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.

Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo / Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up

Objetivos: Analizar la evolución analítica, clínica y de la fibrosis en pacientes F3-F4 curados con antivirales de acción directa (AAD). Pacientes y métodos: Estudio unicéntrico, observacional y prospectivo. Se incluyeron todos los pacientes con hepatitisC F3-F4 curados con AAD del 1 de noviembre de 2014 al 31 de agosto de 2019. Se realizó una visita basal (VB) y a las 12semanas (12s), 1, 2, 3 y 4años tras finalizar el tratamiento. Se recogieron variables demográficas, analíticas, medición no invasiva de la fibrosis, marcadores indirectos de hipertensión portal, presencia de varices esofágicas, descompensaciones de la cirrosis y hepatocarcinoma. Resultados: Se trataron 169 pacientes: 123 (72,8%) hombres, edad 57,5±12 años; 117 (69,2%) presentaban cirrosis, 99 (84,6%) ChildA. El 96,4% consiguieron respuesta virológica sostenida (RVS). La mediana de seguimiento fue de 46,14 (2,89-62,55) meses. Durante el seguimiento se observó precozmente un aumento significativo de plaquetas (155×103/μl [VB]; 163×103/μl [12s]), colesterol (158mg/dl [VB]; 179mg/dl [12s]) y albúmina (4,16g/dl [VB]; 4,34g/dl [12s]), y un descenso significativo de GPT (82UI/l [VB]; 23UI/l [12s]), GOT (69UI/l [VB]; 26UI/l [12s]), GGT (118UI/l [VB]; 48UI/l [12s]), y bilirrubina (0,9mg/dl [VB]; 0,7mg/dl [12s]). La fibrosis disminuyó, también inicialmente, tanto con métodos serológicos como Fibroscan (19,9KPa [VB]; 14,8KPa [12s]); p<0,05). El 8,1% de los pacientes con cirrosis compensada presentaron alguna descompensación. El 4,5% desarrollaron varices esofágicas. Nueve (5,52%) pacientes presentaron hepatocarcinoma de novo; seis (3,68%) lo presentaban basalmente, y el 40% sufrieron recidiva. Durante el seguimiento la mortalidad fue del 9,2%. Conclusiones: Existe mejoría de los parámetros analíticos y de la fibrosis hepática medida por métodos no invasivos en los pacientes F3-F4 curados con AAD.(AU)

Aims: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). Patients and methods: Unicenteric, observational and prospective study. All F3–F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. Results: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/μL (BV); 163×103/μL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. Conclusions: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.(AU)

Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up. / Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo.

AIMS: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). PATIENTS AND METHODS: Unicenteric, observational and prospective study. All F3-F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. RESULTS: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/µL (BV); 163×103/µL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. CONCLUSIONS: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. / Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Polimorfismos del gen de interleucina 10 y respuesta virológica sostenida en pacientes cubanos coinfectados con virus de hepatitis C y virus de inmunodeficiencia humana / Interleukin-10 gene polymorphisms and sustained virological response in Cuban patients coinfected with hepatitis C virus and human immunodeficiency virus

Introducción: En pacientes infectados con el virus de la hepatitis C se demostró que los polimorfismos de un simple nucleótido del gen de la interleucina 10 (IL10), influyen en la respuesta virológica sostenida al tratamiento con interferón y ribavirina, y en la inmunopatogénesis de la enfermedad. Objetivo: Determinar la frecuencia de los polimorfismos de un simple nucleótido de la región promotora del gen de la interleucina 10, según respuesta virológica sostenida y grado de lesión hepática. Métodos: Se realizó un estudio descriptivo, de corte transversal y se determinó la carga del virus de la hepatitis C por RT-PCR en tiempo real. Se estudiaron 25 pacientes cubanos con virus de inmunodeficiencia humana coinfectados con VHC, 24 semanas después del tratamiento con interferón y ribavirina. Para evaluar la variabilidad genética de la interleucina 10, los polimorfismos de un simple nucleótido se identificaron por secuenciación nucleotídica, -592 (A>C) y -819 (T>C). El grado de fibrosis hepática se calculó por el índice aspartato aminotransferasa/plaquetas. Resultados: El 44,0 por ciento (11/25) de los pacientes lograron respuesta virológica sostenida, y en el 56,0 por ciento (14/25) restante no se obtuvo esta. En los individuos en que se dio la respuesta predominaron los genotipos bajos productores de la interleucina 10, -592AA (36,3 por ciento vs. 21,4 por ciento) y -819TT (54,5 por ciento vs. 21,4 por ciento). En estos casos, el análisis de la frecuencia alélica mostró mayor frecuencia del alelo T para el SNP -819 (p= 0,0470). El índice aspartato aminotransferasa/plaquetas fue compatible con fibrosis hepática sin cirrosis en pacientes sin respuesta virológica sostenida, mientras que en los coinfectados que tuvieron respuesta indicó ausencia de lesión hepática. Conclusiones: Los resultados sugieren que las variantes de los polimorfismos de un simple nucleótido del gen de la interleucina 10 evaluados, podrían estar relacionados con la respuesta virológica sostenida y la patogénesis de la hepatitis C en los pacientes estudiados(AU)

Introduction: The study of patients infected with hepatitis C virus revealed that polymorphisms of a single nucleotide of the interleukin-10 (IL10) gene influence the sustained virological response to the treatment with interferon and ribavirin, and the immunopathogenesis of the disease. Objective: Determine the frequency of single-nucleotide polymorphisms from the interleukin-10 gene promoter region according to the sustained virological response and the degree of liver injury. Methods: A descriptive cross-sectional study was conducted and hepatitis C viral load was determined by RT-PCR. A sample of 25 Cuban HIV/HCV coinfected patients were studied 24 weeks after treatment with interferon and ribavirin. To evaluate the genetic variability of interleukin 10, the single-nucleotide polymorphisms were identified by nucleotide sequencing, -592 (A>C) and -819 (T>C). The degree of liver fibrosis was estimated by the aspartate aminotransferase / platelet index. Results: Of the patients studied, 44.0 percent (11/25) achieved a sustained virological response and 56.0 percent (14/25) did not. In individuals displaying the response, a predominance was found of low interleukin-10 producing genotypes, -592AA (36.3 percent vs. 21.4 percent) and -819TT (54.5 percent vs. 21.4 percent). In those cases, allele frequency analysis showed a greater allele T frequency for SNP -819 (p= 0.0470). The aspartate aminotransferase / platelet index was compatible with kidney fibrosis without cirrhosis in patients without a sustained virological response, and indicated an absence of liver injury in coinfected patients displaying a response. Conclusions: Results suggest that the variants evaluated of single-nucleotide polymorphisms of the interleukin-10 gene could be related to the sustained virological response and the pathogenesis of hepatitis C in the patients studied(AU)

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

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

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

Implicaciones de la microbiota intestinal en las enfermedades crónicas del hígado / Implications of the intestinal microbiota in the chronic liver diseases

RESUMEN La microbiota se refiere al conjunto de todos los de microorganismos que se localizan de manera normal en distintos sitios de los cuerpos de los seres vivos pluricelulares, tales como el cuerpo humano. Las modificaciones del eje intestino-hígado se ha convertido en la actualidad en un grave problema científico al haberse encontrado en diversas investigaciones, que esta microbiota está relacionada con el daño hepático con independencia de la causa de la lesión hepática. Se realizó una revisión sistemática sobre las implicaciones demamicrobiota intestinal en las enfermedades hepáticas. Se realizó una revisión de artículos científicos publicados entre 2012 y 2018 en diversas bases de datos en línea. Se presenta el conocimiento existente hasta el momento sobre la microbiota intestinal en pacientes portadores de enfermedades hepáticas, con hincapié en las hepatitis C y la cirrosis hepática. La composición de microbiota de intestino estuvo asociada con el perfil inflamatorio y marcadores de fibrosis hepática, las que mejoraron con el tratamiento de antivirales de acción directa aunque las medidas de permeabilidad intestinal e inflamación permanecían inalteradas. Se reporta mejoría de los pacientes portadores de hepatitis viral tipo C, con antivirales de acción directa la cual estuvo asociada con modificaciones de la microbiota intestinal, que se correlacionó con mejoría en la fibrosis e inflamación hepática, los avances en este campo abren nuevas perspectivas en la biomedicina (AU).

SUMMARY Microbiota refers to the whole of microorganisms located in a normal way in different places of the bodies of pluricelular living beings, like the human body. The modifications of the axis intestine-liver have become a serious scientific problem, because in different researches researchers have found that this microbiota is related to hepatic damage depending on the cause of this hepatic lesion. To carry out a systematic review on the implication of intestinal macrobiota in liver diseases. The scientific articles published in the period 2012-2018 in different databases on line were reviewed. A total of 26 bibliographic sources were used, original articles and reviews. The authors present knowledge existent up to the moment on intestinal microbiota in patients who have liver diseases, making emphasis on hepatitis C and hepatic cirrhosis. The composition of the intestine microbiota was associated to an inflammatory and markers of hepatic fibrosis that improved with the treatment of direct action antivirals although the measures of intestinal permeability and inflammation remained inalterably. It is reported an improvement of patients carriers of viral hepatitis type C with the use direct action retrovirals, what was linked to modifications in the intestinal microbiota, and correlated to an improvement of fibrosis and liver inflammation; the advances obtained in this field open new perspectives in biomedicine (AU).

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease.

BACKGROUND AND AIMS: The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD. METHODS: We performed an observational single-arm multi-centre study in a large (n=198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities. RESULTS: The average baseline eGFR (CKD-EPI equation) was 70.06±20.1mL/min/1.72m2; the most common genotype was HCV 1b (n=93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n=5), glecaprevir/pibrentasvir (n=4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n=40), simeprevir±daclatasvir (n=2), and sofosbuvir-based combinations (n=147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures - eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n=12), which required discontinuation or dose reduction of ribavirin in some cases (n=6); deterioration of kidney function occurred in three (1.7%). CONCLUSIONS: All-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a 'real-world' clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.

Tratamiento actual de la hepatitis C en Colombia / Current treatment for hepatitis C in Colombia

La infección por el virus de hepatitis C (VHC) es una epidemia global que afecta a 71 millones de personas. El diagnóstico inicial se hace mediante la detección de anticuerpos contra el VHC, que luego requiere una prueba confirmatoria molecular, debido a que la determinación de anticuerpos no diferencia los individuos que tienen una infección activa, de aquellos con una infección resuelta y sin viremia. El objetivo del tratamiento de la infección crónica por VHC es curar la enfermedad, lo que se determina cuando se logra una respuesta viral sostenida; es decir, cuando no se detecta carga viral 12 semanas o más después de terminada la terapia. Para un tratamiento óptimo de la infección y alcanzar la curación, se recomienda evaluar previamente de manera no invasiva el estadio de fibrosis, y garantizar la adherencia durante todo el tiempo de tratamiento. En la presente revisión se incluyen las recomendaciones para el tratamiento de la infección crónica por VHC, según el genotipo viral, basadas en los medicamentos disponibles en nuestro medio y en los que próximamente estarán llegando al país.

Abstract Infection with hepatitis C virus (HCV) is a global epidemic that affects 71 million people. Initial diagnosis is made by detecting antibodies against HCV, which then requires a confirmatory molecular assay in order to discriminate individuals who have an active infection from those with a resolved infection and without active viremia. The goal of treating chronic HCV infection is to cure the disease, which is determined when a sustained virological response is achieved; that is, when viral load is not detected 12 weeks or more after completing treatment. For an optimal treatment of the infection and to achieve a cure, it is recommended to previously and non-invasively evaluate the fibrosis stage, and to guarantee adherence throughout the treatment period. This review includes some guidelines for the treatment of chronic HCV infection, according to the viral genotype, and based on the drugs available and soon to be available in our country.

Cascade of care for people living with HIV infection in Southern Brazil: results from a public health network / A cascata de cuidados para pessoas vivendo com a infecção pelo HIV no Sul do Brasil: resultados obtidos em uma rede pública de saúde / Serie de cuidados para personas que viven con una infección de VIH en el sur de Brasil: resultados en una red pública de salud

Abstract: The cascade of care for people living with HIV infection (PLHIV) describes steps in diagnosis, linkage and retention in care, as well as the provision and success of combination antiretroviral therapy (cART). The aim of this study was to evaluate the rates regarding the retention in care, on cART, and suppressed viral load for PLHIV attended at a Brazilian public health network. Data on PLHIV from 116 cities of Paraná, Southern Brazil, attended from 2012 to 2015, were retrospectively collected through the Laboratory Tests Control System (SISCEL). The number of PLHIV related to care increased about 22.5% from 2012 to 2015 (4,106 to 5,030 individuals). The proportion of PLHIV retained in care showed a trend toward stabilization around 81.7-86.9%. Every year, the use of cART increased up to 90.3% for PLHIV retained in care. Viral load suppression was achieved by 72.8% of patients on cART and 57.1% by those linked to care. Retention in care and HIV viral suppression were more likely to occur in older PLHIV than younger ones; similarly, patients living in medium-sized cities were more susceptible to these factors than in large- or small-sized cities. In conclusion, the study showed a high level of retention in care and HIV suppression on cART, as well as emphasized that current efforts for treating already-infected PLHIV remain a challenge for our health public institutions and may contribute to highlight steps for improvement of the HIV cascade of care in our population.

Resumo: A cascata de cuidados para pessoas vivendo com a infecção pelo HIV (PVHIV) representa os passos no diagnóstico, vínculo e retenção em tratamento, assim como, no fornecimento e resultado da terapia antirretroviral combinada (TARVc). O estudo teve como objetivo avaliar as taxas relativas à retenção em atendimento, uso de TARVc e supressão da carga viral em PVHIV atendidas em uma rede pública de saúde. Através do Sistema de Controle de Exames Laboratoriais (SISCEL), os dados foram coletados retrospectivamente, referentes às PVHIV de 116 municípios no Estado do Paraná, Sul do Brasil, atendidas entre 2012 e 2015. O número de PVHIV vinculadas ao atendimento aumentou em 22,5% entre 2012 e 2015 (de 4.106 para 5.030 indivíduos). A proporção de PVHIV retidas no atendimento mostrou uma tendência de estabilização, em torno de 81,7-86,9%. O uso de TARVc aumentou a cada ano, chegando a 90,3% das PVHIV retidas em atendimento. A supressão da carga viral foi alcançada por 72,8% dos pacientes em uso de TARVc e em 57,1% daqueles vinculados ao atendimento. A retenção no atendimento e a supressão da carga viral foram mais frequentes em PVHIV mais velhas e em pacientes residentes em municípios de porte médio. Em conclusão, o estudo mostrou um nível elevado de retenção em atendimento e de supressão da carga viral na vigência do uso de TARVc, além de enfatizar que os esforços atuais de tratamento das PVHIV ainda são um desafio para as instituições de saúde pública, podendo ajudar a identificar passos para melhorar a cascata de cuidados em HIV para a população.

Resumen: Este trabajo describe los pasos en la diagnosis, vinculación y retención en el cuidado, así como la provisión y éxito de la terapia antirretroviral combinada (cART por sus siglas en inglés) para personas que viven con una infección de VIH (PLHIV por sus siglas en inglés). El objetivo de este estudio fue evaluar las tasas en relación con la retención en el cuidado, terapia antirretroviral combinada y carga viral eliminada de las personas que viven con una infección de VIH, y reciben atención en la red pública de salud brasileña. Los datos de PLHIV procedieron de 116 ciudades de Paraná, sur de Brasil, desde 2012 a 2015, se recogieron retrospectivamente a través del Sistema de Control de Exámenes de Laboratorio (SISCEL). El número de PLHIV informado con necesidad de cuidados se incrementó un 22,5% de 2012 a 2015 (de 4.106 a 5.030 individuos). La proporción de PLHIV que fue constante en el cuidado mostró una tendencia hacia la estabilización de alrededor de un 81,7 a un 86,9%. Cada año, el uso del cART se incrementó hasta un 90,3% en el caso de PLHIV que fueron constantes en sus cuidados. La eliminación de la carga viral se consiguió en un 72,8% de los pacientes con cART y en un 57,1% por parte de aquellos vinculados a cuidados. La constancia en el cuidado y la eliminación de la carga viral en VIH eran más factibles de producirse en PLHIV más viejas que en las jóvenes; de igual forma, los pacientes que vivían en ciudades de tamaño medio eran más susceptibles hacia estos factores que en ciudades más grandes o pequeñas. Como conclusión, el estudio mostró un alto nivel de constancia en el cuidado y la eliminación de carga viral del HIV con cART, asimismo enfatizó que los actuales esfuerzos para tratar a las PLHIV ya infectadas continuaba siendo un desafío para nuestras instituciones públicas de salud y quizás podría contribuir a resaltar los pasos necesarios hacia la mejora de la serie de cuidados en VIH sobre nuestra población.

Nuevas perspectivas en el tratamiento farmacológico de la Hepatitis C / New perspectives in the pharmacological treatment of Hepatitis C

Introducción: La infección por el virus de la hepatitis C (VHC) es una de las principales causas de enfermedad hepática a nivel mundial. Alrededor de 60-80 por ciento de los infectados sufren una infección crónica pudiendo desarrollar otras patologías hepáticas como cirrosis y hepatocarcinoma. El tratamiento contra el VHC ha experimentado un enorme avance en la última década, cuya culminación ha llegado con la aparición de los Agentes Antivirales Directos (AAD) que han conseguido obtener tasas de curación superiores a 90 por ciento. Objetivo: Describir los diferentes mecanismos de acción de los AAD, además de contrastar los principales ensayos clínicos que están actualmente en desarrollo, hacer recomendaciones acerca de las opciones de tratamiento disponibles y perfilar los cambios que van a tener lugar en el tratamiento farmacológico de la Hepatitis C. Material y Métodos: Se realizaron varias búsquedas sistemáticas en la base de datos Pubmed, en los artículos expuestos en el Congreso The liver meeting en noviembre de 2014 de la AASLD (American Association for the Study of Liver Diseases), así como en la guía de la EASL (European Association for the Study of the Liver). Desarrollo: La llegada de nuevos fármacos con nuevas estrategias terapéuticas están incrementando la complejidad de la terapia, por ello es necesario conocer estos nuevos fármacos y sus posibles combinaciones. Conclusiones: Los excelentes resultados de la terapia con AAD han producido un intenso cambio en las recomendaciones terapéuticas, al permitir terapias de menor duración, mejor toleradas y de mayor seguridad(AU)

Introduction: The infection by the Hepatitis C virus (HCV) is one of the most common causes of liver's disease worldwide. Approximately between 60-80% of infected people, infection becomes chronic, and can lead in the long-term to the development of other liver's diseases such as cirrhosis and the hepatocellular carcinoma. Treatment of HCV has progressed enormously in the last decade, concluding with the development of Direct-acting Antiviral Agents (DAA), which has achieved cure rates over 90 percent. Objective: To know the different available treatments options as well as which will be available in a near future. Materials and methods: Several systematic searches were made in the PubMed database; in the articles from the liver meeting congress of AASLD (American Association for the Study of Liver Diseases) in November 2014 and in the EASL (European Association for the Study of Liver) guide. Development: The arrivals of new drugs with new therapeutic strategies have made this therapy more complex, and for that reason it is necessary to have knowledge of these drugs and their possible combinations. Conclusions: The excellent results of the therapy with AAD have made a huge change in therapeutic recommendations, making possible shorter therapies, better tolerated by patients and safer for health(AU)

Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection.

BACKGROUND: Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients. AIM: To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR. MATERIAL AND METHOD: A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated. RESULTS: Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p<0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928. CONCLUSIONS: Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.

[Lead-in period and week 8 as predictive tools for response to boceprevir therapy: a retrospective study of Spanish real clinical practice]. / Período de lead-in y semana 8 como herramientas de predicción de la respuesta en el tratamiento con boceprevir: estudio retrospectivo de la práctica clínica real en España.

INTRODUCTION: Most discontinuations due to lack of virological response occur during the first few weeks of hepatitis C virus (HCV) triple therapy. Improved knowledge of baseline factors and their correlation with boceprevir decision points may predict treatment success. METHODS: An observational, retrospective study was conducted to describe the lead-in period as a clinical decision tool in HCV genotype 1 patients treated with boceprevir. Data were collected from the medical records of 186 consecutive patients distributed across 20 Spanish general hospitals. RESULTS: This study included 171 patients. A total of 80% had fibrosis F3/F4, 74% were previously treated, and 26% were treatment-naïve. After the lead-in period, 54.5% of the patients had a reduction of ≥1 log10; this reduction occurred in 52.5% of those with advanced fibrosis. Boceprevir therapy was started in 94% of the patients. Discontinuations at week 4 were limited to null responders with cirrhosis. The baseline factors associated with virological response at week 4 were IL28B, previous response, and fibrosis score. At week 8, HCV-RNA was undetectable in 48.8% of the patients. The correlation between responses at weeks 8 and 12 was 88%. CONCLUSION: In the Spanish clinical setting, lead-in was mainly used as a clinical decision point for non-responders with cirrhosis. The good correlation between stopping rules at weeks 8 and 12 could be used to anticipate discontinuation, thus saving adverse events and costs.

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

INTRODUCTION: Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). OBJECTIVES: To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. METHODS: Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin ß 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin ß (B2; n=13). RESULTS: RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. CONCLUSIONS: G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin ß were safe and well tolerated (Clin Trials Gov NCT00830609).

[Hepatitis C virus genotype 5 in Mexico: a case report with successful treatment and a literature review]. / Hepatitis C genotipo viral 5 en México: reporte de caso con tratamiento exitoso y revisión de la literatura.

Hepatitis C virus (HCV) genotype 5 is extremely rare and there is very little reported on its management in the medical literature. We present herein the case of a patient with HCV genotype 5 that presumably acquired the disease through a blood transfusion during infancy. Sustained virologic response was achieved after 24 weeks of treatment. According to the available information on HCV genotype 5 treatment, it has a similar response to that of HCV genotype 1. Our patient presented with various favorable outcome factors. There is much less reported on the treatment of HCV genotype 5 than there is regarding HCV genotypes 1, 2, 3, and 4. This is mainly due to the low prevalence of genotype 5 in the Mexican environment.

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad(AU)

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease(AU)

Evolución histórica de las terapias antivirales en hepatitis crónica C / Historical course of antiviral therapies in chronic hepatitis C

Dada la creciente incidencia y prevalencia de la infección crónica por el Virus de la hepatitis crónica C, con estimados de infección de alrededor del 3 por ciento de la población mundial, se realizó una revisión bibliográfica sobre los aspectos más relevantes de la evolución histórica que han experimentado las terapias antivirales utilizadas en el tratamiento de esta enfermedad. Se realizó una puesta al día sobre esta temática desde sus orígenes, con especial énfasis en las perspectivas futuras de esta terapéutica, actualmente en estudio por parte de la comunidad científica internacional. Para la realización de esta obra fueron consultadas 69 citas bibliográficas que incluyen metanálisis disponibles en MEDLINE desde 1998 hasta la actualidad, así como las publicaciones de los resultados de las investigaciones realizadas en nuestro país sobre este tema

A bibliographic review on the more significant features of historical course experienced by the antiviral therapies used in treatment of Chronic Hepatitis C virus was carried out due to the increasing incidence and prevalence of this disease with infection estimates about 3 percent of the world population. A updating was carried out on this subject matter from its origins with special emphasis on future perspectives of this therapeutics, nowadays under consideration by the international scientific community. For the carrying out of present work 69 bibliographic references were reviewed including the meta-analyses available in MEDLINE from 1998 up to present time, as well as the publications of researches results performed in our country on this subject

Evolución histórica de las terapias antivirales en hepatitis crónica C / Historical course of antiviral therapies in chronic hepatitis C

Dada la creciente incidencia y prevalencia de la infección crónica por el Virus de la hepatitis crónica C, con estimados de infección de alrededor del 3 por ciento de la población mundial, se realizó una revisión bibliográfica sobre los aspectos más relevantes de la evolución histórica que han experimentado las terapias antivirales utilizadas en el tratamiento de esta enfermedad. Se realizó una puesta al día sobre esta temática desde sus orígenes, con especial énfasis en las perspectivas futuras de esta terapéutica, actualmente en estudio por parte de la comunidad científica internacional. Para la realización de esta obra fueron consultadas 69 citas bibliográficas que incluyen metanálisis disponibles en MEDLINE desde 1998 hasta la actualidad, así como las publicaciones de los resultados de las investigaciones realizadas en nuestro país sobre este tema(AU)

A bibliographic review on the more significant features of historical course experienced by the antiviral therapies used in treatment of Chronic Hepatitis C virus was carried out due to the increasing incidence and prevalence of this disease with infection estimates about 3 percent of the world population. A updating was carried out on this subject matter from its origins with special emphasis on future perspectives of this therapeutics, nowadays under consideration by the international scientific community. For the carrying out of present work 69 bibliographic references were reviewed including the meta-analyses available in MEDLINE from 1998 up to present time, as well as the publications of researches results performed in our country on this subject(AU)