Tratamiento simplificado para pacientes con Hepatitis C / Simplified treatment for hepatitis C patients

El nuevo tratamiento simplificado con antivirales orales para pacientes con Hepatitis C puede ser abordado desde la atención primaria, lo que facilita el acceso de la población afectada por esta infección crónica. En este artículo se repasan los aspectos claves del diagnóstico, el esquema de tratamiento simplificado y los candidatos a recibirlo. (AU)

The new simplified treatment with oral antivirals for hepatitis C patients can be approached at the primary care level, facilitating access for the population affected by this chronic infection. This article reviews the key aspects of the diagnosis, the simplified treatment scheme, and the eligible candidates for the treatment. (AU)

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

A real-life study of the positive response to DAA-based therapies for hepatitis C in Brazil

ABSTRACT A retrospective cohort of 11,308 chronic hepatitis C infected patients treated with regimens that included Sofosbuvir (SOF), Daclatasvir (DCV), Simeprevir (SMV), or an association of Ombitasvir, Veruprevir/Ritonavir and Dasabuvir (3D) with or without Ribavirin (RBV) were assessed for sustained virologic response (SVR) or viral cure after a 12-week treatment. Logistic regression analyses were used to identify factors independently associated with positive response to direct-acting antivirals (DAA)-based therapies.Overall 57.1% were male; 48.3% self-identified as white; 78.3% were over 50 years old; 44.1% were from the Southeast region; 47.7% had genotype 1b; and 84.5% were treated for 12 weeks. The SVR rates with DAAs ranged from 87% to 100%. Genotypes 1 and 4 had higher SVR rates (96.3-100%), and genotypes 2 and 3 had SVR of 90.6-92.2%, respectively. Treatment durations of 12 and 24 weeks were associated with an average SVR of 95.0% and 95.9%, respectively. Females were half as likely (OR 0.5; 95% CI 0.4−0.6) to have a negative response to therapy compared to males, and those with genotypes 2 and 3 were one and half fold more likely (OR 1.5-2.2; 95 CI% 0.7-2.9; 1.2-3.6 and OR 2.7-2.8; 95% CI 2.0-3.8, respectively) to not have SVR compared to genotype 1. Patients in the age-range of 50-69 years old were 1.2-fold (OR 1.2; 95% CI 0.7-1.9) more likely to not have SVR compared to other age groups, although not statistically significant.This study is the first of this magnitude to be held in a Latin-American country with high SVR results, supported by a free-of-charge universal and public health system. The high performance found in this study gives support to the Brazilian public health policy decision of adopting DAA-based therapies as a strategy to eliminate HCV by 2030.

El síndrome de fatiga crónica en el curso de la hepatitis C. Presentación de un caso / Chronic fatigue syndrome in the course of Hepatitis C

RESUMEN Se supone que aproximadamente 80 millones de personas a nivel mundial están infectadas con el virus de la hepatitis C. Un aproximado del 60 % de dichos pacientes aqueja síndrome de fatiga crónica. Se presentó un paciente portador de hepatitis crónica de tipo C, con manifestaciones clínicas de síndrome de fatiga crónica por más de dos años. Se han reportado estudios internacionales que han demostrado la relación existente entre el desarrollo de la respuesta inmune y el daño que ocasiona en el tejido cerebral la infección por virus de hepatitis C. Este trabajo tiene como objetivo la presentación del primer caso que se tiene referencia (AU).

ABSTRACT It is believed that almost 80 million persons are infected with the Hepatitis C virus around the world, and 60 % of them suffer the chronic fatigue syndrome. For that reason we present the case of a patient who is a carrier of the chronic fatigue syndrome for more than two years. Reports of international research have showed the relation between the immune answer and the damage caused by the infection of the hepatitis C virus in the brain tissues. The aim of this work is presenting the first case reported in Cuba (AU).

Incidence of depression in patients with hepatitis C treated with direct-acting antivirals

Objective: Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs. Methods: The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment. Results: The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p > 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]). Conclusions: The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.

Hepatitis C in Hemodialysis Units: diagnosis and therapeutic approach / Hepatite C nas Unidades de Hemodiálise: diagnóstico e abordagem terapêutica

Abstract According to data from the last census of the Brazilian Society of Nephrology (SBN), the prevalence of hepatitis C virus (HCV) in Brazilian hemodialysis units (HU) is 3.3%, about three times higher than what is reported for the Brazilian general population. Often, professionals working in HU are faced with clinical situations that require rapid HCV diagnosis in order to avoid horizontal transmission within the units. On the other hand, thanks to the development of new antiviral drugs, the cure of patients with HCV, both in the general population and in patients with chronic kidney disease and the disease eradication, appear to be very feasible objectives to be achieved in the near future . In this scenario, SBN and the Brazilian Society of Hepatology present in this review article a proposal to approach HCV within HUs.

Resumo De acordo com os dados do último censo da Sociedade Brasileira de Nefrologia (SBN), a prevalência de portadores do vírus da hepatite C (HCV) nas unidades de hemodiálise (UH) no Brasil é de 3,3%, cerca de três vezes maior do que é observado na população geral brasileira. Muitas vezes, os profissionais que trabalham nas UH deparam-se com situações clínicas que demandam rápido diagnóstico do HCV, a fim de evitar uma transmissão horizontal dentro das unidades. Por outro lado, a cura dos pacientes portadores do HCV, tanto na população geral como na portadora de doença renal crônica e a erradicação da doença, em virtude do desenvolvimento de novas drogas antivirais, parecem ser objetivos bastante factíveis, a ser alcançados em futuro próximo. Nesse cenário, a SBN e a Sociedade Brasileira de Hepatologia apresentam neste artigo de revisão uma proposta de abordagem do HCV dentro das UH.

Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

Acciones prioritarias para un programa nacional de detección, tratamiento y seguimiento de pacientes con hepatitis C / Priority actions towards a national program for detection, treatment, and monitoring of patients with hepatitis C

Resumen: En el escenario de la salud mexicana, la epidemia por virus de la hepatitis C se encuentra presente junto con sus comorbilidades y mortalidad prematura. Actuar de manera inmediata permitirá una contención de la misma en el corto plazo dada la existencia de herramientas de prevención, diagnóstico y terapias farmacológicas altamente eficaces. La Coalición para el estudio de la hepatitis C en México ha desarrollado una postura donde aprovecha esas medidas de contención y presenta el desarrollo de un programa nacional para la detección, tratamiento oportuno y seguimiento de pacientes con hepatitis C.

Abstract: In the Mexican health scenario, the hepatitis C virus epidemic is present, along with its comorbidities and premature mortality. Acting immediately will allow its containment in short term with the proper implementation of the current available tools for prevention, diagnosis and highly effective pharmacological therapies. The Coalition for the study of hepatitis C in Mexico has developed a position paper that takes advantage of these containment measures and presents the development of a National program for the detection, timely treatment and follow-up of patients with hepatitis C.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Hand-foot syndrome due to hepatitis C therapy

SUMMARY INTRODUCTION Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

RESUMO INTRODUÇÃO Antivirais de ação direta são as novas drogas utilizadas no tratamento da hepatite C crônica. São geralmente seguros, com boa tolerância, mas eventualmente podem causar efeitos adversos graves, e não há consenso sobre como tratá-los ou preveni-los. Descrevemos um caso de síndrome mão-pé secundária à terapia livre de interferon para hepatite C crônica. Materiais e métodos Relatamos o caso de um paciente de 49 anos com cirrose hepática compensada secundária à hepatite C crônica, genótipo 1, virgem de tratamento, que iniciou terapia com sofosbuvir, simeprevir e ribavirina por 12 semanas. Resultados Na sexta semana de tratamento, apresentou anemia, sendo necessária redução de dose da ribavirina. Na 20a semana, apresentou lesões eritematosas e descamativas, com prurido em mãos e pés, que teve resposta parcial ao uso de anti-histamínico oral e corticoide tópico. Não foi necessário descontinuar os antivirais, mas na primeira semana após o término do tratamento, houve piora das lesões, com sinais de infecção secundária, sendo necessárias hospitalização e terapia com antibiótico e corticoide oral, com melhora progressiva. Biópsias das lesões foram compatíveis com farmacodermia. O paciente teve resposta virológica sustentada, apesar dos efeitos adversos. Tinha história de farmacodermia há um ano, atribuída ao uso de topiramato, responsiva a corticoterapia oral. Conclusão Os tratamentos livres de interferon raramente causam eventos adversos graves, como lesões cutâneas. Pacientes em uso de ribavirina e com história de farmacodermia ou doença cutânea prévia podem ser mais susceptíveis. Não existe consenso sobre como prevenir reações cutâneas nesses pacientes.

Hepatitis C en pacientes con enfermedad renal crónica: ha llegado la oportunidad de erradicarla. Reseña del manejo en esta población con el advenimiento de las nuevas drogas antivirales directas / Hepatitis C in patients with chronic kidney disease: the opportunity to eradicate it has come. Review of management in this population with the advent of new direct-acting antivirals

Con el advenimiento de los nuevos antivirales de acción directa (DAA) para el tratamiento de la Hepatitis C, y su posible utilización en enfermos con insuficiencia renal terminal y trasplantados renales se abre la posibilidad de la erradicación de dicha infección en ésta población. De lograrse la misma tendría enorme impacto clínico dada la mayor tasa de morbimortalidad que dicha infección genera en ésta población ya sea por sus complicaciones hepáticas como extrahepáticas, donde las glomerulopatías juegan un rol preponderante. En éste artículo nos enfocamos en revisar los adelantos publicados con respecto al posible rol patogénico del virus C en el daño endotelial de los pacientes renales, su incidencia e impacto clínico. Asimismo revisamos las guías recientes de KDIGO en lo referente a los criterios de tratamiento y el tipo de régimen recomendado en cada escenario

With the advent of new direct-acting antivirals (DAA) for the treatment of Hepatitis C and their possible use in patients with endstage renal disease and kidney transplantation, the possibility of eradicating this infection in this population opens up. If achieved, it would have an enormous clinical effect given the higher rate of morbidity and mortality that this infection causes in such population, either due to its hepatic or extrahepatic complications, where glomerulopathies play a preponderant role. In this article we have focused on reviewing the pu-blished advances regarding the possible pathogenic role of C virus in the endothelial injury of renal patients, its incidence and clinical effect. We have also reviewed the recent KDIGO Clinical Practice Guideline regarding the treatment criteria and the type of regimen recommended in each scenario

Impact of alcohol consumption among patients in hepatitis C virus treatment / Impacto do consumo alcoólico entre pacientes em tratamento da hepatite C

ABSTRACT BACKGROUND: Recent studies have questioned the recommendation of abstinence from alcohol for at least 6 months for alcoholic patients to be treated for hepatitis C. OBJECTIVE: The present study aimed to assess the impact of alcohol consumption among patients undergoing hepatitis C treatment. METHODS: In this cross-sectional study, 121 patients [78 (64.5%) men; 28-70 years] were evaluated. They were divided as follows: patients who consumed <12 g of ethanol/day throughout life (Group 1), 12-59 g/day (Group 2) and ≥60 g/day (Group 3). Patients were treated with pegyla­ted-interferon plus ribavirin. RESULTS: These three groups could not be distinguished in terms of the severity of liver fibrosis and frequency of HCV genotype-1 infection. In Group 3, treatment discontinuation (32.4%) was higher than in the Group 1 (9.4%) or Group 2 (0%), it was higher among patients who drank during treatment (66.7% vs 21.4%) and among those who had not been abstinent for at least 6 months (72.7% vs 15.4%). Moderate alcohol drinkers showed good adherence and did not discontinue the treatment. The frequencies of sustained viral response among patients in Group 3 (44.4%) were similar to those in Group 1 (61%) and Group 2 (68.4%). CONCLUSION: Heavy drinkers more often discontinued treatment for hepatitis C, but those that received this treatment had acceptable sustained viral response rates. These results suggest that heavy drinkers should not be systematically excluded from the treatment, but they should be monitored to avoid drinking and abandoning treatment, mainly those who have not been abstinent for at least 6 months.

RESUMO CONTEXTO: Estudos recentes têm questionado a recomendação de abstinência do álcool por pelo menos 6 meses para pacientes alcoolistas serem tratados para hepatite C. OBJETIVO: Este estudo objetivou avaliar o impacto do consumo de álcool entre pacientes submetidos ao tratamento para a hepatite C. MÉTODOS: Neste estudo transversal, avaliou-se 121 pacientes [78 (64,5%) homens; 28-70 anos). Eles foram divididos em três grupos: pacientes que consumiam <12 g de etanol/dia na vida (Grupo 1); 12-59 g/dia (Grupo 2) e ≥60 g/dia (Grupo 3). Pacientes foram tratados com interfe­ron-peguilado mais ribavirina. RESULTADOS: Os três grupos não puderam ser distinguidos em relação à gravidade da fibrose hepática e das frequências de infecção pelo genótipo-1 do HCV. No Grupo 3, descontinuação do tratamento (32,4%) foi maior do que no Grupo 1 (9,4%) ou Grupo 2 (0%), foi maior entre pacientes que beberam durante o tratamento (66,7% vs 21,4%) e entre aqueles que não estavam em abstinência por pelo menos 6 meses (72,7% vs 15,4%). Pacientes do Grupo 2 tiveram boa aderência e não descontinuaram o tratamento. As frequências de resposta virológica sustentada entre pacientes do Grupo-3 (44,4%) foi semelhante àquelas do Grupo 1 (61%) e do Grupo 2 (68,4%). CONCLUSÃO: Bebedores pesados mais frequentemente descontinuaram o tratamento da hepatite C, mas aqueles que foram tratados tiveram aceitáveis taxas de resposta virológica sustentada. Esses resultados sugerem que bebedores pesados não deveriam ser sistematicamente excluídos do tratamento, mas sim serem monitorados para evitar beber e abandonar o tratamento, principalmente aqueles que não estão abstinentes por pelo menos 6 meses.

Cúrcuma em combinação com os regimes de terapia tríplice melhora o estresse oxidativo e as alterações histopatológicas em gastrite crônica associada à infecçäo por Helicobacter pylori / Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis-associated helicobacter pylori infection

ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

RESUMO CONTEXTO A infecção gástrica pelo Helicobacter pylori (H. pylori) é principal causa de alterações inflamatórias e de câncer gástrico. OBJETIVO O objetivo deste estudo foi encontrar os efeitos da cúrcuma no estresse oxidativo e as alterações histológicas na gastrite crônica associada ao H. pylori. MÉTODOS Em um estudo randomizado clínico experimental, pacientes foram divididos em dois grupos: um grupo de terapia tríplice padrão e outro com terapia tríplice com e cúrcuma. Exames endoscópicos e histológicos foram analisados para todos os pacientes antes e depois de 8 semanas de tratamento. RESULTADOS A terapia tríplice com grupo de tratamento de cúrcuma diminuiu significativamente os marcadores de malondialdeído, de peróxidos de glutationa, com aumento da capacidade antioxidante total da mucosa gástrica ao final do estudo em comparação com grupos de regime basal e tríplice. Além disso, o dano oxidativo ao DNA diminuiu significativamente em terapia tríplice com grupo de cúrcuma no final do estudo em comparação com a linha de base e comparado à terapia tríplice (P<0,05 para ambos). No grupo de terapia tríplice em combinação com cúrcuma houve diminuição significativa de todas os escores ativos de inflamação crônica e endoscópica dos pacientes em relação ao grupo de terapia de base e tríplice (P<0,05 para ambos). A taxa de erradicação por terapia tríplice + cúrcuma aumentou significativamente em relação à terapia tríplice isolada (P<0,05). CONCLUSÃO A cúrcuma pode ser um complemento útil para melhorar a inflamação crônica e prevenção de alterações cancerígenas em pacientes com gastrite crônica associada ao H.pylori.

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Protocolo clínico e diretrizes terapêuticas para hepatite C e coinfecções / Clinical protocol and therapeutic guidelines for hepatitis C and coinfections

INTRODUÇÃO: As hepatites virais são uma das maiores causas de transplantes hepáticos no mundo - com destaque para a hepatite C (HCV), um agravo que hoje afeta mais de 185 milhões de pessoas em todos os continentes. Inicialmente denominada hepatite não-A não-B, a hepatite C foi elucidada apenas em 1989, com a identificação de seu agente etiológico. Desde então, a infecção pelo HCV adquiriu especial relevância entre as causas de doença hepática particularmente entre pacientes portadores do HIV em terapia antirretroviral, grupo que apresenta importante morbimortalidade para o agravo. A história natural do HCV é marcada pela evolução silenciosa: muitas vezes, a doença é diagnosticada décadas depois da infecção. Os sinais e sintomas são comuns às demais doenças parenquimatosas crônicas do fígado e costumam manifestar-se apenas em fases mais avançadas da doença. Estas características também afetam negativamente o diagnóstico da infecção, contribuindo para os números de portadores assintomáticos em todo o mundo. OBJETIVOS: O novo Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções tem como objetivo oferecer, no âmbito do SUS, uma estratégia custo-efetiva para o tratamento da hepatite C - com novas terapêuticas, acesso flexibilizado, menores índices de efeitos adversos e maior expectativa de cura. Esta proposta inovadora foi pautada também em uma ampla negociação de preços para alcançar a sustentabilidade e o acesso universal à assistência no SUS. O novo PCDT também apresenta uma proposta de cuidado integral ao paciente portador de hepatite viral, além de tratamentos que permitem melhor assistência e ampliação da capacidade do SUS. Assim, são objetivos desta publicação: -Estabelecer novas diretrizes terapêuticas nacionais e orientar os profissionais de saúde no manejo da hepatite C e coinfecções, visando estabelecer uma política baseada nas melhores evidências da literatura científica; -Promover assistência humanizada e especializada; -Buscar melhor qualidade na assistência e uso racional do arsenal terapêutico e demais insumos estratégicos; -Garantir melhores resultados em saúde pública e a sustentabilidade do acesso universal ao tratamento; -Reduzir a probabilidade de evolução para insuficiência hepática e câncer hepático. METODOLOGIA: Com o intuito de apresentar as melhores evidências científicas publicadas e as estratégias estabelecidas, realizou-se a revisão de protocolos internacionais (American Association for the Study of Liver Diseases, 2014; National Institute for Health and Care Excellence; The European Association for the Study of the Liver, 2015; Asian Pacific Association for the Study of the Liver, 2012; World Health Organization, 2014) e de literatura científica. As recomendações deste Protocolo Clínico e Diretrizes Terapêuticas para a Hepatite C e Coinfecções foram pesquisadas nas bases de dados MEDLINE, com o termo de busca "("Hepatitis C/drug therapy"[Mesh] OR "Hepatitis C/therapy"[Mesh])" e com os filtros "Clinical Conference, Clinical Trial (I, II, III, IV), Consensus Development Conference, Evaluation Studies, Guideline, Meta-Analysis, Multicenter Study, Practice Guideline, Randomized Controlled Trial, Review, Systematic Reviews" e "Humans" e data de publicação nos últimos cinco anos; e a base de dados LILACS, com o descritor "hepatite C". Esta busca resultou em 5.336 e 122 publicações, respectivamente. Complementou-se esta pesquisa com uma revisão sistemática realizada pelo Departamento de Gestão e Incorporação de Tecnologias em Saúde (DGITS/SCTIE/MS), que identificou as últimas evidências de estudos clínicos realizados com os medicamentos propostos neste documento. (Departamento de Gestão e Incorporação de Tecnologias no SUS, 2015) Bases de dados consultadas pelo DGITS/SCTIE/MS: MEDLINE, Cochrane Collaboration, DARE, Central, Clinicaltrials.gov e anais dos últimos eventos científicos internacionais em hepatites virais. CONSULTA PÚBLICA: A consulta pública para a aprovação do Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções foi realizada entre os dias 22 de junho e 01 de julho de 2015. Foram recebidas 53 contribuições durante a consulta pública. Somente são consideradas contribuições de consulta pública aquelas que foram encaminhadas no período estipulado em formulário próprio. As 53 contribuições foram analisadas pelo Departamento de DST, Aids e Hepatites Virais, responsável pelo programa/ação de que trata o protocolo e pelo Plenário da CONITEC, tendo sido agrupadas por tema. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 02/07/2015 deliberaram, por unanimidade, recomendar a aprovação do Protocolo Clínico e Diretrizes Terapêuticas para Hepatite viral C crônica. DECISÃO: Portaria nº 37, de 24 de julho de 2015 - Torna pública a decisão de aprovar o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para Hepatite viral C crônica no âmbito do Sistema Único de Saúde - SUS.

Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin / Hanseniase boderline tuberculoide e reacao hansenica do tipo 1 em paciente com hepatite C durante tratamento com interferon e ribavirina

Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.

A hepatite C é uma doença inflamatória fígado causada por um vírus RNA de fita simples, pertencente ao gênero Hepacivirus e à família Flaviviridae, denominado de vírus da hepatite C. Após infecção inicial 70 a 85% dos pacientes infectados evoluem para hepatite C crônica, com fibrose progressiva. Além das alterações hepáticas específicas, várias manifestações extra-hepáticas têm sido relacionadas à infecção pelo vírus da hepatite C ou às medicações utilizadas no seu tratamento. Nesse trabalho, apresenta-se caso de paciente portador de hepatite C crônica, que manifestou um quadro hanseníase boderline tuberculóide e reação hansênica do tipo I, quatro meses após início do tratamento com interferon peguilado associado à ribavirina.

Hepatites virais: B, C e D: atualização / Viral hepatitis: B, C and D: an update

JUSTIFICATIVA E OBJETIVOS: As hepatites causadas pelos vírus da hepatite B (VHB), vírus da hepatite C (VHC) e vírus da hepatite (VHD) têm como aspecto comum a transmissão por via parenteral e a possibilidade de cronificação. Revisar os aspectos clínico-epidemiológicos, diagnósticos, terapêuticos e profiláticos das infecções virais por tais agentes é o escopo do presente artigo. Realizou-se pesquisa bibliográfica nas bases de dados Scielo e Pubmed empregando-se os descritores hepatite B (hepatitis B); hepatite C (hepatitis C); hepatite D (hepatitis D) e hepatite G (hepatitis G), assim como livros texto, consensos e diretrizes relacionadas ao tema.CONTEÚDO: As formas agudas das hepatites B, C e D são usualmente benignas, podendo, sem embargo, ocorrerem quadros de hepatite fulminante. Em situações nas quais o sistema imunológico não é capaz de depurar o VHB e/ou VHC, há cronificação da infecção, com risco de desenvolvimento de cirrose e consequente insuficiência hepática crônica, bem como carcinoma hepatocelular. As hepatites B e D são imunopreveníveis, graças à vacina parao vírus B, mas, até o momento, não há imunoprofilaxia disponível para o vírus C.CONCLUSÃO: As hepatites pelos VHB e VHC constituem importantes desafios para a medicina atual, especialmente pela prevalência das infecções no planeta e pelo risco de desenvolvimento das complicações crônicas. Neste contexto, destaque-se a importância da avaliação diagnóstica, da instituição da terapêutica adequada e do emprego das medidas preventivas para tais infecções, elementos que devem ser solidamente conhecidas pelo clínico.

BACKGROUND AND OBJECTIVES: Hepatitis caused by hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) have in common the transmission by parenteral route and the possibility of chronification. Reviewing the clinic, epidemiology, diagnose, therapeutics and prophylaxis of viral infections by these agents is the scope of this work. Bibliographic research was conducted both at databases Scielo and Pubmed through the chosen descriptors: hepatitis B, hepatitis C, hepatitis D and hepatitis G, and text books, consensus and guidelines related to the subject.CONTENTS: The acute viral B, C and D hepatitis are usually benign, though acute liver failure, fulminant hepatitis, may occur. In the cases when the immune system is unable to debug HBV and HCV the infection becomes chronic, cirrhosis with consequent chronic liver insufficiency and hepatocellular carcinomamay develop. HBV and HDV are immunopreventable, thanks to the hepatitis B virus vaccine, but at this point there's no immunoprophylaxis available for hepatitis C virus. CONCLUSION: HBV and HCV hepatitis are great challenges for medicine, particularly due to the prevalence of infections worldwide and the risk of chronic complications. In this context, diagnostic evaluation, adequate therapeutic care, and preventive measures must be soundly known by the physician.

Nuevos avances en el manejo de la hepatitis C / Current advances in hepatitis C treatment

La hepatitis por virus C constituye un problema de salud importante en México. El diagnóstico de poblaciones de alto riesgo es esencial dada la probabilidad de desarrollar enfermedad crónica, cirrosis, descompensación de la cirrosis y la consecuente necesidad de un trasplante hepático o de desarrollar carcinoma hepatocelular. Actualmente, el tratamiento de elección establecido (TEE) incluye interferón pegilado y ribavirina, los cuales han mostrado una tasa de respuesta de alrededor de 57 por ciento en el caso del genotipo 1, el más prevalente en México. Sabemos que entre 30 y 60 por ciento de la población no muestra una respuesta viral sostenida (RVS) o curación. Por lo tanto, en este artículo se revisan las estrategias terapéuticas existentes para optimizar el tratamiento, y se describen también las estrategias de tratamiento para el futuro. Eventualmente, será posible adicionar una o dos moléculas de los nuevos antivirales que actúan directamente (AAD) sobre áreas específicas del virus al TEE. Cada una de ellas cuenta con mecanismo de acción diferente y se está contemplando la posibilidad de una terapéutica libre de interferón después del año 2015.

Infection by hepatitis C virus constitutes an important health problem in Mexico. Diagnosis of high-risk population is essential given the probability of developing chronic disease, cirrhosis and cirrhosis decompensation, likely leading to the need of a liver transplant and/or the development of hepatocellular carcinoma. Currently, the standard of care (SOC) treatment includes pegylated interferon and ribavirin, which have shown an approximately 57 percent rate response in genotype 1, the most prevalent in Mexico. It is known that between 30 and 60 percent of the infected population does not show a sustained virological response or cure. Therefore, in this article, we review existing therapeutic strategies in order to optimize the treatment. Future treatment strategies are also described. Eventually, it will be possible to add one or two molecules of the new directly acting antiviral drugs, to the SOC treatment. Each of them has a different action mechanism, and we are envisioning the possibility of an interferon-free therapy after 2015.

Resposta virológica sustentada em pacientes com co-infecção pelos genótipos 1 e 2 do vírus da hepatite C, com apenas nove semanas de terapêutica antiviral: relato de caso / Sustained virological response in patients with coinfection by hepatitis C virus genotypes 1 and 2, after just nine weeks of antiviral therapy: case report

Relata-se um paciente do sexo masculino com 67 anos e sorologia positiva para o vírus da hepatite C (HCV). Exames moleculares revelaram a presença do RNA do HCV, com carga viral de 2.000 cópias/mL e genótipos 1 e 2. O tratamento foi com alfapeginterferon-2a, 180mcg/semana e ribavirina, 1.000mg/dia. Na quarta semana de tratamento, a carga viral para o HCV era indetectável. Na nona semana, o paciente apresentou hematêmese, piora do quadro de astenia, inapetência e comprometimento do estado geral, quando o tratamento foi descontinuado. O PCR foi negativo após 6 meses e permaneceu assim após um ano. O paciente encontra-se assintomático.

A report of a 67 year-old male patient with positive serology for HCV. PCR revealed the presence of HCV RNA, viral load of 2,000 copies/mL and genotypes 1 and 2. The pacient was treated with peginterferon alfa-2a at 180mcg/week and ribavirin at 1,000mg/day. In week four of treatment, HCV viral load was undetectable. In week nine, the patient developed hematemesis, worsening of asthenia, anorexia and impaired general condition, so the treatment was discontinued. The PCR was negative six months and one year after the cessation of treatment. The patient remains asymptomatic.