Determination of Causal Relationship Between Bilirubin and Other Liver Biomarker in Case of Hepatitis C

Abstract

Background: Liver works as one of the most versatile organs in the human body. But any kind of disturbance occurs in the liver may cause the liver disease. One of the most common liver infections is hepatitis C which is caused by the Hepatitis C Virus (HCV). It is well known that liver is the largest solid organ in the human body and also it is called the exocrine gland as it secretes bile into the intestine. Aim: The aim of this study is to evaluate the causal relationship of Bilirubin with each liver biomarker using the advanced regression techniques. Methods: We use two advanced regression techniques, namely Joint Generalized Linear Model (JGLM) and Generalized Additive Model (GAM). For model selection, we check the AIC value, GCV score and adjusted R–square as well as the different diagnostic plots like Q–Q plot, Residual vs. Fitted plot etc. are displayed. Results: Bilirubin, a human liver disease biomarker, is a brownish yellow substance found in bile and it is produced in the liver when the old red blood cells break down. The present study reveals that Bilirubin is positively associated (p-value<0.05) with Aspartate Aminotransferase (AST), Creatinine (CREA), Gamma-Glutamyl Transpeptidase (GGT), Protein (PROT), Alkaline Phosphatase (ALP)*Albumin (ALB) and marginally associated with Choline Esterase (CHE)* Cholesterol (CHOL) (p-value=0.0591). While it is negatively associated (p-value < 0.05) with Age, Sex, Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Choline Esterase (CHE), Cholesterol (CHOL), Albumin (ALB), Creatinine (CREA)*Gamma-Glutamyl Transpeptidase (GGT) under JGLM. Besides of that, Bilirubin is positively associated with AST, CREA, GGT, (CREA*GGT), (CHE*CHOL) whereas it is negatively associated with Sex, ALT, CHE, CHOL. Also, ALB is highly positively significant as a non–parametric smoothing term (p-value < 0.001) under GAM. Conclusion: Both the advanced regression models JGLM and GAM explain the association between Bilirubin with other liver diseases biomarker in case of Hepatitis C.