Spread of viral hepatitis in organized children's collectives and the methods for its early diagnosis]

The authors present the results of observations over 407 children aged from 2 months to 16 years from the foci of viral hepatitis in children's collective bodies. During the quarantine a determination was made in children of the glutamic-pyroracemic, glutamic-oxalic transaminases (GPT and GOT, respectively) and of the hepatitis B antigen (HBAg). A necessity of using the enzymatic tests for the purpose of early diagnosis of viral hepatitis was shown, since 84% of the cases developing in the next focus coursed as an unicteric form without any markked clinical signs; HBAg was revealed in 6.1% of the children examined. A complex examination of the personnel and of the persons who came in contact with the patients with viral hepatitis showed the ways of spread of hepatitis B in a collective body; it was found that the viral hepatitis B infection took place both by parenteral and enteral routes. The expediency of active observation over the children, recipients of blood and plasma, with determination in them of the activity of the enzymes and HBAg for early diagnosis of parenteral infection was substantiated. It was also shown that the incidence of the unicteric forms of viral hepatitis in a focus of infection depended not on the periods of gamma-globulin administration but on the age of children who contracted the infection. Thus, the prevalence of the unicteric forms of the disease over the icteric ones in children under 3 years of age was more pronounced than in older children.     

Viral hepatitis A and B as a mixed infection in children

Serological examinations of 1,200 children, hospitalized at the viral hepatitis department over a year, for the presence of hepatitis A (HA) and hepatitis B (HB) markers have revealed a 7% incidence rate of mixed HA and HB infections. Three variants of mixed infection have been established (true mixed infection, HA combined with asymptomatic HBsAg carriership, cross superinfection) and the relative significance of each of them has been determined. Mixed infection took an unfavorable course with a tendency to the prolongation of the pathological process eventuating in chronic hepatitis, especially in cases of true mixed infections (15.9%).     

Underwhelming the immune response: effect of slow virus growth on CD8+-T-lymphocyte responses

The speed of virus replication has typically been seen as an advantage for a virus in overcoming the ability of the immune system to control its population growth. Under some circumstances, the converse may also be true: more slowly replicating viruses may evoke weaker cellular immune responses and therefore enhance their likelihood of persistence. Using the model of lymphocytic choriomeningitis virus (LCMV) infection in mice, we provide evidence that slowly replicating strains induce weaker cytotoxic-T-lymphocyte (CTL) responses than a more rapidly replicating strain. Conceptually, we show a "bell-shaped" relationship between the LCMV growth rate and the peak CTL response. Quantitative analysis of human hepatitis C virus infections suggests that a reduction in virus growth rate between patients during the incubation period is associated with a spectrum of disease outcomes, from fulminant hepatitis at the highest rate of viral replication through acute resolving to chronic persistence at the lowest rate. A mathematical model for virus-CTL population dynamics (analogous to predator [CTL]-prey [virus] interactions) is applied in the clinical data-driven analysis of acute hepatitis B virus infection. The speed of viral replication, through its stimulus of host CTL responses, represents an important factor influencing the pathogenesis and duration of virus persistence within the human host. Viruses with lower growth rates may persist in the host because they "sneak through" immune surveillance.     

Prognosis of children who are carriers of hepatitis B.

Fifteen children who had become positive for hepatitis B surface antigen (HBsAg) by perinatal transmission were traced and re-examined after a mean of 8.1 years; all had been born in England to mothers from ethnic minorities who were carriers of HBsAg. Fourteen of the children remained carriers of HBsAg; of these, more girls than boys developed antibody to hepatitis B e antigen (anti-HBe). Those children whose transaminase activities had been above normal within the first three years of life were more likely to have developed anti-HBe. The earlier production of anti-HBe suggests that girls have a more effective immune response. Increased transaminase activity early in the course of asymptomatic carriage of HBsAg may be a favourable prognostic sign.     

Etiological structure of viral hepatitis in the area about one of the cities in Gorki Province

The etiological structure of viral hepatitides (VH) in one of the towns of the Gorky region was studied with the use of specific methods for diagnosing hepatitis A (detection of IgM to hepatitis A virus) and hepatitis B (detection of HBsAg in the passive hemagglutination test). The study revealed that hepatitis A was the major nosological from in the structure of VH among children and adults in the area under survey, which was documented by the detection of IgM to hepatitis A virus. The form, second in importance among VH cases, was hepatitis B. The ratio of these two forms of VH was determined by the epidemiological situation in the area. The proportion of hepatitis B cases increased at the period between epidemics. Nondifferentiated hepatitis constituted 6.8% of all cases of sporadic hepatitis among adults. In 90% of cases clinical diagnosis coincided with the serological one.     

Etiologic structure of viral hepatitis in children based on data from an comprehensive serologic study of hospitalized patients

During a year an overall serological examination of 1,200 children hospitalized with the diagnosis of viral hepatitis was carried out with a view to establish the presence of hepatitis A and hepatitis B markers (anti-HAV IgM, HBsAg, anti-HBs, anti-HBc and anti-HBe IgM) by means of the enzyme immunoassay and radioimmunoassay. The average annual proportion of cases of hepatitis A (61.4%), hepatitis B (20.4%), hepatitis non A, non B (11.2%) and mixed infection (7.0%) among children, as well as seasonal and age-group fluctuations of this proportion, were established. The etiological structure of viral hepatitides, based on commonly accepted clinico-epidemiological diagnostic criteria, was shown to differ from their true etiological structure as determined in accordance with specific serological markers detected in this investigation.     

Immunopathogenesis of hepatitis C virus infection

Hepatitis C virus, a recently identified member of the family Flaviviridae, is an important cause of chronic viral hepatitis and cirrhosis. There are similarities in the nature of the immune response to this pathogen with immunity in other flavivirus and hepatotropic virus infections, such as hepatitis B. However, the high rate of viral persistence after primary hepatitis C infection, and the observation that neutralizing antibodies are not protective, would suggest that there are a number of important differences between hepatitis C, other flaviviruses, and hepatitis B. The phenomenon of quasispecies evolution and other viral factors have been proposed to contribute to immune evasion by hepatitis C virus. In the face of established persistent infection, virus-specific cytotoxic T lymphocytes may exert some control over viral replication. However, these same effectors may also be responsible for the progressive liver damage characteristic of chronic hepatitis C infection. The nature of protective immunity, including the role of innate immune responses early after hepatitis C exposure, remains to be defined.     

Detection of HBsAg in the familial environment of children with viral hepatitis B

A total of 231 persons from the families of 62 children hospitalized in connection with viral hepatitis B were examined for the presence of HBsAg in their blood over a period of 3 years. Simultaneously with countercurrent electrophoresis (CIE) and the gel precipitation (GP) test, the passive hemagglutination (PHA) test and the GP test with sandwich treatment were used in this work. The presence of HBs-antigenemia in the members of the families of children with viral hepatitis confirmed by laboratory methods were found to occur 6.7 times more frequently than in the families of children with HBsAg-negative hepatitis. The use of the PHA test and the GP test with sandwich treatment increased the frequency of the detection of HBsAg 2.5 times in comparison with CIE and the GP test. The data indicating the possibility of children being infected through everyday contacts in families with cases of HBs-antigenemia among their members are presented, but further studies are necessary to make the final decision on this problem.     

Problems of the epidemiology of viral hepatitis in Ryazan Province

The analysis of some features of the course of the epidemic process of viral hepatitis on the territory of the Ryazan region is presented. Periodic rises and falls in viral hepatitis morbidity, varying in their regularity (4-6 years), have been registered in the region. The general level and the seasonal distribution of viral hepatitis morbidity are determined by the morbidity rate among children, the increase in the proportion of children of senior school age being observed in recent years.     

Hepatitis B viral factors and clinical outcomes of chronic hepatitis B

Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.     

Hepatitis A

Hepatitis A is a disease of worldwide distribution which occurs in endemic and epidemic form and is transmitted primarily by person-to-person contact through the fecal-oral route. Common source epidemics due to contamination of food are relatively common, and water-borne epidemics have been described less frequently. The presumed etiologic agent of hepatitis A has now been visualized by immune electron microscopic (IEM) techniques in early acute-illness-phase stools of humans with hepatitis A as well as in chimpanzees experimentally infected with material known to contain hepatitis A virus. In addition, several new serologic tests for the detection of antibody against hepatitis A virus have been described. These include complement fixation and immune adherence techniques. Current data suggest that hepatitis A is caused by a single viral agent lacking the morphologic heterogeneity of hepatitis B viral components and that there may be relative antigenic homogeneity between strains of virus recovered from various parts of the world. Serologic studies to date also indicate that hepatitis A virus is not a major contributing cause in post-transfusion hepatitis.     

Frequency of finding hepatitis B viral markers in young children born of mothers carrying the HBs-antigen

The present communication deals with the results of investigations on the frequency of HBsAg-carriership among expectant mothers in Fergana (the Uzbek SSR) and on the risk for their children to be infected with hepatitis B virus. To detect the markers of hepatitis B virus, the passive hemagglutination test, the enzyme immunoassay, and the radioimmunoassay were used. The incidence rate of HBsAg-carriership among expectant mothers was rather high (5.1 +/- 0.52%) in comparison with the control group (3.5 +/- 0.70%). The detection of HBsAg in children 3 months after their birth, i.e. at the term corresponding to the possible incubation period of hepatitis B, suggested that the children were infected at birth. As noted in the course of this investigation, the risk for a newborn to be infected was directly related to the titer of HBsAg, as well as to the presence of HBeAg, in the blood of the carrier mother. A high detection rate of HBsAg was registered among children born to HBsAg-carrier mothers, which makes it possible to consider these children as a high risk group with respect to hepatitis B virus infection and necessitates the development of the system of antiepidemic and prophylactic measures for preventing newborns to be infected with hepatitis B.     

Retrospective epidemiologic diagnosis of viral non-A, non-B hepatitis with a fecal-oral mechanism of transmission of the causative agent

The possibility of the retrospective epidemiological diagnosis of viral hepatitis non A, non B with the fecal-oral mechanism of the transfer of infection in three cities of Central Asia on the basis of the analysis of the dynamics of registered hepatitis A morbidity is shown. With the irregularity of morbidity levels among the total population being characteristic of all three cities, in Andizhan one rise in morbidity within a period of 3 years (1975-1978) and in Tashauz one rise within a period of 5 years (1975-1980) were registered. The analysis of the dynamics of morbidity observed in individual age and social groups showed that these rises, especially those registered in 1976 in Andizhan and in 1977 in Tashauz, were determined by morbidity levels among school children and adults. This is also true for a rise in morbidity rate registered in Tashauz in 1985. In Andizhan the highest morbidity rates among adults were registered in districts insufficiently equipped with modern amenities. Cases of infection registered as hepatitis A (HA) among persons immune to HA at territories with high intensity of the epidemic process of HA at the above-mentioned periods seem to be due to viral hepatitis non A, non B with the fecal-oral mechanism of the transmission of the infective agent.     

Mechanisms of viral hepatitis induced liver injury

Among seven human hepatitis viruses (A to E, G and TT virus), hepatitis B (HBV) and C (HCV) viruses are able to persist in the host for years and principally contribute to the establishment of chronic hepatitis. During the course of persistent infection, continuous intrahepatic inflammation maintains a cycle of liver cell destruction and regeneration that often terminates in hepatocellular carcinoma (HCC). While the expression and retention of viral proteins in hepatocytes may influence the severity and progression of liver disease, the mechanisms of liver injury in viral hepatistis are defined to be due not to the direct cytopathic effects of viruses, but to the host immune response to viral proteins expressed by infected hepatocytes. In the process of liver injury, hepatocellular death (apoptosis) induced by the proapoptotic molecules of T cells activated following antigen recognition triggers a cascade of antigen nonspecific effector systems and causes necroinflammatory disease. Accordingly, the regulation of the immune response, e.g., via the cell death pathways, in chronically infected patients should prevent the development of HCC.     

Multiplication of hepatitis B virus in fulminant hepatitis B.

The presence in serum of hepatitis B e antigen (HBeAg) and hepatitis B virus DNA, which are each regarded as reflecting multiplication of hepatitis B virus, were looked for one to five days after the onset of hepatic encephalopathy in 64 patients with fulminant hepatitis B. HBeAg and hepatitis B virus DNA were found in the serum of only 24 (37%) and six (9%) patients, respectively. Hepatitis B virus DNA was absent from the serum in all 13 patients positive for anti-HBs. These findings indicate that replication of hepatitis B virus stopped after the onset of hepatic encephalopathy in most of the patients and support the view that an enhanced immune response stops the replication. Agents that inhibit viral multiplication would probably not have any effect at this stage of the disease.     

The characteristics of an outbreak of non-A, non-B hepatitis with a fecal-oral mechanism of the transmission of the causative agent in Osh Province, the Kirghiz SSR

The results of epidemiological, clinical and laboratory studies revealed that the sharp rise of morbidity in viral hepatitides in Osh Province, the Kirghiz SSR in autumn 1987 was caused by hepatitis non A, non B virus with fecal-oral transmission. At this period the results of the enzyme immunoassay showed the absence of the markers of hepatitides A, B and Delta in 72.2% of viral hepatitis patients. Hepatitis non A, non B occurred only in 2.4% of viral hepatitis patients of preschool age (of these, 83.3% had hepatitis A) and was diagnosed in autumn 1987 in 50% of the patients aged 7-14 years and in 97.4% of the patients aged 15-29 years (in the latter age group 95-98% of the patients had IgG to hepatitis A virus in their blood). The appearance of the outbreak of the above-mentioned infection in Kirghizia is linked with the water route of the transmission of the infective agent. The epidemiological and clinical signs, characteristic of fecal-oral hepatitis non A, non B in Kirghizia, were not different from those registered earlier in other republics of the Central Asia and could be used for the identification of this infection.     

The Role of Viral Mutation in the Pathogenesis of Chronic Viral Hepatitis

The quasispecies nature of hepatitis B and C virus (HBV, HCV) plays an important role in the pathogenesis, immune escape and drug resistance during chronic infection. Although there is still a lack of effective treatment for hepatitis C, a series of nucleoside analogs (NA) have been developed for the treatment of hepatitis B. NA resistant HBV mutants can accumulate during prolonged therapy and lead to the failure of anti-HBV therapy. Switching to other sensitive NAs can inhibit the emerged resistant mutants. Therefore, understanding the evolution of viral quasispecies under drug pressure is crucial for the establishment of antiviral strategy and the monitoring of antiviral process. Immune response and escape are complicated process, during which both host and virus factors may play their roles. Further understanding of the interaction and interrelationship between host and these viruses may lead to optimized prevention, diagnosis and treatment for chronic hepatitis.     

The role of viral mutation in the pathogenesis of chronic viral hepatitis

The quasispecies nature of hepatitis B and C virus (HBV, HCV) plays an important role in the pathogenesis, immune escape and drug resistance during chronic infection. Although there is still a lack of effective treatment for hepatitis C, a series of nucleoside analogs (NA) have been developed for the treatment of hepatitis B. NA resistant HBV mutants can accumulate during prolonged therapy and lead to the failure of anti-HBV therapy. Switching to other sensitive NAs can inhibit the emerged resistant mutants. Therefore, understanding the evolution of viral quasispecies under drug pressure is crucial for the establishment of antiviral strategy and the monitoring of antiviral process. Immune response and escape are complicated process, during which both host and virus factors may play their roles. Further understanding of the interaction and interrelationship between host and these viruses may lead to optimized prevention, diagnosis and treatment for chronic hepatitis.     

Human oncogenic viruses: Hepatitis B and hepatitis C viruses and their role in hepatocarcinogenesis

Chronic infections caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the main risk factors for the development of hepatocellular carcinoma (HCC) in humans. Both viruses cause a wide spectrum of clinical manifestations ranging from healthy carrier state to acute and chronic hepatitis, liver cirrhosis, and HCC. HBV and HCV belong to different viral families (Hepadnoviridae and Flaviviridae, respectively); they are characterized by different genetic structures. Clinical manifestations of these viral infections result from the interaction between these viruses and host hepatocytes (i.e. between viral and cell genomes). Proteins encoded by both viruses play an important role in processes responsible for immortalization and transformation of these cells. Chronic inflammation determined by host immune response to the viral infection, hepatocyte death and their compensatory proliferation, as well as modulation of expression of some regulatory proteins of the cell (growth factors, cytokines, etc.) are the processes that play the major role in liver cancer induced by HBV and HCV.