Conserved core protein sequences in hepatitis B virus infected patients without anti-HBc.

The absence of detectable anti-HBc antibodies in some hepatitis B virus (HBV) infected patients may be due to altered core-protein (HBc) sequences. To investigate this possibility we sequenced the pre-C/C-region of HBV isolated from 12 juvenile cancer patients who incurred a nosocomial infection of HBV during chemotherapy but did not develop anti-HBc antibodies or acute cytolytic episodes. The sequences demonstrated the highest sequence homology to the pre-C/C region of a previously cloned HBV genome (subtype ayw) and no deletions or striking mutations were detected. Up to 7 years after infection almost all the survivors developed low titers of anti-HBc antibodies but no clinical signs of hepatic damage. These results suggest that chemotherapy may induce a tolerance status to HBcAg, the most immunogenic HBV protein.

Detection of hepatitis B virus DNA in serum by spot hybridization technique: sensitivity and specificity of radiolabeled and biotin-labeled probes.

The detection of serum hepatitis B virus (HBV) DNA in 32 chronic HBsAg carriers was performed by spot hybridization technique using both biotinylated and radiolabeled probes, in order to compare their specificity and sensitivity. Our results show that both assays are specific since neither evidence of cross-hybridization between HBV DNA and sera from patients with chronic non-A, non-B (NANB) hepatitis was found, nor HBV DNA was detected both in patients with chronic anti-HBs/anti-HBc-positive hepatitis and in patients negative for all HBV markers. An agreement between the two assays was observed in 94% of the tested sera. Even though in 5 serum samples (6%) low levels of HBV DNA (0.1-1 pg/100 microliter) remained undetected using the biotin-labeled probe, the lower detection limit of the two assays (0.1 pg of HBV DNA) was the same using purified Dane particles as control. This study indicates that the enzymatic detection of HBV DNA is suitable for routine and rapid monitoring of HBV replication in both HBeAg- and anti-HBe-positive patients, as well as for a semiquantitative analysis of serum HBV DNA.

Effects of HIV superinfection on HBV replication in a chronic HBsAg carrier with liver disease.

A case of HIV superinfection observed in an HBsAg/HBeAg-positive male homosexual with chronic persistent hepatitis is described. Soon after the appearance of clinical and serological features of acute HIV infection, a rapid fall to a normal value of ALT was noted with simultaneous recrudescence of HBV replication lasting for several months as detected by an increase of the HBV-DNA concentration in the serum. Our observations suggest that the reduction of hepatocyte necrosis and the increase in HBV replication were a consequence of impaired T cell function during acute HIV infection.

Permanent inhibition of viral replication induced by low dosage of human leukocyte interferon in patients with chronic hepatitis B.

Fourteen out of 28 HBsAg/HBeAg-positive carriers with chronic persistent and active hepatitis were randomly assigned to human leukocyte interferon (a-IFN) treatment for three months. The remaining 14 patients served as controls. Each treated subject received a standard i.m. dose of 0.7-1.0 X 10(5)/kg/day reference units of a-IFN for 28 consecutive days, and then the same dose twice a week for two months. This treatment regimen was well tolerated, and no remarkable side effects were recorded. At six months the number of patients who permanently lost HBV-DNA from serum was significantly higher in the treated group (p = 0.006) than in the untreated group. These results suggest that a less expensive and well tolerated treatment regimen based on low dosage of a-IFN may be as effective in producing permanent inhibition of hepatitis B virus replication as a treatment regimen based on larger dosage.

[Behavior of theophylline-sensitive T lymphocytes in viral A, B, non-A, non-B hepatitis. I. Methodological aspects]. / Comportamento dei linfociti T teofillino-sensibili nell'epatite da virus A, B, non-A, non-B. I. Aspetti metodologici.

To evaluate the behaviour of the Theophylline-sensitive T lymphocytes subpopulation some modifications of the standard procedure are proposed. Lymphoprep purified lymphocytes were counted in a Neubauer hemocytometer after Acridine Orange stain, viability was evaluated by Ethidium Bromide counterstain and monocytes contamination was evaluated by the peroxidase stain. Sheep red blood cells were treated with AET, Theophylline was used at 3 mM (final concentration) and the results compared with untreated lymphocytes; the enumeration of the rosetting lymphocytes was facilitated by adding Acridine Orange prior to the resuspension. The modifications described were able to increase the % of rosetting T lymphocytes, to eliminate differences depending by different lots of sheep red blood cells and to decrease differences depending by subjective evaluation of the rosetting T lymphocytes.

[Behavior of theophylline-sensitive T lymphocytes in viral A, B, non-A, non-B hepatitis. II. Application aspects]. / Comportamento dei linfociti T teofillino-sensibili nell'epatite da virus A, B, non-A, non-B. II. Aspetti applicativi.

The pathogenesis of the hepatic damage in hepatitis is not well understood but an imbalance in immunoregulatory T lymphocytes is probable. We tested the Theophylline-sensitive T lymphocytes in acute and protracted cases of hepatitis A, in hepatitis B and non-A, non-B. A delayed increment of such cells was demonstrated in hepatitis B suggesting a positive role in the recovery from the disease. The results were indicative for a direct action of the HAV and nAnB on the lymphocytes. Theophylline-sensitive lymphocytes were increased in the course of protracted hepatitis A whereas were progressively decreasing in nAnB hepatitis. This behaviour of suppressor cells in nAnB hepatitis may explain the high frequency of evolution in chronic liver disease.