Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series.

BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rate 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. OBJECTIVES: 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.

ANTECEDENTES: El tratamiento del virus de la hepatitis C (VHC) crónica 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.

Clostridium difficile infection in patients with chronic kidney disease in Mexico
.

BACKGROUND: Clostridium difficile infection (CDI) is a leading cause of healthcare-associated diarrhea worldwide. Patients with chronic kidney disease (CKD) are especially vulnerable, as they are exposed to CDI risk factors including frequent antibiotics. MATERIALS AND METHODS: In order to identify the risk factors for CDI in CKD patients, a 33-month long case-control study was carried out at a tertiary-care hospital in Mexico. CDI was confirmed at the genetic level, and univariate and multivariate analyses were performed to identify the association between risk factors, biomarkers, and outcome options (survival, relapse, death). RESULTS: Among the 1,198 patients with healthcare-associated diarrhea, 354 (29.5%) were CDI cases. 105 (29.6%) CDI cases and 192 (22.7%) controls had CKD. 84 (80%) CKD+CDI cases had a favorable outcome, 10 (9.5%) relapsed, and the 3-month mortality rate included 11 (10.4%) patients. Compared with controls, CDI cases had more previous hospitalizations (63.8 vs. 46.9%, p = 0.005), abdominal distension (46.7 vs. 36.5%, p = 0.056), abdominal pain (60.0 vs. 41.1%, p = 0.002), and polymorphonuclear leukocyte in stools (71.4 vs. 40.5%, p = 0.001) as well as poorer outcomes at 3 months. The patients in the 027-strain group were older, and most of the patients had CKD stage 5 (88.5% vs. 71.1%, p = 0.007), while CKD stage-4 patients were more frequently infected with non-027 strains. In the multivariate analysis of risk factors for CDI, only previous antibiotic exposure (odds ratio = 2.01, 95% confidence interval: 1.05 - 3.84; p = 0.034) was independently associated with CDI in patients with CKD stage 5. CONCLUSION: Mexican patients with CKD are at risk for CDI. This susceptible group should be protected by promoting appropriate guidelines.
.

Prevalence of Metabolic-associated Fatty Liver Disease in Mexico and Development of a Screening Tool: The MAFLD-S Score.

Background and Aims: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease. Nowadays, the prevalence of MAFLD in Mexico is unknown with no screening point-of-care tools. We aimed to estimate the prevalence of MAFLD in Mexico and to develop a score for MAFLD screening. Methods: We conducted a cross-sectional study in 5 Mexican states, including adult subjects evaluated in checkup campaigns. Subjects underwent a liver ultrasound to look for hepatic steatosis. Based on the most clinically relevant variables associated with MAFLD, we developed the MAFLD-screening score (MAFLD-S). Discrimination and calibration of the score were evaluated using the area under the ROC curve and observed vs predicted plots, respectively. Results: We included 3357 participants (60% female, mean age 47 ± 12 years). Fifty-two percent had hepatic steatosis, and 47% met MAFLD criteria. Subjects with MAFLD were older (48 ± 11 vs 45 ± 13 years, P < .001), were more frequently males (43% vs 36%, P < .001), and had a higher body mass index (31.6 + 4.9 vs 25.6 + 3.8 kg/m2, P < .001) than subjects without MAFLD. The MAFLD-S includes age, body mass index, gender, diabetes, hypertension, and dyslipidemia and has an area under the curve of 0.852, 95% CI = 0.828-0.877, with a sensitivity of 78.8% and a specificity of 82.8% for the optimal cutoff. Using data from the National Health and Nutrition Survey 2018-2019, we predicted a MAFLD national prevalence of 49.6%. Conclusion: Nearly half of the Mexican population has MAFLD, representing a present and future challenge. With external validation, the MAFLD-S could be a valuable and practical screening tool.

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.