Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection

Chronic hepatitis B (HBV) and C (HCV) virus infections are the most important factors associated with hepatocellular carcinoma (HCC), but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher’s linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV)-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBKβ, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1) were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100% of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment

Hepatite fulminante: estudo dos fatores associados à mortalidade hospitalar de 100 pacientes priorizados para transplante de fígado

Introdução. A despeito dos avanços nos cuidados de terapia intensiva e no transplante de fígado (TF), a hepatite fulminante (HF) ainda hoje apresenta alta taxa de mortalidade. A identificação de fatores prognósticos de maior acurácia deve ajudar a otimizar a priorização dos pacientes em lista de espera para o TF. Objetivo. Avaliar fatores prognósticos de mortalidade hospitalar dos pacientes com HF priorizados para TF. Métodos. Foram estudados retrospectivamente 100 pacientes adultos (78 mulheres, idade média 35,5 ± 14,7 anos) com HF priorizados para TF, em um único centro, de fevereiro de 2002 a junho de 2011. O diagnóstico etiológico foi hepatite viral em 17% dos casos, medicamentosa em 29%, autoimune em 13%, criptogênica em 34% e outras causas em 7%. A indicação do TF foi determinada de acordo com os critérios de O’Grady. Foram avaliados: idade, sexo, etiologia, intervalo icterícia/encefalopatia, intervalo entre a priorização e o TF, grau de encefalopatia, tempo de internação, RNI, fator V, bilirrubina, creatinina, AST, ALT, lactato e Model for End-Stage Liver Disease (MELD). Todos os dados foram coletados do dia da priorização. Resultados. O intervalo entre a priorização e o TF foi de 1,5 dias (0 a 9) e o tempo de internação foi de 18 ± 27 dias. A mortalidade hospitalar foi de 69%. Os pacientes não sobreviventes apresentaram na priorização maior grau de encefalopatia [3 (1 a 4) vs. 2 (1 a 4)], MELD (41 ± 9 vs. 38 ± 7) e lactato (62,2 ± 45,2 vs. 33,9 ± 16,0 mg/dL) quando comparados com os sobreviventes (p<0,05). Dos 100 pacientes, 69% foram submetidos ao TF, os outros 31% morreram antes do TF. Os pacientes não transplantados apresentaram maior grau de encefalopatia [4 (1 a 4) vs. 3 (1 a 4)], MELD (44 ± 8 vs. 38 ± 8), lactato (78,4 ± 48,3 vs. 41,8 ± 30,6 mg/dL) e creatinina (2,60 ± 2,34 vs. 1,55 ± 1,54 mg/dL) quando comparados aos pacientes submetidos ao TF (p<0.05). Conclusão. No momento da priorização para o TF, os pacientes com HF que apresentam condição clínica mais grave, com encefalopatia graus 3 ou 4, insuficiência renal, escores mais elevados de MELD e lactato elevado, têm maior taxa de mortalidade hospitalar mesmo quando submetidos ao TF, indicando pior prognóstico

Clinical spectrum and therapeutic approach to hepatocellular injury in patients with hyperthyroidism

Daniel Ferraz de Campos Mazo,1 Graciana Bandeira Salgado de Vasconcelos,1 Maria Adelaide Albergaria Pereira,2 Evandro Sobroza de Mello,3 Telesforo Bacchella,1 Flair Jose Carrilho,1 Eduardo Luiz Rachid Cançado1,41Department of Gastroenterology, 2Department of Internal Medicine, 3Department of Pathology, 4Laboratory of Immunopathology of Schistosomiasis (LIM 06), Institute of Tropical Medicine, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Liver dysfunction in patients with hyperthyroidism includes abnormalities associated with the effects of thyroid hormone excess, those secondary to drug-induced liver injury, and changes resulting from concomitant liver disease. Our goal was to describe clinical, biochemical, and histopathological patterns in patients suffering from hyperthyroidism and concomitant liver dysfunction and to propose an algorithm of procedures to facilitate diagnosis and management of such cases. This study describes seven patients with liver biochemistry abnormalities detected after diagnosis of hyperthyroidism and one with undiagnosed decompensated hyperthyroidism and acute hepatitis. Two patients showed autoantibody reactivity which, together with liver histology, suggested the diagnosis of classic autoimmune hepatitis. Three patients experienced hepatotoxicity induced by propylthiouracil, the manifestations of which ranged from a benign course after drug withdrawal in one, a longstanding course in another suggesting drug-induced autoimmune hepatitis, and a more severe clinical condition with acute liver failure in a third patient, requiring liver transplantation. The three remaining patients showed no precipitating factors other than thyroid hyperactivity itself. They could be interpreted as having a thyroid storm with different clinical presentations. In conclusion, this series of patients illustrates the most frequent patterns of hepatocellular damage associated with hyperthyroidism and provides an algorithm for their diagnosis and treatment.Keywords: thyroid disease, liver function tests, autoimmune hepatitis, drug-induced hepatitis, thyrotoxicosis hepatiti