A cura da hepatite C crônica com os novos antivirais de ação direta não resultou em melhora da resistência insulínica a curto prazo / Curing hepatitis c with the new direct acting antivirals did not improve insulin resistance after one year

ABSTRACT BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).

RESUMO CONTEXTO: A hepatite C crônica ainda figura como importante causa de morbimortalidade na população brasileira, e está associada a alterações metabólicas, incluindo a resistência insulínica (RI), que pode ser avaliada pelo índice HOMA-IR. A RI pode inclusive implicar em menores taxas de reposta virológica sustentada (RVS) em certos regimes terapêuticos e à uma mais rápida progressão para fibrose hepática avançada. Com o advento dos novos antivirais de ação direta (DAA) oferecidos para hepatite C, há crescente necessidade de observar o impacto dos mesmos no perfil de RI em pacientes submetidos à tais terapêuticas. OBJETIVO: - 1) Comparar os valores do HOMA-IR dos pacientes com hepatite C crônica antes do tratamento com os DAAS com os valores deste índice após 12 meses do término do tratamento com RVS. 2) Avaliar evolução do peso após obtenção da cura da hepatite C crônica. MÉTODOS: Foram incluídos pacientes maiores de 18 anos de dois serviços terciários de Curitiba - PR, de ambos os sexos, portadores de hepatite C crônica, com tratamento com os antivirais de ação direta, no período de julho de 2015 a setembro de 2017. Tais pacientes também foram submetidos a dosagem dos níveis de insulina de jejum, glicemia de jejum e hemoglobina glicada antes de iniciar o tratamento da hepatite C e até 12 meses após o término. Também foram utilizados dados como idade, sexo, grau de fibrose hepática, índice de massa corporal, circunferência abdominal, genótipo viral e presença de diabetes mellitus antes e depois do tratamento. A RI foi estimada antes e após 12 meses do término do tratamento e calculada pelo HOMA-IR. Os resultados de variáveis quantitativas foram descritos por médias, medianas, valores mínimos, valores máximos e desvios padrões. Valores de P<0,05 indicaram significância estatística. RESULTADOS: Foram incluídos 75 pacientes no estudo com média de idade de 55,2 anos, sendo 60% do sexo masculino. Destes pacientes, 43 tinham fibrose avançada. Vinte e um (28%) pacientes tinham o diagnóstico de diabetes mellitus. A RI foi observada em 31 (41,3%) pacientes antes do tratamento antiviral, sendo que este número aumentou para 39 (52%) de acordo com a dosagem do HOMA-IR 12 meses após o término do tratamento. Não houve diferença estatística entre os valores de insulina, glicemia e HOMA-IR antes e após a cura da hepatite. Houve um ganho de peso inicial após a obtenção da cura da hepatite C, mas que não se manteve ao final do estudo. CONCLUSÃO: Não foi vista diferença estatística significante entre os valores do HOMA-IR apresentados pelos pacientes portadores de hepatite C crônica antes do tratamento e 12 meses após a cura da doença. Embora tenha ocorrido ganho de peso após obtenção da cura da doença, este não se deu de forma estatisticamente significativa (P=0,131) ao final de um ano.

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 E crônica - relato de um caso brasileiro / Chronic hepatitis E - a brazilian case report

Hepatite é a quinta forma conhecida de hepatites humanas virais. Apesar de ser muito incomum em nossa prática clínica, a incidência em países ocidentais vem aumentando. O vírus da Hepatite E (HVE) pode estar relacionado à doença aguda, falência hepática, hepatite crônica e cirrose. O HVE é um RNA vírus, com 5 genótipos descritos (1, 2, 3, 4 e 5), sendo que quatro deles podem afetar humanos. Além das manifestações hepáticas, o genótipo 3 pode também levar a manifestações extra-hepáticas, como alterações neurológicas, renais e reumatológicas. O diagnóstico pode ser difícil porque existem poucos testes validados e ainda com baixa sensibilidade e especificidade. A hepatite aguda não precisa ser tratada, já a hepatite E crônica deve ser tratada. Relatamos aqui um caso brasileiro de Hepatite E crônica em um paciente imunossuprimido.

Hepatitis E is the fifth known form of human viral hepatitis. Although not very common in our clinical practice, the incidence in Western countries is increasing. Hepatitis E virus (HEV) may be related to acute illness, liver failure, chronic hepatitis and cirrhosis. HEV is an RNA virus, with 5 described genotypes (1,2,3,4,5), 4 of them can affect humans. Besides liver manifestations, genotype 3 is also related to extra-hepatic manifestations, such as neurological, renal and rheumatological. The diagnosis may be difficult because of the low availability of tests and due to low sensibility and specificity. The acute illness does not have to be treated, but the chronic one does. We presente here a Brazilian case of chronic hepatitis E in an immunosuppressed patient.

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<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 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.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.

ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE / Exame de sonoelastografia é equivalente a biópsia hepática na análise de fibrose em pacientes portadores de hepatite C crônica e doença hepática gordurosa não alcoólica

BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

ContextoA biópsia hepática é considerada padrão-ouro para definição de fibrose hepática em pacientes com doença hepática crônica. No entanto, é um método invasivo, com potenciais riscos e complicações. A elastografia é uma técnica de ultrassonografia que fornece informações sobre variações no tecido hepático, avaliando elasticidade tecidual e sonoelastografia é uma das técnicas disponíveis.ObjetivoO principal objetivo do estudo é avaliar a sensibilidade e especificidade da sonoelastografia comparada a biópsia hepática para análise do grau de fibrose hepática em pacientes com hepatite C crônica e doença hepática gordurosa não alcoólica.MétodosVinte e quatro pacientes foram incluídos no estudo, submetidos a biópsia hepática e sonoelastografia. Os resultados obtidos foram comparados a valores descritos na literatura por diferentes autores.ResultadosNa população de pacientes com hepatite C crônica, os dados melhor se correlacionaram com resultados publicados por Carmen Fierbinteanu-Braticevici e col, com uma acurácia de 82,4%, sensibilidade de 71,4% e especificidade de 90%. Para doença hepática gordurosa não alcoólica, a melhor correlação se deu com dados publicados por Masato Yoneda e col, com acurácia de 85,7%, sensibilidade de 80% e especificidade de 100%.ConclusãoSonoelastografia é um método com boa acurácia para diferenciar fibrose avançada de fibrose inicial e pode substituir a biópsia hepática na maioria das vezes.

Change in platelet count in patients with hypersplenism subjected to liver transplantation / Modificação no número de plaquetas de pacientes com hiperesplenismo submetidos a transplante hepático

CONTEXT: Most patients subjected to liver transplantation presents hypersplenism, which is reversed after the operation. However, some patients remain with moderate to intense hypersplenism. OBJECTIVES: To study the effect of liver transplantation on platelet count in patients with hypersplenism. METHOD: Of a total of 233 patients who underwent liver transplantation, 162 were excluded from the present study because of occurrence of steroid-resistant rejection, absence of hypersplenism before the transplantation, absence of follow-up for at least 2 years or incomplete exams data. The electronic study protocols of the remaining 71 patients were reviewed to determine the demographics, etiology of cirrhosis, and results of pathologic examination of the explanted liver. Serial platelet count was obtained from the study protocol on the day before liver transplantation and 1, 2, 4, and 6 months and 1 year after liver transplantation. Statistical analysis was performed using the Student's t-test, chi-square test, and Spearman's correlation test. RESULTS: Posttransplant platelet count at all time intervals was significantly higher than the pretransplant value (P<0.001 for all time intervals). Thrombocytopenia was reversed (platelet count >100,000/mm³) in 58 patients (81.7 percent) 1 month after liver transplantation. Twelve patients (16.9 percent) remained with thrombocytopenia 1 year after liver transplantation. Three patients (4.2 percent) had recurrence of thrombocytopenia within 1 year after liver transplantation. There was no correlation between pretransplant platelet count and the Child-Pugh class or the MELD score. CONCLUSION: Liver transplantation reverses hypersplenism in most patients.

CONTEXTO: A maioria dos pacientes submetidos a transplante hepático apresenta hiperesplenismo, que é revertido após a operação. Entretanto, alguns pacientes permanecem com hiperesplenismo moderado a intenso. OBJETIVO: Avaliar o efeito do transplante hepático na contagem de plaquetas de pacientes com hiperesplenismo. MÉTODOS: De um total de 233 pacientes que foram submetidos a transplante hepático, 162 foram excluídos do presente estudo devido à ocorrência de rejeição resistente a corticóide, ausência de hiperesplenismo antes do transplante, ausência de seguimento pós-transplante por pelos menos 2 anos ou dados de exames incompletos. O protocolo eletrônico de estudo dos demais 71 pacientes foi revisado para determinar os aspectos demográficos, a etiologia da cirrose e o resultado do exame patológico do fígado explantado. Contagem seriada de plaquetas foi obtida do protocolo de estudo no dia antes do transplante e 1, 2, 4 e 6 meses e 1 ano após o transplante. Análise estatística foi realizada empregando o teste t de Student, o teste qui ao quadrado e o teste de correlação de Spearman. RESULTADOS: A contagem de plaquetas pós-transplante em todos os intervalos de tempo foi significantemente maior que os valores pré-transplantes (P<0,001 para rodos os intervalos de tempo). Trombocitopenia foi revertida (contagem de plaquetas >100.000/mm³) em 58 pacientes (81,7 por cento) 1 mês após o transplante. Doze pacientes (16,9 por cento) permaneceram com trombocitopenia 1 ano após o transplante. Três pacientes (4,2 por cento) tiveram recurrência da trombocitopenia dentro de 1 ano após o transplante. Não houve correlação entre a contagem de plaquetas pré-transplante e a classe de Child-Pugh e o escore de MELD. CONCLUSÃO: O transplante hepático reverte o hiperesplenismo na maioria dos pacientes.

High prevalence of hepatitis C associated with familial history of hepatitis in a small town of south Brazil: efficiency of the rapid test for epidemiological survey

This report describes a cross-sectional survey on the prevalence of hepatitis C antibodies (anti-HCV) in Tamboara, a small community in the northwest area from Paraná State, south of Brazil with a high rate of accumulated detection for HCV. Eight hundred and sixteen residents (17.87 percent from all the population), independently of the age and time living in Tamboara were included in this study by an epidemiologic questionnaire and by testing for anti-HCV. The rapid immuno-chromatographic test was applied for detection of HCV antibodies. The anti-HCV prevalence by rapid test was 4.28 percent. The median age for positive and negative test was 60.49 ± 14.14 and 41.67 ± 20.25, respectively (p < 0.001). By multivariate analysis, only familial history of hepatitis (p = 0.001; OR = 6.41; CI 95 percent = 2.08-19.78) and age (p = 0.007; OR 1.06;95 percent CI = 1.02-1.10) showed statistical significance for positive anti-HCV. The rapid test sensitivity and specificity were 100 percent and 92.7 percent respectively, with an accuracy of 95.8 percent (95 percent CI = 91-100). These findings demonstrated a high prevalence of anti-HCV in Tamboara. The familial history of hepatitis was a significant risk factor to the infection and HCV rapid test showed to be accurate and feasible for epidemiological survey.