Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma.

INTRODUCTION: Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. OBJECTIVE: To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. MATERIAL AND METHODS: A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. RESULTS: Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). CONCLUSION: The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.

[Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis]. / Correlação entre a contagem de plaquetas no sangue e o gradiente de pressão venosa hepática em pacientes cirróticos.

BACKGROUND: Determination of hepatic venous pressure gradient is the main method used to assess portal pressure. Recently, platelet blood levels has been indicated as a non-invasive marker of the presence of portal hypertension. AIM: To correlate platelet blood levels with the hepatic venous pressure gradient among patients with cirrhosis. PATIENTS AND METHODS: A total of 83 cirrhotic patients who had undergone hepatic venous pressure gradient over the last 6 years were included. Patients were divided in groups according to Child-Pugh classification. All had upper digestive endoscopy to assess the presence of esophageal varices and platelet serum levels were recorded. RESULTS: Platelet serum levels range varied between 45,000/mm(3) and 389,000/mm(3) (mean: 104,099; standard deviation: 58,776). Mean hepatic venous pressure gradient was 15.2 mm Hg with a standard deviation of 6.4 mm Hg (range: 1 to 29 mm Hg). Simple linear regression analysis was applied to verify an association of hepatic venous pressure gradient and platelet serum levels, revealing a weak correlation between both variables. We observed a progressive reduction of serum platelet levels as esophageal varices diameter increased and hepatocellular function (established by Child-Pugh classification) decreased. However, these findings did not reach statistical significance. CONCLUSION: Despite the lack of a statistical significant correlation among serum platelet levels and hepatic venous pressure gradient or hepatocellular function, there was a clear tendency indicating that those variables could be involved in the pathogenesis of low platelet levels.