Fatal cases of chronic hepatitis delta: clinical, biochemical and virological characteristics


DOI: https://dx.doi.org/10.18565/therapy.2021.4.48-56

Isaeva O.V., Kyuregyan K.K., Ilchenko L.Yu., Karlsen A.A., Asadi Mobarkhan F.A., Saryglar A.A., Mikhailov M.I.

1) Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia, Moscow; 2) I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow; 3) M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow; 4) N.I. Pirоgov Russian National Research Medical University of the Ministry of Healthcare of Russia, Moscow; 5) Infectious Diseases Hospital, Kyzyl
Abstract. Aim: to present demographic, clinical, biochemical and virological parameters that characterize the course and progression of chronic hepatitis delta and subsequent fatal outcome in patients followed up over 10 years in endemic region of Russia (Republic of Tyva).
Material and methods. Dynamic changes in clinical and laboratory parameters of 14 patients with fatal progression of chronic HDV infection were monitored from 2009 to 2019. Following parameters were monitored annually: the presence of detectable HBV DNA, HDV RNA, quantitative levels of HBsAg in blood serum, levels of serum alanine (ALT) and aspartic (AST) aminotransferases, alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (GGTP) and the content of total bilirubin. HDV and HBV genotypes were determined as well.
Results. The average follow-up period was 5,5±3,3 years. 5 patients (36%) died in the same year or the next year after the first visit. During the follow-up period, 12 patients died from complications associated with decompensated liver cirrhosis, and 2 patients with class C liver cirrhosis developed hepatocellular carcinoma with fatal outcome. The average number of years from inclusion in the study to the formation of LC and to fatal outcome was 3,7±2,3 years and 4,5±3,25 years, respectively. Average ALT and AST levels in patients exceeded the upper limit of normal (ULN) 1,8 and 1,6 times, respectively. The average values of GGTP, alkaline phosphatase, and total bilirubin did not exceed >3 ULN. The dynamics of HBsAg levels in the blood serum were unstable and varied from a minimum value of 3,3 lg IU/ml to a maximum of 5 lg IU/ml. All patients were infected with genotype 1 HDV and were positive for HDV RNA throughout the observation period. In 11 patients, the HBV genotype D was detected, in three patients the HBV genotype was not determined. 9 patients had undetectable levels of HBV viremia throughout the observation period. The proportion of such patients (64,3%) was significantly higher than the proportion of patients with HBV viremia (p <0,05, Fisher’s exact test).
Conclusion. Along with objective pathogenetic factors, late diagnosis and the lack of available therapy determine the high mortality rate in hepatitis delta patients.
Keywords: biochemical and virological indicators, chronic hepatitis delta, hepatitis delta virus (HDV), hepatocellular carcinoma, liver cirrhosis, clinical
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About the Autors

Olga V. Isaeva, candidate of biological sciences, leading researcher of Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia, leading researcher of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera. Address: 125284, Moscow, 7/2 Botkinsky pr. Str. Е-mail: isaeva.06@mail.ru
Karen K. Kyuregyan, Doctor of biological sciences, professor of RAS, Chief researcher, head of the Department of socially significant viral infections, Research Institute of Molecular and Personalized Medicine of Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia, leading researcher of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera. Address: 125284, Moscow, 7/2 Botkinsky pr. Str.
Lyudmila Yu. Ilchenko, MD, professor, professor of the Department of hospital therapy No. 2 of the Faculty of medicine, N.I. Pirоgov Russian National Research Medical University of the Ministry of Healthcare of Russia, leading researcher of Laboratory of modeling immunobiological processes at the experimental clinic of marmoset monkeys, M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, leading researcher of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera. Address: 115516, Moscow, 26 Bakinskaya Str
Anastasia A. Karlsen, researcher of Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia, researcher of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera. Address: 125284, Moscow, 7/2 Botkinsky pr. Str.
Fyodor A. Asadi Mobarkhan, researcher of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera. Address: 105064, Moscow, 5A Maly Kazyonny Lane
Anna A. Saryglar, PhD, Chief physician of Infectious Diseases Hospital (Republic of Tyva). Address: 667003, Kyzyl, 65 Chekhova Str. E-mail: infeksiatuva@mail.ru
Mikhail I. Mikhailov, MD, corresponding member of RAS, head of Laboratory of viral hepatitis, I.I. Mechnikov Research Institute of Vaccines and Sera, Scientific Director of Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuing Professional Education of the Ministry of Healthcare of Russia. Address: 105064, Moscow, 5A Maly Kazyonny Lane


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