Nelia Hernández

Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases

Cyproterone acetate (CPA), an anti‐androgenic drug for prostate cancer, has been associated with drug‐induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA‐induced DILI.

Hepatotoxicity induced by coxibs: how concerned should we be?

ABSTRACT Introduction: The selective inhibitors of COX-2, coxibs, are nonsteroidal anti-inflammatory drugs (NSAIDs) that have much better gastrointestinal safety profile as compared with non-selective NSAIDs. In this review, we analyze both the epidemiological features of coxib-induced hepatotoxicity and the clinical impact of coxib-associated liver damage, based on literature data. Areas covered: We carried out a search of the databases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January 2016, to retrieve studies exploring the real impact of coxibs in liver toxicity as compared to non-selective COX-2 inhibitor NSAIDs. Expert opinion: Although reliable data on the incidence of celecoxib- and etoricoxib-induced hepatotoxicity are lacking, because of cohort studies have been generally underpowered to detect hepatic events, coxibs have been scarcely related to hepatotoxicity. Hence, coxib-induced liver injury seems to be an uncommon event, yet exhibits a wide spectrum of damage. Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, and lumiracoxib, has been associated with higher cardiovascular risk, as well as dermatological and serious hepatic reactions. The actual risk of liver toxicity from the currently approved coxibs compared with non-selective NSAIDs will be discussed. Finally, classical and novel molecular mechanisms of coxib-induced hepatotoxicity are also described.

Hepatocellular carcinoma in South America: Evaluation of risk factors, demographics and therapy

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America.

Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real‐clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real‐world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child‐Pugh B at baseline and one patient died due to multi‐organ failure. Follow up HCV‐RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child‐Pugh A cirrhosis in non‐European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child‐Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.

Early-age hepatocellular carcinoma associated with hepatitis B infection in South America

Fil: Cairo, F. Hospital de Alta Complejidad en Red El Cruce Dr. Nestor C. Kirchner. Servicio de Gastroenterologia. Florencio Varela, Argentina.

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients

BackgroundHost single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection.MethodsDNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR.ResultsThe distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant.ConclusionPatients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of “good” response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.

The influence of drug properties and host factors on delayed onset of symptoms in drug-induced liver injury

Most patients with drug‐induced liver injury (DILI) manifest clinical symptoms while on therapy, while some patients manifest days or weeks after drug cessation (delayed onset). This challenges DILI causality assessment and diagnosis. Factors contributing to the delayed onset phenotype are currently unknown. We explored factors contributing to delayed onset of DILI by analysing culprit drug properties, host factors and their interactions in a large patient population from the Spanish DILI Registry.

High Prevalence of Ibuprofen Drug-induced Liver Injury in Spanish and Latin-American Registries.

*Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Málaga, Spain; Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Unidad de Gestión Clínica de Aparato Digestivo Intercentros, Hospitales Universitarios Virgen Macarena-Virgen del Rocio, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Seville, Spain; kHospital Provincial del Centenario, Facultad de Medicina, Universidad Nacional de Rosario, Rosario, Argentina; Servicio de Aparato Digestivo, Hospital Morales Meseguer, Murcia, Spain; Department of Immunology, Complutense University School of Medicine, Madrid, Spain; **Hospital 12 de Octubre Health Research Institute (i+12), Madrid, Spain; Unidad de Investigación Clínica y Ensayos Clínicos Instituto de Investigación Biomédica de Málaga, Plataforma Spanish Clinical Research Network, Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Málaga, Spain

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

P309 PROGNOSTIC MODEL FOR PREDICTING DRUG-INDUCED ACUTE LIVER FAILURE

P309 PROGNOSTIC MODEL FOR PREDICTING DRUG-INDUCED ACUTE LIVER FAILURE R.J. Andrade, M. Robles-Diaz, C. Stephens, I. MedinaCaliz, A. Gonzalez-Jimenez, A.F. Gonzalez, N. Kaplowitz, M.C. Fernandez, M. Romero-Gomez, M. Jimenez-Perez, M. Bruguera, M. Prieto, F. Bessone, N. Hernandez, M. Arrese, M.I. Lucena, Spanish-Latin DILI Registry. Unidad de Gestion Cĺinica de Enfermedades Digestivas, Servicio de Farmacoloǵia Cĺinica, Hospital Universitario Virgen de la Victoria, Instituto de Investigacion Biomedica de Malaga-IBIMA, Universidad de Malaga. CIBERehd, Malaga, Spain; USC Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, CA, United States; Servicio de Farmacia, Hospital de Torrecardenas, Almeŕia, Unidad de Gestion Cĺinica de Enfermedades Digestivas, Hospital Universitario de Valme, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Sevilla, Unidad de Gestion Cĺinica de Enfermedades Digestivas, Hospital Regional Universitario Carlos Haya, IBIMA, Malaga, Instituto de Enfermedades Digestivas y Metabolismo, Hospital Clinic, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Unidad de Gestion Cĺinica de Enfermedades Digestivas, Hospital La Fe. Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Valencia, Spain; Facultad de Ciencias Medicas, Servicio de Gastroenteroloǵia y Hepatoloǵia, Hospital Provincial del Centenario. Universidad Nacional de Rosario, Rosario, Argentina; Hospital de Cĺinicas, Cĺinica de Gastroenteroloǵia, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay; Departamento de Gastroenteroloǵia, Facultad de Medicina Pontificia. Universidad Catolica de Chile, Santiago, Chile E-mail: mrobles@uma.es