Characterizing Hepatitis Delta in Spain and the gaps in its management.

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated HDV prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs.

BACKGROUND & AIMS: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. METHODS: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. RESULTS: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. CONCLUSION: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. LAY SUMMARY: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.

[Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice]. / Terapia triple en pacientes con fibrosis avanzada y cirróticos: aspectos relevantes en la práctica clínica.

The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy.

[Telaprevir in treatment-naïve patients with HCV monoinfection]. / Telaprevir en el paciente monoinfectado sin tratamiento previo.

Chronic hepatitis due to the hepatitis C virus (HCV) infection affects nearly 180 million people worldwide. This infection is curable. Until 1 year ago, the only treatment for genotype 1 HCV was the combination of pegylated interferon and ribavirin, which was only moderately effective (40-50%). The introduction of new antiviral agents, such as telaprevir, represents a change of paradigm and has revolutionized the treatment of this infection. This drug has increased the likelihood of viral response (to 80%) and has allowed treatment length to be shortened in more than 50% of patients. New stopping rules have been developed to avoid the development of resistances. Finally, special attention should be paid to potentially serious adverse effects, particularly anemia and cutaneous alterations.

¿Es la simulación clínica una herramienta de aprendizaje efectiva en la enseñanza de la ética clínica? / Is clinical simulation an effective learning tool in teaching clinical ethics?

Introducción En la enseñanza de la ética clínica se han utilizado numerosos métodos tradicionales que persiguen el desarrollo de competencias frente a los desafíos éticos actuales. Estas situaciones pueden ser reproducidas en forma estandarizadas mediante la simulación clínica para ser presentadas y evaluadas en el proceso de formación de los profesionales de salud. Sin embargo, se requiere disponer de evidencias sobre su efectividad. Objetivo Identificar y sintetizar la evidencia disponible sobre la efectividad de la enseñanza de la ética clínica usando la simulación como herramienta de aprendizaje. Métodos Revisión bibliográfica, con búsqueda en bases de datos PubMed, LILACS y Cochrane usando palabras clave en idiomas inglés y español: "Ethics, Clinical/education" [Mesh]) AND "Simulation Training" [Mesh], sin filtros metodológicos, publicados desde el inicio de cada base de datos hasta julio de 2019, sin restricciones idiomáticas, geográficas o temporales, considerando como desenlace primario: la identificación, resolución o reflexión de problemas éticos. Resultados Se encontraron 116 estudios, de los que 15 cumplieron los criterios de selección; el resto se trataba de revisiones narrativas y artículos de opinión. La población a la cual se le aplicó la intervención era de enfermería, medicina, odontología y un estudio a un comité de ética multidisciplinario. La intervención se ejecutó usando simulación con paciente estandarizado. Sólo dos estudios realizaron comparación con métodos tradicionales y el 60% consideró el desenlace primario de interés con resultados favorables. Conclusiones Hasta la fecha existen pocos estudios y con muy baja calidad de evidencia, que evalúen la efectividad de la simulación clínica en la enseñanza de la ética clínica. Los estudios encontrados demuestran que a corto plazo esta metodología logra que los participantes puedan identificar, resolver o reflexionar sobre los problemas éticos con el uso de pacientes estandarizados. Es aconsejable su incorporación como método de enseñanza y evaluación de la ética clínica, considerando los recursos disponibles.

Introduction In the teaching of clinical ethics, many traditional methods have been used that aim to develop competencies in the face of ethical challenges. Situations that can be reproduced in a standardized way through clinical simulation can be presented and evaluated in the training process of health professionals; however, its use requires evidence of effectiveness. Objective To identify and synthesize the available evidence on the effectiveness of teaching clinical ethics using simulation as a learning tool. Methods We conducted a bibliographic review, with searches in PubMed, LILACS and Cochrane databases using English and Spanish: "Ethics, Clinical/education" [Mesh]) AND "Simulation Training" [Mesh], without methodological filters, published from inception of each database until July 2019, without language, geographical or temporal restrictions. We considered as a primary outcome the identification, resolution or reflection on ethical problems. Results One hundred sixteen studies were retrieved. Fifteen studies met the selection criteria. Narrative reviews and opinion articles were excluded. The population to whom the intervention was applied were mainly students in nursing, medicine, and dentistry. A study in a multidisciplinary ethics committee was also included. The intervention was the use of the simulation technique with a standardized patient. Only two studies compared with traditional methods. Sixty percent considered the intervention to have favorable results on the primary outcome. Conclusions To date, there are few studies with very low quality of evidence that evaluate the effectiveness of clinical simulation in teaching clinical ethics. The studies found that, in the short term, this methodology allows participants to identify, solve or reflect on ethical problems by using standardized patients and it seems to be advisable to incorporate simulation techniques as part of the teaching and evaluation curriculum of clinical ethics, to the extent that resources are available.