Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals

ABSTRACT Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after direct-acting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3­%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Resistência insulínica interfere na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina? / Does insulin resistance impair the virological response to peginterferon/ribavirin in chronic hepatitis c genotype 3 patients?

ABSTRACT BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

RESUMO CONTEXTO: A resistência insulínica e o diabetes mellitus são frequentes manifestações extra-hepáticas da hepatite C crônica. A resistência insulínica medida pelo HOMA-IR está associada a uma baixa taxa de resposta virológica sustentada, principalmente em pacientes portadores de hepatite C crônica genótipo 1 tratados com peginterferon/ribavirina. Em relação aos pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina, a influência da resistência insulínica na resposta virológica sustentada ainda não está esclarecida. OBJETIVO: Avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3. MÉTODOS: Estudo multicêntrico retrospectivo foi realizado para avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes não-diabéticos portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina. Um total de 200 pacientes portadores de hepatite C crônica genótipo 3 foi incluído no estudo. Todos os pacientes eram não diabéticos e apresentavam medida de HOMA-IR antes do início do tratamento da hepatite C crônica com peginterferon/ribavirina. A duração do tratamento foi de pelo menos 24 semanas. O cut-off de HOMA-IR foi definido para este estudo como ≥2,5 devido ao coeficiente de correlação com a resposta virológica sustentada de 0,202 (P=0,004). RESULTADOS: Na análise univariada, idade, aspartato aminotransferase, plaquetas, grau de fibrose e HOMA-IR foram preditores de resposta virológica sustentada. No entanto, na análise multivariada, apenas fibrose avançada [OR=2,01 (95%IC: 0,986-4,119) P=0,05] e idade [OR=1,06 (95%IC: 1,022-1,110) P=0,002] estavam relacionados como preditores negativo de resposta virológica sustentada. CONCLUSÃO: Neste estudo multicêntrico, retrospectivo, em pacientes não diabéticos portadores de hepatite C genótipo 3, a resistência insulínica não estava associada à resposta virológica sustentada em pacientes tratados com peginterferon/ribavirina.

Disease burden of chronic hepatitis C in Brazil

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n= 45,000) cirrhosis; hepatocellular carcinoma (n= 19,100); and liver-related deaths (n= 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively.Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

The use of ustekinumab in a patient with severe psoriasis and positive HBV serology

Psoriasis is a chronic inflammatory, immune-mediated disease that affects 1% to 2% of the world's population. Immunobiological medications are prescribed for certain patients with severe forms of psoriasis, however, these drugs increase the risk of reactivation of viral diseases such as hepatitis B. We report the case of a patient with severe psoriasis with positive serology for the Hepatitis B virus, who received ustekinumab (a human monoclonal antibody against interleukin 12 and 23). In this patient, the use of ustekinumab did not reactivate the Hepatitis B virus. Given the high prevalence of chronic viral infections in patients who are candidates for biologic therapy, as well as the potential for reactivate chronic viral illness, randomized controlled studies are needed to assess the risks and benefits of such therapy in these populations.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin / Efeito do polimorfismo do gene HFE sobre a resposta viral sustentada em portadores de hepatite crônica C com ferritina sérica elevada

CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

CONTEXTO: Níveis séricos anormais de ferritina são encontrados em aproximadamente 20%-30% dos pacientes com hepatite crônica C e estão associadas a uma baixa taxa de resposta à terapia com interferon. OBJETIVO: Avaliar a associação entre a presença de mutações do gene HFE e a taxa de resposta virológica sustentada ao interferon em pacientes portadores de hepatite crônica C com ferritina sérica elevada. MÉTODOS: Um total de 44 pacientes, virgem de tratamento, infectado pelo vírus da hepatite C de genótipos não-1 (38 genótipo 3; 6 genótipo 2) e ferritina sérica acima de 500 ng/mL foi tratado com interferon (3 MU, três vezes por semana) e ribavirina (1000 mg/dia) por 24 semanas. Resposta virológica sustentada foi definida como HCV-RNA indetectável 24 semanas após o fim do tratamento. Foi utilizado técnica de reação em cadeia da polimerase em tempo-real com limite de detecção de 200 UI /mL. RESULTADOS: Mutações do gene HFE foram detectadas por "restriction-enzyme digestion" com RsaI (análise de mutação C282Y) e BclI (análise de mutação H63D) em 16 pacientes (37%), todos heterozigotos (11 H63D, 2 C282Y e 3 ambos). Resposta virológica sustentada foi alcançada em 0 de 16 pacientes com mutações do gene HFE e 11 (41%) dos 27 pacientes sem mutações do gene HFE (P = 0,002; teste exato de Fisher). CONCLUSÃO: A heterozigose para os genes H63D e/ou C282Y HFE está associada à redução significativa da taxa de resposta virológica sustentada ao tratamento com interferon e ribavirina em pacientes com hepatite crônica C, genótipo não-1 e com níveis séricos de ferritina acima de 500 ng/mL.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55 percent) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3 percent) vs. 8 (17 percent) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Prevalence of hepatitis C virus in alcoholic patients: role of parenteral risk factors / Prevalência do vírus da hepatite C em alcoolistas: a atuação dos fatores de risco parenterais

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection is elevated in alcoholic patients, but the risk factors are unclear. The role of parenteral risk factors are indeterminated in this population. AIMS: To determine the prevalence of hepatitis C virus infection in alcoholic patients admitted to a detoxification unit and to evaluate the presence of underlying parenteral risk factors. METHODS: A total of 114 consecutive unselected alcoholic patients admitted to a single chemical dependency unit during 14 month were included. Epidemiological data and history of parenteral risk factors for hepatitis C virus infection were obtained with a standardized questionnaire. Blood was collected for determination of aminotransferases and anti-hepatitis C virus antibodies (ELISA-3). Positive samples were confirmed by polymerase chain reaction and tested for genotype. RESULTS: Among the 114 alcoholics, 17 (15 percent) were anti-hepatitis C virus positive. Of these, 12 (71 percent) had detectable serum HCV-RNA by PCR. Genotype 1 was found in six cases and genotype 3 in five (one patient was undetermined). Forty-nine (43 percent) patients had elevated serum ALT and/or AST at baseline. The comparison between the 17 positive and the 97 negative patients showed significant differences in mean serum ALT levels (42 ± 41 IU/L vs. 22 ± 20 IU/L), rate of elevated ALT (65 percent vs. 34 percent), and presence of parenteral risk factors (94 percent vs. 10 percent). Comparison between alcoholic patients with and without elevated aminotransferases showed significant difference only in the rate of positive anti-hepatitis C virus antibodies (24 percent vs. 7 percent). Furthermore, among the 17 anti-hepatitis C virus positive patients, the rate of detectable HCV-RNA was significantly higher in the 12 with elevated aminotransferases versus the 5 with normal aminotransferases (92 percent vs. 20 percent). CONCLUSIONS: There was a high prevalence of anti-hepatitis C virus antibodies in alcoholics and the majority was confirmed by the presence of detectable HCV-RNA. Intravenous drug use was the main risk factor for hepatitis C virus infection in this population.

RACIONAL: A prevalência da infecção pelo vírus da hepatite C (VHC) é elevada em pacientes alcoolistas, porém os fatores de risco não estão bem estabelecidos. O papel dos fatores de risco parenterais permanece ainda indefinido nessa população. OBJETIVOS: Determinar a prevalência da infecção pelo VHC em alcoolistas internados em uma unidade de desintoxicação, e avaliar a presença de fatores de risco parenteral subjacentes. PACIENTES E MÉTODOS: Foram estudados 114 alcoolistas, não selecionados, consecutivamente admitidos em uma unidade de dependência química durante 14 meses. Através de questionário estruturado, obtiveram-se os dados epidemiológicos e história de fatores de risco parenteral para infecção pelo VHC. Foi coletado sangue para determinação de aminotransferases e anticorpos anti-VHC (ELISA-3). As amostras positivas foram confirmadas pela PCR e determinado o genótipo. RESULTADOS: Entre os 114 alcoolistas, 17 (15 por cento) eram anti-VHC positivos. Doze (71 por cento) tinham RNA do VHC detectável por PCR no soro. O genótipo 1 foi encontrado em seis casos e o genótipo 3 em cinco (em um paciente foi indeterminado). Quarenta e quatro (43 por cento) pacientes tinham ALT e/ou AST elevadas. A comparação entre os 17 pacientes positivos e os 97 negativos mostrou diferenças significativas na média do nível da ALT (42 ± 41 UI/L vs. 22 ± 20 UI/L), na taxa de ALT elevada (65 por cento vs. 34 por cento), e na presença de fatores de risco parenteral (94 por cento vs. 10 por cento). A comparação entre alcoolistas com e sem aminotransferases elevadas mostrou diferença significativa apenas na taxa de anti-VHC positivo (24 por cento vs. 7 por cento). Entretanto, entre os 17 pacientes anti-VHC positivos, a taxa de RNA do VHC detectável no soro foi significativamente maior entre os 12 com aminotransferases elevadas do que entre os 5 com aminotransferases normais (92 por cento vs. 20 por cento). CONCLUSÃO: A prevalência de anti-VHC foi elevada em alcoolistas, sendo a maioria confirmada pela presença do RNA do VHC no soro. O uso de drogas injetáveis foi o principal fator de risco para infecção pelo VHC nesta população.

Correlação entre a contagem de plaquetas no sangue e o gradiente de pressão venosa hepática em pacientes cirróticos / Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis

RACIONAL: A medida do gradiente de pressão venosa hepática é o método mais utilizado para a avaliação da pressão portal. Mais recentemente, a contagem de plaquetas no sangue tem sido apontada como um marcador não-invasivo da presença de hipertensão portal. OBJETIVO: Correlacionar a contagem de plaquetas com os valores do gradiente de pressão venosa hepática em uma população de pacientes cirróticos. PACIENTES E MÉTODOS: Foram estudados 83 pacientes com hepatopatia crônica que realizaram estudo hemodinâmico hepático, em período de 6 anos. Os pacientes foram divididos em grupos conforme a classificação de Child-Pugh e todos realizaram endoscopia digestiva alta para constatar a presença de varizes de esôfago, assim como tiveram a contagem sérica de plaquetas determinada. RESULTADOS: O número de plaquetas variou entre 45.000/mm³ e 389.000/mm³, com média 104.099 e desvio-padrão 58.776. O gradiente de pressão venosa apresentou média igual a 15,2 mm Hg e desvio-padrão igual a 6,4 mm Hg, variando de 1 a 29 mm Hg. Realizou-se regressão linear simples para verificar a correlação entre o gradiente de pressão venosa e o número de plaquetas, o que permitiu constatar fraca correlação entre ambos. Embora se tenha observado menor número de plaquetas, à medida que o calibre das varizes aumentava e nos pacientes com maior grau de disfunção hepatocelular - medida pela classificação de Child-Pugh - não se encontrou significância estatística. CONCLUSÃO: A despeito de não haver demonstrado correlação estatística entre o número de plaquetas com o gradiente de pressão venosa hepática e o grau de disfunção hepatocelular, pelas tendências observadas, acredita-se que ambos os fatores podem estar implicados na patogenia da plaquetopenia em pacientes cirróticos.

Hepatite C em casais inférteis do setor de Reprodução Humana do Hospital de Clínicas de Porto Alegre / Hepatitis C virus in a population of infertile couples

A possibilidade transmissão do vírus da hepatite C através dos gametas pode acarretar riscos para o pessoal técnico, bem como para os envolvidos no processo e para o próprio feto. Este estudo teve como objetivo determinar a prevalência e os fatores de risco da infecção pelo vírus da hepatite C em um grupo de casais inférteis. Em 409 pacientes atendidas no ambulatório de infertilidade do Hospital de Clínicas de Porto Alegre (HCPA), entre 1997 e 1998, realizou-se triagem sorológica para anti-HCV (ELISA) e HBsAg (ELFA). A infecção pelo vírus da hepatite C (HCV) e a viremia seminal também foram investigadas com detecção de HCV-RNA. A prevalência geral de anti-HCV foi de 3,2 por cento (8/248) entre as mulheres e 3,7 por cento (6/161) entre os homens. Todos os indivíduos eram negativos para o vírus da hepatite B (HBV) e HIV. Das 14 pacientes HCV-positivas, duas foram perdidas, e foi coletado soro das 12 pacientes remanescentes para detecção de HCV-RNS, resultando em cinco casos HCV- positivos (uma mulher e quatro homens). Apenas um dos casos positivos tinha nível de viremia > 500.000 cópias de RNA/ml. Houve uma associação de risco significativa da positividade para HCV nas mulheres com parceiros HCV-positivos (P<0,001). Em pacientes masculinos, a correlação entre uso de drogas endovenosas e positividade para HCV também foi significativa (P<0,001). Pacientes inférteis deveriam ser triados para HCV antes dos procedimentos de tecnologia de reprodução assistida (TRA), uma vez que o risco de infecção vertical e laboratorial pelo HCV não está bem determinado e a prevalência do HCV não é desprezível neste grupo.