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Antiviral treatment for chronic hepatitis B in renal transplant patients

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World Journal of Hepatology 2015年第2期7卷 189-203页

作者： ezequiel ridruejo Hepatology Section Department of Medicine Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC" Ciudad Autónoma de Buenos Aires Hepatology and Liver Transplant Unit Hospital Universitario Austral Pilar

Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some datashowing a favorable safety and efficacy profile of nucleos(t)ide analogue(NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC na?ve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under anti HBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population.

关键词： Tenofovir Long term outcome Hepatitis B Renal transplantation Entecavir

Hepatocellular carcinoma in Latin America: Diagnosis and treatment challenges

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World Journal of Gastroenterology 2018年第37期24卷 4224-4229页

作者： Federico Pinro Jaime Poniachik ezequiel ridruejo Marcelo Silva Hospital Universitario Austral Facultad de Ciencias BiomédicasUniversidad AustralPilarBuenos Aires B1629HJArgentina American Liver Research Educational and Awareness Network Buenos Aires B1629HJArgentina Hepatology Hospital Clínico Universidad de ChileSantiago de ChileRegión Metropolitana Santiago 46010Chile Santa María Santiago de ChileRegión Metropolitana Santiago 834-0518Chile Médica e Investigaciones Clínicas Norberto Quirno Ciudad de Buenos Aires C1425ASGArgentina

Latin America, a region with a population greater than 600000000 individuals, is well known due to its wide geographic, socio-cultural and economic heterogeneity. Access to health care remains as the main barrier that challenges routine screening, early diagnosis and proper treatment of hepatocellular carcinoma(HCC). Therefore, identification of population at risk, implementation of surveillance programs and access to curative treatments has been poorly obtained in the region. Different retrospective cohort studies from the region have shown flaws in the implementation process of routine surveillance and early HCC diagnosis. Furthermore, adherence to clinical practice guidelines recommendations assessed in two studies from Brazil and Argentina demonstrated that there is also room for improvement in this field, similarly than the one observed in Europe and the United States. In summary, Latin America shares difficulties in HCC decision-making processes similar to those from developed countries. However, a transversal limitation in the region is the poor access to health care with the consequent limitation to standard treatments for overall population. Specifically, universal health care access to the different World Health Organization levels is crucial, including improvement in research, education and continuous medical training in order to expand knowledge and generation of data promoting a continuous improvement in the care of HCC patients.

关键词： Latin America Liver cancer Limitations Challenge

Imatinib-induced fatal acute liver failure

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World Journal of Gastroenterology 2007年第48期13卷 6608-6611页

作者： ezequiel ridruejo Roberto Cacchione Alejandra G Villamil Sebastián Marciano Adrián C Gadano Oscar G Mandó Hepatology Section Hematology Section Department of Medicine Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC Buenos Aires Argentina Liver Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d. Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

关键词： Imatinib mesylate Hepatotoxicity Acute liver failure Liver transplantation

Hepatitis C virus treatment failure:Clinical utility for testing resistance-associated substitutions

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World Journal of Hepatology 2021年第9期13卷 1069-1078页

作者： ezequiel ridruejo Matias Javier Pereson Diego M Flichman Federico Alejandro Di Lello Hepatology Section Department of MedicineCentro de Educacion Medica e Investigaciones Clinicas Norberto Quirno“CEMIC”Ciudad Autonoma de Buenos Aires C1425ASUnspecifiedArgentina Facultad de Farmacia y Bioquimica Instituto de Investigaciones en Bacteriologea y Virologea Molecular(IBaViM)Universidad de Buenos AiresCiudad Autonoma de Buenos Aires 1113Argentina Instituto de Investigaciones Biomedicas en Retrovirus y Sindrome de Inmunodeficiencia Adquirida(INBIRS) Universidad de Buenos AiresCiudad Autonoma de Buenos Aires 1113Argentina

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic *** fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been *** the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still ***,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

关键词： Hepatitis C virus Treatment failure Resistance Direct-acting antiviral

Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

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World Journal of Gastroenterology 2019年第27期25卷 3607-3618页

作者： Federico Pinero Sebastián Marciano Nora Fernández Jorge Silva Margarita Anders Alina Zerega ezequiel ridruejo Gustavo Romero Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hospital Universitario Austral Facultad de Ciencias BiomédicasUniversidad AustralBuenos Aires B1629HJArgentina Latin American Liver Research Educational and Awareness Network(LALREAN) Buenos Aires B1629HJArgentina Hospital Italiano de Buenos Cuidad Autónoma de Buenos AiresBuenos Aires C1424BYEArgentina Hospital Británico Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Hospital G Rawson San Juan 5400Argentina Hospital Aleman Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Sanatorio Allende from Córdoba Córdoba 5016Argentina Centro de Educación Médica e Investigaciones Clínicas“Norberto Quirno”(CEMIC) Ciudad de Buenos Aires 1431Argentina Hospital Udaondo Cuidad Autonoma de Buenos Aires C1264AAAArgentina Hospital Ramos Mejía Ciudad de Buenos Aires C1221ADCArgentina Centro Especialidades Medicas Ambulatorias(CEMA) Mar del PlataBuenos Aires 7600Argentina Clínica de Nefrología Santa Fe 3000Argentina Hospital del Centenario RosarioSanta Fe S2002KDTArgentina

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of *** To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic *** This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or *** Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage *** median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results we

关键词： Hepatocellular carcinoma Therapeutics Survival Real-life

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

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World Journal of Hepatology 2018年第1期10卷 41-50页

作者： Federico Pinero Josefina Pages Sebastián Marciano Nora Fernández Jorge Silva Margarita Anders Alina Zerega ezequiel ridruejo Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Manuel Cobos Carlos Rosales Gustavo Romero Lucas McCormack Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hepatology and Liver Transplantation Unit Hospital Universitario AustralBuenos Aires 1629Argentina Hepatology Section Liver Transplant ProgramDepartment of Academic ResearchHospital Italiano from Buenos AiresBuenos Aires 1424Argentina Sanatorio Trinidad San Isidro Buenos Aires 1642Argentina Clínica Privada San Fernando Buenos Aires 2013Argentina Hepatology and Gastroenterology Hospital BritánicoBuenos Aires 1280Argentina Hepatobiliary Surgery Hospital G RawsonSan Juan 5400Argentina Department of Hepatology and Liver Transplant Program Hospital AlemanBuenos Aires 1118Argentina Department of Hepatology and Liver Transplantation Sanatorio AllendeCórdoba 5016Argentina Hepatology Section Department of MedicineCentro de Educación Médica e Investigaciones Clínicas Norberto Department of Hepatology Hospital Ramos MejíaBuenos Aires 1221Argentina Department of Hepatology Centro Especialidades Medicas Ambulatorias(CEMA)Mar del Plata 7600Argentina Department of Hepatology and Liver Transplantation Clínica de Nefrología de Santa FeSanta Fe 3000Argentina Department of Hepatology and Gastroenterology Hospital C Bonorino UdaondoBuenos Aires 1264Argentina Department of Hepatology and Gastroenterology Hospital CentenarioSanta Fe 2002Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical *** A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher *** The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

关键词： Hepatocellular carcinoma Etiology Fatty liver South America

Hepatitis C virus infection in Argentina: Burden of chronic disease

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World Journal of Hepatology 2016年第15期8卷 649-658页

作者： ezequiel ridruejo Fernando Bessone Jorge R Daruich Chris Estes Adrián C Gadano Homie Razavi Federico G Villamil Marcelo O Silva Hepatology Section Department of Medicine Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno Hepatology and Liver Transplant Unit Hospital Universitario Austral Hepatology Section Escuela de Medicina Universidad de Rosario Hepatology Section Hospital de Clínicas San Martín Universidad de Buenos Aires Center for Disease Analysis Louisville Hepatology and Liver Transplant Unit Hospital Italiano de Buenos Aires Liver Transplantat Unit Hospital Británico

AIM: To estimate the progression of the hepatitis C virus(HCV) epidemic and measure the burden of HCVrelated morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed:(1) increased sustained virologic response(SVR); and(2) increased SVR and ***: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liverrelated deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.

关键词： Diagnosis Disease burden Epidemiology Incidence Mortality Prevalence Treatment Argentina Hepatitis C

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

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World Journal of Hepatology 2015年第4期7卷 703-709页

作者： Sebastian Marciano Silvia M Borzi Melisa Dirchwolf ezequiel ridruejo Manuel Mendizabal Fernando Bessone Maria E Sirotinsky Diego H Giunta Julieta Trinks Pablo A Olivera Omar A Galdame Marcelo O Silva Hugo A Fainboim Adrian C Gadano Liver Unit Hospital Italiano de Buenos Aires Hepatology Section Hospital R. Rossi La Plata Buenos Aires Argentina Liver Infectious Disease Unit Hospital F.J Muniz Uspallata 2272 Buenos Aires Argentina Hepatology Section Department of Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Avenida Galvan 4102 Buenos Aires Argentina Hepatology and Liver Transplant Unit Hospital Universitario Austral Hepatology Unit Sanatorio del Parque Rosario Argentina HEPATOSUR group Comodoro Rivadavia Chubut Argentina Internal Medicine Research Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina Basic Science and Experimental Medicine Institute Hospital Italiano de Buenos Aires Internal Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Buenos Aires Argentina

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.

关键词： Sustained virological response Direct antiviral agents Sofosbuvir Cirrhosis Viral load

Impacts of brood parasitism by shiny cowbird Molothrus bonariensis on the breeding success of a small host, the black-backed water tyrant Fluvicola albiventer

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Current Zoology 2024年第4期70卷 539-547页

作者： Lorena Vanesa Sovrano Evelina Jesica Leon Rodrigo ezequiel Lorenzón Pamela Fernanda Olguin Adolfo Héctor Beltzer Alejandro Raúl Giraudo Laboratorio de Biodiversidad y Conservacion de Tetrapodos Instituto Nacional de Limnologia(INALICONICET-UNL)Paraje El Pozo s/nSanta Fe(3000)Argentina Departamento de Biologia Universidad Autonoma de Entre RiosKm 10.5 RP 11Oro Verde(3100)Entre RiosArgentina Departamento de Biologia Universidad Nacional del LitoralFacultad de Humanidades y CienciasParaje Ei Pozo s/nSanta Fe(3000)Argentina

The shiny cowbird Molothrus bonariensis parasitizes many species with different life-history traits and has a detrimental effect on the survival of the progeny of the *** response,hosts have developed numerous antiparasitic ***,we examined the effects of brood parasitism by shiny cowbird on the clutch and brood sizes(83 nests)in a small host,the black-backed water tyrant Fluvicola *** also studied whether the death of parasite nestlings was related to the care of the foster parents and whether the host had any antiparasitic defense against the shiny *** results indicate that brood parasitism significantly decreased the host hatching and fledging *** majority of nest failures(57%)were caused by brood *** cowbird parasitism occurred in 52%of nests and the intensity of parasitism was 1.23±0.53 eggs per parasitized *** the total host eggs,54%were *** the incubation stage,20 nests(47%)were abandoned because of egg punctures by shiny cowbirds *** two parasitic fledglings were recorded,while the remaining nestlings either died from starvation(n=12)or predation(n=3).Foster parents abandoned parasitic nestlings between 5 and 10 days *** findings demonstrate that the shiny cowbird has very low rates of fledging success when parasitizing black-backed water ***,parasitism had a high reproductive cost in the black-backed water tyrant because a very low proportion(7%)of the parasitized nests(n=43)were successful.

关键词： brood parasitism host defenses nest desertion shiny cowbird small host.