Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

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 1085 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/trans-arterial chemoembolization (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 (receiving operator curve 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 < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.

The Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado; ALEH) represents liver professionals in Latin America with the mission of promoting liver health and quality patient care by advancing the science and practice of hepatology and contributing to the development of a regional health policy framework. Fatty liver disease associated with metabolic dysfunction is of specific concern in the ALEH region, where its prevalence is one of the highest globally, second only to the Middle East. A recent consensus from an international panel recommended a new definition of fatty liver disease associated with metabolic dysfunction, including a shift in name from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), and adoption of a set of positive criteria to diagnose the disease, independent of alcohol intake or other liver diseases. Given, the importance of this proposal, ALEH invited leading members of regional nations to come to a consensus on it from a local perspective. We reached a consensus to endorse the proposal that the disease should be renamed as MAFLD and that the disease should be diagnosed by the proposed simple and easily applicable criteria. We expect that this change in nosology will result in improvements in disease awareness and in advances in scientific, economic, public health, political, and regulatory aspects of the disease.

[Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs]. / Experiencia peruana en el tratamiento de hepatitis crónica C con las nuevas drogas antivirales de acción directa.

OBJECTIVE: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. MATERIAL AND METHODS: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. RESULTS: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. CONCLUSIONS: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.

Experiencia peruana en el tratamiento de hepatitis crónica C con las nuevas drogas antivirales de acción directa / Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs

Objetivos: La terapia ideal para la hepatitis crónica C consiste en el uso de drogas antivirales de acción directa (DAA). En el Perú la experiencia en vida real con DAA no se conoce, por lo que el objetivo del presente estudio es reportar la alta eficacia terapéutica con estos esquemas. Material y métodos: Mediante correo electrónico se invitó a participar a través de una encuesta a médicos hepatólogos a nivel nacional. Se incluyeron los datos de 4 médicos. Los resultados fueron analizados con estadística descriptiva. Resultados: Se incluyeron 63 pacientes, la edad promedio fue 59 años, varones fueron 49,21%, cirrosis estuvo presente en el 49,21% (31/63), 34,92% había sido no respondedor a terapia con PEGIFN/RBV. El Genotipo 1 estuvo presente en 93,65% de casos, siendo el 1a el predominante (58,73%). Solo hubo dos casos de genotipo 2 y uno de genotipo 3. Se utilizaron 10 esquemas de combinación con DAA, siendo los más eficaces, Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/ Ribavirina y Sofosbuvir/Simeprevir, en todos ellos se logró Respuesta Viral Sostenida (RVS) de 100%. Con los otros 7 esquemas la RVS fue menor a 90% o solo se había incluido uno o dos pacientes. La tolerancia a la terapia fue adecuada y todos los pacientes culminaron la terapia. Conclusiones: En vida real los esquemas de terapia antiviral para hepatitis C con DAA tienen alta eficacia y seguridad. Las mejores respuestas se obtuvieron con Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina y Sofosbuvir/Simeprevir. Esta data puede ser útil para considerar estrategias de tratamiento con el enfoque de salud pública.

Objective: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. Material and methods: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. Results: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/ Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. Conclusions: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.

[Liver transplant and hepatocellular carcinoma in Peru: outcome after 15 years in the transplant department of the Guillermo Almenara Hospital - EsSalud]. / Hepatocarcinoma y trasplante hepático en Perú: resultados de 15 años del Departamento de Trasplantes del Hospital Nacional Guillermo Almenara Irigoyen - EsSalud.

Hepatocellular carcinoma (HCC) is a neoplasm with significant incidence and prevalence in the world. In large percentage it originates from a cirrhotic liver. Liver transplantation under special conditions is effective in the simultaneous treatment of both conditions. Information is scarce in Latin America. This is a cross-sectional study of the first 200 liver transplants of our series (Years 2000-2015). During this period, 26 (13%) patients had a diagnosis of HCC. Of the 26 transplanted with HCC, 21 (81%) patients were male. The average age was 59.7 years. The most frequent cirrhotic etiology was NASH with nine (35%) cases, followed by HCV and OH with six (23%). The average of AFP pre-transplant was 113.3. Downstaging was performed in four patients. The overall survival obtained is 90.9% over 5 years. The recurrence-free survival in our series is 95.5% at 5 years.

Hepatocarcinoma y trasplante hepático en Perú: resultados de 15 años del Departamento de Trasplantes del Hospital Nacional Guillermo Almenara Irigoyen - EsSalud / Liver transplant and hepatocellular carcinoma in Peru: outcome after 15 years in the transplant department of the Guillermo Almenara Hospital - EsSalud

El carcinoma hepatocelular (CHC) es una neoplasia con incidencia y prevalencia significativa en el mundo. Ésta en gran porcentaje se origina en el hígado cirrótico. El trasplante hepático bajo condiciones especiales, ha demostrado ser efectivo en el tratamiento simultáneo de ambas condiciones. En América latina la información es escasa. Este es un estudio de tipo descriptivo retrospectivo de corte transversal, cuyo universo es conformado por los primeros 200 trasplantes de hígado de nuestra serie (Años 2000-2015). Durante el periodo mencionado 26 (13%) pacientes tuvieron diagnóstico de CHC. De los 26 trasplantados con CHC, 21 (81%) pacientes fueron de sexo masculino. El promedio de edad fue 59,7 años. La etiología cirrótica más frecuente fue NASH con 9 (35%) casos, seguida de VHC y OH con 6 (23%). El promedio de AFP pre trasplante fue de 113,3. El ¨downstaging¨ fue realizado en 4 pacientes. La sobrevida global obtenida es de 90,9% a más de 5 años. La sobrevida libre de recurrencia en nuestra serie es de 95,5% a 5 años.

Hepatocellular carcinoma (HCC) is a neoplasm with significant incidence and prevalence in the world. In large percentage it originates from a cirrhotic liver. Liver transplantation under special conditions is effective in the simultaneous treatment of both conditions. Information is scarce in Latin America. This is a cross-sectional study of the first 200 liver transplants of our series (Years 2000-2015). During this period, 26 (13%) patients had a diagnosis of HCC. Of the 26 transplanted with HCC, 21 (81%) patients were male. The average age was 59.7 years. The most frequent cirrhotic etiology was NASH with nine (35%) cases, followed by HCV and OH with six (23%). The average of AFP pre-transplant was 113.3. Downstaging was performed in four patients. The overall survival obtained is 90.9% over 5 years. The recurrence-free survival in our series is 95.5% at 5 years.

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America.

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.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

BACKGROUND & AIMS: The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. METHODS: Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. RESULTS: Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. CONCLUSIONS: The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV.

Problemática del trasplante de órganos y tejidos en el Perú / Problem of organ and tissue transplantation in Peru

El presente documento tiene como finalidad el de presentar de forma resumida la problemática de los principales Trasplantes de Órganos y Tejidos, revisada y expuesta por expertos nacionales en lo referente a trasplante de hígado, riñón y de progenitores hematopoyéticos, analizando el contexto regional y mundial, la situación actual y resultados de la actividad de trasplante en nuestro país, así como las perspectivas futuras y alternativas de solución de un problema que es de carácter universal.

This document aims to present in summary form the main problem of Organ and Tissue Transplantation, revised and posted by national experts in relation to liver transplants, kidney and hematopoietic progenitors, evaluating regional and global context, current status and results of transplant activity in our country as well as future perspectives and alternative solutions to this universal problem.

Guía de práctica clínica para el diagnóstico y tratamiento de la hepatitis crónica por el virus de la hepatitis B / Practice guideline for diagnosis and treatment of chronic hepatitis virus hepatitis B

La presente guía establece los criterios técnicos para el diagnóstico y tratamiento de la hepatitis crónica secundaria a hepatitis viral B con la finalidad de contribuir a reducir la morbimortalidad de esta enfermedad. Da las definiciones para comprender las recomendaciones aquí dadas. Descripción de aspectos epidemiológicos, factores de riesgo asociados; aspectos clínicos y de diagnóstico de la hepatitis crónica por virus B. Se dan las recomendaciones de manejo incluyendo circunstancias especiales tales como el paciente con cirrosis, el paciente con coinfección VIH ó con coinfección con hepatitis C. Las recomendaciones aquí mencionadas se convierten en la guía nacional para el manejo de la Hepatitis crónica por hepatitis B.

This guide sets out the technical criteria for the diagnosis and treatment of chronic hepatitis secondary to viral hepatitis B. The guide intend to reduce the morbidity and mortality of this disease. The Guide give practical definitions to help understand the terminology, describe epidemiology, risk factors, and clinical aspects and the diagnosis of chronic hepatitis B. Finally the guide give recommendations for the management including special circumstances such as patients with cirrhosis, patients coinfected with HIV or coinfected with hepatitis C. The recommendations of the guide become the national guide for the management of chronic hepatitis B.