CLINCAL SIGNIFICANCE OF CYP2D6*4 POLYMORPHYSM IN PATIENTS WITH LIVER CIRRHOSIS

Abstract

Chronic liver diseases (CLD) and its end-stages; cirrhosis, are leading causes of morbidity and mortality worldwide with enormous socioeconomic costs. In nearly all liver diseases, progression from healthy tissue to cirrhosis is mediated by a chronic inflammatory reaction within the liver parenchyma that activates stellate cells and leads to the excess deposition of extracellular matrix proteins. The recruitment of immune cells into the damaged liver is orchestrated by chemokines, a class of soluble immune mediators with variable chemotactic and cytokine-like functions that alter the architecture of the liver as a result of excessive scarring, development of small nodules, and changes in liver tissue. CYP2D6 is one of the enzymes that are genetically polymorphic and are responsiable for wild inter-individual variation in drug metabolism. The aim of this work was to study the association between Cytochrome P450 2D6*4 genotype and liver cirrhosis and to evaluate its clinical utility for screening of cirrhosis. This study was carried out at Ain Shams University Hospitals on 20 healthy subjects (control group) and 20 cirrhotic patients (patients group) with different etiologies, recruited from the inpatients' department and outpatients' tropical clinic. They were 14 males (70%) and 6 females (30%) cirrhotic patients whose ages ranged from 43 to 81 years. The results of the current study showed that routine liver function tests including ALP, AST and bilirubin were higher with disease progression. The same is applied for hematological findings including hemoglobin and platelets they were significantly lower in diseased group versus control whereas PTT was higher among diseased groups. In the present study we observed that the CYP2D6 genotype distribution was different among patient's group, EM was reduced among patient's group compared with control group, and PM was equal in both groups while IM was higher in patient's group compared to the healthy group. However, there was no statistic significantly difference.