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.

Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis.

BACKGROUND: Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). OBJECTIVES: Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. METHODS: Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness <8kPa). RESULTS: Forty-eight patients were included (May 2017-March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA>800000UI in 63% and medium liver stiffness 4.9kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. CONCLUSIONS: Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Sustained virological response at week 12 after interferon-free therapy as criterion for HCV cure definition: Validation in a real-life cohort of HIV-coinfected patients.

INTRODUCTION: Sustained virological response (SVR) 12 weeks after the end-of-therapy (EOT) has been correlated with SVR24 for HCV-monoinfection. We aim to validate SVR12 as criterion for definition of HCV cure in HIV-coinfected patients treated with all-oral direct-acting antivirals (DAA). METHODS: Prospectively observational study including HIV/HCV-coinfected subjects who received DAA and had HCV-RNA measures at weeks 12 and 24 after EOT. Every patient who took ≥1 drug dose was analyzed. RESULTS: DAA were prescribed to 423 patients, of whom 387 had HCV-RNA measures both at weeks 12 and 24 after EOT. SVR12 was confirmed in 379/387 patients, while SVR24 was confirmed in 377/387 subjects. The positive-predictive-value (PPV) of SVR12 for SVR24 was 99.5% (95%CI: 98.1-99.9). One of the recurrences was clinically suspected to be a late relapse. CONCLUSIONS: SVR12 has a high PPV for HCV cure in HIV/HCV-coinfection, though further follow-up could be necessary for those with deeper immunosuppression.

Coinfección virus de inmunodeficiencia humana-virus de la Hepatitis C: hacia un nuevo escenario terapéutico / Human Immunodeficiency Virus-Hepatitis C virus coinfection: towards a new therapeutic scenario

Introducción: Las terapias contra el virus de la Hepatitis C han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar debido a la elevada morbimortalidad hepática y sistémica, reacciones adversas e interacciones medicamentosas. Objetivo: Analizar las opciones farmacoterapéuticas más modernas disponibles para los pacientes coinfectados con VIH y VHC, con énfasis en los nuevos antivirales de acción directa, a fin de ofrecer una herramienta útil en el abordaje terapéutico en estos pacientes. Material y métodos: Se revisaron artículos originales, ensayos clínicos y revisiones sistemáticas hasta septiembre de 2016, bases de datos internacionales de interacciones medicamentosas y Guías de Práctica Clínica actualizadas. Desarrollo: Las terapias contra el virus de la Hepatitis C (VHC) han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar que, además, asociaba una elevada morbimortalidad hepática y sistémica, más reacciones adversas y complejas interacciones medicamentosas. Conclusiones: En este nuevo escenario es fundamental dedicar esfuerzos a identificar el elevado porcentaje de infectados no diagnosticados, potenciales interacciones, especialmente con fármacos para patologías asociadas al envejecimiento de los pacientes, reacciones adversas a medio-largo plazos y desarrollo de resistencias, además de garantizar la cobertura universal en todos los contextos clínicos(AU)

Introduction:Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens, achieve an equate response rates to treatment in cases of HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat due to a high hepatic and systemic morbidity-mortality, adverse reactions and drug interactions. Objective: To analyse the current Pharma-therapeutic options available for co-infected HIV-HCV patients, with emphasis I the new direct-acting antiviral agents, in order to offer a useful tool for the therapeutic approach in these patients. Material and Methods: Original articles, clinical studies and systematic reviews until September 2016 were carried out, as well as international drug interactions databases and updated Practical Guidelines. Development: Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens achieve an equate response rates to treatment in HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat, which also associate a high hepatic and systemic morbidity-mortality, adverse reactions and complex drug interactions. Conclusions: In this new scenario efforts must be addressed to identify the high percentage of undiagnosed patients; potential interactions, especially with drugs related with patient aging; medium and long-term adverse reactions and development of drug resistances, as well as to guarantee universal coverage in all clinical contexts(AU)

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection.

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.

Coinfección con los virus VIH-VHC y su evolución clínico-inmunológica / HIV-CHV virus coinfection and its immunological-clinical course

OBJETIVO: Determinar la evolución clinico-inmunológica de pacientes coinfectados con los virus VIH-VHC, atendidos en el Instituto de Medicina Tropical Dr. Pedro Kourí, entre los años 2002-2006. MÉTODOS: Se realizó un estudio de cohorte prospectivo donde fueron incluidos 170 pacientes: 40 coinfectados con los virus VIH-VHC (expuestos) y 130 infectados con el VIH (no expuestos). RESULTADOS: La edad media fue de 33,4 años (34,1 años en los pacientes expuestos y 33,4 en los no expuestos). Predominaron el sexo masculino y el color blanco de la piel (143: 84,1 por ciento y 94: 55,3 por ciento, respectivamente). Los niveles de transaminasas glutamicooxalacética (TGO), glutámico-pirúvica (TGP) y deshidrogenasa láctica (LDH) fueron más elevados en los pacientes coinfectados (p<0,05) que en los monoinfectados. El tiempo medio de diagnóstico del VIH se relacionó de manera significativa con el diagnóstico de VHC y con el SIDA. Hubo menos casos con conteo de CD4+ por debajo de 200 cel/mm³ en los expuestos que en los no expuestos y no existieron diferencias significativas cuando se compararon los grupos según los niveles de CD4+ mayores de 200 cel/mm³. No hubo diferencias significativas entre los valores medios de CD4+ según el tiempo de diagnostico del VIH entre ambos grupos de pacientes. CONCLUSIONES: El daño tisular reflejado por un aumento del nivel de transaminasas (TGO y TGP) y de deshidrogenasa lßctica (LDH) es más elevado en los pacientes infectados con HVC, y la coinfección por el VHC no se relaciona con un mayor deterioro inmunológico ni con un aumento de la frecuencia del SIDA

OBJECTIVE: To determine the immunological-clinical course of HIV-CHV coinfected patients, seen in the Pedro Kourí Tropical Medicine Institute between 2002-2006 years. METHODS: A prospective study was conducted including 170 patients: 40 coinfected with HIV-CHV virus (exposed) and 130 infected by HIV virus (no exposed). RESULTS: The mean age was of 33,4 years (34,1 years in exposed patients and 33,4 in those no exposed). There was predominance of white male sex (143: 84,1 percent and dd94: 55,3 percent, respectively. The glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic (GPT) and lactic dehydrogenase (LDH) levels were higher in coinfected patients (p < 0,05) than those monoinfected. The mean time of HIV diagnosis was significantly related to the C hepatitis virus (CHV) and t AIDS. There were less cases with a CD4+ count under 200 cel/mm3 in those exposed that in those no exposed and there were not significant differences when were compared with the groups according to the DC4+ over 200 cel/mm3. Also, there were not marked differences among the mean values of CD43 according to the HIV diagnosis time among both groups of patients. CONCLUSIONS: The tissue damage reflected by an increase of transaminase levels (GOT and PGT) and of lactic dehydrogenase (LDH) is higher in the C hepatitis virus and the coinfection by CHV it is neither related to the great immunologic deterioration nor an increase of AIDS frequency