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Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects.

Sera from 35 fulminant hepatitis patients admitted to the hospital at the USSR AMS Research Institute of Virology in 1985-1989 were studied for specific markers of NB and delta infection. Delta-infection as etiological factor of the disease proved in 26 patients (74.3%). Acute hepatitis of mixed etiology (HBV and HDV) occurred in 17, acute hepatitis delta in 9 patients carrying chronically HBsAg. Acute hepatitis B was verified in the rest 9 patients. Clinical, biochemical and serological aspects typical for the variety of etiological variants of hepatitis running a fulminant course are considered.

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.

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 incidence of HBs- and HBe-antigens detection in future mothers was studied in Moscow, Uzbekistan, and Moldavia, and the incidence of hepatitis B (HB) virus transmission from mothers with persisting HBs-antigenemia to their offspring. In reverse passive hemagglutination test, HBsAg was detected in 1.1% of pregnancies in Moscow, in 6.3% of pregnancies in Uzbekistan, and in 5.4% of pregnancies in Moldavia. In these regions, immunofluorescence revealed HBe-antigen in HBsAg carriers in 5.2, 13.9, and 16.3%, respectively. Perinatal infection with HB virus was found in 26.1% of births to HBsAg carriers in Moscow and in 40% in Uzbekistan and Moldavia; in the latter two regions 16.0% and 13.3% of these births were found to become chronic carriers of HBsAg. In the presence of persistence of HBeAg in HSsAg carriers, from 89 to 100% births to these mothers showed the development of durable HBs-antigenemia, while in the presence of anti-HBe such outcome was noted in only 3%. Specific anti-HBs-immunoglobulin administered to infants born to HBsAg carriers exerted a protective effect by reducing the HB virus infection rate in the first 6 months of life, but failed to prevent completely the development of HB virus infection. The necessity of a wide-scale vaccination against HB in order to prevent HB virus infection of neonates is emphasized.

The author summarizes the experience of many years (1956-1989) gained with studies into the relationship between the gravity of viral hepatitides in the pregnant and etiology of disease. Virus A hepatitis runs a favourable course in the pregnant, i.e. without severe and fulminant forms. In virus B hepatitis, the pregnant women are threatened with the development of hepatic coma associated with a high maternal lethality. The latter one has noticeably been decreasing over the recent years (from 1.79% in 1956-1965 to 0.29% in 1966-1980 and to 0.21% in 1981-1989, which is not so much related to the perfection of the treatment methods as to the diminution of the share of virus B hepatitis. Virus E hepatitis may be of the greatest mortal danger for mothers in conditions of water epidemic. In that case the lethality among pregnant women may reach 12.1% (in the Turkmenian SSR) and 15.6% (in the Kirghiz SSR). The aggravating influences of virus C and D hepatitides on the pregnancy outcomes and maternal lethality have not been studied much. Estimation of etiological factors in viral hepatitis occurring in the pregnant is an important prerequisite for organization of the rational preventive and treatment measures.

The presence of HBs antigen and antibody to it was studied in 516 patients with acute viral hepatitis, convalescents, and patients with chronic liver diseases, 613 pregnant women, and 265 newborn babies using the gel precipitation test, and some of them (747 persons) by the reverse passive hemagglutination (RPHA) test. A high rate of HBs findings was observed both in patients with acute viral hepatitis (54.2%, RPHA) and in convalescents and patients with chronic liver diseases (44.9%, RPHA). Despite wide occurrence of hepatitis B virus carrier state among pregnant women (10.1%, RPHA), the rate of infection in newborn babies was only 0.6% by RPHA. The data are also presented on the distribution of the main subtypes of HBs and HBe antigens and antibody to them in the observed of patients and carriers.

In December, 1983 to December, 1985, blood sera of 14,603 pregnant women were tested for the detection of HBsAg carriers among them. A low level (1.1%) of HBsAg carrier state was demonstrated. HBeAg was detected in 5.2% of women-carriers of HBsAg, anti-HBe in 68.8%. The follow-up observations involved 59 babies born to the mothers HBsAg-carriers. The babies were divided into an experimental and a control group. The experimental group consisted of 22 babies who were given specific anti-HBs immunoglobulin, 37 babies of the control group did not receive this preparation. In the experimental group, 3 babies were found to be infected, all of them at the age of 9-12 months. In the control group the infection was detected in 9 babies, among them in 5 the markers of hepatitis B virus were detected at the age of 1-2 months. Based on these data, the efficacy of using anti-HBs immunoglobulin for prevention of neonatal hepatitis B is discussed.

Ribavirin-virazole (I-beta-D-Ribofluranosyl-1,2,4-triazole-3-carboxamide) inhibits human cytomegalovirus reproduction in cell cultures, as manifested by a decrease in the number of foci of lesions by 37-45% in virus-infected tubes propagated in the medium containing 100 micrograms/ml virazole as well as by a decrease of virus titre. In contrast to its marked inhibiting effect in tissue culture, virazole exerted no suppressive effect on virus excretion in the saliva and urine in chronic human CMV infection when given orally for 12-24 days in a dose of 9.6 g per course. The study of lymphocyte populations in patients with CMV infection revealed a decrease in the number of Ea-RFC and E-RFC. Inhibition of leukocyte migration to CMV antigen was found in about 40% of the patients examined. No significant changes in lymphocyte populations were observed after treatment with virazole which could be indicative of the immunosuppressive effect of the drug in the above-mentioned doses used.

Acyclovir was capable to delay for some time the development of the cytopathic effect in cell cultures. When acyclovir was added to the infected tube cultures in a concentration of 250 micrograms/ml, virus reproduction was inhibited for 6 days. Then foci of lesions were observed, and by the 12-13th days the intensity of involvement of the cell layer was 80-90% and did not differ from that in control tubes infected with cytomegalovirus (CMV). No significant differences were observed in the inhibiting effect of acyclovir on the freshly isolated strains or the reference Ad-169 strain. A course of therapy with acyclovir showed the inhibiting effect of this drug on CMV reproduction in women with the CMV infection to be of short duration. The temporary improvement observed on the first day after treatment was accompanied by reduced virus excretion with both the urine and saliva. Antibody titres remained the same before and after treatment. After 1-2 months virus excretion was observed practically in all the women similarly to that before the treatment.

A study was made of experimental acute liver failure induced in rabbits by administering D-galactosamine. Thirty-three rabbits were examined with the use of a set of the clinical, biochemical, electrophysiological and histomorphological methods. The results attest to the adequacy of the model studied to the tasks set up, since it provides for the reversibility of liver injuries, high reproducibility of the pathological process, death of the animal from the growing liver failure, large size of the experimental animal, the minimal risk for the laboratory staff and maximal approximation to the pathogenesis of viral hepatitis B in man. The evidence derived may be used for further development of the correcting pathogenetic therapy.

Five HBsAg carriers were examined by clinical, biochemical, radionuclide, immunologic and histomorphologic methods. Different variants of structural and functional relations were established. Attempts were made to eradicate the persistent virus carrierstate with the aid of the antiviral drug virasol, the immunomodulating drug levamisole, nonspecific (BCG vaccine) and specific (original corpuscular vaccine against hepatitis B) immunostimulants. No positive therapeutic effect was obtained. The difficulties and possibilities of a further study into the title problem with due regard for integration mechanisms of infection and prospects of the effective prophylaxis of virus transmission from the mother to the child at birth are discussed.

The therapeutic effect of orally given levamisole in the treatment of women with chronic cytomegalovirus infection was studied. The patients were examined serologically, cytologically, virologically; the factors of cell-mediated immunity were also studied. Oral therapy with levamisole resulted in a definite increase of the cell-mediated immunity with a trend for decrease in antibody titres and reduced virus excretion. Evaluation of the clinical effect of levamisole therapy, however, revealed no distinct difference in the outcomes of pregnancy in the groups of women treated or not treated with levamisole.

Thymotropic hormone was given subcutaneously in a dose of 100 mg twice a week for 3 months to 10 women with verified chronic cytomegalovirus infection. After termination of the treatment, in 8 women the virus excretion was decreased and this was accompanied with some improvement in immunological parameters: increased activity of natural killers, enhanced interferon-producing activity of lymphocytes, higher theophylline-resistant lymphocytes, and lower theophylline-sensitive T-cells. The above results confirm the association between the activity of cytomegalovirus infection and the state of immunity and allow thymotropic hormone to be recommended for treatment of other groups of patients with cytomegalovirus infection.

The results of detailed clinical, hematological, immunological, and virological investigations of a female patient who within 16 months after hemotransfusion acutely developed a long-term disease with a undulant course accompanied by high fever, lymphadenopathy, hepatolienal syndrome, stomatitis, leukopenia, and thrombocytopenia, are presented. Significant disorders in cell-mediated and humoral immunity were detected. Cytomegalovirus was isolated from the urine and saliva. The pathogenetic role of cytomegalovirus in the development and course of the disease is evaluated, and its etiological importance is discussed on a broader scale with regard to a possible association with retroviruses.

A series of long-term prospective studies was carried out to investigate the possibilities and manifestations of perinatal infection in Moscow. The observations included 45 mothers, chronic carriers of HBsAg, and their 48 babies. In most of the mothers (31 out of 41), HBs antigenemia was accompanied by the presence of anti-HBe. No persisting HBsAg carrier state was ever detected in the newborns, although in 9 out of 48 babies transitory ephemeral infection was recorded with minimal clinico-biochemical disorders in 6 and complete lack of any such disorders in 3. The above results are compared with the observations in the countries of South-East Asia, West Africa, Europe and the USA. The causes of significant differences in the epidemiological role of perinatal infection in different world regions are discussed. The primary role of anti-HBe formation, ecological, and genetic factors is emphasized.

Activity of kallikrein, content of prekallikrein, antitryptic and BAEE-esterase activities as well as content of alpha 1-antitrypsin and heparin were studied in blood serum of patients with the B type of serum hepatitis (SH) of various severity. Presence of kallikrein in the active form, increase in content of prekallikrein, distinct increase in BAEE-esterase and antitryptic activities as well as in content of alpha 1-antitrypsin and heparin were observed in blood serum of the patients with middle and severe forms of the impairment. Severe form of the hepatitis complicated with the acute liver encephalopathy was characterized by the radically new state exhibiting further increase in activity of free kallikrein, decrease in content of prekallikrein as well as in BAEE-esterase activity as compared with middle and severe forms of SH not complicated with the acute liver encephalopathy. Immunochemical analyses showed distinct decrease in the content of alpha 1-antitrypsin in blood serum of the patients with SH impaired also by acute liver encephalopathy. Besides, high level of the antitryptic activity was observed in severe forms of the hepatitis both with the encephalopathy and without of its. Further increase in the activity of free heparin was found in all the three forms of SH. Elevation of the antithrombin III inhibitory activity in presence of heparin was apparently responsible for an increase in the antitryptic activity under conditions of severe forms of SH when content of alpha 1-antitrypsin decreased. Activation of the kinin system and decrease in the alpha 1-antitrypsin synthesis, caused by destructive processes in liver tissue, are considered as factors deteriorating the disease development.

The results of virological investigation of a rare clinical instance of familial disease with a localized form of cytomegalovirus infection which, as a rule, is not diagnosed in life are presented. The infection localized in the salivary glands was the source of generalization of the process with a high fever, eruptions, lymphadenopathy, inflammatory changes in the excretory ducts of the salivary glands. Exacerbation of the chronic process was accompanied with high antibody titres (1:256--1:1024) with inhibition of the cellular immunity reactions in the mother. The latent form of infection in the father and two daughters ran without clinical manifestations, with low antibody titres and moderate inhibition of cellular reactions. The isolated strains of cytomegalovirus were identical in all the subjects under study and antigenically close to the Ad-169 strain.

Correlations between titres of complement-fixing antibody, levels of E-RFC, Ea-RFC, EAC-RFC, EA-RFC, and the intensity of virus excretion in the saliva and urine of women with chronic form of cytomegaly, as well as the effect of decaris in vitro on the level of E-RFC were studied. The highest antibody titres were found in subjects with generalized infection (virus excretion in the saliva and urine) and in cases where high concentrations of the virus were found in the salivary gland cells. In these subjects, total levels of E-RFC and their active subpopulations were decreased. The lowest antibody titres were found in women excreting no virus in the study period. Relative amounts of E-RFC and Ea-RFC in them were within normal ranges. No correlation between the levels of EAC-RFC, EA-RFC, and virus excretion was found. Decaris in vitro normalized the reduced values of E-RFC. Theoretical substantiation of the possibility of using this drug for treatment of patients with cytomegalovirus infection is presented.

Sixty-two women suffering from hepatitis B (HB) and their newborn babies were examined by a highly sensitive radioimmunoassay (RIA). The fluorescent antibody technique was also used to examine autopsy specimens of livers of 7 fetuses, 1 stillborn, and 3 babies dying in the first days of life whose mothers during pregnancy or delivery had experienced HB. Frequent infection of babies (77.8%) was observed at high concentrations of HBsAg in mothers in labor with subsequent development of persisting HBs-antigenemia, and in half of the babies of chronic hepatitis. HBsAg was detected in the first days of life not only in the blood serum, but also in the liver tissue which may be explained by intrauterine infection. At low concentrations of HBsAg in mothers the babies were infected less frequently (26.1%) and half of them were shown to have anti-HBs in the umbilical blood and blood serum in the first days and months of life. Anti-HBc transmission from mothers was also demonstrated. In babies born to convalescents after HB in the absence of HBsAg, anti-HBs in combination with anti-HBc were determined.

The author reviews virus associations on combination (1) of virus hepatitides A and B, (2) virus hepatitides A and "non-A, non-B", (3) virus hepatitides B and "non-A, non-B", (4) virus hepatitis B during superinfection with a delta-agent; (5) virus hepatitis B and the acquired immunodeficiency syndrome. Describes clinical observations, summarizes the clinical data. Analyzes theoretical aspects (interference, cumulative and potentiating effects) as well as the clinical objectives including the problems of the diagnosis and prophylaxis of cross virus infections.

The results of the study of functional activity of normal killers in different liver diseases: acute virus hepatitis A (26 patients), acute virus hepatitis B (24 patients including 3 with hepatic coma), and 12 patients with chronic liver diseases including 8 with chronic persisting hepatitis and 4 with chronic active hepatitis are presented. A control group included 17 apparently normal subjects. The most marked decrease of the level of activity of normal killers was found in hepatic coma and in chronic active hepatitis. The expedience of determinations of the activity level of normal killers for prognosis of immediate and remote outcomes of viral hepatitides as well as for the development of new methods of immunocorrecting therapy is discussed.