Una visión integral del manejo de la hepatitis C y el objetivo de erradicarla / A comprehensive view of hepatitis C management and the goal of eradication

La hepatitis C es una enfermedad viral causada por el virus de la hepatitis C (VHC), que fue identificada por primera vez en 1989 por un equipo de científicos liderado por Michael Houghton en Chiron Corporation. Esta forma de hepatitis era conocida como "hepatitis no-A no-B", ya que no se podía identificar el agente infeccioso responsable. Puede afectar a personas de diferentes géneros y orientaciones sexuales, incluidos los hombres que tienen sexo con hombres (HSH); y su transmisión ocurre a través de situaciones en las que hay un intercambio de sangre, como el uso compartido de agujas o equipo para la inyección de drogas, o durante prácticas sexuales que pueden causar microlesiones en la mucosa anal. Es importante destacar que la hepatitis C también puede transmitirse a través de otras vías, como la transfusión de sangre no segura, la exposición a instrumentos médicos contaminados, o el compartir objetos personales que puedan tener sangre infectada.

Hepatitis C is a viral disease caused by the hepatitis C virus (HCV), which was first identified in 1989 by a team of scientists led by Michael Houghton at Chiron Corporation. This form of hepatitis was known as "non-A non-B hepatitis" as the infectious agent responsible couldn't be identified. It can affect individuals of different genders and sexual orientations, including men who have sex with men (MSM); transmission occurs through situations involving blood exchange, such as needle sharing or equipment for drug injection, or during sexual practices that may cause microlesions in the anal mucosa. It's important to note that hepatitis C can also be transmitted through other routes, such as unsafe blood transfusion, exposure to contaminated medical instruments, or sharing personal items that may have infected blood.

Antivirales de acción directa contra la hepatitis C: revisión narrativa / Direct acting antivirals against hepatitis C: Literature review

Desde los años ochenta se ha explorado el tratamiento para el virus de la hepatitis C, aunque en ese entonces los medicamentos disponibles eran poco toleradas y poco eficaces. En el 2011, la introducción de antivirales de acción directa transformó significativamente el curso de la enfermedad, logrando tasas de curación superiores al 90 % en los pacientes. Este avance ha permitido prevenir complicaciones futuras con efectos adversos mínimos. La presente revisión aborda la línea de tiempo del descubrimiento de los antivirales, su mecanismo de acción, sus indicaciones y potencial impacto en la salud pública.

Since the 1980s, the treatment of hepatitis C has been explored, although at that time, the available medications were poorly tolerated and ineffective. In 2011, the introduction of direct-acting antivirals significantly transformed the course of the disease, achieving cure rates of over 90% in patients. This advance has made it possible to prevent future complications with minimal adverse effects. This review addresses the timeline of the discovery of antivirals, their mechanism of action, and their impact on medicine.

Effect of Direct-acting Antivirals Treatment on Renal Function Among HCV-infected Patients / 中山大学学报(医学科学版)

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

Células supressoras mieloides derivadas dois anos após a erradicação do vírus da hepatite C usando antivirais de ação direta / Myeloid-derived suppressor cells two years after hepatitis c virus eradication using directly acting antivirals

ABSTRACT Background: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. Objective: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. Methods: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. Results: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001). Conclusion: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.

RESUMO Contexto: As células supressoras derivadas de mieloides (CSDMs) possuem morfologia imatura, atividade fagocítica relativamente fraca e algumas funções imunossupressoras. A capacidade das CSDMs de inibir respostas imunológicas mediadas por células T é sua característica funcional mais notável. A expansão e ativação das CSDMs contribuem significativamente para a ocorrência e progressão de tumores, regulando negativamente a vigilância imunológica antitumoral. Níveis aumentados de CSDMs em pacientes com infecção crônica pelo vírus da hepatite C (HCV) poderiam suprimir respostas das células T, promovendo a fuga viral e a progressão da hepatite. Isso pode tornar os indivíduos infectados pelo HCV mais vulneráveis a infecções graves, tumores hepáticos e extra-hepáticos, e a uma capacidade diminuída de reagir à imunização. Ainda não se sabe se a erradicação eficaz do HCV com antivirais de ação direta (AAD) pode restaurar as funções imunológicas e a capacidade de vigilância imunológica. Objetivo: O objetivo deste estudo foi observar a frequência de M-CSDMs (CD33+, CD11b+ e HLA-DR-) em pacientes com histórico anterior de HCV, 2-3 anos após a erradicação do vírus usando terapia com AADs. Métodos: Este estudo foi realizado em 110 indivíduos: 55 indivíduos sem cirrose hepática que foram tratados com AADs para HCV e atingiram resposta virológica sustentada (SVR) por um período de 2-3 anos e 55 controles saudáveis pareados por idade e gênero. O estudo foi conduzido no período de janeiro a julho de 2022. Os pacientes foram recrutados da Unidade Nacional de Tratamento de Hepatites Virais, da clínica ambulatorial de Hepatologia da Universidade de Alexandria e da clínica ambulatorial de Medicina Tropical da Universidade de Alexandria. As frequências de CSDMs (CD33+CD11b+HLA-DR-) foram avaliadas por citometria de fluxo. Resultados: Mesmo após a erradicação do vírus por mais de dois anos, os níveis de CSDMs em indivíduos tratados para HCV foram consideravelmente mais altos. No grupo tratado para HCV, o número mediano de CSDMs foi de 5, com um intervalo interquartil (IQR) de 3,79-7,69. Em contraste, a mediana para o grupo controle foi de 3,1, com um IQR de 1,4-3,2 (P<0,001). Conclusão: A terapia bem-sucedida com AADs leva a uma reconstituição imunológica lenta e parcial, como demonstrado pela falha em atingir níveis normais de CSDMs 2 anos após a erradicação bem-sucedida do HCV, apesar da normalização dos parâmetros laboratoriais e da ausência de fibrose hepática. As implicações clínicas desses achados devem ser estudadas minuciosamente.

Sofosbuvir más glecaprevir/pibrentasvir como terapia de rescate postrasplante hepático en pacientes con exposición previa a inhibidores de NS5A. Serie de casos / Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series

Resumen Antecedentes: El tratamiento de la infección crónica por el virus de la hepatitis C (VHC) con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). Objetivo: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). Material y métodos: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. Resultados: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. Conclusión: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.

Abstract Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rates higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. Objective: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. Material and methods: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. Results: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. Conclusion: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.

Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism

ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.

An Update on the Pharmacological Aspects of Vaccines and Antivirals for the Management of Monkeypox

Monkeypox is a self-limiting zoonotic disease caused by the monkeypox virus belonging to the genus of orthopox viruses. Initially considered an ‘African disease’, this infection has crossed the boundaries to affect other continents and it has raised tremendous concerns among the general public as well as the medical fraternity all over the world, particularly because of the lack of specific vaccinations and drugs for the management of the illness. Epidemiological evaluation of the current infection has reported that it is mainly transmitted through sexual contact in bisexual men, mostly whites, and in those with pre-existing human immunodeficiency virus infection. The most common presentations were skin rash, anogenital lesions, or mucosal lesions along with systemic symptoms. It has been established that the vaccines and drugs approved for the management of smallpox could be used for the management of the current monkeypox outbreak. Vaccinia Immune Globulin (VIG) and vaccines like JYNNEOS and ACAM2000 and antiviral drugs like tecovirimat, cidofovir (CDV), and brincidofovir are being considered for those patients with serious diseases. It is imperative for physicians to understand the pharmacological aspects of these drugs for delivering better care to patients with monkeypox, which is eventually essential for the containment of this infection. This review covers updates on vaccines as well as drugs for the prevention and management of monkeypox.

Management of Hepatitis C in Children – A New Paradigm

Introduction: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. Methods: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0-18 years, and the English language. Results: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. Conclusion: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India.

Key points in hepatitis C guidance 2023 update： American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing， managing， and treating hepatitis C virus infection / 临床肝胆病杂志

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis， management， and treatment of hepatitis C virus （HCV） infection since 2013. A panel of clinicians and investigators with extensive expertise in infectious diseases or hepatology specific to HCV infection periodically reviews related evidence and update existing recommendations or introduce new recommendations based on such evidence. This update focuses on the changes to the guidance since the update in 2020， including recommendations for extensive universal screening， simplified treatment and testing regimens， treatment of poor compliance， and management of unique and key populations such as children aged <3 years and patients undergoing transplantation.

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.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan

Abstract 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.

RESUMO 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.

Terapia antiviral de acción directa para infección del virus de hepatitis C en pacientes en hemodiálisis

Introducción: La infección por el virus C de la hepatitis resulta común en pacientes en hemodiálisis y se considera endémica en estas unidades. El tratamiento utilizado lo componían el interferón pegilado y la ribavirina, combinación que presentaba niveles de toxicidad y baja respuesta. Las drogas actuales aportan mejores resultados. Objetivos: Determinar la eficacia y seguridad de la terapia antiviral de acción directa para la infección del virus de la hepatitis C en pacientes con insuficiencia renal crónica en hemodiálisis. Métodos: Estudio descriptivo prospectivo en 19 pacientes en régimen de hemodiálisis y con infección por virus C, pertenecientes al Hospital General Docente "Dr. Mario Muñoz Monroy", desde diciembre de 2020 hasta septiembre de 2021," A todos se les prescribió durante 12 semanas Sofosbuvir® 400 mg más Daclatasvir® 60 mg diarios. Se caracterizaron las variables edad, sexo, fibrosis hepática por el índice aspartato-aminotransferasa/plaquetas, reacciones adversas y respuesta viral 12 semanas después del tratamiento. Resultados: La infección predominó en el grupo de 51 a 60 años (36,84 %). La mayoría de los pacientes mostró un índice aspartato-aminotransferasa/plaquetas ≤ 0,5, lo que correspondió con ausencia de fibrosis hepática significativa (14 pacientes). Una minoría de pacientes registró reacciones adversas. No se demostró toxicidad cardiovascular ni hepática. La totalidad de los pacientes manifestaron carga viral no detectable 12 semanas después del tratamiento. Conclusiones: La combinación de Sofosbuvir® con Daclatasvir® para el tratamiento de la infección por virus de la hepatitis C en pacientes con insuficiencia renal crónica en tratamiento de hemodiálisis resultó eficaz, bien tolerada y segura.

Introduction: Hepatitis C virus infection is common in hemodialysis patients and is considered endemic in these units. The treatment used consisted of pegylated interferon and ribavirin, a combination that presented levels of toxicity and low response. Current drugs bring better results. Objectives: To determine the efficacy and safety of direct-acting antiviral therapy for hepatitis C virus infection in patients with chronic renal failure on hemodialysis. Methods: Prospective descriptive study in 19 patients on hemodialysis and with virus C infection, belonging to "Dr. Mario Muñoz Monroy" Teaching General Hospital, from December 2020 to September 2021. All were prescribed for 12 weeks with Sofosbuvir® 400 mg plus Daclatasvir® 60 mg daily. The variables age, sex, liver fibrosis were characterized by the aspartate aminotransferase/platelet index, adverse reactions and viral response 12 weeks after treatment. Results: Infection predominated in the group of 51 to 60 years (36.84%). Most patients showed an aspartate aminotransferase/platelet ratio ≤ 0.5, corresponding to the absence of significant liver fibrosis (14 patients). A minority of patients reported adverse reactions. No cardiovascular or hepatic toxicity was demonstrated. All patients had an undetectable viral load 12 weeks after treatment. Conclusions: The combination of Sofosbuvir® with Daclatasvir® for the treatment of hepatitis C virus infection in patients with chronic renal failure undergoing hemodialysis was effective, well tolerated and safe.

Reinfección por virus de la hepatitis C: revisión de tema y presentación de un caso / Hepatitis C virus reinfection: A review of the topic and case report

Resumen La infección crónica por el virus de la hepatitis C (VHC) afecta a 58 millones de personas y es una importante causa de morbimortalidad alrededor del mundo. La reinfección por VHC es un problema creciente en personas con factores de riesgo como consumo pesado de alcohol, sexo anal, sexo grupal y compartir agujas y jeringas; este tipo de infección se define como un nuevo contagio de VHC con un genotipo viral diferente al de la primera infección en un paciente luego de lograr una respuesta viral sostenida (RVS). La reinfección se presenta, en parte, debido a la ausencia de estrategias de promoción y prevención. Teniendo en cuenta estos antecedentes, se han propuesto estrategias más pragmáticas para controlar la infección por VHC y evitar la reinfección, tales como la microeliminación. En el presente artículo se presenta un caso de un paciente que presenta alteración en los marcadores de la bioquímica hepática, por lo que se solicita una prueba diagnóstica de infección por VHC y luego genotipificación viral, y se evidenció una infección por VHC genotipo 1, subgenotipo 1A. Se inició el manejo con antivirales de acción directa y se documentó una adecuada RVS12. Tres meses después el paciente regresó a consulta y en los exámenes de control se evidenció una carga viral elevada de VHC, por lo que se solicitó genotipificación y se demostró una nueva infección por VHC genotipo 4.

Abstract Chronic hepatitis C (HCV) infection affects 58 million people and is a significant cause of morbidity and mortality worldwide. HCV reinfection is a growing problem in people with risk factors such as heavy alcohol use, anal sex, group sex, and sharing needles and syringes. This type of infection is defined as a new HCV infection with a different viral genotype than the first infection in a patient after achieving a sustained viral response (SVR). Reinfection occurs, in part, due to the absence of promotion and prevention strategies. Taking this background into account, more pragmatic approaches have been proposed to control HCV infection and avoid reinfection, such as micro elimination. This article reports the case of a patient with alterations in biochemical liver markers, for which a diagnostic test for HCV infection and then viral genotyping was requested. Infection by HCV genotype 1, subgenotype 1A, was evidenced. Management with direct-acting antivirals was started, and an adequate SVR12 was documented. Three months later, the patient returned, and the control tests showed a high HCV viral load, for which genotyping was requested, showing a new HCV genotype 4 infection.

Hepatitis C associated membranoproliferative glomerulonephritis treated with directly acting antivirals for hepatitis C

Hepatitis C virus (HCV) infection affects kidneys with different histopathological patterns on kidney biopsy, which commonly include membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy and small to medium vessel vasculitis. Type 1 MPGN associated with type II mixed CG is the most common glomerulopathy associated with hepatitis C infection. Treatment of these glomerulopathies and cryoglobulinemic renal disease associatedwith HCV infection includes antiviral therapy for HCV, B-cell depletion therapy for prevention of immune complexes and cryoglobulins or nonspecific immunosuppressive therapy. We describe a patient who presented to us with HCV associated MPGN type 1 with cryogloblinemia and detectable HCV RNA, who recovered completely with directly acting antiviral agents (DAA) alone without immunosuppression.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience / Infecção por SARS-CoV-2 em receptores de transplante renal: impacto clínico e outcomes - uma experiência de centro único

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

Interacciones farmacológicas entre antivirales y plantas medicinales / Pharmacological interactions between antivirals and medicinal plants

Resumen: Objetivo: Identificar las plantas medicinales que presentan interacciones farmacológicas con los fármacos antivirales. Materiales y métodos: Se realizó una revisión bibliográfica mediante la recolección de artículos en las bases de datos PubMed, Scielo, Google académico. Se recuperó información de cada una de las plantas estudiadas hasta mayo de 2018. Se confeccionó una ficha instructiva a partir de la información obtenida, se tuvo en cuenta su utilidad y actualidad. Resultados: El 57.9% de la información fue recuperada de Google académico. El 47.9% del total de estudios revisados se referían a estudios clínicos y el 27% fueron investigaciones realizadas en Cuba. Allium sativum L. (19.7%), Hypericum perforatum (7.8%) y Panax quinquefolius (7.6%) fueron las plantas que presentaron mayor número de estudios concernientes a interacciones con antivirales. Las acciones sobre el citocromo P450 y la glicoproteína-P fueron las principales responsables de la ocurrencia de interacciones entre las plantas medicinales y los antivirales. La curcumina metabolito secundario de la Curcuma longa L. mostró potencial actividad antiviral ante virus de inmunodeficiencia humana tipo 1 sin obtenerse resultados concluyentes. Conclusiones: Podemos concluir que a pesar de que las interacciones farmacológicas entre antivirales y plantas medicinales son escasas, cuando se presentan lo hacen, en su mayoría, en forma de alteraciones farmacocinéticas. Los antirretrovirales fueron los fármacos de este grupo más involucrados en interacciones con plantas de uso común como el ajo. Los resultados encontrados fueron contradictorios en ocasiones y no todos estaban basados en evidencias clínicas.

Abstract: Objective: To identify medicinal plants that show pharmacological interactions with antiviral drugs. Materials and methods: A literature review carried out through the collection of articles in the PubMed, Scielo, Google academic databases. Information retrieved from each of the plants studied up to May 2018. An information sheet was prepared based on the information obtained and taking into account its usefulness and topicality. Results: 57.9% of the information was retrieved from academic Google. 47.9% of the total studies reviewed referred to clinical studies and 27% were investigations carried out in Cuba. Allium sativum L. (19.7%), Hypericum perforatum (7.8%) and Panax quinquefolius (7.6%) were the plants that presented the highest number of studies concerning interactions with antivirals. Actions on cytochrome P450 and P-glycoprotein were mainly responsible for the occurrence of interactions between medicinal plants and antivirals. The secondary metabolite curcumin of Curcuma longa L. showed potential antiviral activity against human immunodeficiency virus type 1 without obtaining conclusive results. Conclusions: We can conclude that although the interactions between antivirals and medicinal plants are rather rare when they occur, they do so mostly in the form of pharmacokinetic alterations. Antiretroviral drugs are the drugs of this group most involved in interactions with commonly used plants such as garlic. The results found are not all base on clinical evidence and sometime they were contradictories.

Hepatitis & Nanomedicine: A Review

In the year 1989, hepatitis C virus (HCV) was specifically established as causative factor accountable for many more occurrences of hepatitis. It's a chronic disease which majorly contributes to Carcinoma and Cirrhosis. The hepatitis C virus belongs a family Flaviviridae (+) enveloped ssRNA virus. It has been described that seven major genotypes of HCV and their subtypes (a, b). Around 3 percent among global residents has been infected by HCV. HCV Transmission is frequently associated with direct percutaneous blood contact, via blood transfusions, health-related injections and substance use injections. Several new therapies have been developed to treat HCV, such as polyethylene glycol (PEG)-ylated interferon / ribavirin, antivirals acting directly and antivirals targeting the host. Despite progress in anti-HCV therapy, there is still an urgent need for new approaches of targeted drug delivery systems using nanomedicine which are affordable and reliable. Nanotechnology has the ability to play a pivotal role in lowering viral load levels and drug-resistant HCV by targeting drugs directly to the disease site. In addition to tissue targeting, a wide variety of drugs need to be administered intracellularly to achieve a therapeutic effect in the organ affected. The contribution of nanoparticles as a promising delivery mechanism for HCV immunizing, diagnostic and therapeutic agents and there latest developments of drug carriers as well as their role in anti-HCV therapy were addressed in this review.

Primer reporte en Perú sobre terapia con antivirales de acción directa para hepatitis C crónica en pacientes VIH-positivos / First report in Peru on direct-acting antiviral therapy for chronic hepatitis C in HIV-positive patients

RESUMEN Objetivo : Presentar la experiencia clínica con antivirales de acción directa (AAD) para hepatitis C crónica en pacientes VIHpositivos. Materiales y métodos : Serie de casos longitudinal y prospectiva de pacientes VIH-positivos tratados con AAD para hepatitis C crónica entre mayo de 2019 y abril de 2020 en el Servicio de Infectología del Hospital Nacional Guillermo Almenara Irigoyen, EsSalud. El desenlace primario fue la respuesta viral sostenida del virus de hepatitis C (VHC) a las 12 semanas de completada la terapia con AAD. Los desenlaces secundarios fueron tolerabilidad y seguridad. Resultados : Diez pacientes fueron incluidos en el estudio, dos fueron mujeres (20%). Dos pacientes presentaron cirrosis (20%). La totalidad de los pacientes tuvo la carga viral del VIH suprimida antes de la terapia con AAD. Los pacientes recibieron un esquema de 12 semanas con base en sofosbuvir: uno con daclatasvir por separado, y los nueve restantes con velpatasvir combinados en una sola tableta por día. La respuesta viral sostenida del VHC fue evaluable en nueve casos. En estos, la carga viral del VHC fue no detectable. No se registraron ocurrencias en cuanto a tolerabilidad y seguridad durante la terapia con los AAD indicados. Conclusiones : La presente investigación es la primera experiencia clínica en Perú con AAD para hepatitis C crónica en pacientes VIH-positivos. La respuesta virológica, la tolerabilidad y la seguridad frente a daclatasvir y velpatasvir, cada uno junto o combinado con sofosbuvir, fueron óptimas en la serie de casos presentada.

ABSTRACT Objective : To present the clinical experience with direct-acting antivirals (DAAs) for chronic hepatitis C in HIV-positive patients. Materials and methods : Longitudinal and prospective case series of HIV-positive patients treated with DAAs for chronic hepatitis C between May 2019 and April 2020 at the Infectious Diseases Service of Hospital G. Almenara, EsSalud. The primary outcome was sustained virologic response to hepatitis C virus (HCV) 12 weeks after completion of DAA therapy. Secondary outcomes were tolerability and safety. Results : Ten patients were included in the study, two were women (20%). Two patients had cirrhosis (20%). All patients had suppressed HIV viral load prior to DAA therapy. Patients received a 12-week regimen based on sofosbuvir: one with daclatasvir separately, and the remaining nine with velpatasvir combined in a single tablet per day. The sustained virological response of HCV was evaluable nine cases. In these, the HCV viral load was undetectable. No occurrences were recorded regarding tolerability and safety during therapy with the indicated DAAs. Conclusions : This present investigation is the first clinical experience in Peru with DAAs for chronic hepatitis C in HIV-positive patients. Virologic response, tolerability, and safety against daclatasvir and velpatasvir, each in conjunction or in combination with sofosbuvir, were optimal in the case series presented.

Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy / 中华肝脏病杂志

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

Three regimens for re-treatment failure of Sofosbuvir-based therapy for chronic hepatitis-C genotype-4: a cohort study

ABSTRACT Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.