The epidemiological differential diagnostic signs of viral hepatitis A and viral hepatitis E]

A retrospective epidemiologic analysis of cases diagnosed as hepatitis A (HA) has been made in territories characterized by high intensity (4 towns in Central Asia) and low intensity (Novomoskovsk, Tula Province) of the epidemic process development. Morbidity structures for different age and social groups of the population, as well as the morbidity time course, both annual and over many years, were analyzed over 1973-1986. Specific features in the development of the epidemic process in HA and hepatitis E (HE), formerly called hepatitis non-A, non-B with the fecal/oral mechanism of the infection transmission, were studied. Twelve epidemiological differential diagnostic signs of these two infections were formulated, classified, and validated. Contribution of centralized water supply and sewage systems to the development of HE epidemic process and the regulating role of infectious immunological mechanisms in the development of HA epidemic process were demonstrated.     

Serologic studies in viral hepatitis]

Comparative studies of sera from 710 patients with viral hepatitis and contacts were made during the 1958-1973 period for hepatitis antigens (Au antigen and the Botevgrad antigen). The percentage of virus hepatitis in patients positive for the Au and the Botevgrad antigens varied in different years. The percentage of those positive for the Au antigen ranged from 50 in 1958 to 8.8 in 1970-1971, while for the Botevgrad antigen--it ranged from 32.6 in 1962-1963 to 6.1 in 1966. In case of contacts, mostly in the 7-14 age group the sera positive for the Au antigen were found in a low percentage (2.09 percent) of cases; as to the Botevgrad antigen, 20 persons were found positive during various epidemics (55 percent). Simultaneous presence of both antigens was found in 4 of the 710 patients with virus hepatitis (0.56 percent), and in 2 of 431 contacts (0.46 percent).     

Plasma and urine biomarkers in acute viral hepatitis E

Background  

Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatitis E.     

Immunoglobulin level in viral hepatitis patients]

The results of studying the dynamics of serum immunoglobulins in patients with viral hepatitis varying in severity are presented. At the acute stage of the disease pronounced shifts in the content of all the three classes of immunoglobulins were found to occur in the patients irrespective of their age. Higher levels of IgM detected in women seem to be due to the physiological peculiarities of the female organism. Gamma globulin prophylaxis, when carried out at the incubation period, has been shown to exert a negative influence on humoral immunity.     

Procollagen type III peptides in chronic viral hepatitis]

Blood serum concentration of procollagen type III peptides was assayed in 37 patients with chronic active hepatitis, 14 patients with persisting chronic hepatitis, and 11 normal subjects. Mean concentration of these peptides was significantly higher in patients with chronic active hepatitis than in those with persisting chronic hepatitis (25.6 +/- 11.5 ng/mL vs. 14.0 +/- 4.5 ng/mL; p < 0.001), and in individuals without lesions to the liver (25.6 +/- 11.5 ng/mL vs. 12.5 +/- 2.9 ng/mL; p < 0.001). Blood serum concentration of procollagen type III peptides may be helpful in the differential diagnosis of hepatitis.     

The hepatitis E virus polyproline region is involved in viral adaptation

Genomes of hepatitis E virus (HEV), rubivirus and cutthroat virus (CTV) contain a region of high proline density and low amino acid (aa) complexity, named the polyproline region (PPR). In HEV genotypes 1, 3 and 4, it is the only region within the non-structural open reading frame (ORF1) with positive selection (4-10 codons with dN/dS>1). This region has the highest density of sites with homoplasy values >0.5. Genotypes 3 and 4 show ～3-fold increase in homoplastic density (HD) in the PPR compared to any other region in ORF1, genotype 1 does not exhibit significant HD (p<0.0001). PPR sequence divergence was found to be 2-fold greater for HEV genotypes 3 and 4 than for genotype 1. The data suggest the PPR plays an important role in host-range adaptation. Although the PPR appears to be hypervariable and homoplastic, it retains as much phylogenetic signal as any other similar sized region in the ORF1, indicating that convergent evolution operates within the major HEV phylogenetic lineages. Analyses of sequence-based secondary structure and the tertiary structure identify PPR as an intrinsically disordered region (IDR), implicating its role in regulation of replication. The identified propensity for the disorder-to-order state transitions indicates the PPR is involved in protein-protein interactions. Furthermore, the PPR of all four HEV genotypes contains seven putative linear binding motifs for ligands involved in the regulation of a wide number of cellular signaling processes. Structure-based analysis of possible molecular functions of these motifs showed the PPR is prone to bind a wide variety of ligands. Collectively, these data suggest a role for the PPR in HEV adaptation. Particularly as an IDR, the PPR likely contributes to fine tuning of viral replication through protein-protein interactions and should be considered as a target for development of novel anti-viral drugs.     

Synthesis of nitric oxide in patients with viral hepatitis]

The end products of nitric oxide (NO) metabolism in human organism, i.e. anions, nitrites (NO2) and nitrates (NO3), are excreted predominantly (95%) via urine. The quantity of these products in urine is an adequate index of NO synthesis in human organism. We measured the quantities of of NO2 and NO3 excreted during of monoviral hepatitis A, B, C, D and in the course of mixed viral hepatic infections, which were caused by the above mentioned viruses. The hyperexcretion of NO2 and NO3 was higher and longer during hepatitis C and D versus hepatitis B, and during the latter versus hepatitis A. The inability of NO to stop the infection may be caused by low sensitivity of the viruses to NO and/or by local low concentration of NO in the site of inflammation.     

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.     

Expression and secretion of hepatitis B viral surface antigen in E. coli

Hepatitis B viral surface antigen (HBsAg) gene was subcloned into the BglII site of Bacillus licheniformis penicillinase (penP) gene of secretory vector pJP104. Expression and secretion of HBsAg protein was achieved by the E. coli CS412 carrying the plasmid pJPS2 in which the penP:HBsAg hybrid gene was under the control of two promoters, lipoprotein (lpp) and penP, spaced 450 bases apart. The secreted form of HBsAg encoded by the hybrid penP: HBsAg gene of plasmid pJPS2 was purified by immunoaffinity chromatography and found to be a 25 kilodalton protein.     

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.