de 40 años de edad o mayores. RESULTADOS: Las comparaciones no ajustadas entre los entrevistados infectados por el VHC (n = 100) y los controles (n = 11 694) mostraron puntuaciones de MCS y PCS similares, pero los pacientes infectados por el VHC obtuvieron puntuaciones de utilidad del SF-6D inferiores (0,70 frente a 0,73, P < 0.05). Las regresiones de ajuste de las características demográficas y de salud proporcionaron resultados similares a los de las comparaciones no ajustadas. Los análisis del subgrupo de entrevistados de 40 años de edad o mayores mostraron disminuciones tanto en la MCS (45,95 frente a 49,72, P < 0.05) como en el SF-6D (0,71 frente a 0,76, P < 0.05). Las puntuaciones de la PCS fueron comparables en los pacientes infectados por el VHC y los controles. CONCLUSIONES: La infección por el VHC en el Brasil causa una carga significativa en cuanto a CVRS, especialmente en la población de mayor edad. Las medidas preventivas para reducir la propagación del virus en el Brasil deben proporcionar beneficios sociales en cuanto a calidad de vida, además de prevenir la morbilidad y la mortalidad causadas por la infección crónica.

Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.

ELF (Enhanced Liver Fibrosis) como marcador não invasivo de fibrose hepática na hepatite C crônica / ELF (Enhanced Liver Fibrosis) as a non invasive predictor of liver fibrosis in hepatitis C

A fibrose hepática é o aspecto mais relevante e o mais importante determinante de morbimortalidade na hepatite C crônica (HCC). Historicamente, a biópsia hepática é o método de referência para avaliação da fibrose causada pela HCC, apesar de apresentar limitações. O estudo de marcadores não invasivos, que possam obviar a necessidade da biópsia, é uma área de constante interesse na hepatologia. Idealmente, a avaliação da fibrose hepática deveria ser acurada, simples, prontamente disponível, de baixo custo e informar sobre o prognóstico da patologia. Os marcadores não invasivos mais estudados são a elastografia hepática transitória (EHT) e os laboratoriais. A EHT já foi extensamente validada na HCC e está inserida na rotina de avaliação destes pacientes. Dentre os laboratoriais, existem diversos testes em continua experimentação e, até o momento, nenhum foi integrado à prática clínica no Brasil, embora já aplicados rotineiramente em outros países. O Enhanced Liver Fibrosis (ELF), um teste que dosa no soro ácido hialurônico, pró-peptídeo amino-terminal do colágeno tipo III e inibidor tissular da metaloproteinase 1, tem se mostrado bastante eficaz na detecção de fibrose hepática significativa e de cirrose na HCC. Neste estudo o ELF teve o seu desempenho avaliado em relação a biópsia hepática e demonstrou apresentar boa acurácia na detecção tanto de fibrose significativa quanto de cirrose. Na comparação com a EHT apresentou acurácia semelhante para estes mesmos desfechos, com significância estatística. No entanto, foi observada uma superestimação da fibrose com a utilização dos pontos de corte propostos pelo fabricante. Este achado está em acordo com a literatura, onde não há consenso sobre o melhor ponto de corte a ser empregado na prática clínica. Com a ampliação da casuística foi possível propor novos pontos de corte, através da análise clássica, com a biópsia hepática como padrão ouro...

Liver fibrosis is the most relevant issue concerning chronic hepatitis C (CHC) and determines its prognosis. Historically, liver biopsy has been the reference method for evaluating fibrosis related to CHC, though it presents many drawbacks. There is a continuing interest in the development of non invasive markers capable of replacing liver biopsy. The ideal surrogate for fibrosis evaluation should be accurate, simple, low cost and yield prognostic information. So far, the most well known non invasive methods are transient hepatic elastography (TE) and laboratory panels. TE has already been extensively validated and is integrated in patients routine. There is plenty of laboratory panels in continuing evaluation and some are already integrated in daily practice abroad. In Brasil, until the present moment, it is not a reality. Enhanced Liver Fibrosis (ELF) panel comprises the serum concentration of hyaluronic acid, tissue inhibitor of matrix metalloproteinases-1, and aminoterminal propeptide of type III procollagen and has demonstrated good performance in detecting significant fibrosis and cirrhosis in CHC patients. In the present study ELF had it’s performance evaluated against liver biopsy and obtained satisfactory accuracy in detecting significant fibrosis and cirrhosis. In comparison to TE no statistically significant diference was observed, for the same endpoints mentioned before. However, the application of manufacturer’s cutoff points produced overestimation of fibrosis stages. These findings are in accordance with other author’s results, in that there is no consensus so far on the most adequate cutoff points for main clinical end points. Enlarging the data permited calculating new cutoff points, through the classical statistical approach, using liver biopsy as the gold standard...