P.Martin Padilla-Machaca
@unmsm.edu.pe
Universidad Nacional Mayor de San Marcos Facultad de Medicina de San Fernando
Scopus Publications
Scopus Publications
Liana Codes, Rodrigo Zapata, Manuel Mendizabal, Alfeu de Medeiros Fleck Junior, Juan Carlos Restrepo, Leonardo de Lucca Schiavon, Luiz Marcelo Sá Malbouisson, Wellington Andraus, Adrian Gadano, P. Martin Padilla-Machaca,et al.
Elsevier BV
Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas,et al.
BMJ
Background and aimsQuantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.MethodsStandard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients.ResultsThe CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission.ConclusionsIn patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.
E. Sarmiento, I. Ezzahouri, Maricela Jimenez-Lopez, Kristofer M. Limay Carré, Rocio Alonso, C. Ortiz-Bautista, M. Salcedo Plaza, M. L. Rodríguez-Ferrero, P. Padilla-Machaca, A. Cerron,et al.
Background Infection is a cause of morbidity and mortality in solid-organ transplantation (SOT). We evaluated a new score that is applied during the first month after transplantation. The score comprises biomarkers of innate and acquired immunity to predict infections in SOT. Material/Methods Prospectively collected blood samples from 377 heart, liver, or kidney recipients were analyzed at 2 centers in Madrid (Spain) and Lima (Peru). Biomarkers were tested before transplantation and at days 7 and 30 after transplantation. During the first 6 months after transplantation, 183 (48.5%) patients developed severe infections (bacterial infections and/or CMV disease). Risk for severe infection was assessed using logistic regression analysis. We designed a score, the routine immunity score (RIS2020), which is based on the sum of the hazard ratios (HRs) of each biomarker. Results The risk factors for severe infection were as follows: Moderate IgG hypogammaglobulinemia (IgG <600 mg/dL at days 7 or 30, HR 2.07, 95% CI 1.37–3.12, p=0.0005, 2 points), CD4 <400 cells/uL at day 30 (HR 1.76, 95% CI 1.03–3.04, p=0.039, 2 points), C3 <80 mg/dL at day 30 (HR 2.18, 95% CI 1.16–4.06, p=0.014, 2 points), and CRP >3 mg/dL at day 30 (HR 2.11, 95% CI 1.12–3.97, p=0.02, 2 points). In patients with ≥4 points, the HR for infection was 5.18 (95% CI 3.06–8.75; p<0.001). RIS2020 was an independent predictor of severe infection in multivariate models. Conclusions An immunological score combining moderate IgG hypogammaglobulinemia and other parameters of innate and acquired immunity could better identify the risk for severe infection in SOT.
Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, Quentin M. Anstee,et al.
Ovid Technologies (Wolters Kluwer Health)
Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, Marco Arrese,et al.
Elsevier BV
Alberto Queiroz Farias, Anna Curto Vilalta, Patricia Momoyo Zitelli, Gustavo Pereira, Luciana L. Goncalves, Aldo Torre, Juan Manuel Diaz, Adrian C. Gadano, Angelo Z. Mattos, Liliana S.C. Mendes,et al.
Elsevier BV
BACKGROUND & AIMS
Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (e.g., Covid-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure and high risk of short-term death.
METHODS
This prospective cohort study analyzed a comprehensive set of data including genetic ancestry and race, among several others, in 1274 patients with acutely decompensated cirrhosis (ADC) who were nonelectively admitted to 44 hospitals from 7 Latin American countries.
RESULTS
395 (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native Americans and a lower percentage of patients with ACLF than patients without were European Americans or African Americans. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% confidence interval [CI], 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs. European American race.
CONCLUSIONS
In a large cohort of Latin American patients with ADC, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.
P. Martin Padilla-Machaca, Eduardo Luna-Victoria, Ada Cabrera, Juan-Carlos Gómez-De la Torre, Rocio Galloso, and Pedro Montes
Elsevier BV
Federico Piñero, Marcos Thompson, Ilka Boin, Aline Chagas, Emilio Quiñonez, Carla Bermúdez, Mario Vilatobá, Luisa Santos, Margarita Anders, Sergio Hoyos Duque,et al.
Liver International Wiley
BACKGROUND & AIM
Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout due to tumor progression. The aim of this study was to compare the alfa-fetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout.
METHODS
A multicenter cohort study was conducted in 20 Latin American transplant centers, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumor characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics.
RESULTS
HCC dropout rate was significantly higher in patients beyond [24% (95% CI 16-28)] compared to those within Milan criteria [8% (95% IC 5-12%); P<.0001], with a SHR of 3.01 (95% CI 2.03-4.47)], adjusted for waiting list time and bridging therapies (c-index 0.63 (95% CI 0.57;0.69). HCC dropout rates were higher in patients with AFP scores >2 [adjusted SHR of 3.17 (CI 2.13-4.71)], c-index of 0.71 (95% CI 0.65-0.77; P=0.09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout [SHR 1.68 (95% CI 1.08-2.61)].
CONCLUSIONS
Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.
Luis Antonio Díaz, Eduardo Fuentes-López, Gustavo Ayares, Francisco Idalsoaga, Jorge Arnold, Andrea Márquez-Lomas, Carolina A Ramírez, María Paz Medel, Francisca Viñuela, Lucas Lacalle,et al.
The Lancet Gastroenterology and Hepatology Elsevier BV
Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan,et al.
Elsevier BV
Manuel Mendizabal, Ezequiel Ridruejo, Federico Piñero, Margarita Anders, Martín Padilla, Luis G. Toro, Aldo Torre, Pedro Montes, Alvaro Urzúa, Esteban Gonzalez Ballerga,et al.
Elsevier BV
Carmen Ana Cerron Cabezas, Rosa Luz Lopez Martinez, Gino Salcedo Bermudez, Pedro Martin Padilla Machaca, Bertha Eliana Cardenas Ramirez, Wilmer Bacilio Calderon, Omar Mantilla Cruzatti, Jose Rivera Romani, Alfonso Solar Peche, Augudberto Montufar Valer,et al.
Sociedad de Gastroenterologia del Peru
Liver transplantation is the major treatment for end-stage liver disease. Postoperative care is a great challenge to reduce morbidity and mortality in patients. In this sense, management in the liver ICU allows hemodynamic management, coagulation monitoring, renal support, electrolyte disturbances, respiratory support and early weaning from mechanical ventilation and evaluation of the liver graft. Objective: The present study shows the results of the management of liver transplant patients in 20 years of experience in a transplant center in a low- to middle-income country. Materials and methods: The medical records of 273 adult patients in the ICU in the immediate postoperative liver transplant were reviewed, from March 20, 2000 to November 30, 2020, including the effect of the pandemic caused by COVID-19. Liver-kidney, retransplanted, SPLIT, and domino transplant patients were excluded. Results: The most frequent etiology for LTx was NASH (35%), the mean age was 49 years, MELD Score ranged 15 - 20 (47.5%), 21 - 30 (46%) > 30 (6.2%). ICU pre transplant stay 7%, average ICU stay: 7.8 days. APACHE average admission: 14.9 points. Weaning extubation of 91.8% patients in ICU and Fast Track in 8.2%. The most frequent respiratory complication was atelectasis 56.3%, pneumonia (31.3%); AKI 1 (60.9%), and 11.1% with hemodyalisis support (AKI3). Immunosuppression: Tacrolimus (8.9%). Post-operative ICU mortality was 6.2%. Conclusions: The management of liver transplantation in the ICU is essential to achieve optimal results in patients who present advanced liver disease and require advanced life support in the immediate postoperative period and thus optimize graft survival.
Milagros Davalos, María Cabrera Cabrejos, César García Delgado, Martin Padilla, Carlos Yanar Pereda Vejarano, Romina Andrea Vera Mujica, Jorge Huaringa-Marcelo, Jose Montes-Alvis, Sergio Goicochea-Lugo, Naysha Becerra-Chauca,et al.
Sociedad de Gastroenterologia del Peru
Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la infección crónica por el virus de Hepatitis C en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la infección crónica por el virus de Hepatitis C en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas y metodólogos. El GEG formuló 4 preguntas clínicas. Se realizó búsquedas sistemáticas de revisiones sistemáticas y estudios primarios en PubMed y Central de Cochrane durante el 2019. Se seleccionó la evidencia para responder a las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). El GEG usó la metodología GRADE para revisar la evidencia y formular recomendaciones, los puntos de buena práctica clínica y el flujograma de tratamiento. Finalmente, la GPC fue aprobada con Resolución N° 151-IETSI-ESSALUD-2019. Resultados: La presente GPC abordó 4 preguntas clínicas, divididas en cuatro temas: tamizaje, diagnóstico, estadiaje y tratamiento. En base a estas preguntas se formularon 13 recomendaciones (8 fuertes y 5 condicionales), 27 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la infección crónica por el virus de Hepatitis C en EsSalud.
Claudia Maccali, Aline L. Chagas, Ilka Boin, Emilio Quiñonez, Sebastián Marciano, Mario Vilatobá, Adriana Varón, Margarita Anders, Sergio Hoyos Duque, Agnaldo S. Lima,et al.
Wiley
BACKGROUND & AIM
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS.
METHODS
This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence.
RESULTS
From a total of 1,085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/TACE. Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination [ROC of 0.81 (CI 0.72;0.88)]. After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P<0.0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P=0.003, and for surgery/TACE HR of 0.4 (0.18;0.78); P=0.009.
CONCLUSION
Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS. Word Count: 246.
Federico Piñero, Margarita Anders, Ilka F. Boin, Aline Chagas, Emilio Quiñonez, Sebastián Marciano, Mario Vilatobá, Luisa Santos, Sergio Hoyos Duque, Agnaldo Soares Lima,et al.
Transplant International Wiley
Juan Pablo Arab, Melisa Dirchwolf, Mário Reis Álvares-da-Silva, Francisco Barrera, Carlos Benítez, Marlene Castellanos-Fernandez, Graciela Castro-Narro, Norberto Chavez-Tapia, Daniela Chiodi, Helma Cotrim,et al.
Annals of Hepatology Elsevier BV
Alfonso Solar Peche, P. Martin Padilla-Machaca, Carmen Cerron Cabezas, Bertha Cárdenas Ramírez, José Rivera Romaní, Omar Mantilla Cruzatti, Carlos Rondón Leyva, and José-Carlos Chaman Ortiz
Sociedad de Gastroenterologia del Peru
Introducción: La no función primaria del injerto (NFPI) después del trasplante hepático es la falla aguda del injerto, en ausencia de algún factor causal, como trombosis aguda de arteria hepática o vena porta. Objetivos: Describir las características perioperatorias de los pacientes trasplantados de Hígado que presentaron NFPI en el Departamento de Trasplantes del Hospital Guillermo Almenara Irigoyen. Materiales y métodos: Estudio retrospectivo, descriptivo y transversal. Desde marzo del 2000 a marzo del 2018 se realizaron 249 Trasplantes de hígado. La NFPI fue definida con los criterios de OPTN/UNOS, se manifiesta por aumento de transaminasas (>3 000 UI/ml), coagulopatía (INR >2,5), niveles altos de lactato (>4 mEq/l), PH en acidosis: PH arterial ≤7,30 y/o PH venoso ≤7,25 e inestabilidad hemodinámica que requiere soporte con drogas vasoactivas; puede llevar a la muerte sin retrasplante de emergencia. Resultados: Se diagnosticaron 8 pacientes con NFPI siendo una prevalencia de 3,7% de 216 trasplantes de hígado en adultos, la edad de los receptores fue 51,5±8,45 años, score de MELD basal 13,13±3,8 (rango 6-18). Las características de los donantes, la edad fue 38,5±14,48, todos ABO idénticos al receptor, la distribución geográfica: 7 de Lima metropolitana y 1 en Tacna. La causa de muerte encefálica 75% ACV Hemorrágico y 25% TEC grave. Respecto a factores transoperatorios el TIF 431±143 min [265 - 645 min], y TIC 81,8±46 min [57- 195 min], La estancia en UCI hasta el deceso del paciente fue 11,13±9,3 días (rango 2-31 días), el 12,5% fue retrasplantado. Conclusiones: La prevalencia de NFPI en nuestro centro después del trasplant a las series reportadas por otros centros, y se asocia con mortalidad alta sin retrasplante hepático.
Federico Piñero, Ilka Boin, Aline Chagas, Emilio Quiñonez, Sebastián Marciano, Mario Vilatobá, Luisa Santos, Margarita Anders, Sergio Hoyos Duque, Agnaldo Soares Lima,et al.
Wiley
The association between direct‐acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait‐list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait‐list progression and post‐LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait‐list progression adjusted by a propensity score matching (pre‐LT DAA effect) and for post‐LT HCC recurrence (pre‐ or post‐LT DAA effect). From 994 included patients, 50.6% were HCV−, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait‐list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC‐related dropout rate (12.1% [95% CI, 0.4%‐8.1%] versus 12.9% [95% CI, 3.8%‐27.2%]), adjusted for baseline tumor burden, alpha‐fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6‐1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre‐ or post‐LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%‐4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait‐list tumor progression and HCC recurrence after LT.
Federico Piñero, Paulo Costa, Yuri Longatto Boteon, Sergio Hoyos Duque, Sebastian Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Jaime Poniachik, Alejandro Soza,et al.
Elsevier BV
BACKGROUND AND AIM
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America.
METHODS
From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant.
RESULTS
Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD.
CONCLUSION
There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.