Predicting the rate of liver fibrosis in patients with chronic hepatitis C virus infection based on the combination of genetic and environmental factors

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Abstract

Rationale: Search for predictors of aggressive course of chronic hepatitis C virus (HCV) infection in individual patients, including genetic studies, is considered  to be a major urgent  goal. High rates of fibrosis progression  in chronic HCV infection is associated with several gene polymorphisms  coding for the components of renin-angiotensin system and involved in the formation of endothelial dysfunction and oxidative stress.

Aim: To develop a predictive  model  to  assess  the  probability  of rapid fibrosis progression  in patients  with chronic HCV infection based on the combination of the known genetic markers, clinical and demographic parameters.

Materials and methods:  One hundred  and  nine  patients  with  chronic  HCV  infection (79 women  and 30 men) of known duration and liver fibrosis were categorized  into the groups with “rapid fibrosis” (n = 54, the rate of fibrosis progression ≥ 0.13 fibrosis units / year) and with “slow fibrosis”  (n = 55, the  rate  of progression < 0.13  fibrosis units / year). Polymorphisms  of the studied genes were assessed by molecular genetic assays. Multivariate analysis of the influence of combination of genetic  variants, as well as of the interaction of genetic, clinical and demographic factors on the rate of fibrosis progression  in the patients with chronic HCV infection was performed by logistic  regression   method. 

Results:  The  rapid rate of fibrosis progression  was significantly associated with patient's  age at the time of infection (Wald statistics  14.955;  p = 0.00011), male gender (Wald statistics  6.787;  p = 0.00918),  (-6)АА genotype  of the  AGT  gene  carriage  (Wald statistics 6.512;  p = 0.01072), 242ТТ-genotype  of the  CYBA gene   (Wald  statistics   4.347;   p = 0.03708),   and 235МТ genotype of the AGT gene  (Wald statistics 4.306; p = 0.03799). The model to predict the probability of rapid fibrosis progression  in individuals with chronic HCV infection included the above mentioned factors; its use was demonstrated with two clinical cases.

Conclusion: The analysis of the AGT  gene  (M235T and  G-6A loci) and  the  СYBA gene  (C242T  locus) polymorphisms  are  relevant to  identify patients  at  risk of rapid  liver fibrosis progression. In this case, 242ТТ genotype of the CYBA gene  and  (-6)AA and  235MT genotypes of the AGT gene  are considered  unfavorable. To refine the prognosis, it is necessary to take into account  demographic parameters (gender  and age at the moment of infection contraction), because male gender and older age of getting the infection would increase the probability of rapidly progressive of hepatitis C.

About the authors

O. V. Taratina

Moscow Regional Research and Clinical Institute (MONIKI)

Author for correspondence.
Email: taratina.o@gmail.com

Taratina Olesya V. – MD, PhD, Research Fellow, Department of Gastroenterology; Associate Professor, Chair of Gastroenterology, Postgraduate Training Faculty.

61/2–9 Shchepkina ul., Moscow, 129110, +7 (926) 245 66 59

Россия

L. M. Samokhodskaia

Lomonosov Moscow State University

Email: fake@neicon.ru

Samokhodskaia Larisa M. – MD, PhD, Associate Professor, Head of Department of Diagnostic Laboratory, Medical Research and Educational Center.

Leninskie Gory, Moscow, 119991

Россия

T. N. Krasnova

Lomonosov Moscow State University

Email: fake@neicon.ru

Krasnova Tatiana N. – MD, PhD, Associate Professor, Chair of Internal Medicine, Faculty of Fundamental Medicine.

Leninskie Gory, Moscow, 119991

Россия

N. A. Mukhin

Lomonosov Moscow State University

Email: fake@neicon.ru

Mukhin Nikolay A. – MD, PhD, Professor, Member of Russian Academy of Sciences, Head of the Chair of Internal Medicine, Faculty of Fundamental Medicine.

Leninskie Gory, Moscow, 119991

Россия

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