Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.Fil: Bessone, Fernando. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Hospital Nacional del Centenario; ArgentinaFil: Hernandez, Nelia. Hospital de Clinicas Dr. Manuel Quintela; UruguayFil: Tagle, Martin. Universidad Peruana Cayetano Heredia; PerúFil: Arrese, Marco. Pontificia Universidad Católica de Chile; ChileFil: Parana, Raymundo. Universidade Federal da Bahia; BrasilFil: Mendez-Sánchez, Nahum. Fundacion Clinica Medica Sur; México. Universidad Nacional Autónoma de México; MéxicoFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Dagher, Lucy. Policlinica Metropolitana; VenezuelaFil: Contreras, Fernando. Universidad Pedro Henriquez Urena; República DominicanaFil: Fassio, Eduardo. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Pesoa, Mario. Hospital de Clincas; BrasilFil: Brahm, Javier. Clinica Las Condes; ChileFil: Silva, Marcelo. Universidad Austral. Hospital Universitario Austral; Argentin

Evaluación del paciente asintomático con alteración de pruebas hepáticas

El descubrimiento incidental de elevación de transaminasas, durante una evaluación médica en el paciente asintomático es un problema clínico común, el cual puede estar presente entre el 1% y el 4% de una población asintomática, además es posible identificar la causa de dicha elevación evaluando el patrón de la elevación y solicitando algunos exámenes adicionales. Así, el seguimiento clínico expectante es la mayor estrategia costo - beneficio que puede tomarse para el manejo de pacientes asintomáticos, con elevación persistente de transaminasas, con marcadores virales, metabólicos y auto inmunes negativos

Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved?

Hepatocellular carcinoma (HCC) is a complex condition associated with a poor prognosis. Treatment outcomes are affected by multiple variables, including liver function, performance status of the patient, and tumor stage, making a multidisciplinary approach to treatment essential for optimal patient management. Only ∼30% of patients are eligible for curative therapies (surgery or ablation); palliative treatments include transcatheter arterial chemoembolization (TACE) and sorafenib. Treatment choice is guided by staging systems and treatment guidelines, although numerous systems exist and treatment guidelines vary by region. The current standard of care for patients unsuitable for potentially curative therapy is locoregional therapy with TACE. This treatment is associated with survival benefits, but there is no consensus regarding the optimum treatment/retreatment strategy. For patients with more advanced disease or who have failed locoregional therapy, sorafenib is the standard of care. Sorafenib is a targeted agent with proven survival benefits as monotherapy in these patients, and ongoing studies will clarify its role in combination with other agents and in patients with impaired liver function. Although other novel agents and therapeutic approaches are emerging, such as radioembolization and various targeted agents, further suitably designed randomized clinical trials (RCTs) comparing these agents with the standard of care are needed. In addition to RCTs, the collection of real-life data will also be important to allow physicians to make fully informed treatment decisions. The Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study is a global, noninterventional study of patients with unresectable HCC receiving sorafenib. The aim of that study is to compile a large robust database to evaluate local, regional, and global factors influencing the management of patients with HCC. It is hoped that findings from the GIDEON study along with phase III RCT data will lead to better outcomes for patients with intermediate-advanced HCC

A dataset of multi-contrast unbiased average MRI templates of a Parkinson's disease population

Parkinson's disease (PD) is a complex neurodegenerative disorder affecting regions such as the substantia nigra (SN), red nucleus (RN) and locus coeruleus (LC). Processing MRI data from patients with PD requires anatomical structural references for spatial normalization and structural segmentation. Extending our previous work, we present multi-contrast unbiased MRI templates using nine 3T MRI modalities: T1w, T2*w, T1-T2* fusion, R2*, T2w, PDw, fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging, and neuromelanin-sensitive MRI (NM). One mm isotropic voxel size templates were created, along with 0.5 mm isotropic whole brain templates and 0.3 mm isotropic templates of the midbrain. All templates were created from 126 PD patients (44 female; ages=40–87), and 17 healthy controls (13 female; ages=39–84), except the NM template, which was created from 85 PD patients and 13 controls, respectively. The dataset is available on the NIST MNI Repository via the following link: http://nist.mni.mcgill.ca/multi-contrast-pd126-and-ctrl17-templates/. The data is also available on NITRC at the following link: https://www.nitrc.org/projects/pd126/

Trends and projections of hepatitis C virus epidemiology in Latin America

The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research

Genotype f prevails in Venezuelan urban patients with chronic hepatitis B(a)(a)This project was supported, in part, by an award to Intediag-HV granted by Fondo Pro-Salud 2007, Cámara Venezolana de Fabricantes de Cerveza (CAVEFACE), Venezuela. A preliminary report of this work was presented in an abstract form at the 13th International Symposium on Viral Hepatitis and Liver Disease, March, 2009, Washington, USA. www.ishld2009.org/pdf/ISVHLD_Poster_Presentation_Abstractspdf

Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H). Genotypes A, D and F have been identified in some South American countries, but in Venezuela studies have been more restricted to aboriginal communities where genotype F is predominant. The aim of the present study was to identify the prevalence of HBV genotypes among native HBsAg carriers in Venezuelan urban areas. In addition, we correlated the predominant HBV genotype with epidemiological, serological and virological features of the infection. Non-Venezuelan migrant patients were excluded from this study. Serum samples from 90 patients (21 children and 69 adults) with chronic hepatitis B (CHB) were analyzed. Seventy-four patients had CHB e-antigen positive and 16 CHB e-antigen negative. HBV DNA serum levels of the whole group ranged from 4.1 to 8.8 log1H IU/mL. Patients with CHB e-antigen positive showed significantly higher viral loads (P = 0.0001) than the group with CHB e-antigen negative. Eighty-eight patients (97.8%) exhibited HBV genotype F while two non-related patients (2.2%) were infected with A + F genotypes. Genotype F is the main circulating HBV strain among HBsAg carriers from Venezuelan urban areas. This genotype is associated mostly with CHB e-antigen positive and high rate of transmission. Progression to cirrhosis and hepatocellular carcinoma could be major clinical events of this patient population independently of age at acquisition or transmission route

Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study

Background & Aims: Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. Methods: GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included. Results: 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1â\u80\u9324.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8â\u80\u9325.0 months). Conclusions: Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients