[Impact of changes in the amino acid sequence of the "a" determinant on the diagnostic capacities of test systems for the detection of HBsAg].

The diagnostic capacities of 4 commercial test systems were comparatively estimated for the detection of HBsAg, by applying a panel of samples with the established amino acid sequence of the "a" determinant of HBsAg. The Roche Elecsys HBsAg test system demonstrated the highest sensitivity - the maximum HBsAg concentrations were found in 19 of 31 cases. Escape mutations in the major hydrophilic region (MHR) of HBsAG (P120S, M133T) were responsible for differences in the sensitivity of 4 test systems by 10- to 40-fold. There were also samples that showed differences in the diagnostic capacities of the test systems to detect HBsAg, but without amino acid replacements in the area of the "a" determinant, which seems to be associated with amino acid replacements in other regions of HBsAg.

[Diagnostic significance of type IV collagen and hyaluronic acid in the serum of patients with chronic hepatitis C for staging hepatic fibrosis].

AIM: To evaluate diagnostic value of serologic fibrosis markers (hyaluronic acid--HA and type IV collagen C-IV) in patients with chronic hepatitis C (CHC) and hepatic cirrhosis (HC). MATERIAL AND METHODS: HA and C-IV were measured in 88 CHC patients with fibrosis stage 1 (n = 63) and 3 (n = 25), 13 patients with acute hepatitis C (AHC), 28 patients with hepatic cirrhosis (HC), 19 patients with pulmonary fibrosis (PF). The control group consisted of 32 healthy subjects. RESULTS: HA concentrations in the serum of CHC patients with mild to severe inflammation and fibrosis (F1 and F3) were normal (100 ng/ml). For HC diagnosis, HA test proved highly sensitive and specific (in HA 100 ng/ml sensitivity was 100%, specificity 84.6%), but this method cannot stage hepatic fibrosis. HA test was inferior to C-IV test. A mean C-IV concentration in the serum of CHC patients at the stage of marked fibrosis (F3) is significantly higher than in F1, in HC (A) patients higher than in patients with CHC F3. CONCLUSION: It is shown than concentration of C-IV above 196 ng/ml can differentiate fibrosis stage 1 from stage 3 with specificity 58.7 and sensitivity 88%.

[A comparative evaluation of detection of antibodies to hepatitis C virus in different immunoassay test system and verification tests]. / Sravnitel'naia otsenka rezul'tatov opredeleniia antitel k virusu gepatita C pri ispol'zovanii razlichnykh immunofermentnykh test-sistem i podtverzhdaiushchikh testov.

Control tests and subsequent comparative analysis of their results related with the detection of anti-hepatitis C virus (anti-HCV) by different ELISA systems were made at a laboratory of the "Vector-Best" Company, Novosibirsk (A), a clinical diagnostic laboratory of Infection Clinical Hospital No. 1, No. 1 (B), and at a laboratory of chronic viral infections of Andjaparidze Institute of Viral Drugs of the Russian Academy of Medical Sciences (C). Two thousand three hundred and fifty blood sera of donors and 236 blood sera of patients with acute and chronic renal pathology were examined. The comparative research made at the above facilities by different ELISA systems produced diversified results. An analysis of 2350 blood samples from donors made in 3 ELISA systems at laboratory A showed divergence in 19 (0.8%) cases. At laboratories B and C, 5 ELISA systems (a set of 236 samples) denoted differences in 28 (11.9%) cases. Significant variances were registered in confirmation of disputable results of ELISA with immunoblot, which is apparently related with differing criteria applicable to confirming the positive results from using the confirmative tests. A possibility is discussed of using different ELISA systems in screening examination.

[Spectrum of antibodies to HCV antigens in patients with different clinical patterns of chronic HCV infection]. / Spektr antitel k razlichnym antigenam HCV pri raznykh variantakh techeniia khronicheskoi HCV-infektsii.

Correlations between the spectra of antibodies to HCV proteins represented by various antigenic determinants and clinical variants of chronic HCV infection were studied. Synthetic peptides core-16, NS4-20, and NS5-23 simulating the immunodominant regions of the core, NS4 and NS5 proteins and recombinant proteins core-114 and NS4-86 were used as antigens. The results indicate that if the serum of an HCV patients contains no IgG to both antigenic determinants of NS4 or to NS5 in combination with any core antigenic determinant, a clinical and biochemical remission is highly probable. Chronic hepatitis C is characterized by the presence of IgG in high titers to both antigenic determinants of NS4 protein, particularly in combination with anti-NS5 IgG in low titers or none at all, or high titers of anti-core-16 IgG in combination with high titers of anti-NS4-20 IgG.

[Diagnostic significance of antibody detection to various hepatitis C virus antigens in patients with acute and chronic HCV-infection]. / Diagnosticheskaia znachimost' opredeleniia antitel k razlichnym antigenam virusa gepatita C u patsientov s ostroi i khronicheskoi HCV-infektsiei.

AIM: To examine diagnostic value of antibodies to various HCV antigens in patients with acute and chronic HCV-infection. MATERIAL AND METHODS: Enzyme immunoassay has tested blood sera from 136 patients with icteric acute hepatitis C (AHC) and 45 patients with chronic HCV infection for IgG antibodies to antigens of proteins core, NS4, NS5, HCV. Synthetic peptides core-16, NS4-20, NS5-23 were used as antigens. RESULTS: Patients with icteric AHC had IgG antibodies to antigens of both structural protein core and non-structural proteins NS4, NS5 of HCV as early as the first 10 days of jaundice. Occurrence of anti-core and anti-NS4 increases with the disease duration. Incidence of anti-NS4 correlated with duration of previous intravenous drug addiction. In patients with AHC early in the icteric period anti-core, anti-NS4, anti-NS5 were present less frequently than in patients with chronic HCV infection having elevated levels of AlAT. Significant differences were found neither with the group with normal AlAt nor in the spectrum of the detected antibodies between patients with acute and chronic HCV infection. CONCLUSION: Despite different frequency of anti-core, anti-NS4, anti-NS5 detection in patients with icteric AHC and patients with chronic HCV-infection and high AlAT, their high incidence rate in this or that group and absence of differences by the spectrum of the studied antibodies do not allow the fact of their detection to be a diagnostic marker differentiating acute HCV-infection with chronic one.

[Acute hepatitis C in the presence of chronic HBV infection]. / Ostryi gepatit C na fone khronitseskoi GBV-infektsii.

Acute HCV superinfection was studied in 23 patients with chronic hepatitis B virus infection. HBsAg, anti-HCV (C-100, core, NS3, NS5) were detected in patients' sera at first investigation. Predominant replication of HBV DNA was detected in the sera of 68% patients and HCV RNA in only 24% patients. The clinical course of acute hepatitis C in patients with chronic HBV infection in general corresponded to HCV monoinfection except for more pronounced biochemical shifts and shorter intoxication. The role of HBV and HCV in infectious process is discussed.

[The role of hepatitis C virus RNA detection in various substrates of patients with chronic hepatitis C]. / Znachenie viiavleniia RNK virusa gepatita C v razlichnykh substratakh u bol'nykh khronicheskim gepatitom C.

Puncture biopsy of the liver and blood count were made in 72 patients with chronic hepatitis C (CHC). Morphological alterations in the liver were assessed by Knodell index. The blood serum, lymphocytes and hepatic tissue were examined for a genome form of hepatitis C virus (HCV) RNA, blood lymphocytes and hepatic tissue--for a relevant replication form. HCV RNA was detected using "nested" RT-PCR. Only 26% patients had symptoms of asthenovegetative and dyspeptic syndromes. Normal alaninaminotransferase (ALT) level was observed in 24% patients, the rest had it high. HCV RNA was encounted more frequently in hepatic tissue than lymphocytes or serum (83, 68 and 46%, respectively). A replication form of HCV RNA was present in hepatic tissue of 31% patients and was absent in the lymphocytes. The incidence of the RNA detection was not related either to the disease symptoms or morphological alterations in hepatic tissue. The occurrence of the genome and replication forms in hepatic tissue does not correlate to ALT level. HCV RNA occurs more often in the serum, blood lymphocytes and in three substrates simultaneously in patients with hyperalatemia.

[Serological study of hepatitis C virus NS5 protein epitopes and their clinical and diagnostic significance]. / Serologicheskoe issledovanie épitopov belka NS5 virusa gepatita C i ikh znachenie dlia kliniki i diagnostiki.

Three peptides corresponding to the 2295-2317 aa NS5 HCV region and individual parts of this region were synthesized. Antigenic properties of these peptides were investigated. The 2295-2317 aa region contains at least two epitopes of different nature. The full-sized peptide is more promising for the diagnostic studies. Optimal conditions for ELISA with this peptide were defined, allowing the maximum complete utilization of the potentialities of both epitopes.

[The treatment of pneumonias in influenza using antioxidants]. / O lechenii pnevmonii pri grippe antioksidantami.

Lipid peroxidation (LPO) has been studied in patients with influenza complicated by pneumonia as shown by GPL and MDA serum levels of GPL and MDA. Acute period of the disease was characterized by a sharp rise in LPO products production, especially in seriously ill patients. Administration of alpha-tocopherol promoted a significant decrease of MDA and GPL levels and more apparent clinical response. Dibunol caused minimal changes in the disease clinical pictures and LPO activity.

[The clinical manifestations and differential diagnosis of Yersinia hepatitis and viral hepatitis A and B]. / Klinicheskie proiavleniia i differentsial'naia diagnostika iersinioznykh i virusnykh gepatitov A i B.

Hepatic involvement in yersiniosis is associated with clinical symptoms of hepatitis, sometimes dominant in the clinical picture. Such cases need differentiation of yersiniosis with viral hepatitides A and B. Clinical and biochemical findings were compared for matched patients with yersiniosis-induced hepatic lesions, viral hepatitis A and viral hepatitis B verified at specific laboratory examination. This permitted introduction of differential diagnostic signs able to recognize one disease from the other.

[The course and outcome of chronic hepatitis B in children]. / Techenie i iskhody khronicheskogo gepatita B u detei.

Overall 98 children aged 1 to 14 years suffering from chronic hepatitis B (CHB) were followed up clinically for 1 to 6 years. CHB was diagnosed on the basis of the clinical and laboratory data. In the majority of the children, the diagnosis was verified by the results of a histological study of liver biopsy specimens. Chronic active hepatitis (CAH), was revealed in 27 children, chronic persistent hepatitis (CPH) in 31. CHB was marked by the presence of HBe-antigenemia in 89 patients (90.8%). The studies have demonstrated that CHB associated with HBe-antigenemia runs its course with insignificant clinical manifestations and enzymic exacerbations without jaundice. In the presence of persistent HBs-antigenemia, the natural course of CHB (in CAH and CPH) is characterized by seroconversion (from HBeAg to anti-HBe) with a simultaneous decrease and normalization of aminotransferase activity and a reduction of the pathological process activity in the liver (transformation of CAH to CPH). Seroconversion and clinico-biochemical amelioration supervene at different observation periods (after 1-6 years) and do not depend on the initial activity of hepatitis. As the observation period increases, the rate of anti-HBe appearance in the blood rises, amounting to 90% with the observation period exceeding 5 years. The conclusion is made that CHB patients do not need active drug therapy but require long and permanent observation.

[Clinico-biochemical evaluation of the effectiveness of plasmapheresis in the treatment of severe forms of viral hepatitis]. / Kliniko-biokhimicheskaia otsenka éffektivnosti plazmafereza v terapii tiazhelykh form virusnogo gepatita.

The study was performed of clinico-biochemical effect of plasmapheresis (PA) in severe viral hepatitis B, mixed hepatitis and hepatitis delta. Altogether 24 patients, all of them HBsAg carriers, were examined. With associated acute hepatic encephalopathy, clinical effect in hepatitis of PA was insignificant notwithstanding positive biochemical changes. In the absence of hepatic encephalopathy PA effect was pronounced both clinically and biochemically.

[Patterns in perinatal infection with the hepatitis B virus in areas contrasted by the level of HBsAg and HBeAg carriage]. / Zakonomernosti perinatal'nogo infitsirovaniia virusom gepatita B na territoriiakh, kontrastnykh po urovniu nositel'stva HBsAg i HBeAg.

In 1984-1988, the levels of HBsAg carrier state and the status of the "e"-system components in pregnant women in Moscow and in the Uzbek SSR, as well as the rate of infection with hepatitis B virus (HBV) in babies born to women carriers of HBsAg in regions with different levels of HBsAg and HBeAg carrier state were studied. The levels of HBsAg carrier state among pregnant women were different in Moscow and Uzbekistan (1.1% and 6.9%, respectively). It was noted that in female HBsAg carriers in these regions the rate of HBeAg detection differed greatly: 5.2% in Moscow and 13.9% in Uzbekistan. The frequency of perinatal infection with HBV in Moscow was 26.1%, in Uzbekistan 40.0%, the frequency of persistent carrier state of HBsAg in the infected babies of Uzbekistan was 16.0%. The possibility of formation of HBsAg persistence in babies born to women with HBsAg and anti-HBe in the blood was demonstrated. The problem of the use of specific prophylaxis measures to prevent perinatal transmission of HBV is discussed.

[The danger of hepatitis B virus infection from transfusions of plasma in which the HBs-antigen was detected retrospectively by highly sensitive methods]. / Opasnost' zarazheniia virusom gepatitia B pri perelivaniiakh plazmy, v kotoroi retrospektivno vysokochuvstvitel'nymi metodami vyiavlen HBs-antigen.

The prospective dynamic laboratory and clinical study of premature children was carried out: 55 children who received plasma transfusion during the first weeks of their life and were retrospectively (i. e. after plasma transfusion) found to have HBsAg detected by the passive hemagglutination (PHA) test, the enzyme immunoassay (EIA) and the radioimmunoassay (RIA) and 127 children who received the transfusion of plasma found to be HBsAg-negative according to the results of EIA and RIA. As revealed in this study, the risk of hepatitis B virus infection in such children after the transfusion of plasma containing HBsAg at low concentrations, determined only in the PHA test or in EIA and RIA, was, respectively, 7.5 and 6.3 times greater than in children receiving plasma found to be HBsAg-negative according to the results of EIA and RIA. The results of this investigation showed the tendency towards a decrease not only in the total contamination of plasma recipients with hepatitis B virus, but also in morbidity rate in icteric forms of acute posttransfusion hepatitis B, depending on the concentration of HBsAg in plasma used for transfusion.

[Reaferon treatment in acute HBsAG-positive viral hepatitis]. / Lechenie reaferonom ostrogo HBsAg-polozhitel'nogo virusnogo gepatita.

Clinical, biochemical and serological examinations of 412 patients with acute HBsAg-positive virus hepatitis were conducted to assess therapeutic efficacy of Soviet recombinant alpha 2-interferon (reaferon). There were 309 cases of acute virus hepatitis B, 103 of delta infection (71--coinfection, 32--superinfection). The study and control groups were assigned randomly. Reaferon i.m. administration started on jaundice day 1-5 and lasted for 10-11 days. The treatment proved effective in acute hepatitis B running a moderately severe and severe course up to the development of acute hepatic encephalopathy. In delta infection reaferon produced response in coinfection only. In fulminant hepatitis the treatment was uneffective.

[The risk of infecting premature newborn infants with the HB virus in transfusions with plasma HBsAg-negative by counterimmunoelectrophoresis]. / Risk infitsirovaniia nedonoshennykh novorozhdennykh detei HB-virusom pri transfuziiakh HBs-antigenotrisatel'noi po vstrechnomu immunoélektroforezu plazmy.

The prospective dynamic study of 229 premature infants with the use of highly sensitive methods, such as the passive hemagglutination test and the enzyme immunoassay, for the detection of HBsAg and anti-HBs antibodies. Of these, 182 infants received plasma (blood) transfusions in the first days of their life. Plasma (blood) used for transfusions was known to contain no HBsAg in accordance with the results of countercurrent immunoelectrophoresis. 47 infants had no plasma (blood) transfusions. In the group of 182 plasma recipients the presence of hepatitis B virus infection was detected in 17.0% of infants, the ratio of icteric, nonicteric and inapparent forms being 1:4.2:2. In the group of 47 infants no case of hepatitis B virus infection was observed.