Trial of a Soviet diagnostic kit for determining class M immunoglobulins to the hepatitis A virus by immunoenzyme analysis (an anti-HAV IgM test system)

The authors have studied the effectiveness of the first Soviet test system for the diagnosis of hepatitis A by means of the enzyme immunoassay (Diagn-A-Hep), developed at the Institute of Poliomyelitis and Viral Encephalitides, Moscow, under the conditions of different epidemic situations. In the process of this trial the high specificity and sensitivity of this test system, established earlier in the certification and commission trials, have been confirmed. Diagn-A-Hep has proved to be highly effective in the diagnosis of acute forms of hepatitis A and permitted its detection in patients during the incubation period, as well as in patients with anicteric and asymptomatic subclinical forms. Besides clinical diagnosis, the kit Diagn-A-Hep may be used in large-scale seroepidemiological surveys of the immune structure of the population, as well as in detection of HAV in different material under test.     

Development of a Soviet diagnostic kit for determining class M immunoglobulins to the hepatitis A virus by immunoenzyme analysis (a test system for anti-HAV IgM)

A new test system Diagn-A-Hep for the laboratory diagnosis of hepatitis A (HA) by means of the enzyme immunoassay has been developed at the Institute of Poliomyelitis and Viral Encephalitides (Moscow). The sensitivity and specificity of the newly developed test system have proved to be similar to those of the well-known commercial diagnostic system HAVAB manufactured by Abbott Laboratories (USA). Diagn-A-Hep permits the diagnosis of HA with 96-100% effectiveness both in patients with the acute form of the disease and in patients with its anicteric or inapparent forms. This system is simple and convenient, it may be employed in inadequately equipped laboratories or even under field conditions. The rules for the selection of immunobiological preparations to be included in the test system have been worked out.     

Effect of the content of hepatitis A antibodies in immunoglobulin preparations on the effectiveness of the immunoglobulin prophylaxis of hepatitis A

The results of a strictly controlled experiment showed that prevention of hepatitis A by the injection of immunoglobulin with hepatitis A virus (HAV) antibody titer 1:10000 was 3 times as effective as that achieved with immunoglobulin containing HAV antibodies in titer 1:2500. It is recommended to determine the level of specific HAV antibodies in immunoglobulins and to use immunoglobulins with a high level of HAV antibodies for prevention of hepatitis A.     

Patients with chronic viral hepatitis as sources of infection

Dynamic observation on 126 foci of infection formed by patients with manifest forms of chronic hepatitis B, 41 foci of chronic hepatitis of unknown etiology, and 37 foci formed by chronic "healthy" carriers was made. In the foci of type 1 the epidemic process developed intensively and was manifested mainly by HBsAg carriership in persons having had contacts with the patients. During the period of observation 43.0% of new cases of infection were detected. In the foci of types 2 and 3 the frequency of contacting infection was not different from that in the control group of the population.     

Perinatal transmission of hepatitis B virus.

Transmission of hepatitis B virus from carrier mothers to their infants seems most likely to occur during birth. Both cord blood and breast milk have been found to be positive (in 35% and 72% of cases respectively) for hepatitis B surface antigen (HBsAg), but they do not appear to play an important role in transmission. To control this problem high-risk women should be tested during pregnancy for HBsAg. The infants of infected women should be given several doses of hepatitis B immunoglobulin starting at birth. In less developed regions, where hepatitis B is endemic, administration of the immunoglobulin in combination with vaccine, or even the vaccine alone, may be preferable in order to provide infants with lasting protection.     

Qualitative and quantitative behavior of B-lymphocytes and immunoglobulins in the serum of children with acute leukemia after a single immunoglobulin concentrate substitution

In 19 children affected with acute leukaemia the serum immunoglobulin level was examined. An Ig deficiency treated with a single administration of IgA or IgM concentrate could be detected in 16 of these children. The impact of this single Ig substitution on the serum immunoglobulin level and on B-lymphocytes in the peripheral blood was thrice examined after this substitution. A significant increase of the corresponding Ig class in the serum and a significant decrease of B-lymphocytes in the peripheral blood could be observed.     

A trial of using immunoglobulins of known specificity for preventing hepatitis A in regions with high epidemic activity

The economic effectiveness of immunoglobulin prophylaxis (IGP), carried out among children aged 1-3 at the beginning of a seasonal rise in hepatitis A (HA) morbidity with high coefficients of protection (80-85%), was directly related to the activity of the epidemic process. Preparations with sufficiently high content of antibodies to HA virus sharply decreased the manifestation of this infection. The detection rate of the manifest forms of the infection among children covered by prophylactic measures in the foci of HA was considerably lower than among children who had not received the preparation. IGP exerted no essential influence on the dynamics of the formation of population immunity. A high share of children aged 3-4 years, seropositive to HA virus (up to 90%), validates the inadvisability of carrying out IGP in older groups of children.     

The spread of HB virus infection in familial foci in a territory hyperendemic for hepatitis B

Epidemiological surveillance with the use of highly sensitive techniques for the indication of markers of hepatitis B (HB) virus infection in their dynamics has made it possible to find out that at a territory, hypersensitive for HB, along the existing high risk of this infection as the result of parenteral medical manipulations the intensive natural transmission of HB virus infection occurs under the conditions of everyday contacts with sources of the infection, patients with chronic forms of HB virus infection being of the highest epidemic importance. Under these conditions, children aged up to 7 years have been found to belong to the highest risk group. As a consequence, children of this age should be covered in future by specific preventive measures against HB. The spread of the epidemic process of HB virus infection in family foci is usually manifested by anicteric (usually not diagnosed) forms of this infection. All these circumstances make it expedient to develop antiepidemic and prophylactic measures in the foci of HB.     

Immunologic effects of interferon-alpha in man: treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis

The effect of human recombinant interferon-alpha on lymphocyte proliferation and differentiation was studied in 18 patients with chronic type B hepatitis who were participating in a randomized controlled trial of interferon-alpha therapy. Peripheral blood mononuclear cells (PBMC) were obtained by lymphopheresis before and during a 4 mo course of interferon. Pokeweed mitogen-induced immunoglobulin synthesis by PBMC obtained from patients before therapy was similar to that of PBMC from normal individuals. However, after 2 wk treatment with human recombinant interferon-alpha mitogen-induced immunoglobulin production was decreased by an average of 50%. Staining for cytoplasmic immunoglobulin revealed decreases that paralleled secreted immunoglobulin, indicating that interferon-alpha treatment inhibited immunoglobulin synthesis. Mixing autologous T and B cell enriched populations from before and during interferon treatment revealed that the decrease in immunoglobulin synthesis involved a defect in the B cell-enriched population. In contrast to immunoglobulin synthesis, pokeweed mitogen-induced lymphocyte proliferation was not significantly affected by in vivo administration of interferon-alpha. Thus a major effect of in vivo interferon-alpha on immunoregulation in patients with chronic type B hepatitis appears to be an inhibition of the late stages of B cell differentiation into immunoglobulin producing and secreting plasma cells.     

An immunosorbent method for the quantitative determination of antiliver autoantibodies in patients with viral hepatitis

Autoimmune processes in patients with mild, moderate and severe forms of viral hepatitis B have been studied with the use of a new immunosorbent method for the quantitative determination of autoantibodies (auto-Ab), developed by the authors. The immunosorbent has been obtained on the basis of granulated aerosil, an active protein-adsorbent agent used as a solid antigen carrier. The level of auto-Ab in patients with all forms of viral hepatitis B has been found to exceed the content of such antibodies in practically healthy persons. Besides, in patients with severe and prolonged forms of the disease the content of antihepatic auto-Ab has been found to remain high even after clinical convalescence, which is indicative of the continuation of the autoimmune process.     

Modulation of hepatitis B infection by intravenous application of an immunoglobulin preparation that contains antibodies to hepatitis B e and core antigens but not to hepatitis B surface antigen.

Repeated administration of an intravenous immunoglobulin containing antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc) but free of antibody to hepatitis B surface antigen (anti-HBs) before and after the inoculation of 10(4.9) 50% chimpanzee infective doses of hepatitis B virus (HBV) markedly prolonged the incubation period of HBV in experimentally infected chimpanzees. Similar administration of an immunoglobulin preparation containing anti-HBc but free of anti-HBe and anti-HBs or intramuscular administration of a single dose of immunoglobulin containing anti-HBe and anti-HBc 3 days before or after inoculation with HBV did not appear to modulate HBV infection. These observations suggested that anti-HBe, or an unidentified antibody associated with it, may have biological activity in the modulation of HBV replication.     

Everyday contact spread of viral hepatitis B

The results obtained in the study of the characteristic features of the spread of viral hepatitis B under the conditions of family foci are presented. Children with viral hepatitis B have been found to infect 4-5 persons per 1,000 contacts, while adults infect not more than 1 person per 1,000 contacts. The results of the study have led to the conclusion that the idea of the potential danger of hepatitis B patients as the source of infection depends on the forms of the infectious process taken into account in evaluating its epidemiological significance. Latent cases of hepatitis B virus infection appear more frequently among the contacts of sick children than among those of sick adults, but the manifest forms of the disease are more frequently caused by infection contacted from sick adults.     

血小板参数、hs-CRP与免疫球蛋白联合检测对肝炎患者的临床意义

目的:探讨和研究血小板参数、超敏C反应蛋白(hs-CRP)与免疫球蛋白联合检测对肝炎患者的临床意义,为临床中肝炎患者的诊治提供参考。方法:收集各种病毒性肝炎患者共156例(急性肝炎组48例、慢性肝炎组56例、重型肝炎组24例和肝硬化组28例),选择40例健康体检者作为对照组,对5组研究对象的血小板参数((血小板计数(PLT)、平均血小板体积(MPC)、血小板压积(PCT)和血小板分布宽度(PDW))、血清超敏C反应蛋白和免疫球蛋白(IgA、IgG和IgM)水平进行检测和测定,并对这些指标的变化进行对比分析。结果:除重型肝炎组与肝硬化组的血小板计数(PLT),慢性肝炎组与重型肝炎组的PCT,急性肝炎组、肝硬化组与对照组3组间的PDW的差异无统计学意义外,任意两组之间的差异均有统计学意义(P0.05);各组肝炎患者的hs-CRP均比健康对照组显著升高(P0.01),且免疫球蛋白也较对照组差异有统计学意义。结论:肝炎患者的血小板参数、超敏C反应蛋白(hs-CRP)与免疫球蛋白水平可以提示肝炎病情的变化,三者的联合检测为指导肝炎患者的判断、治疗方案的选择和疗效评定提供有一定的参考依据。     

Epidemiological characteristics and the importance of carriers of the surface antigen of the hepatitis B virus (HBsAg)

The occurrence of HBsAg carriership in Leningrad has been found to be 1.4% according to the results of countercurrent immunoelectroosmophoresis (CIEO) and 2.1% according to the results of the passive hemagglutination (PHA) test. In children HBsAg occurs with higher frequency: 1.9% according to the results of CIEO and 3.4% according to the results of the PHA test. The latter test reveals HBsAg carriers more completely, especially in women who have usually less pronounced antigenemia than men. Most of chronic HBsAg carriers are patients with chronic forms of hepatitis B (chronic active hepatitis and chronic persistent hepatitis); frequently they become the source of infection among their relatives under the conditions of family contacts. A complex of antiepidemic measures is necessary in the foci of chronic HBsAg carriership.     

Monthly dynamics of the epidemic process in viral hepatitis B

Monthly fluctuations in the number of registered cases of acute viral hepatitis B and HBsAg carriership have been studied. The study has revealed that, similarly to other infectious diseases, viral hepatitis is characterized by monthly fluctuations in the intensity of the epidemic process. Such fluctuations are characteristic of all known clinical forms of this infection; they are determined by the specific pathogenetic features of the process and by the ways of the transfer of the virus. The vernal rise of the infection is explained by activation of the manifest and asymptomatic chronic variants of the infectious process and, as the consequence of a rise in the number of asymptomatic cases, by a higher incidence rate of post-transfusion hepatitis infection. The autumnal rise of the infection results from the action of natural factors contributing to the transfer of the virus. Both rises are interrelated and interdependent. The seasonal fluctuations of the epidemic process should be taken into consideration when planning and implementing prophylactic and epidemic-control measures.     

血小板参数、hs—CRP与免疫球蛋白联合检测对肝炎患者的临床意义

目的：探讨和研究血小板参数、超敏C 反应蛋白（hs-CRP）与免疫球蛋白联合检测对肝炎患者的临床意义,为临床中肝炎患者的诊治提供参考。方法：收集各种病毒性肝炎患者共156 例（急性肝炎组48 例、慢性肝炎组56 例、重型肝炎组24 例和肝硬化组28 例）,选择40 例健康体检者作为对照组,对5 组研究对象的血小板参数（（血小板计数（PLT）、平均血小板体积（MPC）、血小板压积（PCT）和血小板分布宽度（PDW））、血清超敏C 反应蛋白和免疫球蛋白（IgA、IgG 和IgM）水平进行检测和测定,并对这些指标的变化进行对比分析。结果：除重型肝炎组与肝硬化组的血小板计数（PLT）,慢性肝炎组与重型肝炎组的PCT,急性肝炎组、肝硬化组与对照组3 组间的PDW 的差异无统计学意义外,任意两组之间的差异均有统计学意义（P＜0.05）;各组肝炎患者的hs-CRP 均比健康对照组显著升高（P〈0.01）,且免疫球蛋白也较对照组差异有统计学意义。结论：肝炎患者的血小板参数、超敏C 反应蛋白（hs-CRP）与免疫球蛋白水平可以提示肝炎病情的变化,三者的联合检测为指导肝炎患者的判断、治疗方案的选择和疗效评定提供有一定的参考依据。     

The dynamics of [3H]-cholesterol incorporation into the liver and aortic tissue of guinea pigs on long-term ethanol administration]

The effect of ethanol administration to guinea pigs (4 g/kg, per os) on the dynamics of [3H]-cholesterol incorporation into the liver and aorta tissues was studied for 3 months. It has been discovered that specific radioactivity of the control animals linearly increased during 24 hours in the blood serum. Ethanol reduced it as compared with the control only 0.5 h after a label has been introduced. Cholesterol renovation in the liver remained unchanged under the prolonged effect of ethanol. In the aorta the ethanol effect was characterized by a decrease of [3H]-cholesterol specific radioactivity 0.5 h after its administration. However, in this case the ratio of aorta/blood serum radioactivity increased. A day after the labelled cholesterol administration to alcoholized animals the radioactivity calculated per 1 mg of cholesterol and per unit of tissue weight and referred to the blood serum radioactivity was lower as compared to the control level.     

Phosphatidylcholine-induced repair of damaged hepatocyte membranes in heliotrine poisoning

Hepatocyte membranes destruction in experimental toxic hepatitis caused by heliotrine administration was accompanied by a 10-fold increase in blood serum activity of aldolase fructose-I-monophosphate, a decrease in cytochrome P-450 content, an increase in the rate of cytochrome P-450 inactivation, as well as a decrease in microsomal glucose-6-phosphatase activity. Administration of phosphatidylcholine liposomes decreased the activity of aldolase twofold, which indirectly shows partial reconstitution of liver cell membranes. Phosphatidylcholine protective action is also manifested in an increase in the activity of glucose-6-phosphatase, a microsomal marker enzyme, up to its control level and in a 20% reduced rate of cytochrome P-450 inactivation. It has been shown that destroyed liver cell membranes may be repaired by the introduction of phosphatidylcholine in the form of multilayer liposomes.     

Epidemiology of viral hepatitis in the Estonian SSR

The epidemiological peculiarities of viral hepatitis in the Estonial SSR as a whole, as well as in Tallinn and in the surrounding Harju region were studied. The study revealed that during the last 10 years the total decrease of morbidity in viral hepatitis was observed due to a decrease in infectious hepatitis, pronounced periodic and seasonal morbidity fluctuations being absent. A sharp decrease in infectious hepatitis morbidity had been achieved by carrying out planned gamma globulin prophylaxis among children. Viral hepatitis morbidity in the republic was determined by the adult population and manifested as sporadic cases of infectious and serum hepatitis. Infectious hepatitis was transmitted mainly through every day contacts, while the leading factor in the transmission of serum hepatitis consisted in various injections. The relatively high morbidity level of serum hepatitis was mainly determined by morbidity in large cities.     

Curcumin protects mice against concanavalin A-induced hepatitis by inhibiting intrahepatic intercellular adhesion molecule-1 (ICAM-1) and CXCL10 expression

The effect of curcumin on liver injury caused by Concanavalin A (Con A) has not been carefully examined. This study was designed to evaluate the protective effect of curcumin on Con A-induced hepatitis in mice. Liver injured mice received curcumin by gavage at a dose of 200 mg/kg body weight before Con A intravenous administration. Curcumin was effective in reducing the elevated plasma levels of aminotransferases and the incidence of liver necrosis compared with Con A-injected control group. Enzyme-linked immunosorbent assay (ELISA) showed that curcumin suppressed proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-4 production in Con A-injected mice. The reduced severity of hepatitis in curcumin pretreated mice correlated with decrease in numbers of liver CD4(+) T cells but not CD8(+) T cells by immunohistochemical analysis. Furthermore, the expression levels of intercellular adhesion molecule-1 (ICAM-1) and the interferon-inducible chemokine CXCL10 in hepatic tissue were significantly decreased by curcumin pretreatment. In conclusion, curcumin pretreatment protects against T cell-mediated hepatitis in mice.