Different Types Of Hepatitis Research Articles

The origin of hepatitis C virus genotypes.

For many RNA viruses, relatively recent times of origin of extant viruses are implied by the high rate of substitution observed in longitudinal studies. However, extrapolation of short-term rates of substitution can give misleading estimates of times of divergence. We show here that the common ancestor of different types of hepatitis C virus (HCV) is older than previously thought. The rate of HCV sequence change was measured amongst a cohort of individuals infected following administration of anti-D immunoglobulin. Virus sequences were obtained in the E1 and NS5B genes and compared with each other and with sequences from an infective batch. Taking account of the bias towards synonymous transition substitutions, the time of divergence of variants of subtype 1b is estimated to have occurred 70-80 years ago. The numerous subtypes of HCV are proposed to derive from more than 300 years of endemic infection in certain geographical regions, with recent spread of some subtypes to other parts of the world. Estimation of the time of origin of the major HCV genotypes (types 1-6) is problematic, but our data and analogy with other viruses suggest that divergence occurred at least 500-2000 years ago.

Clinical backgrounds of the patients having different types of hepatitis C virus genomes.

Hepatitis C virus (HCV) genomes were recently detected in biological materials, and variations of nucleotide sequences were reported. In the present study, typing of the HCV genomes was performed in 91 HCV-RNA-positive patients and the clinical features of patients with different types of HCV were compared. From the nucleotide sequences of the cDNA fragments, HCV can be divided into at least two types: HCV-K1-PT and HCV-K2. All cDNAs amplified from 91 patients were hybridized with cDNA probes of either HCV-K1-PT or HCV-K2. HCV-K1-PT was found in about 80% of the patients, and HCV-K2 was found in about 20% of the patients. These results indicate that types of HCV are limited to two types, i.e., K1-PT and K2, and the major type is HCV-K1-PT, at least in Japan. Detection rate of antibodies to C-100-3 protein were not different between the patients having HCV-K1-PT and HCV-K2, indicating that the antibodies may develop in HCV-related patients without relation to the types of the HCV genomes. Prevalence of the two types of HCV were nearly the same in various forms of NANB-related liver disease. However, the prevalence was somewhat different in alcoholic liver disease. HCV-K2 was found in patients younger than the patients with HCV-K1-PT. Frequency of a history of blood transfusion tended to be lower and the initial response to interferon treatment was clearly better in patients having HCV-K2 versus patients having HCV-K1-PT. These results suggest the possibility that clinical features due to HCV-K1 may be somewhat different from those due to HCV-K1-PT. However, the number of patients examined was too small to allow a definite conclusion, indicating a necessity for further study with a larger number of patients.

Immunoglobulin G subclasses of antibodies to hepatitis B core antigen in HBs antigen positive liver diseases

Serum immunoglobulin G (IgG) subclasses of hepatitis B core antibody (anti-HBc) in 54 patients with different types of hepatitis B surface antigen positive (HBsAg+) liver diseases (asymptomatic carrier (ASC), acute hepatitis (AH), chronic hepatitis (CH) and liver cirrhosis (LC)) and 18 normal controls were estimated by enzyme-linked immunosorbent assay (ELISA) using subclass specific anti-human mouse monoclonal antibodies. In 11 cases, the estimations were carried out at both exacerbation and remission stages of chronic active hepatitis (CAH). In 4 cases of CAH, serial observations of anti-HBc IgG subclasses were made according to the clinical course. In 5 cases of CAH, the estimations were carried out at the HBe antigen positive (HBeAg+) stage and after sero-conversion to anti-HBe positive (anti-HBe+) stage. In ASC the main anti-HBc IgG subclasses were restricted to one subclass--anti-HBc IgG1. In AH on the other hand, all the subclasses were represented. In CH all the subclasses were detected under different diagnostic conditions but anti-HBc IgG1 was the main subclass. In LC the mean concentration of anti-HBc IgG3 was higher than the concentration of anti-HBc IgG1. In exacerbation stages of CAH, the different anti-HBc IgG subclasses had higher concentrations than in remission stages. The concentrations of different anti-HBc IgG subclasses fell just after seroconversion from HBeAg+ stage to anti-HBe+ stage. These data suggest that the estimation of anti-HBc IgG subclasses may be helpful in establishing the diagnosis of different types and stages of HBsAg+ liver diseases.

Cellular cytotoxicity against autologous hepatocytes in children with different forms of chronic hepatitis B

Cell-mediated immune reactions play the most important role in the pathogenesis of chronic viral and auto-immune hepatitis. Cellular cytotoxicity (CC) of peripheral blood lymphocytes against autologous hepatocytes isolated from liver biopsies was studied in 29 children with different types of hepatitis B surface antigen (HBsAg)-positive hepatitis. Children with chronic hepatitis B showed higher cytotoxicity than control patients. However, a correlation of cytotoxicity to serum amino-transferases, HBeAg-/Anti-HBe-status, and hepatitis B virus DNA in serum could not be found. Children with a higher percentage of hepatitis B core antigen (HBcAg) expression in their liver tissue presented lower CC values, and vice versa. This supports the hypothesis that virus elimination occurs via T-cell attack against HBcAg expressing hepatocytes. Furthermore, children with a longer duration of chronic hepatitis B had considerably higher cytotoxicity values. Possibly, CC plays a role in perpetuating liver damage after infection with hepatitis B virus.

Kinetics of C-reactive protein in acute viral hepatitis

The significance of C-reactive protein (CRP) in acute viral hepatitis was studied by measuring the serum CRP level in patients with acute hepatitis type A (AHA), B (AHB), and non-A, non-B (AHNANB) and examining its localization in liver biopsy specimens by the immunohistochemical method. The mean value of the serum CRP level determined by enzyme immunoassay (EIA), was markedly increased in the acute phase of AHA and AHB, particularly the former. It decreased rapidly in both AHA and AHB during the convalescent phase, but was generally low in AHNANB with no marked difference between the acute phase and the convalescent phase. Under light microscopy, CRP was stained in the cytoplasm of hepatocytes, and immuno-reactive products were observed in the rough endoplasmic reticulum (RER) by electron microscopy. In the acute phase, the intensity of staining was slightly greater in AHA, decreasing during the convalescent phase in AHA and AHB, but only weak staining was observed in all patients with AHNANB. Evaluation of CRP may be useful for clarification of differences in clinical manifestations and the mechanisms of inflammation among different types of hepatitis.

Quantitative aberrations in serum immunoglobulins in children with acute viral hepatitis

Serum levels of IgG, IgA and IgM were determined by LASER nephelometry in 134 patients with acute viral hepatitis. Different types of hepatitis were serologically differentiated by radioimmunoassays. 102 patients had hepatitis A, 27 patients hepatitis B and 5 hepatitis non-A-non-B infections. 30 patients with hepatitis A and 9 with hepatitis B were checked in a follow-up-study. The IgA levels showed the least changes and were found to be within normal range in over 75% in hepatitis types A and B. On the other hand, IgG levels and - to a greater extent - IgM levels were found to be elevated in a great number of these patients. Levels below the 2s-range were found only rarely. Children with hepatitis B had elevated IgG and IgM in 44,4% and 33,3% of the cases. In patients with hepatitis A IgG level elevations (above 2s-range) were found in 44,2% and IgM level elevations in 96, 1% of the cases. No significant differences were found between the age Groups 0-1 year, 1-2, 3-5, 6-8 and 9-15 years of patients with hepatitis A regarding their serum immunoglobulin levels. 14 days after diagnosis a decrease of the elevated IgM was found in patients with hepatitis A parallel to an increase in the IgG values. No significant changes were observed in patients with hepatitis B. The IgA levels remained constant both in patients with hepatitis A and B infections. For hepatitis non-A-non-B a statistical evaluation was not possible due to the small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)