Asymptomatic Hepatitis C Virus Carriers Research Articles

Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection

Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFN-γ) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype lb) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype lb. To identify the immunodominant epitopes, IFN-γ production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region. It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-α treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-γ production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4 + T cells. This study suggests the presence of immunodominant T cell epitopes within the HCV core protein in association with HLA DR phenotypes in patients with HCV-associated liver disease.

Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus.

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-alpha. The sIL-2R levels of 40 asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20 with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.

Increased IgM-Containing Circulating Immune Complexes in Patients Co-infected with Hepatitis C and Hepatitis B

To assess the role of circulating immune complexes (CIC) in chronic hepatitis C virus (HCV) infection, the relative frequency of CIC was determined in 60 patients with chronic hepatitis C alone, 19 patients co-infected with hepatitis B and C, 15 asymptomatic HCV carriers, and 54 healthy controls. Levels of CIC were determined with immunoglobulin-specific C1q-binding and conglutinin (K)-binding immune complex assays. Although there was no statistical difference in the levels of each type of CIC between asymptomatic HCV carriers and healthy controls, elevated levels of CIC containing IgM and IgG were common in patients with chronic HCV infection. Compared to patients with hepatitis C alone, patients co-infected with hepatitis B and C have a higher frequency of abnormal IgM-containing CIC and significantly higher levels of IgM-containing CIC. CIC levels in patients with chronic active hepatitis were significantly higher than those in patients with chronic lobular hepatitis or chronic persistent hepatitis. In conclusion, although CIC containing IgM and IgG were common in patients with chronic hepatitis C, abnormal IgM-containing CIC are the major types of CIC in patients co-infected with hepatitis B and C. An immune-mediated mechanism may play a role in the pathogenesis of chronic hepatitis C.

Correlation of serum antibody titers against hepatitis C virus core protein with clinical features by western blot (immunoblot) analysis using a recombinant vaccinia virus expression system.

In order to study the relationships among the clinical features of hepatitis C patients, the presence of hepatitis C virus (HCV) RNA in their blood, and their serum antibody titers against the core protein of virus and to study the antibody levels in asymptomatic HCV carriers, a recombinant vaccinia virus containing a core protein gene was constructed. The recombinant virus expressed a protein with a molecular mass of 22 kDa in RK-13 cells as determined by Western blot (immunoblot) analysis. By using the cell lysate of virus-infected cells and serially diluted serum samples, core antibody titers in the groups of patients in the chronic hepatitis phase and in the convalescent phase as well as in asymptomatic carriers were determined by enhanced chemiluminescence Western blot analysis. Almost all patients in the chronic phase were shown to have high antibody titers of more than 1:500,000 and with no exception had of HCV RNA in their sera. On the other hand, patients who had recovered naturally and were in the convalescent phase were shown to have significantly lower antibody titers, and the antibody was not detected in the lowest serum dilution of 1:500 in 43% of these patients (three of seven total patients). Antibody levels of patients who showed a good response to interferon treatment decreased to intermediate levels between those of patients in the chronic phase and those of patients in convalescent phase. The antibody titers in asymptomatic carriers varied considerably from 1:500,000 to 1:500, and 41% (11 of 27 total individuals) of these carriers showed a high titer equivalent to that of those in the chronic phase. Core antibody was detected consistently in the individuals in whom HCV RNA was detected. This system for core antibody might be useful for identifying the stage of an apparent HCV infection.