Anti-CD3-activated T cells from chronic nonviremic HBV carriers are hyperreactive to monocytic accessory signals.

We analyzed T cell responses through the CD3 activation pathway in a group of chronic HBV carriers. PBMC stimulated with the mAb OKT3 showed higher proliferative response in HBV-DNA(-) carriers compared to HBV-DNA(+) carriers and to controls. In contrast, no differences in proliferative responses were observed between HBV-DNA(-) carriers and controls in cell cultures stimulated with immobilized 64.1 mAb (SPB-64.1) which induces proliferation in the absence of monocytes. We further examined T cell responses in the presence of monocytes and their soluble factors to immobilized OKT3 mAb (SPB-OKT3). Purified T cells did not proliferate to SPB-OKT3. When autologous monocytes were added, higher proliferative response, IL-2 production, and IL-2 receptor expression were observed in HBV-DNA(-) carriers than in controls. An enhanced cell proliferation was also obtained when monocyte supernatants were added to T cells cultured with SPB-OKT3. Moreover, when IL-6 alone or combined with IL-1 was added to SPB-OKT3-stimulated T cell cultures, a significantly higher increase in T cell proliferation was detected in HBV-DNA(-) carriers. Our results thus show a T cell hyperreactivity to accessory signals from monocytes (mainly IL-6) in HBV-DNA(-) carriers, that is probably related to an ongoing viral clearance.

Assessment of former and newly developed HBV assays in a Third World setting.

Newly available HBV serological assays have not been established routinely in most underdeveloped countries. Utilizing enzyme-immune assays to determine the presence of pre-S1 antigen and anti-pre-S2, and using two conventional hybridization techniques and the PCR assay to detect HBV-DNA, we studied 30 HBsAg chronic carriers and as a reference group 10 subjects whose only HBV routine marker was anti-HBc. Seventy-nine percent of the HBeAg positive carriers showed detectable HBV-DNA by a non-radioactive slot-blotting technique. The PCR assay was more sensitive than the slot-blotting technique, detecting HBV-DNA in anti-HBe positive patients with moderate or normal ALT activity. Pre-S1 antigen was mostly related to the presence of HBsAg and anti-pre-S2 was associated with active viremic state, increased ALT activity (ranges 51 to 640 IU/L), and with self-limited HBV infection. The presence of HBV-DNA in the group with anti-HBc only was detectable solely by the PCR assay. For an underdeveloped country the addition of a PCR assay or pre-S/anti-pre-S protein tests to the current assessment procedures of HBV chronic infection should be used only in selective cases. HBeAg/anti-HBe serological evaluation and HBV-DNA detection by a non-isotopic conventional hybridization technique still remain as useful tools to screen initially for the presence of viremia in chronic HBsAg carriers. The presence of HBV-DNA in individuals with anti-HBc only suggests that anti-HBc screening should be maintained and expanded to all the blood banks of less industrialized countries where the rate of HBV infection in apparently healthy people tends to be high.

Risk factors for dialysis-associated hepatitis C in Venezuela.

Utilizing the first and second generation of enzyme immunoassays which detect antibodies to the C virus we investigated the frequency of anti-HCV antibodies in 315 patients undergoing hemodialysis. Other subpopulations at risk were used as reference groups. One hundred and twenty-three samples (39%) from the hemodialysis group repeatedly showed anti-HCV positive antibodies while only 19% and 1% were positive in the reference groups. The rate of anti-HCV reactive patients correlated with time on hemodialysis (less than 1 year, 17%; 1 to 5 years 43%; greater than 5 years, 64%; r = 0.94, P less than 0.001) and with the number of blood transfusions (1 to 10, 40%; greater than 10, 76%; r = 0.97; P less than 0.001). Length of time on hemodialysis was shown to be the major risk factor in thirty-three anti-HCV positive patients who had no previous record of blood transfusions. Co-infection with HBV was demonstrated in 41% out of 123 anti-HCV reactive patients, and increased alanine aminotransferase (ALT) activity was documented in this co-infected group. Our results further extend the observations on the predisposing factors to HCV spread in hemodialysis units, and suggest that in these renal patients co-infection with C and B viruses is a major cause of rising ALT activity.