Study of Factors Influencing Chronic Viral Hepatitis C Treatment Results. Summary of the Doctoral Thesis
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Date
2012
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Rīga Stradiņš University
Abstract
The theme of promotional thesis. Study of factors influencing chronic viral hepatitis C treatment results. Background. Due to its distribution and clinical course, chronic viral hepatitis C has become one of the most common infectious diseases in the world. At present the number of the infected in the world is about 170 million [1, 2], but in Europe it exceeds 9 million [6]. The incidence of chronic viral hepatitis C in Latvia is relatively high. The antibody prevalence is 2.4%, HCV-RNS prevalence is 1.7% [7], and it means that in Latvia there might be almost 40 000 chronic hepatitis C patients. If not treated, about 20% of patients are known to develop liver cirrhosis within 10-20 years and hepatocellular carcinoma [5]. The progression of the chronic viral hepatitis C can be stopped with medical treatment. The combination of pegylated interferon and ribavirin for 24 to 48 weeks is the most effective regimen nowadays; nevertheless, SVR can be achieved not more than in 63% of patients [5, 8, 9, 10]. Due to length, side effects and relatively high expenses of the treatment of chronic viral hepatitis C, it is crucial to identify the factors influencing therapy results. Various factors are known to determine and affect the outcome of treatment. First of all, these are the patient’s own factors and co-morbidities – age, sex, race, genetic factors, obesity, insulin resistance, smoking, alcohol consumption, each individual’s body reaction by developing neutralizing antibodies against alpha interferon, consequently, reducing its effectiveness [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21], secondly, viral factors – genotype, viral load [5, 22], thirdly, morphological changes before the therapy – fatty liver, degree of fibrosis, activity of inflammation, cirrhosis [23, 24]. It is, therefore, important to find any factor influencing the treatment result and to correct it, as far as possible, prior to starting the therapy, in order to achieve maximum good therapeutic result. Aim. To determine and analyze the factors influencing chronic viral hepatitis C treatment result in order to predict SVR. Methods. 299 chronic viral hepatitis C patients were included in the study, who had attended LIC out-patient department in the period from 2009 till 2011. The diagnosis of chronic VHC was confirmed performing HCV-RNA test by PCR method. All patients were white race individuals, their mean age was 38 years, males – 165 (55%), females – 134 (45%). Within this study 223 (74%) patients received pegylated interferon alpha 2a 180 μg/week, 71 (23.7%) patients received pegylated interferon alpha 2b 1.5 μg/kg/week in combination with ribavirin 800 – 1200 mg/day, 2 patients received interferon alpha 2a 180 μg/week in monotherapy, 1 patient received multiferon in combination with ribavirin, 2 patients did not undertake hepatitis C therapy. All patients who completed the treatment course (n=264) were divided into 2 groups regarding therapy result – responders (achieved SVR) and nonresponders (have not achieved SVR). In order to make the analysis of the factors influencing results of chronic VHC treatment, there were different factors analyzed for the patients of both groups (patient’s factors, viral factors, morphological changes). The research was confirmed by The Independent Ethics Committee for clinical investigation of drugs and pharmaceutical products, and the work was done in accordance with the international and LR laws and Helsinki declaration. Before undertaking the study, each patient gave a written consent for the participation in the study. The data statistical processing was done using the computer programs SPSS v.15.0, MelCalc v12.0 and Microsoft Office Excel v.11. Binary logistic regression was used to develop the model for chronic VHC treatment result prognosis. Results. From all the included and treated chronic hepatitis C patients in the study –responders are 140 (53%), nonresponders – 124 (47%). Patients of younger age (under 45 years) responded to therapy more often (58.6%, n=112), comparing to much older patients (over 46 years) (responded – 38.9%, n=28). In the group of responders there was diagnosed a lower body weight, on average 76.8 (±14.1) kg, in comparison to a nonresponders group, where it was on average 83.5 (±16.6) kg, p=0.005. In responders group there was observed a lower BMI, on average 25.09 (±4.13) kg/m2 in comparison to nonresponders group where it is on average 27.25 (±4.54) kg/m2, p=0.002. In the nonresponders group the mean GGT activity was higher (Me = 63.5 U/l) in comparison to the responders group (Me = 36.0 U/l), p=0.000. The mean insulin level in nonresponders group was higher – Me=11.0 μIU/ml, in comparison to the mean insulin level in the responders group Me=8.3 μIU/ml, p=0.026. The differences between the groups were observed comparing the mean insulin resistance parameters. In the nonresponders group IR HOMA was 2.51, but in the responders group – 1.78, p=0.031. In the responders group the mean HAI index was 6.38, in the nonresponders group – 7.11, p=0.038. In the nonresponders group more often – 11 patients (9.7% cases) were diagnosed hemosiderin in the liver tissues in comparison to the responders group were it was observed only in 2 patients (1.6% cases), p=0.008. Positive neutralizing antibodies to alpha interferon were found in 5% of patients in both groups. Patients with HCV 2nd or 3rd genotype responded more often to therapy – 82.3% (65 patients), comparing to the 1st genotype patients who responded rarer to therapy – 40.5% (75 patients), p=0.000. Patients with IL 28B gene CC genotype achieved SVR in 89.7% (n=35), but patients with non-CC genotype achieved SVR in 59.8% (n=52), p=0.001. On the basis of 3 significant factors influencing the treatment result (HCV genotype, BMI and HAI), the model to predict the possibility to respond to therapy was developed, using binary logistic regression. The possibility to achieve SVR can be predicted for every patient by equation: p=1/(1+e-z), z = BMI × (-0.126) + HCV genotype × 2.377 + HAI index × (-0.191) + 2.502. HCV genotype: 1st genotype – 1, 2nd or 3rd genotype – 2. Using this model, prognosis for response to therapy can be calculated by 78.7% precision. Conclusions. The patient’s age, body weight, BMI, GGT activity, level of insulin, insulin resistance, hemosiderosis, IL 28B gene polymorphism, HCV genotype, fibrosis stage and HAI are factors influencing treatment result of chronic viral hepatitis C. Body weight and BMI possibly can be corrected prior to starting the therapy, in order to achieve maximum good therapeutic result. It is possible to predict the treatment result of chronic viral hepatitis C, using developed predictive model.
Description
Promotion thesis has been developed at Riga Eastern University Hospital, hospital „Infectology Centre of Latvia”. Defence: on 4th of December at 15.00 p.m. at Riga Stradins University open meeting of Promotion Council of Internal Medicine in Riga Stradins University Hippocrate auditorium, 16 Dzirciema Street, Riga.
Keywords
Summary of the Doctoral Thesis
Citation
Tolmane, I. 2012. Study of Factors Influencing Chronic Viral Hepatitis C Treatment Results: Summary of the Doctoral Thesis: Speciality – Internal Medicine / Infectology. Rīga: Rīga Stradiņš University. https://doi.org/10.25143/prom-rsu_2012-22_dts