Liver transplantation in Latin America: reality and challenges.

Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.

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.

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.

Immunotolerance in liver transplantation: a primer for the clinician.

The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.

Humoral response to different SARS-CoV-2 vaccines in orthotopic liver transplant recipients.

BACKGROUND: The safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients. METHODS: Participants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA). RESULTS: A total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response. CONCLUSION: The serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.

Liver Transplantation in Mexico.

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Impact of the COVID-19 pandemic on the clinical training of last year medical students in Mexico: a cross-sectional nationwide study.

BACKGROUND: The COVID-19 pandemic has brought unprecedented changes to medical education. However, no data are available regarding the impact the pandemic may have on medical training in Mexico. The aim of our study was to evaluate and identify the medical school students' perceptions of the changes in their clinical training due to the pandemic in Mexico. METHODS: This was a cross-sectional study where a previous validated online survey was translated and adapted by medical education experts and applied to senior medical students from March to April of 2021. The 16-item questionnaire was distributed online combining dichotomous, multiple-choice, and 5-point Likert response scale questions. Descriptive and multivariate analyses were performed to compare the student's perceptions between public and private schools. RESULTS: A total of 671 responses were included in the study period. Most participants were from public schools (81%) and female (61%). Almost every respondent (94%) indicated it was necessary to obtain COVID-19 education, yet only half (54%) received such training. Students in private schools were less likely to have their clinical instruction canceled (53% vs. 77%, p = 0.001) and more likely to have access to virtual instruction (46% vs. 22%, p = 0.001) when compared to students from public schools. Four out of every five students considered their training inferior to that of previous generations, and most students (82%) would consider repeating their final year of clinical training. CONCLUSIONS: The impact of the COVID-19 on medical education in Mexico has been significant. Most final-year medical students have been affected by the cancellation of their in-person clinical instruction, for which the majority would consider repeating their final year of training. Efforts to counterbalance this lack of clinical experience with virtual or simulation instruction are needed.

Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.

Transplant trends in Mexico during the COVID-19 pandemic: Disparities within healthcare sectors.

Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic (pre-COVID: March 2019-February 2020 vs. COVID era: March 2020-February 2021) and by type of institution (public vs. private). The global reduction in transplantation was higher in public institutions compared with private institutions, 89% versus 62%, respectively, p < .001. When analyzing by organ, kidney transplantation decreased by 89% at public versus 57% at private, p < .001; cornea by 88% at public versus 64% at private, p < .001; liver by 88% at public versus 35% at private, p < .001; and heart by 88% in public versus 67% at private institutions, p = .4. The COVID-19 pandemic along with the implemented health policies were associated with a decrease in donations, waiting list additions, and a decrease in transplantation, particularly at public institutions, which care for the most vulnerable.

Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature.

BACKGROUND Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. CASE REPORT We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. CONCLUSIONS The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase.