Editorial

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFleury Medicina e SaúdeUNIFESP, EPMSciEL

Progressão da fibrose hepática em portadores de coinfecção HIV/vírus da hepatite C com níveis de aminotransferases normais

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.INTRODUÇÃO: Aproximadamente, 30% dos portadores de hepatite crônica C apresentam níveis de aminotransferases persistentemente normais (APNL). A maioria destes pacientes tem lenta progressão da fibrose hepática. Em portadores de coinfecção VHC-HIV, estudos têm demonstrado que a progressão da fibrose hepática é mais rápida que a observada em indivíduos infectados somente pelo VHC. Há poucos estudos que verificaram as características histológicas da hepatite crônica C em pacientes coinfectados pelo HIV APNL. MÉTODOS: Portadores de coinfecção VHC-HIV (HCV-RNA e anti-HIV positivos) com tempo de infecção pelo VHC conhecido (uso de drogas intravenosas) foram selecionados. Aqueles com hepatitis B surface antigen (HbsAg) positivo ou que tenham sido submetidos à terapia antiviral para hepatite C antes da biópsia hepática foram excluídos. Pacientes com pelo menos 3 determinações normais da ALT nos últimos 6 meses antes da biópsia hepática foram considerados como tendo APNL. Todos foram submetidos a biópsia hepática que foi classificada de acordo com a escala METAVIR. RESULTADOS: Foram incluídos 50 pacientes, 40 (80%) homens. Todos receberam terapia antirretroviral. Os níveis de ALT foram persistentemente normais em 13 (26%) pacientes. Pacientes coinfectados com APNL apresentaram menor média dos estágiosde fibrose hepática (0,77±0,44 versus 1,86±1,38; p<0,001), dos índices de atividade inflamatória periportal (0,62±0,77 versus 2,24±1,35; p<0,001) e progressão mais lenta da fibrose hepática (0,058±0,043 unidades de fibrose /ano versus 0,118±0,102 unidades de fibrose/ano) quando comparados àqueles com aminotransferases elevadas. CONCLUSÕES: Portadores de coinfecção VHC-HIV com APNL apresentam progressão mais lenta da fibrose hepática. Nesses pacientes o desenvolvimento de cirrose hepática é improvável.Universidade Federal de Juiz de Fora Centro de Referência em Hepatologia Departamento de GastroenterologiaUniversidade Federal de Juiz de Fora Unidade de Endoscopia DigestivaUniversidade Federal de São Paulo (UNIFESP) Divisão de Gastroenterologia Seção de HepatitesUNIFESP, Divisão de Gastroenterologia Seção de HepatitesSciEL

Evaluation of an enzyme immunoassay for hepatitis C virus antibody detection using a recombinant protein derived from the core region of hepatitis C virus genome

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott®), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95%) sera from patients in the study group and negative in 38 of the 39 (97%) sera from those in the control group, showing an accuracy of 96%. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaInstituto BioMérieuxUNIFESP, EPMSciEL

Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-alpha

Background: A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up.Methodology/Results: 597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p47% tested positive for anti-RR. the anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment.Conclusions: the exquisite association of anti-RR reactivity with combined interferon-a/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Brazilian National Council for Research and Technological DevelopmentUniversidade Federal de São Paulo, Div Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilFleury Med & Hlth Labs, Div Immunol, São Paulo, BrazilUniv Florida, Dept Oral Biol, Gainesville, FL 32610 USAUniversidade Federal de São Paulo, Div Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilFAPESP: 2010/50710-6Brazilian National Council for Research and Technological Development: 305064/2011-8Web of Scienc

Características clínicas associadas a esteatose hepática à ultrassonografia em pacientes com alanina aminotransferase elevada

CONTEXT AND OBJECTIVE: The main causes of hepatic steatosis (HS) are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90% of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT) levels. DESIGN AND SETTING: Cross-sectional study in a single tertiary care center. METHODS: Individuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded. RESULTS: Among 94 individuals included, 40% presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043), with higher body mass index (BMI) (P = 0.003), diabetes prevalence (P = 0.024), fasting glucose levels (P = 0.001) and triglycerides (P = 0.003). Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95% confidence interval, CI: 1.049-1.341; P = 0.006) and diabetes mellitus (OR = 12.721; 95% CI: 1.380-117.247; P = 0.025) were independently associated with HS. CONCLUSIONS: Simple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.CONTEXTO E OBJETIVO: Doença hepática alcoólica e doença hepática esteatótica não alcoólica (DHENA) são as principais causas de esteatose hepática (EH). Apesar de a biópsia hepática ser o método de escolha para diagnóstico DHENA, o achado de aminotransferases elevadas em indivíduos abstêmios, sem doença hepática conhecida, sugere o diagnóstico de DHENA em 80-90% dos casos. A identificação de variáveis clínicas associadas à EH na ultrassonografia abdominal pode permitir o diagnóstico de DHENA de forma não invasiva e custo-efetiva. O objetivo foi identificar variáveis clínicas associadas à EH em indivíduos com níveis elevados de alanina aminotransferase (ALT). TIPO DE ESTUDO E LOCAL: Estudo transversal em um único centro de atendimento terciário. MÉTODOS: Indivíduos com ALT elevada e sorologias negativas para os vírus de hepatite B e C foram avaliados por meio de revisão de prontuários. Os pacientes não submetidos à ultrassonografia foram excluídos. RESULTADOS: Foram incluídos 94 indivíduos, 40% deles com EH à ultrassonografia. Quando comparados aos indivíduos sem EH, aqueles com EH apresentaram maior prevalência de diabetes (P = 0,024), maiores idade (P = 0,043) e índice de massa corpórea (IMC) (P = 0,003), glicemia de jejum mais elevada (P = 0,001) e triglicerídeos mais elevados (P = 0,003). A análise multivariada evidenciou que o IMC (odds ratio, OR = 1,186, 95% intervalo de confiança, IC 1,049-1,341, P = 0,006) e o diabetes mellitus (OR = 12,721, 95% IC 1,380-117,247, P = 0,025) foram associadas independentemente à EH. CONCLUSÕES: Achados clínicos simples como história de diabetes e o IMC elevado podem predizer a presença de EH à ultrassonografia de indivíduos com ALT elevada e sorologias negativas para hepatite.Universidade Federal de São Paulo (UNIFESP) Division of Gastroenterology Hepatitis SectionUNIFESP, Division of Gastroenterology Hepatitis SectionSciEL

High incidence of tuberculosis in patients treated for hepatitis C chronic infection

AbstractBrazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p 465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, RJ, BrazilCtr Referencia & Treinamento DST Aids, Sao Paulo, SP, BrazilCDH, Rio De Janeiro, RJ, BrazilHosp Fed Servidores Estado Rio de Janeiro HFSE, Setor Gastrohepatol, Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Clin Med, Div Gastroenterol, Sao Paulo, SP, Brazil| Univ Fed do Maranhao UFMA, HUPD, Ctr Pesquisa Clin, Sao Luis, MA, BrazilUniv Fed Estado Rio de Janeiro UNIRIO, Disciplina Clin Med & Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Rio do Grande Sul UFRGS, Dept Med Interna, Porto Alegre, RS, BrazilUniv Fed Espirito Santo, Ambulatorio HIV AIDS Hepatites Virais, Vitoria, ES, BrazilSMS, Ctr Orientacao & Aconselhamento, Foz Do Iguacu, PR, BrazilUniv Estado Rio de Janeiro UERJ, Serv Gastroenterol, Rio De Janeiro, RJ, BrazilIMT, Lab Virol LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc