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.     

急性病毒性肝炎的发病率慢性肝炎患病率和肝病死亡率的研究

1984～1987年,在黑龙江、河北、河南、湖南、上海五个省市城乡10.08855人口中进行急性肝炎发病率、慢性肝炎患病率、与病毒性肝炎有关的肝病死亡率的研究。急性肝炎标化发病率为152.19/10万,主要发生在20～50岁组人群;因无甲肝暴发流行,除上海外各点季节发病率分布均衡。慢性肝炎标化患病率为158.25/10万(诊断标准为6个月前有明确急性肝炎病史,现有明显的临床症状或体征,肝功能异常,故实际慢肝患病率要高于此数字);与病毒性肝炎有关的肝病死亡(包括肝癌)标化率为22.65/10万,其中肝病为 13.14/10万。男性死亡率显著高于女性。     

Spread of hepatitis virus as a threat to national security

Information on viral hepatitis A, B and C morbidity in Russia is presented. A distinct trend to decreased viral hepatitis B and C morbidity in 2001-2002 in comparison with the 1990-ies is noted. Nevertheless, there is still unfavorable prognosis regarding high hepatitis B morbidity among the population of reproductive age, as well as among adolescents, which increases the risk for children at an early age. In addition, a new specific feature of hepatitis A spread is observed: morbidity in this infection is shifted to older age groups. The role of vaccinal prophylaxis in the decrease of hepatitis A and B morbidity, virus safety of blood and its components, the quality of the diagnostics of chronic hepatitis, especially hepatitis C, are discussed. The complex of measures for the prophylaxis of viral hepatitis is proposed.     

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.     

Family incidence of type B hepatitis

Family incidence of HBsAg-positive viral hepatitis was confirmed to be high. In 499 families with a type B viral hepatitis patient, type B viral hepatitis morbidity among 1116 contacts amounted to 2.24% within 6 months of the primary patients' hospitalization (being 188.2 times higher than semiannual morbidity of the population of the Czech Socialist Republic, CSR) and the prevalence of HBsAg amounted to 8.96% (being 22.4 times higher than among the population of CSR). On deducting positive findings at first blood samplings, which at least partially eliminated individuals who could themselves have been the source of infection for the first patient in each family, the rate for contact cases equalled 0.70% (58.8 times higher morbidity than among the population) and the rate for HBsAg prevalence equalled 2.50% (6.25 times higher than among the population). Among 917 members of 335 families where a case of HBsAg-negative viral hepatitis occured, 0.32% developed HBsAg-positive viral hepatitis within 6 months (26.8 times higher morbidity than population morbidity) and the HBsAg prevalence was 2.94% (7.35 greater than among the population). On deducting the first positive findings no clinical illness remained and HBsAg prevalence equalle 0.98% (2.45 times higher than among the population). The highest HBsAg prevalence was found among contacts aged 0-5 years (17.09% for the whole period, 3.41% after deducting first positive findings) and 40 years and over (10.82% and 3.39%, respectively). Type B viral hepatitis morbidity was again highest in the age groups of 0-5 years (5.12%) and 40 years and over (2.54%) for the whole period. On deducting first positive findings, the 40+ years group displayed the highest morbidity (1.27%), whereas the 0-5 years group displayed zero morbidity. Disclosure of the mechanisms of nonparenteral or inapparently parenteral transmission specific for family environments would be important for the prospect of introducing adequate measures to limit or prevent the spread of type B viral hepatitis.     

Reasons for the decrease in viral hepatitis morbidity in Orekhovo-Zueve]

Factors of action on the epidemic process in viral hepatitis in Orekhovo-Zuevo leading to a sharp reduction of the incidence of this disease (which before failed to differ from the mean level in the USSR) -- from 154.0 per 100 thousand residents in 1970 to 36.5 per 100 thousand residents in 1975 are considered from the point of view of discussion of the work of Gromashevsky and Birinboim (ZMEI No. 11, 1976). The decisive significance of measures directed to reduction of the incidence of intestinal infections and gamma-globulin vaccinations is refuted. There was revealed a direct 100% correlation between the incidence of positive benzidine tests for blood contamination of medical instruments and the changes in the viral hepatitis morbidity. Planned measures directed to the elimination of factors of parenteral transmission of the infection carried out intensively from 1970 led to reduction of the incidence of viral hepatitis.     

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.     

Nosogeography of viral hepatitis in the Ukraine over the last 25 years (1952-1976)]

For 25 years of observation the morbidity rate of viral hepatitis in the Ukraine was irregular. In individual regions the morbidity level fluctuated within 2 to 3-fold range. Regions with invariably high or low morbidity levels for viral hepatitis were distributed over the territory of the republic not chaotically, but in zones: a zone with invariably high morbidity rate (western), a zone with morbidity rate corresponding to the average level for the republic (south-western), and a zone with an invariably low morbidity rate (north-eastern). The expediency of dividing the territory into epidemiological areas in respect of viral hepatitis on a regional or republican level is discussed.     

慢性重型乙肝继发侵袭性真菌感染的研究

目的明确侵袭性真菌感染(invasive fungal infections,IFI)在慢性重型乙肝患者中发病情况及主要病因。方法依据IFI和乙肝诊断标准,筛选上海长征医院感染科慢性重症乙肝患者,60例IFI者为病例组,66例未发生IFI为对照组,进行回顾性分析。结果 IFI患病率47.62%,病死率40%。乙肝病毒DNA水平是最主要的危险因素,当DNA高于3.16×103copies/mL,IFI发病可能性增大。结论慢重肝患者IFI的患病率和病死率超出临床预期,降低DNA拷贝可延缓乙肝进展,在预防及治疗IFI中亦具积极意义。     

Prevalence of viral hepatitis among the hospital staff in CSR between 1980 and 1982

The hepatitis morbidity data were used to study prevalence rate of manifest viral hepatitis among the hospital staff members in CSR over a 3-year period between 1980 and 1982. This study showed that the overall hepatitis morbidity rate was 2.68 per 1,000 health personnel and was 3.6 times as high as that recorded in a normal population matched by age. The mean HBsAg positivity rate was 1.67 per 1,000 and was 5.8 times the rate in the control population group. The rate of HBsAg-negative cases of hepatitis was 1.01 per 1,000 health personnel and was higher than double the rate of morbidity encountered in an age-matched normal population. The highest morbidity rates were recorded in the lower-grade and auxiliary health personnel. When compared with an age-matched normal population the hospital staff members at all departments had distinctly higher morbidity rates than the general population, but the highest risk of acquiring viral hepatitis was evidently run by the personnel at departments of renal dialysis, biochemistry, hematology, infectious diseases, internal medicine, surgery, urology and TRD (tuberculosis and respiratory diseases). Of a total number of recorded cases of viral hepatitis those with HBsAg positivity predominated, especially at departments of urology, TRD, internal medicine, renal dialysis, psychiatry and hematology. Analyzed by specialty and professional status of personnel these viral hepatitis morbidity rates encountered among the hospital staff members seem to point to at least two conclusions: this infection in the health personnel is work-related and its transmission and spread is dependent on the frequency and intensity of contact with the blood and other secretions of infectious patients.     

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.     

Evaluation of serum guanase in hepatic diseases

Serum guanase activity was measured in 20 healthy adults and in 62 patients with acute viral hepatitis, chronic active hepatitis, chronic persistent hepatitis, liver cirrhosis and fatty liver. Guanase and gamma-GT in patients were elevated in 87 and 64%, respectively. Elevated guanase activities were found in most cases of acute viral hepatitis, as well as in chronic hepatopathies. In patients with acute viral hepatitis pathologic activities of guanase were found following partial or total normalization of other liver function tests.     

The epidemiological aspects of viral hepatitides in Estonia]

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.     

Morbidity and mortality in acute viral hepatitides in a hyperendemic region. The role of viral hepatitis E

Official annual statistical data on morbidity in acute viral hepatitides (AVH), including the number of lethal cases, for 1985-1995 were analyzed. Mortality rates per 100,000 of the population at the period of 11 years were calculated for different age groups, sex and the place of residence. 396 and 99 patients were examined for the presence of serological markers of hepatitides A, B and E, respectively, at the periods of epidemic rises in morbidity and satisfactory epidemic situation. In the course of 11 years AVH caused the death of 22,405 persons. In 1985-1987 the average mortality level (ML) reached 12.3-17.8 per 100,000 of the population (with morbidity being 1,200-1,400 and was essentially higher among the rural population in comparison with the urban population. During these years the highest ML, was registered among children aged 0-2 years (190-50 per 100,000) and, among adults, mainly among women aged 20-29 years (21.4-19.6 per 100,000). During the years when the epidemic of AVH was absent, ML among these groups was essentially lower: 40-20 among children aged 0-2 years and 4-5 among women aged 20-29 years. In 1987 in the Fergana Valley hepatitis E was detected in 72.2% of all examined patients, and in the southern areas of the country in 68.7%. A sharp rise on mortality among women of the productive age at the period of the epidemic rise of AVH morbidity in the endemic region indicated that this epidemic was linked with hepatitis E. High ML among young children may be indicative of a highly unfavorable course of hepatitis E in the group of infants, which had never been registered before. This newly established regularity may be used for the retrospective diagnostics of the outbreak of hepatitis E.     

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.     

Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 helicase showed the most marked expression. In hepatitis B, TLR1, 3, 9, NOD1 and NALP expression were the most conspicuous. Expression PRRs in liver from hepatitis of unknown origin was much lower. It was also the case in cytospins from human hepatoma cell line. Several correlations between PRRs expression and clinical findings in patients could be shown by statistical exploration. In conclusion, this data suggests some role for PRRs in the pathogenesis of chronic viral hepatitis.     

The cause of the activation of an epidemic process of intestinal infections in the 70s]

In the seventies a considerable rise in dysentery morbidity was observed in all republics of the USSR, in the whole of the USSR, in Bulgaria and in the German Democratic Republic. An increase in cholera morbidity in the world, as well as in the number of countries affected by this infection, was registered. A tendency towards a rise in virus hepatitis incidence was observed in the USSR. The dynamic study of the ozone content in the stratosphere, solar activity, disturbances in the magnetic field of the Earth, air temperature for the period of 1967-1980 was carried out. Strong and moderate correlation between dysentery and air temperature in summer was established. The maximum morbidity level in the USSR in 1972 was probably the consequence of unusually high air temperature in summer.     

Apoptosis and apoptosis related proteins in chronic viral liver disease

Background: Apoptosis may be an important mechanism of hepatocyte death in chronic viral liver disease. Methods: We studied apoptosis in liver biopsies from 30 patients with chronic viral hepatitis and 8 patients with viral cirrhosis by the TUNEL method. 12 cases of non-alcoholic steatohepatitis and 12 cases of primary biliary cirrhosis were used as non-viral disease controls. Immunohistochemical expression of p53, p21/waf1, bcl-2 and mdm-2 proteins was also studied in the same patients. Results: A statistically significant increase of apoptotic liver cells was found in severe chronic viral hepatitis (5.3 ± 0.3%), cirrhosis (3.4 ± 0.5%) and PBC (4.4 ± 0.4%) cases compared to patients with non-alcoholic steatohepatitis (0.8 ± 0.3%). The expression of p53 protein was increased in the cases of viral cirrhosis and in chronic severe viral hepatitis whereas in the cases of chronic mild hepatitis, PBC and non-alcoholic steatohepatitis we found no expression of p53. P21/waf1 expression was increased in severe chronic hepatitis, cirrhosis and PBC cases compared to mild hepatitis and non-alcoholic steatohepatitis cases. However no induction of mdm-2 was observed in the subgroups of chronic liver disease. Bcl-2 was expressed only in epithelium of bile ducts and mononuclear cells of the portal tracts and liver lobules. A weaker Bcl-2 expression was noted in the epithelium of bile ducts of 7/12 PBC cases. Conclusion: Our results provide evidence of increased apoptosis in severe chronic viral liver disease, suggesting that apoptotic cell death might be involved in the pathogenesis of hepatocellular damage of viral hepatitis and cirrhosis. Furthermore we analysed part of the apoptotic pathways implicated in the above process and found an increased expression of p21/waf1, probably p53 mediated, without overexpression of the apoptosis inhibiting bcl-2 and mdm-2 proteins. By contrast p21/waf1 overexpression in PBC seems to be propagated by a p53 independent mechanism.     

Methodological bases for the study and the patterns of the seasonality of viral hepatitis A

On the basis of the study of the data on the incidence of viral hepatitis A in one of the districts of a big city for 20 years the authors come to the conclusion on the advisability of a comparative study of the monthly changes in the incidence of hepatitis A within individual uniform morbidity cycles covering the periods of many years and the use of average monthly data for many years for plotting the typical curve, as well as the use of the simplified for the calculation of the upper limit of annual morbidity. Similarities and differences in the monthly dynamics of morbidity in the years of high and low morbidity levels have been revealed, and the age group of the population (20-39 years) which ensures the continuity of the epidemic process all the year round has been determined. The factors contributing to the seasonal activation of the epidemic process start operating in June among schoolchildren aged 11-14 years, and later their operation spreads to other groups of the population.