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Viral hepatitis B, C acute, chronic and mixed (particularities of clinical picture, evolution, immunology and treatment)


Author: Holban Tiberiu
Degree:doctor habilitat of medicine
Speciality: 14.00.10 - Infections Diseases
Year:2009
Scientific consultants: Constantin Andriuţă
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Constantin Spînu
doctor habilitat, professor, National Center of Public Health
Institution:
Scientific council:

Status

The thesis was presented on the 8 April, 2009
Approved by NCAA on the 18 June, 2009

Abstract

Adobe PDF document0.44 Mb / in romanian

Thesis

CZU 616.36-002-036.11/.12-08+616-097

Adobe PDF document 1.19 Mb / in romanian
213 pages


Keywords

Viral hepatitis B, Viral hepatitis C, Viral hepatitis of mixed etiology, Pacovirin, Interferon-α, Drug users, Lamivudine, anti-VHB vaccine, Cellular immunity.

Summary

It was accomplished a complex scientific investigation of the clinical, developmental and immunological particularities of viral hepatitis B, C acute, chronic and mixed. A number of 380 patients was included in the study and revealed the evolution of clinical, biochemical, virusological, immunological and histomorphological particularities under the influence of etiological treatment, including new remedy with antiviral, immunomodulation and interferonogen activity. The advancement of VHB lead to the intensification of the hepatic lesions, quantified by the Knodell score, and liver fibrosis level, reflected on increased mezenchimal inflammation syndrome indices such as tymole probe and g-globulin level. The indices of humoral immunity such as IL-12 and IF-g are in close relations with the length of the disease, liver dimensions, intensity of the cytolytic and mezenchimal inflammation syndromes, the evolution of the disease usually causing the decrease of IL-12 and appearance of serum IF-g. The level of viral load does not correlate with the degree of histomorphological liver lesions and is higher in AgHBe-positive patients with more severe cytolytic syndrome. A higher Knodell score and a greater liver fibrosis level was revealed in the patients with prolonged disease, suffering from other concomitant chronic diseases of gastrointestinal tract, disclosing a close correlation between Knodell score and AST activity, tymole probe and g-globulin level.

In chronic viral hepatitis B treatment with Lamivudine, 100 mg per day, during one year has a benefic influence on the disease evolution, assuring clinical amelioration, disappearance or decrease of viral load in 70% of patients. The association of anti-VHB vaccine to the treatment with Lamivudine does not improve the results of treatment.

A benefic action on the disease evolution has Pacovirin fitodrug as a complex treatment of mild or moderate severity acute VHB, leading to shortens of intoxication and jaundice syndromes, rapid improvement of biochemical indices and disappearance of blood AgHBs, preventing the chronicisation. The normalization of cellular immunity indices occur reflected on increasing T-active and T-inductor lymphocytes level, T-suppressor lymphocytes amount, favorable evolution of T-helper/suppressor immunoregulatory index.

The presence of ARN-HCV was established in 79,3% of patients with chronic VHC, from them - 97,8% with genotype 1b. Treatment with Pacovirin leads to amelioration of clinical and biochemical indices, normalization of TNF-α levels and increase of IL-1β. Under the one year treatment with Intron A the biochemical answer was revealed in 80,5% and virusological response in 43,9% of patients with chronic VHC replicate stage.

An increased incidence of acute and chronic mixed hepatitis was revealed in the hospitalized patients, chronic viral hepatitis was established in 57,1% of cases acute viral hepatitis in 14,9%, with the predominance of chronic hepatitis B+C and viral hepatitis A on the basis of chronic VHB. The evolution of viral hepatitis A and B is more severe when developing on the base of chronic hepatitis B or C, comparing with monoinfection, manifested by intensification and prolongation of the main clinical and biochemical signs and syndromes. In the IV drug abusers the etiological component of acute viral hepatitis is characterized by the prevalence of parenteral mechanism of transmission - 93,2%. The mixed etiology was established in 40% of cases with acute viral hepatitis. Viral hepatitis B and D had a severe and very severe evolution in 36,7% of cases, in the same category of patients acute VHC was established in younger age and characterized by the absence of severe forms of the disease with the earlier appearance of anti-HCV.