Clinical course and outcomes of chronic viral hepatitis D in patients from Republic of Tuva as endemic region

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Abstract

Introduction. Hepatitis D (delta, 5) is caused by an RNA virus (hepatitis D virus, HDV) from genus Deltavirus, and is the most severe and difficult to treat disease among both viral hepatitis and infectious diseases in general. The development of HDV infection in the host organism is possible only in the presence of hepatitis B virus (HBV). Coinfection with HBV and HDV is associated with a more rapid progression of chronic viral hepatitis (CVH) to liver cirrhosis (LC) and an unfavorable outcome in comparison with HBV monoinfection. Data on the influence of clinical, biochemical and virological factors on the infectious process in patients with hepatitis D are limited due to the insufficient amount of research on this theme.

The study aimed to determine demographic, clinical, biochemical, and virological factors influencing the course and progression of CVH D in patients followed during 10 years, residing in the territory of the Tuva Republic, one of the endemic regions of the Russian Federation.

Material and methods. Changes in clinical and laboratory parameters were analyzed in dynamics in 121 HDV infected patients with a different course of the disease, who were under observation from 2009 to 2019. Three groups of patients were identified: group 1 - 61 patients with disease progression of chronic hepatitis to LC (Child-Pugh class B-C), group 2 - 49 patients with non-progressive chronic hepatitis, and group 3 - 11 patients with slowly progressive LC (class A). Demographic data, the presence of detectable HBV DNA, indicators of the functional state of the liver: alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total bilirubin content were analyzed. The severity of hepatic encephalopathy was assessed by the duration of the numbers connection test (NCT).

Results. All patients belonged to the same ethnic group (Tuvinians), were infected with HDV genotype 1 and were positive for HDV RNA throughout the entire follow-up period. There were no significant differences in sex ratio and mean age at the time of inclusion in the study between the groups. In group 1, the average number of years from inclusion in the study to the formation of LC was 3.65 ± 2.3 years, years to the lethal outcome: 4.5 ± 3 years. Significantly higher levels of AST/GOT, ALP, GGT, total bilirubin (TB) and NCT grade were found in group 1 compared to group 2. ALT/GPT levels did not differ significantly in these groups. When comparing groups with disease progression and slowly progressive LC (groups 1 and 3), no significant differences were found in any of the clinical and biochemical parameters. ALT/GPT, GGT, TB and NCT values were significantly higher in patients with slowly progressive LC (group 3) compared to group 2. No differences in AST/GOT and ALP levels were found between these groups. Detectable HBV DNA was significantly more frequent in patients with progressive disease and with chronic viral hepatitis than in patients with slowly progressive LC. There were no significant differences in the frequency of HBV DNA detection in patients from groups 1 and 2.

Conclusion. The results obtained on a relatively homogeneous cohort demonstrated that age and gender are not the factors influencing the progression of chronic viral hepatitis D to cirrhosis. The lack of detectable HBV DNA is associated with the slow progression of LC. The revealed differences in clinical and biochemical parameters reflect the degree of functional liver damage in chronic viral hepatitis D and HDV-associated cirrhosis.

About the authors

O. V. Isaeva

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBEI FPE Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia

Author for correspondence.
Email: isaeva.06@mail.ru
ORCID iD: 0000-0002-2656-3667

Olga V. Isaeva - PhD, Mechnikov RIVS.

Maly Kazenny lane. 5a, Moscow, 105064

Russian Federation

L. Yu. Il'chenko

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBSI M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences; FSAEI HE N.I. Pirogov Russian Research Medical University of the Ministry of Health of Russia

Email: ilchenko-med@yandex.ru
ORCID iD: 0000-0001-6029-1864

Lyudmila Yu. Ilchenko - Professor, Dr. Sci. (Medicine), Federal state educational institution of higher education RNRMU named after N. I. Pirogov MHR; FSBSI «M.P. Chumakov Federal Scientific Center for Research and     Development of Immune-and-Biological Products of RAS; Moskovskiy settlement, the settlement of the Institute of poliomyelitis; Mechnikov RIVS.

Ostrovityanov str. 1 (A - autonomous), Moscow, 117997; house 8, building 1, 108819, Moscow; Maly Kazenny lane. 5a, Moscow, 105064

Russian Federation

A. A. Saryglar

SBHI RT Infectious Diseases Hospital

Email: anna_kyzyl@mail.ru
ORCID iD: 0000-0002-2116-9839

Anna A. Saryglar  - PhD.

Chekhov st. 65, Kyzyl, Republic of Tuva, 667003

Russian Federation

A. A. Karlsen

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBEI FPE Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia

Email: karlsen12@gmail.com
ORCID iD: 0000-0002-6013-7768

Anastasiya A. Karlsen

Maly Kazenny lane. 5a, Moscow, 105064; Barrikadnaya str. 2/1, Moscow, 125993

Russian Federation

K. K. Kyuregyan

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBEI FPE Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia

Email: karen-kyuregyan@yandex.ru
ORCID iD: 0000-0002-3599-117X

Karen K. Kyuregyan  - Professor, Dr. Sci. (Biology), MechnikovRIVS; RMACPE.

Maly Kazenny lane. 5a, Moscow, 105064; Barrikadnaya str.2/1, Moscow, 125993

Russian Federation

M. I. Mikhailov

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBEI FPE Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia

Email: michmich2@yandex.ru
ORCID iD: 0000-0002-6636-6801

Mikhail I. Mikhailov - Corr. member of RAS, Dr. Sci. (Medicine), Mechnikov RIVS; RMACPE.

Maly Kazenny lane. 5a, Moscow, 105064; Barrikadnaya str. 2/1, Moscow, 125993

Russian Federation

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Copyright (c) 2021 Isaeva O.V., Il'chenko L.Y., Saryglar A.A., Karlsen A.A., Kyuregyan K.K., Mikhailov M.I.

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