Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan / Recorrência do vírus da hepatite C após tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Embora aumentem as taxas de resposta concomitantes no vírus da hepatite C (HCV), há risco de recidiva após o tratamento. Portanto, é um requisito terrível avaliar a resposta do interferon peguilado e antivirais de ação direta em Punjab, Paquistão. O estudo foi conduzido para encontrar a taxa de recorrência da infecção por HCV após o tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão. Este estudo foi conduzido no Departamento de Patologia Nawaz Sharif Medical College Gujrat, enquanto os efeitos do tratamento foram monitorados em diferentes hospitais públicos e privados de Punjab, Paquistão. Total de 973 pacientes que administraram a dose recomendada foram divididos em dois grupos: (i) Terapia baseada em interferon, (ii) antivirais de ação direta (DAAs). Outros parâmetros como ALT e carga viral foram estudados. A taxa de recorrência foi maior em mulheres infectadas com o genótipo 2b e em homens com genótipo misto 3a / 2b após seis meses de terapia antiviral. O genótipo 3a mostrou resposta significativa à terapia após três meses. 32 entre 374 (8,5%) foram positivos após 24 semanas de tratamento com interferon, 29 (7,7%) pacientes têm o mesmo genótipo, enquanto 3 pacientes foram reinfectados com diferentes cepas de HCV. Com DAAs, apenas 27 (4,8%) pacientes foram positivos entre 558 após duas semanas e um paciente reinfectado com genótipo diferente. Resposta virológica precoce e sustentada observada em DAAs. ALT e carga viral diminuíram mais rapidamente com DAAs, que não alcançou após 4 semanas com interferon peguilado. A resposta virológica sustentada aparece em DAAs, e a taxa de recorrência é alta na terapia com interferon em comparação com DAAs. Portanto, a reinfecção tem implicações para a eficiência do tratamento correto e para selecionar estratégias para casos de retratamento.

Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model / 中华肝脏病杂志

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Drug selection for simultaneous treatment of tuberculosis combined with hepatitis C virus infection / 中华肝脏病杂志

Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.

Occurrence and recurrence of hepatitis C-related hepatocellular carcinoma after direct antiviral treatment / 中华肝脏病杂志

Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.

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)

Avaliação audiológica em pacientes com hepatite C crônica tratados por antivirais de ação direta / Audiological evaluation in patients with chronic hepatitis C treated by direct-action antivirals

RESUMO Objetivo Verificar se o tratamento com os antivirais de ação direta para a hepatite C provocam efeitos adversos na audição. Métodos A casuística foi composta por 16 indivíduos portadores do vírus da hepatite C, de ambos os gêneros, com média de idade de 51 anos. Foram excluídos do grupo indivíduos com perda auditiva do tipo condutiva ou mista e que apresentassem fatores de risco para perda auditiva. A avaliação foi realizada em dois momentos: antes do uso dos antivirais de ação direta e após o término do tratamento de três meses. Incluiu os seguintes procedimentos: anamnese, inspeção do meato acústico externo, audiometria tonal liminar, limiar de recepção de fala, índice de reconhecimento de fala, medidas de imitância acústica e emissões otoacústicas evocadas por estímulo transiente e produto de distorção. Resultados: Houve baixa ocorrência de zumbido e vertigem. Não houve diferença estatisticamente significativa entre os resultados da avaliação pré-tratamento e pós-tratamento. Conclusão O tratamento com antivirais de ação direta contra o vírus da hepatite C não provocou efeitos adversos na função auditiva.

ABSTRACT Purpose To verify whether treatment with hepatitis C direct-acting antivirals has adverse effects on hearing. Methods The sample consisted of 16 individuals with hepatitis C virus, of both sexes, with an average age of 51 years. Individuals with conductive or mixed hearing loss who presented risk factors for hearing loss were excluded from the group. The evaluation was carried out in two moments: before the use of direct-acting antivirals and after the three-month treatment. It included the following procedures: anamnesis, external auditory canal inspection, pure tone audiometry, speech reception threshold, speech recognition index, acoustic immittance measures and transient and distortion product otoacoustic emissions. Results There was a low incidence of tinnitus and vertigo. There was no statistically significant difference between the results of the pre- and post-treatment assessment. Conclusion The treatment with direct-acting antivirals against the hepatitis C virus did not cause any adverse effects on hearing function.

Tratamento farmacológico para Hepatite C: a incorporação dos antivirais de ação direta pelo Sistema Único de Saúde de 2012 a 2021 / Pharmacological treatment for Hepatitis C: the incorporation of direct-acting by the Unified Health System from 2012 to 2021

A erradicação do vírus da hepatite C (HCV), por meio de tratamento farmacológico, é a única intervenção que pode deter a progressão dessa doença. Os antivirais de ação direta (AAD) de segunda geração respondem por altas taxas de cura em terapias seguras e totalmente orais. No Brasil, diferentes AAD vêm sendo ofertados no Sistema Único de Saúde (SUS), a partir das recomendações da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde (CONITEC) e mediante critérios de inclusão do Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para hepatite C. Essa dissertação tem como objetivo analisar a dinâmica de incorporação e a efetividade da oferta dos AAD para tratamento da hepatite C no SUS, de 2012 a 2021. Foram realizadas análises documentais dos relatórios de recomendação da CONITEC e das atualizações de PCDT, além de busca nos bancos de dados do Ministério da Saúde sobre compras federais e sobre a dispensação dos medicamentos incorporados na produção ambulatorial do SUS. Dez tratamentos antivirais, compreendendo quinze AAD, foram incorporados ao SUS e, dentre eles, quatro tratamentos antivirais foram posteriormente excluídos no período estudado. Os AAD foram rapidamente demandados à CONITEC para análise de incorporação logo após seus registros na Agência Nacional de Vigilância Sanitária (ANVISA), sendo todos de comercialização global recente e com pouca experiência acumulada de uso. O tempo de conclusão do processo administrativo da CONITEC foi sempre inferior ao prazo máximo legal, com tempo de consulta pública abreviado algumas vezes e sem audiência pública. Essa celeridade, entretanto, esbarra no intervalo entre a incorporação dos AAD e a primeira dispensação no SUS, com média de tempo maior que o prazo legal para a oferta na rede de atenção. Em diversas situações, atrasos na primeira compra pública regular efetuada pelo Ministério da Saúde contribuíram para esses prazos. Incorporada em 2018 e presente no PCDT vigente, a associação elbasvir/grazoprevir não possui registros de compra ou dispensação, conferindo uma situação em que as alternativas terapêuticas permanecem incorporadas e poderiam participar de futuras negociações de preço, conforme critérios de custo-minimização ou de simplificação do tratamento por capacidade pangenotípica. Sinaliza-se que a dinâmica de incorporação e exclusão dos AAD, embora baseada em critérios científicos, pode admitir outras interferências, sejam financeiras ou políticas. O tratamento tornou-se mais simples a partir dos tratamentos pangenotípicos e o país pôde passar a dispensar os AAD na rede de atenção primária, com vistas a melhorar questões de acesso universal ao tratamento.

Eradication of hepatitis C virus (HCV) through pharmacological treatment is the only intervention that can halt the progression of hepatitis C. Second-generation direct-acting antivirals (DAA) account for high cure rates in safe therapies and fully oral. In Brazil, different DAA have been offered in the Unified Health System (SUS), based on the recommendations of the National Commission for the Incorporation of Technologies in the Unified Health System (CONITEC) and through the inclusion criteria of the Clinical Protocol and Therapeutic Guidelines (PCDT) for hepatitis C. This dissertation aims to analyze the dynamics of incorporation and the effectiveness of the offer of DAA for the treatment of hepatitis C in the SUS, from 2012 to 2021. Documentary analyzes of the CONITEC recommendation reports and the PCDT updates were carried out, in addition to a search in the Ministry of Health databases on federal purchases and on the dispensing of medicines incorporated in he SUS outpatient production. Ten antiviral treatments, comprising fifteen DAA, were incorporated into the SUS and, among them, four antiviral treatments were excluded during the study period. The DAA were quickly requested to CONITEC for analysis of incorporation soon after their registration with the National Agency for Sanitary Surveillance (ANVISA), all of them being very recent global marketing and with little accumulated experience of use. The time taken to complete the CONITEC administrative process was always shorter than the maximum legal deadline, with public consultation time shortened a few times and without a public hearing. This speed, however, comes up against the interval between the incorporation of the DAA and the first dispensation in the SUS, with an average time longer than the legal deadline for offering them in the care network. In several situations, delays in the first regular public purchase made by the Ministry of Health contributed to these deadlines. Incorporated in 2018 and present in the current PCDT, the elbasvir/grazoprevir association does not have purchase or dispensing records, giving a situation in which therapeutic alternatives remain incorporated and could participate in future price negotiations, according to cost-minimization or simplification criteria of treatment by pangenotypic capacity. It is pointed out that the dynamics of incorporation and exclusion of DAA, although based on scientific criteria, can admit other interferences, whether financial or political. Treatment became simpler with pangenotypic treatments and the country was able to start to dispense DAA in the primary care network, improving universal access to treatment.

Simplified treatment of hepatitis C: another strategy to overcome the barriers to its elimination / Tratamiento simplificado de la hepatitis C: otra estrategia para superar las barreras hacia su eliminación

Abstract The clinical management of hepatitis C virus (HCV) infection presents several challenges today. WHO's goal is to eliminate it by 2030. It is an ambitious goal and difficult to meet given the barriers to care that arise. This is possible today thanks to the discovery of direct-acting antivirals (DAAs). This treatment achieves a high cure rate and is virtually free of adverse effects. To try to comply with this, in addition to the use of DAAs, it is necessary to reduce the rate of undiagnosed patients and facilitate the access of those diagnosed to care and treatment. For that, it is proposed to carry out a simplified treatment of HCV. This involves reducing controls during and after treatment. This simplification varies according to whether patients have cirrhosis or not. In this way, it seeks to increase significantly the number of patients treated and cured to reduce the burden on public health of this disease.

Resumen El manejo clínico de la infección por el virus la hepatitis C (HCV) presenta varios desafíos en la actualidad. El objetivo de la OMS es eliminarlo para el 2030. Es un objetivo ambicioso y muy difícil de cumplir dadas las barreras al cuidado que se presentan. Sin embargo, esto es posible hoy gracias al descubrimiento de los antivirales de acción directa (AAD). Este tratamiento logra una alta tasa de curación y prácticamente está libre de efectos adversos. Para tratar de cumplirlo, además del uso de los AAD, es nece sario reducir la tasa de pacientes no diagnosticados y facilitar el acceso de los diagnosticados al cuidado y el tratamiento. Para eso se propone llevar adelante el tratamiento simplificado del HCV. Esto implica reducir los controles durante y después del tratamiento. Esta simplificación varía según los pacientes tengan o no cirrosis. De esta manera se busca aumentar significativamente el número de pacientes tratados y curados para así poder reducir el impacto en la salud pública de esta enfermedad.

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.

Tratamiento de la hepatitis C en el conurbano de Buenos Aires / Hepatitis C treatment in the surrounding area of Buenos Aires

Resumen La principal infección viral transmisible por sangre es actualmente la debida al virus de hepatitis C (VHC). Uno de los mayores obstáculos para el logro de su control en la Argentina se relaciona con las dificultades de acceso al diagnóstico y tratamiento oportuno de las personas infectadas. Este estudio se realizó con el objetivo de caracterizar a los pacientes infectados con VHC que iniciaron tratamiento con antivirales de acción directa (AAD) y describir la experiencia vinculada al tratamiento. Se seleccionaron las historias clínicas de 82 pacientes, 44 (53.7%) de sexo masculino, 37 (45.1%) de sexo femenino, y uno (1.2%) transgénero. La media de edad fue de 49 años. Se halló una frecuencia de cirrosis de 39%, 32 pacientes, coinfección con HIV en 48 (58.5%) y con VHB en 27 (32.9%). En 52 (63.4%) no se observó ningún factor de riesgo claramente asociado a infección. Todos completaron la terapia, de ellos 72 (87.8%) efectuaron el control para confirmar respuesta viral sostenida (RVS), que fue de 98.6%. Concluimos que el testeo universal debe implementarse por sobre el testeo con enfoque de riesgo, y que debe promoverse un criterio de atención simplificado y descentralizado, reservando la atención especializada para pacientes con cirrosis descompensada y cáncer de hígado.

Abstract Hepatitis C virus (HCV) infection is currently the main blood-borne viral infection. One of the main obstacles to achieving its control in Argentina is related to difficulties in accessing the diagnosis and timely treatment of infected people. We carried out this study with the aim of characterizing the HCV-infected patients who started treatment with direct-acting antivirals (DAAs) and to describe the experience related to treatment. The medical records of 82 patients, 44 (53.7%) male, 37 (45.1%) female, and one (1.2%) transgender, were selected. The mean age was 49 years. We report a frequency of cirrhosis, 39%, in 32 patients, coinfection with HIV in 48 (58.5%) and with HBV in 27 (32.9%). In 52 patients (63.4%), no risk factor clearly associated with infection was observed. All completed the therapy, of them 72 (87.8%) carried out the control to confirm sustained viral response (SVR), that attained 98.6%. We conclude that universal testing should be implemented over testing based on a risk approach, and that a simplified and decentralized care criterion should be promoted, reserving specialized care for patients with decompensated cirrhosis and liver cancer.

The Current Status and Research Progress of Antiviral Therapy in HCV-Associated Lymphoma --Review / 中国实验血液学杂志

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. HCV is not only related to hepatic malignancies but may also promote lymphoid neoplasms. Currently, research has confirmed HCV-related lymphoma, including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL). Many types of research have shown that antiviral therapy can improve or even remission several HCV-related lymphomas. The direct-acting antiviral agents (DAAs) (such as NS5A protease inhibitors, NS4/4A protease inhibitors and viral polymerase inhibitors) have shown clinical advantages of high efficacy and low side effects for both virus elimination and tumor regression in several HCV-related lymphomas, which may make the selected HCV-related lymphoma patients treated without chemotherapy. In this review the research progress and development direction of antiviral therapy in treating HCV-related lymphoma has summarized briefly.

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.

Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Respuesta virológica sostenida en pacientes con hepatitis C crónica, tratados con antivirales de acción directa: un estudio retrospectivo en Costa Rica / Sustained virological response in patients with chronic hepatitis C treated with direct acting antivirals, a retrospective study from Costa Rica

Resumen Introducción: Costa Rica es un país con un sistema de salud pública que ha permitido detectar oportunamente a los pacientes con hepatitis C, y ofrecer un tratamiento con base en antivirales de acción directa (AAD) de última generación. No obstante, no se han publicado estudios que evalúen la respuesta de la población costarricense a estos fármacos. Objetivo: Describir la efectividad clínica del tratamiento con AAD en una cohorte tratada en la Caja Costarricense de Seguro Social (CCSS). Materiales y métodos: Estudio retrospectivo de los expedientes clínicos de los pacientes tratados con sofosbuvir / ledipasvir, sofosbuvir / velpatasvir y ombitasvir / paritaprevir / ritonavir / dasabuvir, en tres hospitales nacionales para adultos de la CCSS, en 2017 - 2018. Se recolectaron variables epidemiológicas, clínicas y analíticas, y se compararon los resultados pre y postintervención. Resultados: Se reclutaron 139 pacientes; 22 fueron excluidos porque no cumplían los criterios. El análisis se realizó con 117 pacientes, de los cuales 101 tenían viremia documentada para determinación de la respuesta virológica sostenida (RVS). La mayoría de los pacientes fue costarricense, nacida en 1945 - 1965, con factores de riesgo para hepatitis C no documentados, sin cirrosis e infectada por el genotipo 1b. La RVS general de la población estudiada fue del 98 %, sin notarse diferencia significativa entre pacientes cirróticos (94 %) y no cirróticos (100 %). Hubo una reducción significativa (p < 0,01) en: El índice de aspartato-aminotransferasa: número de plaquetas (APRI), el puntaje del Modelo para Enfermedad Hepática Terminal (MELD), la alaninoaminotransferase (ALT) y la bilirrubina total, para los pacientes tratados con AAD. Conclusión: Los antivirales de acción directa fueron efectivos en la población tratada en Costa Rica, con respuesta viral sostenida similar a aquella reportada en otros ensayos de vida real.

Abstract Introduction: Costa Rica has a public healthcare system that made possible the detection of hepatitis C (HCV) infected patients and offer them treatment with last-generation direct-acting antivirals (DAA). Nonetheless, there has not been any published studies that evaluate the response of the Costa Rican population to these drugs. Aim: To describe the clinical effectiveness of direct acting antiviral treatment in a cohort treated in the Social Security Care from Costa Rica (CCSS). Materials and Methods: Retrospective review of clinical records of all patients who were treated with: sofosbuvir/ledipasvir, sofosbuvir/velpatasvir and ombitasvir/paritaprevir/ritonavir/dasabuvir in three national adult hospitals from between 2017-2018. Epidemiological, clinical and laboratory data were collected, and pre- and post- treatment results were compared. Results: 139 patients were recruited, 22 were excluded because they did not fulfill the inclusión criteria. The analysis was made with 117 patients; from which 101 had their viremia documented in their records for the determination of sustained virological response (SVR). The majority of patients were Costa Ricans born between 1945-1965, whose risk factors for hepatitis C were not documented, with a non-cirrhotic, genotype 1b infection. Overall SVR was 98%. There was not a significant difference of response between cirrhotic (94%) and non-cirrhotic population (100%). There was a significant reduction (p< 0,01) in: Aspartate Aminotranferase to Platelet Ratio Index (APRI), the score of the Model for End-Stage Liver Disease (MELD), Alanine Aminotransferase (ALT) and total bilirubin in patients treated with DAA. Conclusion: The direct acting antivirals were effective in population treated in our country, with SVR similar to those reported in real life studies from other regions of the world.

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.

Clinical and epidemiological profile of HCV genotype 3 patients in southern Brazil

Introduction: Despite the emergence of new treatments for HCV genotype 3 (HCV G3), there is still a lack of data about this particular subgroup in Brazil. Our objective was to describe clinical and sociodemographic variables and treatment profile of HCV G3 Brazilian patients. Methods: This was a descriptive, retrospective study, performed in a specialized center for HCV treatment in the South Region of Brazil. Medical records of patients diagnosed with HCV G3 were reviewed to collect clinical, sociodemographic, and treatment information. Results: Participants included total of 564 patients, with a mean age of 59.3 years (SD = 10.5). Cirrhosis was present in 54.4% of patients. The most common coexisting conditions were systemic arterial hypertension (36.6%) and diabetes mellitus (30%). Regarding treatment, 25.2% of the patients were treatment-naïve and 74.8% were currently under treatment (11.6%) or had received a previous treatment (87%). The most frequent ongoing treatment was sofosbuvir + daclatasvir (± ribavirin) (87.8%). Of the 388 patients who had at least one previous treatment, 67% achieved sustained virologic response in the last treatment. Caucasian / white, non-obese, transplanted patients, those with longer time since diagnosis and with cirrhosis were more likely to receive treatment, according to multivariate analysis. Patients with hepatocellular carcinoma were 64.1% less likely to be on treatment during the study period than those without this condition; patients with chronic kidney disease were 2.91-fold more likely to have an interruption of treatment than those without this condition. Conclusion: This study describes a large sample of Brazilian patients with HCV G3. Treatment patterns were mainly influenced by the presence of HCV complications and comorbidities.(AU)

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.