[Immune-regulating Th1- and Th2-cytokines in chronic infections caused by hepatitis B and C viruses]. / Immunoreguliatornye Th1- i Th2-tsitokiny pri khronicheskikh infektsiiakh, vyzvannykh virusami gepatitov B i C.

The serum levels of Th1 (gamma-IFN and sIL-2r) and of Th2 (IL-10) cytokines were measured in 33 patients (23 males and 10 females, mean age 23.1 +/- 1.9) with chronic viral hepatitis (CVH) according to a disease etiology (6 patients with hepatitis B--CVHB, 15 patients with hepatitis C--CVHC, and 12 patients with a mixed form of chronic hepatitis B and C--HBV + HCV). Besides, the contents of the studied cytokines were compared with the traditional infection markers and the presence of viremia. The similar indices taken from 10 healthy persons served as controls. The concentration of gamma-IFN was found to be reliably higher (p < 0.05) in patients of all three groups (0.32 +/- 0.07, 0.34 +/- 0.09 and 0.25 +/- 0.06 pg/ml, respectively) regardless of a disease etiology and as compared with the control value (0.09 +/- 0.04) pg/ml). At the same time, the levels of gamma-IFN, sIL-2r and IL-10 (0.25 +/- 0.06 pg/ml, 166.5 +/- 31.3 IU/ml and 48.1 +/- 8.4 pg/ml, respectively) was found to be reliably (p < 0.05 and p < 0.01) higher, as compared to the controls (0.09 +/- 0.04, 57.1 +/- 5.6 and 10.8 +/- 7.8, respectively), only in patients with the mixed infection of hepatitis. Like in our previous study, a trend was established towards the growing mean values of the IL-r level from its lowest parameters in the group of CVHB patients towards its highest parameters in the group with the mixed hepatitis form. According to our data, the IL-2r level correlated reliably with the activity of AlAt (r = 0.452; p < 0.05), while the gamma-IFN content correlated reliably with the IL-10 concentration (r = 0.805; p < 0.05), and the gamma-IFN content correlated with the IL-10 concentration (r = 0.805; p < 0.01) irrespective of disease pathology.

[Th1-cytokines in chronic hepatitis B and C]. / Th1-tsitokiny pri khronicheskikh formakh virusnykh gepatitov B i C.

Forty-four patients with chronic HBV and HCV were observed. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and soluble IL-2 receptor (IL-2r) were measured by enzyme immunoassay in 29 patients divided into 3 groups: group 1 (n = 9) with chronic HBV, group 2 (n = 9) with chronic HCV, and group 3 (n = 11) with mixed HBV + HCV infection. Control group consisted of 10 normal subjects without HBV, HCV, or HIV infection markers. The most informative of Th1 cytokines was IL-2r: its concentration was increased significantly (p < 0.01) in all patients with hepatitis B and/or C in comparison with the control. In addition, there was a trend to an increase in the mean concentrations of IL-2r from group 1 to groups 2 and 3. The concentrations of IFH-gamma and IL-2 did not differ significantly in the patients and controls. However, the concentrations of IFN-gamma were increased significantly (p < 0.01) in comparison with the control in 3 patients from group 1 and 4 patients from group 3 with more pronounced inflammation.

[Hepatitis A in Estonia (1990-1999)]. / Gepatit A v Estonii (1990-1999).

During recent 10 years (1990-1999) essential changes occurred the epidemiology of viral hepatitis A (VHA) in Estonia: simultaneously with a decreased level of morbidity (morbidity rate per 100,000 of the population was 78.4 in 1990 and 7.7 in 1996, or 1,241 and 112 cases, respectively), a shift in the age structure of patients from children of preschool age to older age groups took place. Everyday contacts were the main established route of VHA transmission in recent years, but in more than 80% of cases the risk factors of the virus transmission remained obscure. During the regional outbreak of VHA in North Estonia in 1998 (937 out of 989 cases registered in the country) a rise in morbidity was observed among young people aged 15-29 years, when a wide spread of parenteral viral hepatitides B and C and drug addiction were registered in this region. During this outbreak VHA was transmitted mainly through everyday contacts. Still the considerable prevalence of injection drug users who practiced the group use of syringes and needles and took drugs from common containers, a sufficiently high level of the mixed forms of the disease (more than 18% of all registered cases of VHA), detected for the first time, make it possible to suggest that the parenteral transmission route could appear among persons belonging to the above mentioned group. Vaccination is regarded as the most effective measure for the prophylaxis of VHA.

[Functional and metabolic activity of peripheral blood neutrophils in acute viral hepatitis B and C]. / Funktsional'naia i metabolicheskaia aktivnost' neirofilov perifericheskoi krovi pri ostrykh virusnykh gepatitakh B i C.

The functional metabolic activity of peripheral blood neutrophils in acute virus hepatitis B (VHB) and/or virus hepatitis C (VHC) was evaluated. 48 patients were examined; of these, VHB was diagnosed in 28 patients and VHC was diagnosed in 9 patients and the mixed form of virus hepatitis (VHB + VHC), in 11 patients. Determination of adhesive capacity of neutrophils, production of superoxidase anion in the nitro blue tetrazolium (NBT) test, activity of myeloperoxidase (MPO) and acidic phosphatase (AP), the amount of cation proteins (CP) was made. Most pronounced functional dysbalance of neutrophil leukocytes and considerable changes in biochemical characteristics of the activity of the infectious process in patients with the mixed form of virus hepatitis were established. These data demonstrated that in acute virus hepatitis B and C at the peak of the disease such characteristics of the functional activity of neutrophils as results of the NBT test, the activity of MPO and AP, as well as the amount of CP, were highly informative.

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C in northern Estonia.

Distribution of hepatitis C virus (HCV) genotypes among 30 patients with chronic liver diseases and antibodies to HCV (anti-HCV) was investigated. Sera of these patients were analyzed for HCV genotype by reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) analysis of the 5'-non-coding region (5'-NCR) of the virus genome and for HCV serotype by detecting antibodies to HCV NS4 peptides by enzyme-linked immunosorbent assay (ELISA). The following distribution of genotypes was found: genotypes 1b in 32.0%, 3a in 20.0%, 2a in 12.0% and 1a/b (double infection) in 28.0%. The results of serotyping were interpretable in 92.0% and concordant with those of genotyping in 80.0% of the patients. In Northern Estonia, the genotypes 1b and 3a seem to be most common in chronically infected patients. Serotyping is an generally available and cheap assay and can be performed in most diagnostic laboratories in comparison to genotyping. However, genotyping is a more sensitive and more specific assay.

[Interferon system status in hemodialysis patients infected with hepatitis B and C viruses]. / Sostoianie sistemy interferona u patsientov na gemodialize, infitsirovannykh virusami gepatita B i C.

The production of alpha- and gamma-interferon (IFN) by peripheral blood cells in vitro and the concentration of serum IFN were studied in patients treated by hemodialysis at the Pelgulinna Tallinn Hospital and compared to controls. Out of 108 patients on hemodialysis, 19.4% were infected with hepatitis B (HBV), and antibodies to hepatitis C virus (HCV) were detected in 7.4%. During 3.5 years of observation, cases of hepatitis B and C infection among patients and medical staff were rare. The production of alpha- and gamma-IFN in 23 patients with HBV and/or HCV markers on hemodialysis and in 38 patients without markers was similarly decreased in comparison with the controls and the titers of serum IFN were similarly increased. Lack of reliable difference between IFN status of two groups of patients may be explained by the absence of clinical symptoms of hepatitis, confirmed by laboratory findings.

[The epidemiological aspects of viral hepatitides in Estonia]. / Epidemiologicheskie aspekty virusnykh gepatitov v Estonii.

The etiological structure of viral hepatitides among the adult population of Tallinn and the occurrence of markers of hepatitis B and hepatitis C virus infections in medical workers, addict introducing drugs intravenously and hemodialysis patients were studied. Changes in the etiological structure of viral hepatitides were established: they took the form of a decrease in the level of hepatitis A morbidity and the considerable growth of the role of hepatitides B and C, as well as the newly detected circulation hepatitis D virus. About one-third in the structure of morbidity in viral hepatitides were hepatitis cases without markers of hepatitis A, B or C viruses (non-A, non-B, non-C). The highest rates of hepatitis B virus infection (78.9%) and hepatitis C virus infection (82.5%) were detected among drug addicts. Their level of HBsAg was 8.8%. In the group of medical workers, 25% of the examinees, i.e. every fourth person, had markers of hepatitis B virus, while antibodies to hepatitis C virus were detected in 5% of cases. Among hemodialysis patients these rates were 21.4% and 10.7% respectively.

[Experimental study of the prophylactic anti-influenza and interferon-inducing activity of epsilon-aminocaproic acid]. / Eksperimental'noe izuchenie profilakticheskoi protivogrippoznoi i interferonindutsiruiushchei aktivnosti épsilon-aminokapronovoi kisloty.

Epsilon-aminocaproic acid, an original antifibrinolytic had a rapid and prolonged protective effect, thus lowering the death rate of experimental mice contaminated with virulent strains of the influenza virus. The protective effect of the acid was observed after its intraperitoneal administration in a dose of 20 mg/mouse 24 hours before contamination by the strain with the H3N2 antigenic formula and after intranasal application of 15 mg of epsilon-aminocaproic acid divided into 2 doses 2 days before contamination by the strain with the H1N1 antigenic formula. In the animals contaminated by the H1N1 influenza virus 5 days after subcutaneous administration of the drug in a dose of 30 mg there was detected in the lungs a much lower number of the infectious viruses 3 days after the contamination. It was shown that 3 and 6 weeks after initiation of the 5-day treatment course with subcutaneous administration of epsilon-aminocaproic acid in a daily dose of 90 mg/mouse the animal resistance to the H1N1 influenza virus increased. No interferonogenic activity after administration of epsilon-aminocaproic acid was observed in the mice.