Presentation of autoantibody to proliferating cell nuclear antigen in patients with chronic hepatitis B and C virus infection.
(17/1741)
OBJECTIVES: To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection. METHODS: Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay. RESULTS: By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG. CONCLUSION: These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE. (+info)
Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection.
(18/1741)
Cytokines that are secreted as a response to viral antigen not only have direct antiviral properties but also crucially influence immune reactions determining the outcome of infection. As an advantageous alternative to the study of cytokines present in the supernatants of antigen-specific T cell clones and lines, we have used ELISPOT assays to determine the number of interferon-gamma (IFN-gamma)- and IL4-producing cells generated by peripheral blood mononuclear cells from patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB) infection in response to HBcAg in a short-term culture (48 h). In response to HBcAg IFN-gamma was predominantly produced. In contrast to the results obtained in acute hepatitis B, the typical lymphokine pattern in CHB was characterized by a weak or absent antigen-specific IFN-gamma production. A predominance of IL-4-producing cells was not observed in either AHB or CHB. A significant number of IFN-gamma-producing cells was usually detectable during phases of viral elimination and the quality of the lymphokine response seemed to be epitope independent. Comparison of the results obtained in proliferation assays and ELISPOT assays clearly shows that lymphokine production upon stimulation with viral protein is totally independent of T cell proliferation and more sensitively reflects antiviral reactivity. (+info)
Prevalence and significance of naturally occurring mutations in the surface and polymerase genes of hepatitis B virus.
(19/1741)
The prevalence and clinical significance of naturally occurring mutations in the full-length surface and overlapping polymerase genes of hepatitis B virus (HBV) were analyzed in 42 patients with chronic hepatitis. Mutations were observed in 10 patients (24%) in the a determinant region, which is the neutralizing epitope within the major hydrophilic region of the surface gene. A high proportion of these mutations (17/18; 94%) occurred in the first loop, unlike mutations induced by immunization. The presence of serum antibody to hepatitis B surface antigen was significantly associated with these mutations. No other region of the surface gene contained any cluster of mutations. These results suggest that escape mutations commonly contribute to persistency in the natural course of HBV infection. In contrast, mutations affecting the major catalytic domains of the polymerase gene, which could alter susceptibility to antiviral nucleoside analogues, were not detected at all. (+info)
Lamivudine as initial treatment for chronic hepatitis B in the United States.
(20/1741)
BACKGROUND AND METHODS: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). RESULTS: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. CONCLUSIONS: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were generally sustained after treatment. (+info)
Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis.
(21/1741)
The Fas ligand (FasL)/Fas and the perforin-granzyme cytotoxic pathways presumably play a central role in the development of hepatocellular injury in viral hepatitis. To recognize the potential contribution of FasL and perforin-based cell killing in hepadnaviral infection, we adopted a cytotoxic assay using murine Fas+ P815 and human Fas- K562 cells as targets. Freshly isolated peripheral blood mononuclear cells (PBMC) from woodchucks with newly acquired woodchuck hepatitis virus (WHV) infection (n = 6), with chronic WHV hepatitis (n = 9), and from healthy animals (n = 11) were used as effector cells. We have found that woodchuck lymphoid cells kill cell targets via both the FasL/Fas and the perforin death pathways. The contribution of Fas-dependent cytolysis was ascertained in blocking experiments with anti-Fas antibody and by incubation of PBMC with cyclohexamide to prevent de novo synthesis of FasL. The involvement of the perforin pathway was confirmed by treatment of K562 cells with colchicine to inhibit the microtubule-dependent perforin release. Comparative analysis showed that peripheral lymphoid cells from acute WHV hepatitis, but not those from chronic WHV infection, are more cytotoxic and that this increase seems to be entirely due to activation of perforin-mediated killing. The data indicate that acute infection in woodchucks is associated with the augmented capacity of lymphoid cells to elicit perforin-dependent killing, but in chronic infection, independent of the severity of liver disease and duration of chronicity, these cells have the same or lower cytotoxic potential as PBMC from healthy controls. These findings suggest a role for non-specific cellular immunity, presumably natural killer (NK) cells, in the control of early WHV infection and in the progression of chronic hepatitis. (+info)
Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine.
(22/1741)
Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >104 genomes/mL in 11 patients and decreased to <104 genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >104 genomes/mL seroconverted. Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <104 genomes/mL) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance. (+info)
Inactivated hepatitis A vaccine in Chinese patients with chronic hepatitis B infection.
(23/1741)
BACKGROUND: Hepatitis B (HBV)-infected patients have a higher morbidity and mortality when super-infected by hepatitis A (HAV). AIM: To evaluate the immunogenicity and safety of a commercial inactivated HAV vaccine in Chinese patients with chronic HBV infection. METHODS: Sixty-five HBV-infected patients (30 carriers, 22 chronic hepatitis, 13 cirrhosis), who were seronegative for HAV, received a dose of 1440 ELISA units of HAV vaccine at weeks 0 and 24. Twenty-eight healthy individuals aged 18-57 years, who were seronegative for both HBV and HAV infection, also received the same vaccination regimen. Seroconversion was defined as an anti-HAV titre >/= 33 mIU/mL. RESULTS: The seroconversion rates for the HBV-infected patients at weeks 2, 4 and 24 were 72, 91 and 80%, respectively. The corresponding geometric mean titres (GMTs) were 103, 311 and 123 mIU/mL. In the healthy control group the seroconversion rates were 86, 93 and 89% at weeks 2, 4 and 24. The corresponding GMTs were 112, 158 and 250 mIU/mL. There was no difference in the seroconversion rates between the two groups, but healthy controls had a significantly higher GMT at week 24 (P=0.04). Side-effects were more common in HBV patients. CONCLUSION: The HAV vaccine is equally efficacious in patients with chronic HBV infection. (+info)
Risk of hepatitis B transmission after amniocentesis in chronic hepatitis B carriers.
(24/1741)
OBJECTIVE: To measure the risk of perinatal transmission of HBV in chronic carriers who undergo amniocentesis. METHODS: This was a prospective, longitudinal study from 1990 to 1995 of women who were HBV carriers and underwent amniocentesis. The infants of these women were followed from birth to one year of age. Maternal data examined included HBV antigen and antibody status, liver function tests (LFTs) and the amniocentesis report. RESULTS: Twenty-eight women were identified. Two of 28 neonates were stillborn unrelated to hepatitis. Five infants were lost to follow-up leaving 21 mother-child pairs to evaluate. All 21 women were chronic HBV carriers at the time of amniocentesis for delivery. No mother had abnormal LFTs, and only one of 21 women was positive for hepatitis B e antigen (HBeAg). Thirteen amniocenteses were for advanced maternal age, and four were for abnormal maternal serum alphafetoprotein (MSAFP) screening. None of the amniocenteses were recorded as bloody, and the placenta was anterior in 6 of 21 procedures. None of the 21 infants (95% CI: 0-16.8%) were positive for HbsAg during the first month of life or at 12 months of age. All infants received HBV vaccine and HBIG immunoprophylaxis. CONCLUSION: The risk of transmission of HBV to the fetus after amniocentesis in women who are HBV carriers is low. Immunoprophylaxis in these infants was successful. (+info)