Chronic Hepatitis C: Biochemical and Immunogenetic Diagnostic Markers for Predicting Efficacy of Etiotrop Therapy. Summary of the Doctoral Thesis

Abstract

Doctoral Thesis „Chronic hepatitis C: biochemical and immunogenetic diagnostic markers for predicting efficacy of etiotrop therapy” is devoted to one of the most topical contemporary problems of infectology in the group of blood born infectious diseases. In spite of essential achievements in the field of the CHC treatment as the result of the implementation of PEG IFN and RBV in a clinical practice, more than one third of the CHC patients infected with the first HCV genotype, prevailing in Europe and Latvia, still fail to get rid of HCV during the first course of the treatment. Up till now a success in the treatment of CHC, doses of medication and its application time have mostly been related to laboratory parameters characterizing the virus – HCV genotype and HCV RNA load before the therapy. Since according to the clinical practice the results of the therapy are associated with characteristics or specificities of every patient, the experts, including us, have focused on evaluation of the HCV patients’ health condition before the start of the CHC therapy. For predicting the efficacy of the treatment in case of CHC, we determined the biochemical, morphological, immunological and immunogenetic parameters that turned out to be very essential. The determination of certain characteristic parameters would allow to prescribe the CHC therapy individually. While by detecting a prevalence of negative prognostic factors, patients could be protected from ineffective, sometimes not advisable and even harmful courses of the treatment. The objective of the study was to find, analyze and specify the biochemical, morphological, immunogenetic and demographic parameters and markers allowing to predict the efficacy of the etiotrop therapy for CHC patients. To achieve the set objective, there were more than two hundred CHC patients enrolled in the study that had received the CHC etiotrop therapy. The patients were divided into groups according to the content of the therapy, i.e., monotherapy or combination therapy, and according to the outcome of the applied therapy. The patients for whom the applied therapy had proven to be effective were named responders, while the group of patients who had failed to clear the HCV - non-responders. The biochemical and immunogenetic parameters of responders and non-responders were compared to evaluate the results. All laboratory investigations and tests were carried out in the accredited and certified laboratories. The statistical analysis of the data was performed, using computerprograms SPSS and Microsoft Office Excel. It was found that the biochemical and immunogenetic factors could affect the outcome of the CHC therapy. The results of the study indicated the correlation between inefficiency of the CHC etiotrop therapy and the following parameters: • demographic parameters of the patients, i.e., older age and male gender; • the presence of fibrotic changes in liver tissues; • the varied blood biochemical parameters of the patients upon the start of the therapy – increased GGT level, elevated glucose, γ globulin, cholesterol, HA and Fe levels. The significant reduction in the CK-18 level was observed after the CHC etiotrop therapy in the patients who had succeeded in clearing the HCV. Furthermore, the elevation of AFP level in the patients that had failed to clear the HCV was observed during the further observation period. The frequency of HLA class II gene alleles was analyzed and higher, if compared with the control group, frequencies of certain alleles and haplotypes in the CHC patients were found. The above mentioned allows to conclude that the biochemical, morphological and immunogenetic status of the CHC patient plays an essential role in the efficacy of the etiotrop therapy. During the study the marker indicating the risk of relapse was found and that marker was elevated (4 times higher than the reference range) ALT acivity before the start of the therapy. It was found that the clearance from the HCV was associated with the reduction in the CK-18 neoepitop level. There was very valuable data obtained confirming that in the CHC patients in Latvia the most frequently found were MHC HLA II class gene alleles DRB1*03, DRB1*05, DRB1*07, DQA1*0201, DQB1*0201-2 and haplotypes DRB1*01/DQB1*0201-2/DQA1*0101. MHC HLA II class gene alleles DRB1*04, DRB1*06, DQA1*0301 and haplotypes DRB1*04/DQB1*0301/DQA1*0301, DRB1*04/DQB1*0302/DQA1*0501 and DRB1*05/DQB1*0601DQA1*/0103 are associated with the efficacy of the PEG IFN+RBV combination therapy in Latvia. Following the above mentioned it can be concluded that for the most effective treatment of the patient an individual and personalized patient’s examination is necessary, based on the pre-therapy examination algorithm designed during the study.