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.

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.

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma as the initial presentation in patients with hepatitis C virus infection

ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Management of hepatitis C in children and pregnant women / 临床肝胆病杂志

Hepatitis C virus infection is a global public health issue， and the emergence of direct-acting antiviral agents has brought revolutionary breakthroughs in the treatment of hepatitis C patients. Although direct-acting antiviral agents have a marked therapeutic effect in adult patients， there are still many challenges in the treatment of special populations such as pregnant women， infants， young children， and adolescents. This article reviews the current status of antiviral therapy for these special populations with hepatitis C and the problems that need to be solved， in order to provide reference and guidance for clinical workers.

Current status of hepatitis C virus infection and progress in its elimination in China / 临床肝胆病杂志

Hepatitis C virus （HCV） can develop into liver cirrhosis or hepatocellular carcinoma， imposing a heavy burden on the patient’s family and the society. Hepatitis C is one of the major public threats for humans， and eliminating hepatitis C is a common goal of all humans. Direct-acting antiviral agents （DAAs） are currently a relatively safe treatment regimen for hepatitis C that can reach a relatively high cure rate and can target different HCV genotypes， making it possible to eliminate HCV infection. China actively promotes the clinical application of DAAs， accelerates drug approval， improves the accessibility of DAAs， and strengthens population intervention. National Medical Insurance Administration has gradually included DAAs in the national medical insurance directory， providing strong support for eliminating HCV infection. In response to the WHO’s goal of eliminating viral hepatitis as a public health hazard by 2030， China has successively released national strategic plans and action plans in recent years， making significant achievements in HCV infection elimination， forming a joint prevention and control system across multiple sectors of the society， and ultimately achieving the goal of eliminating HCV infection. With a focus on the current status of HCV infection in China and prominent prevention and control strategies， this article analyzes and summarizes the practical process of the prevention， control， and micro-elimination of HCV infection， in order to provide a policy reference for carrying out HCV elimination in China and help to achieve the goal of comprehensive elimination of HCV infection.

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.

Effect of treatment with direct-acting antiviral agents on the prognosis of extrahepatic diseases in patients with hepatitis C / 临床肝胆病杂志

The prognosis of patients with hepatitis C virus infection depends not only on liver lesions， but also on extrahepatic sequelae. Direct-acting antiviral agents （DAAs）， as the first-line drugs in the treatment of hepatitis C， have helped more and more patients achieve sustained virologic response and clinical cure， but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure.

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

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

Regressão espontânea do carcinoma hepatocelular: foco nos fatores de risco associados / Spontaneous regression of hepatocellular carcinoma: focusing in the associated risk factors

ABSTRACT Background: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. Objective: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. Methods: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. Results: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. Conclusion: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

RESUMO Contexto: A evidência da regressão espontânea (RE) no carcinoma hepatocelular (CHC) é rara. Objetivo: Revisar todos os casos de RE de CHC em dois centros de referência do Sul do Brasil, destacando as principais características. Métodos: Os dados de todos os pacientes com CHC foram revisados retrospectivamente buscando a ocorrência de RE em pacientes de dois centros terciários do Sul do Brasil, nos últimos 5 anos. O diagnóstico de cirrose foi estabelecido de acordo com dados clínicos, laboratoriais e de imagem, além de endoscopia digestiva alta ou exame histopatológico quando necessário. O diagnóstico de CHC foi baseado em achados típicos de acordo com critérios radiológicos (LIRADS) ou exame histopatológico. A RE foi definida como uma involução parcial ou completa de um CHC na ausência de terapia específica. Resultados: Do total de casos de CHC nos últimos 5 anos (n=433), houve cinco casos de RE. Três (60%) eram homens, a média de idade foi de 62,6 (50,0-76,0) anos, a etiologia foi virus da hepatite C em 3 (60%). A regressão completa foi observada em três pacientes (60%), um paciente (20%) apresentou regressão parcial e um (20%) apresentou recidiva e evoluiu a óbito. O tempo de seguimento variou entre 12 e 21 meses. Nesta apresentação foi destacado um caso (20%) de RE observado após infecção por COVID-19 em paciente com cirrose. Foram revisados os possíveis mecanismos envolvidos nesta situação, enfatizando os mais comuns como hipóxia e imunológicos. Houve também um paciente submetido a procedimento cirúrgico como possível fator envolvido e três pacientes sem fatores de risco evidentes. Conclusão: Este fenômeno possivelmente contribuirá para uma melhor compreensão dos mecanismos fisiopatológicos do CHC.

Impact du traitement par les antiviraux à action directe sur la qualité de vie des patients atteints d'hépatite C à Cotonou / Impact of treatment with direct-acting antivirals on quality of life in hepatitis C patients in Cotonou

Introduction: L'altération de la qualité de vie est l'une des conséquences de l'infection chronique au virus de l'hépatite C. L'objectif de cette étude était d'évaluer l'impact du traitement par les antiviraux à action directe (AAD) sur la qualité de vie des patients atteints d'hépatite C à Cotonou. Méthodes : Il s'agissait d'une étude transversale descriptive et analytique, avec un recueil de données à la fois rétrospectif et prospectif sur une période de 5 ans allant du 1er décembre 2015 au 1er septembre 2020. Etaient inclus tous les patients atteints d'hépatite C traités par les AAD dans la Clinique Universitaire d'hépato-gastroentérologie du Centre National Hospitalier et Universitaire Hubert Koutoukou Maga (CNHU-HKM) de Cotonou. L'efficacité était évaluée par la réponse virologique soutenue (RVS) à 12 semaines après la fin du traitement. Le questionnaire SF-36 était utilisé pour évaluer la qualité de vie des patients atteints d'hépatite C, avant et après traitement. Résultats : Pendant la période d'étude, 206 patients ont été colligés. Ils étaient constitués de 33,5% d'hommes et 66,5 % de femmes, soit une sex-ratio de 0,5. La moyenne d'âge des patients était de 62,0 ± 1,7 ans (extrêmes de 18 et 87 ans). La charge virale moyenne en UI/ml était de 3.507.336,9 ± 1.156.443,98 (extrêmes de 3422 et 75.674.348 UI/ml). Le score SF-36 était statistiquement plus élevé pour tous les items après le traitement par AAD (p˂0,05). Conclusion: Les antiviraux à action directe constitue un traitement qui améliore significativement la qualité de vie des patients atteints d'hépatite C à Cotonou.

Background: Impaired quality of life is one of the consequences of chronic infection with the hepatitis C virus. The aim of this study was to assess the impact of treatment with direct-acting antivirals (DAAs) on quality of life in patients with hepatitis C in Cotonou. Methods: This was a descriptive and analytical cross-sectional study, with both retrospective and prospective data collection over a 5-year period from 1 December 2015 to 1 September 2020. All patients with hepatitis C treated with DAAs at the University Hepato-Gastroenterology Clinic of the National and University Hospital Hubert Koutoukou Maga (CNHU-HKM) in Cotonou were included. Efficacy was assessed by the sustained virological response (SVR) at 12 weeks after the end of treatment. The SF-36 questionnaire, the reference measurement instrument, was used to assess the quality of life of hepatitis C patients before and after treatment. Results: A total of 206 patients were enrolled during the study period. They comprised 33.5% men and 66.5% women, giving a sex ratio of 0.5. The mean age of the patients was 62.0 ± 1.7 years, (extremes 18 and 87 years). The mean viral load in IU/ml was 3,507,336.9 ± 1,156,443.98 (extremes 3,422 and 75,674,348 IU/ml). The SF-36 score was statistically significantly higher for all items after DAA treatment (p˂0.05). Conclusion: Direct-acting antivirals are a treatment that significantly improves the quality of life of hepatitis C patients in Cotonou.

Predominant amino acid substitutions in NS5B gene of hepatitis C virus in blood donors and treatment-naïve hepatitis and HIV patients in Nigeria

Background: Hepatitis C virus (HCV) genome undergoes high rate of mutation, which results in generation of genetically diverse HCV isolates. There is paucity of data on mutations in the nonstructural 5b (NS5b) gene of circulating HCV and their implications in the Nigerian population. Here, we identified clinically-important mutations in HCV isolates, which may influence response to therapy and disease prognosis. Methodology: HCV RNA was extracted from a total of 301 blood samples collected from 99 symptomatic treatment-naïve hepatitis patients, 125 HIV-infected individuals and 77 asymptomatic blood donors in Ibadan, Nigeria. The RNA was reverse­transcribed to complimentary DNA and HCV NS5B gene amplified by nested PCR. The amplified products of 42 HCV were sequenced and sequences were aligned with those from GenBank and HCV databases in MEGA 7.0. Nucleotide sequences were translated to amino acids while substitutions in the amino acids were analyzed with reference to H77 prototype strain of HCV. Results: A total of 10 amino acid polymorphisms were observed from the 42 sequenced NS5B gene, with the major clinically-important amino acid mutations being S15G in 28 (66.7%) participants, T7N (24, 57.1%), G61R (23, 54.8%), S54L (22, 52.4%), G89E (14, 33.3%), T79M (12, 28.6%), and T711 (11, 26.2%). Others were Q67R (7, 16.7%), Q47H (7, 16.7%) and S84F (2, 4.8%). S15G/A/V mutations were more predominant in patients with HIV (76.9%, 10/13) followed by patients with clinical hepatitis (75.0%, 12/16) and blood donors (46.1%, 6/13). Q67R and T71I mutations were not predominant in patients with clinical hepatitis as they were detected in only 31.3% (5/16) and 43.8% (7/16) participants respectively, compared to S15G (75.0%, 12/16), S54L (68.8%, 11/16), G61R/E (68.8%, 11/16) and T7N/S (56.3%, 9/16). There was no statistically significant difference in the distribution of each of the 10 amino acid polymorphisms detected within patients with symptomatic clinical hepatitis (x 2=9.311, p=0.409), HIV-infected patients (x 2=13.431, p=0.1440) and asymptomatic blood donors (x 2=3.775, p=0.9256). Similarly, there was no significant difference in the distribution between the 3 categories of the study participants except for T79M mutation, which was significantly higher in HIV-infected patients (61.5%, 8/13) compared to patients with clinical hepatitis (18.8%, 3/16) and asymptomatic blood donors (7.7%, 1/13) (x 2=10.456, p=0.0054). Conclusion: Mutations in the NS5B gene could be associated with worse prognosis of the disease or antiviral failure due to viral resistance in patients undergoing therapy. The absence of Q47H mutations in majority of the study participants in our study implies that they will not respond well to daprevir and mericitabine. Screening of patients for pre-existing resistant mutations before commencement of therapy and monitoring during and after therapy are recommended.

Epidemiología de infección por hepatitis B y C en personas con VIH/SIDA. Villa Clara 1986-2021 / Epidemiology of hepatitis B and C infection in people with HIV/AIDS. Villa Clara 1986-2021

Se realizó un estudio observacional descriptivo retrospectivo con el objetivo de caracterizar la infección por hepatitis B y C en pacientes seropositivos al VIH de la provincia Villa Clara, durante el período del 1 de enero de 1986 al 31 de diciembre de 2021. Esta coinfección se presentó con mayor frecuencia en pacientes adultos del sexo masculino de 60 años en adelante (22 casos, 18,48 %), seguido de pacientes con las edades 50-54 años (21, 17,64 %). Santa Clara fue el municipio de mayor prevalencia (25, 21%). Los factores de riesgo asociados fueron: la conducta sexual de riesgo (81 casos, 68,06%) y estado civil soltero (65, 54,62 %); predominó el nivel de escolaridad secundaria básica (53, 44,53 %); en la ocupación, amas de casa (42, 35,29 %) y desocupados (34, 28,57 %). En el 70,58 % de los casos, les fue diagnosticada la coinfección en el mismo año.

A retrospective, descriptive and observational study was carried out with the aim of characterizing hepatitis B and C infection in HIV seropositive patients in Villa Clara province from January 1, 1986 to December 31, 2021. This coinfection occurred more frequently in adult male patients, between 60 years and older (22 cases, 18.48%), followed by patients aged 50-54 years (21, 17.64%). Santa Clara was the municipality with the highest prevalence (25 cases, 21%). The associated risk factors were risky sexual behaviour (81 cases, 68.06%) and single marital status (65, 54.62%); secondary school level predominated (53, 44.53%); as well as, housewives (42, 35.29%) and unemployed people (34, 28.57%). The coinfection was diagnosed in 70.58% of the cases in the same year.

Lipoproteína de alta densidade e hipertensão arterial sistêmica estão associados à atividade necroinflamatória hepática em pacientes com hepatite C crônica / High-density lipoprotein cholesterol and systemic arterial hypertension are associated with hepatic necroinflammatory activity in patients with chronic hepatitis c

ABSTRACT Background: Approximately 71 million people are chronically infected with hepatitis C virus (HCV) worldwide. A significant number of these individuals will develop liver cirrhosis and/or hepatocellular carcinoma. Beyond the liver, there is a sizeable body of scientific evidence linking cardiovascular disease and chronic hepatitis C (CHC); however, the biological mechanisms behind the concurrence of these conditions have not been completely clarified yet. Objective: To evaluate associations between hepatic histology, clinical comorbidities and lipid profile in patients with CHC. To investigate associations between liver histology and demographic, nutritional, biochemical and virological parameters. Methods: Eight-five patients with CHC prospectively underwent hepatic biopsy. Liver fragments were obtained from each patient by percutaneous route using a Menghini needle. Fibrosis was evaluated according to the METAVIR scoring system, as follows: F0, no fibrosis; F1, fibrous portal expansion; F2, fibrous portal widening with few septa; F3, bridging fibrosis with architectural distortion; and F4, liver cirrhosis. The activity was classified based on the degree of lymphocyte infiltration and hepatocyte necrosis, from A0 to A3. The diagnosis of liver disease was based on clinical, biochemical, histological, and radiological methods. The data were analyzed by logistic regression models. Results: This cross-sectional study included 85 outpatients followed at the tertiary care ambulatory centre with a mean age of 57.2±10.7 years and 45 (52.9%) were females. There were 10 patients with cirrhosis. Patients with a METAVIR F3-F4 were significantly older (P=0.02) and had higher levels of ALT (P=0.0006), AST (P<0.0001), γ-GT (P=0.03) and bilirubin (P=0.001) and higher prothrombin time than patients with F0-F2 score. Albumin levels (P=0.01) were significantly lower in METAVIR F3-F4. Age (OR=1.09; 95%CI=1.02-1.16; P=0.02), steatosis (OR=4.03; 95%CI=1.05-15.45; P=0.04) and high-density lipoprotein cholesterol (HDL-C) <60 mg/dL (OR=7.67; 95%CI=1.71-34.49; P=0.008) were independently associated with fibrosis. Hypertension (OR=6.36; 95%CI=1.31-30.85; P=0.02) and HDL-C <60 mg/dL (OR=9.85; 95%CI=2.35-41.39; P=0.002) were independently associated with necroinflammatory activity. Hypertension (OR=6.94; 95%CI=1.92-25.05; P=0.003) and HDL-C <60 mg/dL (OR=3.94; 95%CI=1.27-12.3; P=0.02) were associated with interface inflammatory activity. Triglycerides (TG ≥150 mg/dL) remained associated with lobular inflammatory activity. Conclusion: cholesterol levels <60 mg/dL were independently associated with necroinflammatory activity in chronic hepatitis C. Patients with hypertension are at an increased risk of developing necroinflammatory activity.

RESUMO Contexto: Aproximadamente 71 milhões de pessoas estão infectadas pelo vírus da hepatite C em todo o mundo. Um número significativo desses indivíduos desenvolverá cirrose hepática e/ou carcinoma hepatocelular. Além do fígado, há evidências científicas que associam doenças cardiovasculares e hepatite C crônica; no entanto, os mecanismos biológicos implicados na ocorrência dessas condições ainda não foram completamente esclarecidos. Objetivo: Avaliar a associação entre histologia hepática, comorbidades clínicas e perfil lipídico em pacientes com hepatite C crônica. Investigar associações entre histologia hepática e parâmetros demográficos, nutricionais, bioquímicos e virológicos. Métodos: Oitenta e cinco pacientes com hepatite C crônica foram prospectivamente submetidos à biópsia hepática. Biópsias hepáticas foram obtidas de cada paciente por via percutânea com agulha de Menghini. A fibrose foi avaliada de acordo com o sistema de pontuação METAVIR, como segue: F0, sem fibrose; F1, expansão portal fibrosa; F2, alargamento portal fibroso com poucos septos; F3, fibrose em ponte com distorção arquitetônica; e F4, cirrose hepática. A atividade foi classificada com base no grau de infiltração de linfócitos e necrose de hepatócitos, de A0 a A3. O diagnóstico da doença hepática foi baseado em métodos clínicos, bioquímicos, histológicos e radiológicos. Os dados foram analisados por modelos de regressão logística. Resultados: Neste estudo transversal, realizado em um ambulatório do hospital universitário, foram incluídos 85 pacientes que tinham média de idade de 57,2±10,7 anos, sendo 45 (52,9%) do sexo feminino. Havia 10 pacientes com cirrose. Os pacientes com METAVIR F3-F4 eram significativamente mais velhos (P=0,02) e tinham níveis mais elevados de ALT (P=0,0006), AST (P<0,0001), γ-GT (P=0,03) e bilirrubina (P=0,001) e, maior tempo de protrombina do que pacientes com escore F0-F2. Os níveis de albumina (P=0,01) foram significativamente mais baixos naqueles classificados como METAVIR F3-F4. Idade (OR=1,09; IC95%=1,02-1,16; P=0,02), esteatose (OR=4,03; IC95%=1,05-15,45; P=0,04) e HDL-C <60 mg/dL (OR=7,67; 95%IC=1,71-34,49; P=0,008) foram independentemente associados à fibrose. Hipertensão (OR=6,36; IC95%=1,31-30,85; P=0,02) e HDL-C <60 mg/dL (OR=9,85; IC95%=2,35-41,39; P=0,002) foram independentemente associados à atividade necroinflamatória. Hipertensão (OR=6,94; IC 95%=1,92-25,05; P=0,003) e HDL-C <60 mg/dL (OR=3,94; IC95%=1,27-12,3; P=0,02) foram associados à atividade inflamatória de interface. Os triglicerídeos (TG >150 mg/dL) permaneceram associados à atividade inflamatória lobular. Conclusão: Níveis de coleterol HDL <60 mg/dL foram independentemente associados à atividade necroinflamatória na hepatite C crônica. Pacientes com hipertensão têm risco aumentado de desenvolver atividade necroinflamatória.

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.

Judicialização de medicamentos para tratamento da hepatite C no estado do Rio Grande do Sul, Brasil / Judicialization of drugs for the treatment of hepatitis C in the state of Rio Grande do Sul, Brazil

O artigo tem por objetivo identificar os motivos que levaram as pessoas a buscarem o Poder Judiciário visando obter medicamentos para tratamento da hepatite C. Trata-se de um estudo descritivo transversal, de natureza quantitativa, no qual foram analisados 235 acórdãos e decisões monocráticas proferidas pelo Tribunal de Justiça do Estado do Rio Grande do Sul entre 2010 e 2020. Os resultados evidenciaram que a razão principal é insuficiência de renda. Também apontou-se que a judicialização da saúde não é um fenômeno adstrito às pessoas de baixa renda; que os medicamentos mais requeridos são Ribavirina, Interferon, Sofosbuvir e Daclatasvir; e que o percentual de concessão judicial de medicamentos é de 93,6%. Conclui-se que há necessidade de reavaliação do Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções, do Plano Nacional de Hepatites Virais e do Plano para Eliminação da Hepatite C.

This article aims to identify which reasons lead people to seek the Judiciary in order to obtain medication for the treatment of hepatitis C. This is a quantitative cross-sectional descriptive study where 235 judgements and lower court decisions rendered by the state of Rio Grande do Sul Court of Justice between the years of 2010 and 2020 were analyzed. The results showed that the main reason why people turn to the Judiciary is low-income. It was also pointed that the health judicialization is not a phenomenon connected to low-income; the most required drugs are Ribavirina, Interferon, Sofosbuvir and Daclatasvir; and the percentage of judicial medicine concession is 93.6%. The data obtained lead to the conclusion that there is a need to reassess the Clinical Protocol and Therapeutic Guidelines for Hepatitis C and Coinfections, the National Plan for Viral Hepatitis and the Plan for the Elimination of Hepatitis C.

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.

Calidad de vida relacionada con la salud en pacientes con infección crónica por virus de la Hepatitis C y B

Introducción: La calidad de vida relacionada con la salud medida a través de los "resultados reportados por pacientes", del inglés: patient reported outcomes (PROs) permite la detección efectiva de problemas físicos y psicológicos en pacientes con hepatitis crónica. Objetivo: Describir las dimensiones de calidad de vida más afectadas reportados por pacientes con infección crónica por virus de la Hepatitis C y B. Material y Métodos: Se realizó un estudio descriptivo, transversal desde junio 2018 hasta diciembre 2020 en el Instituto de Gastroenterología (IGE). Entre 1 706 pacientes con diagnóstico VHB y VHC atendidos, la muestra quedó constituida por 366 adultos con infección crónica por los virus de hepatitis B (VHB) y C (VHC). Se registraron los resultados de las encuestas: Evaluación Funcional para el Tratamiento de Enfermedades Crónicas -Fatiga (FACIT-F) y Cuestionario de Impedimento de la Productividad y Actividad Laboral- Problema de salud específico (WPAI-SPH) y parámetros clínico-demográficos. Resultados: Se identificaron 271 (74,0 %) pacientes con diagnóstico de VHC y 95 (26,0 %) de VHB, con edad media 54,0 ± 12,7 años, 209 (57,1 %) mujeres. La puntuación total de la FACIT-F estuvo más afectada en VHC (FACIT-F: HVB: 129,0 ± 15,9 vs. VHC: 111,2 ± 23,5; p<0,0001), quienes a su vez tuvieron mayor deterioro de la actividad laboral (WPAI-SPH: VHB: 0,309 ± 0,312 vs. VHC: 0,386 ± 0,333; p<0,05). Conclusiones: Los pacientes con VHC vivencian una peor calidad de vida que compromete su bienestar, rendimiento laboral y cotidiano.

Introduction: Health-related quality of life measured through "patient-reported outcomes" (PROs) allows effective detection of physical and psychological problems in patients with chronic hepatitis. Objective: To identify the quality of life outcomes reported by patients with chronic hepatitis C and B virus infection. Material and Methods: A descriptive, cross-sectional study was conducted from June 2018 to December 2020 at the Institute of Gastroenterology. Of 1 706 patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, 366 adults were included in the sample. Data was collected using validated instruments: Functional Assessment for Chronic Illness Treatment-Fatigue Scale (FACIT-F) and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SPH). Clinical and demographic parameters were also recorded. Results: A total of 271 (74.0%) patients with HCV and 95 (26.0%) HBV diagnosis were identified, mean (SD) age 54.0 ± 12.7, and 209 (57.1%) women. The FACIT-F total score was more affected in HCV (FACIT-F: HBV: 129.0 ± 15.9 vs. HCV: 111.2 ± 23.5; p<0.0001); these patients also had greater impairment in work activity (WPAI-SPH: HBV: 0.309 ± 0.312 vs. HCV: 0.386 ± 0.333; p<0.05). Conclusions: Patients with HCV have a worse quality of life that compromises their well-being, work and daily performance.

Computer-Aided vaccine design for selected positive-sense single stranded RNA viruses

Spontaneous mutations and lack of replication fidelity in positive-sense single stranded RNA viruses (+ssRNA virus) result in emergence of genetic variants with diverse viral morphogenesis and surface proteins that affect its antigenicity. This high mutability in +ssRNA viruses has induced antiviral drug resistance and ability to overcome vaccines that subsequently resulted in rapid viral evolution and high mortality rate in human and livestock. Computer aided vaccine design and immunoinformatics play a crucial role in expediting the vaccine production protocols, antibody production and identifying suitable immunogenic regions or epitopes from the genome sequences of the pathogens. T cell and B cell epitopes can be identified in pathogens by immunoinformatics algorithms and methods that enhance the analysis of protective immunity, vaccine safety, immunity modelling and vaccine efficacy. This rapid and cost-effective computational vaccine design promotes development of potential vaccine that could induce immune response in host against rapidly mutating pathogens like +ssRNA viruses. Epitope-based vaccine is a striking concept that has been widely employed in recent years to construct vaccines targeting rapidly mutating +ssRNA viruses. Therefore, the present review provides an overview about the current progress and methodology in computeraided vaccine design for the most notable +ssRNA viruses namely Hepatitis C virus, Dengue virus, Chikungunya virus and Coronaviruses. This review also highlights the applications of various immunoinformatics tools for vaccine design and for modelling immune response against +ssRNA viruses.

Membranoproliferative glomerulonephritis: current histopathological classification, clinical profile, and kidney outcomes / Glomerulonefrite membranoproliferativa: classificação histopatológica atual, perfil clínico e desfechos renais

Abstract Introduction: Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease with a variable prognosis. A new classification based on the presence or absence of immunoglobulins and complement deposits in immunofluorescence microscopy (IF) of kidney biopsy has recently been proposed. The objectives of the study were to determine and compare the clinical, laboratory, and histopathological characteristics of those with primary or secondary MPGN, reclassify the primary ones based on IF findings, and evaluate kidney outcomes. Methods: This was an observational retrospective cohort study carried out in a single center (UNIFESP), based on the data collected from medical records of patients followed from 1996 to 2019. Results: Of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. Most patients were hypertensive (84.9%) and had edema (88.7%) and anemia (84.9%); 33 (91.7%) patients classified as primary MPGN were reclassified as immune-complex-mediated and 3 (8.3%) as complement-mediated. The secondary MPGN group had hematuria more frequently (p <0.001) and a higher prevalence of deposits of IgG (p = 0.02) and C1q (p = 0.003). Regarding the outcome, 39% of the patients achieved partial or complete remission. Lower initial serum albumin and higher initial 24-hour proteinuria were factors associated with worst renal prognosis. Conclusions: According to the new histological classification, the vast majority of MPGN cases were classified as being mediated by immune complexes. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics.

Resumo Introdução: Glomerulonefrite membranoproliferativa (GNMP) é uma doença glomerular rara com prognóstico variável. Recentemente, foi proposta uma nova classificação baseada na presença ou ausência de imunoglobulinas e depósitos de complemento na microscopia de imunofluorescência (IF) da biópsia renal. Os objetivos do estudo foram determinar e comparar as características clínicas, laboratoriais e histopatológicas daqueles com GNMP primária ou secundária, reclassificar as primárias com base em achados da IF e avaliar os desfechos renais. Métodos: Este foi um estudo de coorte observacional retrospectivo realizado em centro único (UNIFESP), com base nos dados coletados de prontuários de pacientes acompanhados de 1996 a 2019. Resultados: Dos 53 casos de GNMP, 36 (67,9%) foram classificados como GNMP primária e 17 (32,1%) como GNMP secundária. A maioria dos pacientes era hipertensa (84,9%) e apresentava edema (88,7%) e anemia (84,9%); 33 (91,7%) pacientes classificados como GNMP primária foram reclassificados como mediados por imunocomplexo e 3 (8,3%) como mediados por complemento. O grupo de GNMP secundária apresentou mais frequentemente hematúria (p <0,001) e maior prevalência de depósitos de IgG (p = 0,02) e C1q (p = 0,003). Com relação ao desfecho, 39% dos pacientes alcançaram remissão parcial ou completa. Albumina sérica inicial mais baixa e proteinúria de 24 horas inicial mais elevada foram fatores associados a pior prognóstico renal. Conclusões: De acordo com a nova classificação histológica, a grande maioria dos casos de GNMP foram classificados como sendo mediados por imunocomplexos. Houve poucas diferenças entre GNMP primária e secundária em relação às suas características clínicas e laboratoriais.