Immune response to HBsAg, HBcAg and e-antigen in patients with acute hepatitis and HBsAg carriers with and without liver diseases

Humoral and/or cell-mediated (CMI) immune responses to HBAg components, human and rabbit liver specific proteins (HLP and RLP) and tuberculin were tested in patients with acute virus B and non-B-hepatitis, asymptomatic HBsAg carriers and HBsAg positive chronic active hepatitis (CAH). Furthermore, the presence of HBsAg, HBcAg and/or "e"-antigen has been studied in patients with sera and/or liver tissue. Asymptomatic HBsAg carriers are characterized by a status of immunological tolerance against HBsAg. HBcAg in liver nuclei could not be detected. All sera were positive for anti-HBc, some had anti "e". - Patients with uneventful acute virus-B-hepatitis developed CMI against HBsAg 4-6 weeks and anti-HBs 4-6 months after onset of the disease. Acute virus hepatitis without detectable HBsAg are defined as non-B-hepatitis by negative humoral and cell-mediated immune reaction against HBsAg 1-12 months after onset of the disease. - Patients with type B chronic active hepatitis are characterized by inadequate CMI against HBsAg without immune elimination of virus and virusantigens. Acute and chronic type-B-hepatitis showed temporary or constant CMI against HLP. These findings suggest an alteration or a carrier function of membrane antigens of virus infected hepatocytes or an induction of new membrane antigens by a virus. The results indicate that recovery from type B-hepatitis is associated with the ability to elicit a specific immune response to HBsAg. Furthermore immune responses to virus, virus antigens and virusinfected hepatocytes seemed to be the pathogenic principle of virus induced acute and chronic liver diseases.     

Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection

Previous studies have demonstrated that demographic characteristics of subject populations influence both the incidence of periodontal diseases and various aspects of host responses to periodontal bacteria. In this study we analyzed the components of the subgingival microflora from individuals with adult periodontitis, early onset periodontitis, gingivitis, and periodontal health as a function of gender and race (black and white). Clinical categories were analyzed individually so that there were no differences in the clinical characteristics of the sampled sites. No significant differences were noted in the subgingival microflora between males and females. When either the first two bacterial samples from each subject or all bacterial samples taken from each subject were included in the analysis, it was found that Porphyromonas gingivalis was more significantly associated with black subjects in the adult periodontitis group. When all samples were considered in the analysis, it was found that Peptostreptococcus anaerobius was associated with black subjects in the adult periodontitis group, while Fusobacterium nucleatum was associated with white subjects in both the adult periodontitis and early onset periodontitis groups. Thus a limited number of important bacterial components of the subgingival microflora are influenced by the race and diagnosis of the subject group.     

GB virus C RNA in serum, liver, and peripheral blood mononuclear cells from patients with chronic hepatitis B, C, and D

We examined fiber density, compound muscle action potential (CMAP) amplitude, and motor unit number estimate (MUNE) of the abductor digiti minimi and grip strength longitudinally. We sought to determine the effects of ALS on these measurements and to evaluate which of these tests may be more sensitive in evaluating progression of ALS and possibly predicting survival. Ten patients were examined at months 0, 3, and 6. A significant decrease in MUNE and increase in fiber density were observed at months 3 and 6 (p < 0.02) compared with baseline (month 0). Mean CMAP and grip strength declined, but not significantly. The decrease in MUNE over 6 months was significantly greater than that of CMAP and grip strength (p < 0.025). The significant changes in MUNE and fiber density over time suggest that they are more sensitive in measuring the rate of progression of ALS. To evaluate further the utility of these tests, we arbitrarily divided the patients into equal groups based on length of survival. MUNE declined significantly in the group with shorter survival (p < 0.01). Conversely, fiber density increased significantly in patients with longer survival (p < 0.01). With similar statistical analysis there were no significant differences in decline of CMAP or grip strength in either subgroup over 6 months. Our study suggests that MUNE and fiber density are more sensitive than CMAP and grip strength in detecting progression of ALS. Furthermore, we raise the hypotheses that a greater increase in fiber density identifies a group of patients with ALS who will have longer survival, and that a greater decline in MUNE identifies a group with a worse prognosis.     

Determination of hepatic zinc content in chronic liver disease due to hepatitis B virus

BACKGROUND/AIMS: Zinc is an essential, mostly intracellular, trace element which participates in many physiologic mechanisms. Some liver functions like urea formation require the presence of zinc; thus the determination of hepatic zinc content may contribute to the understanding of probable zinc-related clinical consequences of chronic liver disease. In this study, we aimed to determine the hepatic zinc concentrations in patients with chronic liver disease due to the Hepatitis B virus and to ascertain the relationship between the severity of liver disease and hepatic zinc content, if one in fact exists. METHODOLOGY: A total of 99 HBsAg positive subjects were included in the study. We performed a liver biopsy on all subjects. Hepatic zinc concentrations were determined by atomic absorption spectrophotometry. RESULTS: The liver biopsies were normal in 25 subjects. There were 33 chronic active hepatitis (CAH), 34 cirrhosis and 7 chronic persistent hepatitis (CPH) patients in the study group. In the control group, CAH, cirrhosis and CPH groups, the mean liver zinc concentrations were 3.83 +/- 1.86, 1.86 +/- 0.92, 1.14 +/- 0.68 and 3.74 +/- 1.81 mumol/g dry weight, respectively. Hepatic zinc in the CAH and cirrhosis groups were lower than that of the control group (p < 0.05). We also found that liver zinc in the cirrhosis group was lower than in the CAH group (p < 0.05). CONCLUSION: According to these results, as the severity of liver damage increases, the hepatic zinc concentration decreases. Therefore, it can be suggested that zinc supplementation may improve hepatic encephalopathy by increasing the efficiency of the urea cycle.     

Histopathologic and immunohistochemic correlations in virus B chronic hepatitis

Complete diagnosis of chronic hepatitis relies on exploring the liver by bipsic punction, performing the classic histopathologic and immunohistochemic exams. We worked out viral antigens hepatocytes by using avidin-biotin-peroxidase complex technique as following: Ag HBs placed in cytoplasm or at the level of the cell membrane. Ag HBc preferably placed in nucleus and, a small part of it, in cytoplasm. Ag HD present especially in nucleus. A correlation between tissular antigen expression and hepatic histopathologic aspect was established. Two main types of viral expression were remarked: a regressive type reflected by cytoplasmatic Ag HBs in the absence of generalised nuclear Ag HBc--situations linked to persistent chronic hepatitis: an aggressive type characterised by the presence of the focal nuclear Ag HBc, cytoplasmatic Ag HBc or antigen HD--situations linked to active chronic hepatitis with various degrees of severity.     

HBsAg, chronic lymphoproliferative disorders, and cirrhosis of liver

This study reports the incidence of HBsAg in a series of chronic lymphoproliferative disorders in which a high incidence of cirrhoses had been previously observed. Twenty-three cases were collected from the necropsy records. The type of lymphoma was reviewed in the light of the new functional classifications of non-Hodgkin malignant lymphomas introduced by Lennert and Lukes. The presence of HBsAg in the liver was investigated by the indirect immunofluorescence technique. Eleven cases showed plasmocytoid features and were considered as immunocytomas. Seven cases showed cirrhosis of the liver; six of them belonged to the immunocytoma group. Four cases were positive for HBsAg. Three of them were found among the group combining cirrhosis and immunocytoma. They presented the abundant nodular distribution of HBsAg typical of inactive cirrhosis.A parallel is drawn between the often reported association of Waldenstr?m's syndrome and cirrhosis and the association of immunocytoma and cirrhosis observed in this study. The analogy is all the more justified since most of the lymphomas associated with Waldenstr?m's syndrome happen to be immunocytomas. Therefore the association between HB virus infection and cirrhosis on the one hand and chronic lymphoproliferative disorders on the other may not be purely coincidental. A chronic antigenic stimulus such as persisting HBsAg could trigger the proliferation of a malignant lymphoid clone.     

Concentration of hepatitis A and B virus antigens using water-soluble polymers

A possibility of using reversibly sedimented polymeric system for the concentration of hepatitis A and B virus antigen has been demonstrated. As polymeric systems, tetrasole-containing polyelectrolytes and interpolymeric complex polymethacryl acid-poly-1-vinylpyrrolidone were used, capable of sedimenting in acid medium and dissolving in media with the neutral pH.     

Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection

Heterogeneity of the hepatitis B virus (HBV) core gene has been reported to be associated with the presence of active liver disease in Japanese patients with chronic HBV infection. This study evaluated the significance of HBV core gene heterogeneity in Western patients with chronic HBV infection. The hepatitis B virus precore/core gene from 45 patients (inactive:active liver disease ratio 16:29) was amplified from serum by polymerase chain reaction (PCR). Gel electrophoresis was employed to detect large deletions. The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced. Hepatitis B surface antigen (HBsAg) serotypes were tested by enzyme immunoassay (EIA) and hepatic expression of HBV antigens was assessed by immunohistochemistry. The HBV core gene was amplified from the serum of all 45 patients. Three patients had mixed infection with both precore mutant and wild-type HBV and all three had active liver disease. No patient had a large deletion of the HBV core gene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of silent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or encoded amino acid substitutions and the clinical and biochemical parameters, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression. Variation of the HBV core gene was not found to be preferentially associated with active liver disease in Western patients with chronic HBV infection. The pattern of hepatitis B core gene variation is in accord with the genomic organization of HBV.     

Hepatitis in used syringes: the limits of sensitivity of techniques to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, and antibodies to HBV core and HCV antigens

Hepatitis virus infections are common among injecting drug users. Syringes containing hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were identified by polymerase chain reaction (PCR); syringes containing antibodies to HBV core antigen and HCV were identified by EIA. Syringe use was simulated to determine the sensitivity of these assays. The mean limits for PCR were 0.082 microliter of blood for HBV and 0.185 microliter for HCV; the mean limits for EIA were 0.185 microliter for HBV and 0.023 microliter for HCV. HBV PCR testing of 681 syringes returned to the needle exchange program in New Haven, Connecticut, revealed a decline from 7.8% HBV-positive at the program's outset to 2.6%. HCV antibodies were found in 12.1% of 207 syringes tested. Syringe testing can help estimate the prevalence and incidence of hepatitis virus infections when standard seroepidemiologic analyses cannot be applied.     

Mixed cryoglobulinemia in chronic virus diseases of the liver

OBJECTIVE: To establish the tolerance of breast irradiation by women aged 65 and older. DESIGN: Retrospective chart review. PATIENTS AND SETTING: Women undergoing partial mastectomy and postoperative radiation therapy at the H. Lee Moffitt Cancer Center and Research Institute between 1986 and 1990. Of 163 women eligible for the study, 100 were under age 65, and 63 were aged 65-78. MEASUREMENTS: Comparison of total treatment dose, treatment duration, number of treatment interruptions, incidence of cutaneous, mucosal, and hematological toxicity between women aged 65 and older and women younger than age 65. MAIN RESULTS: All study measurements were comparable among younger and older women: total radiation dose (P = 0.5); treatment interruptions (P = 0.063); treatment duration (P = 0.78); cutaneous toxicity (P = 0.37); anemia (P = 0.83); leukopenia (P = 0.07), and thrombocytopenia (P = 0.94). There was no mucosal toxicity, nor higher than grade 2 hematological or cutaneous toxicity. The incidence and severity of toxicity was not higher for women aged 70 and older. CONCLUSIONS: Postoperative breast irradiation is well tolerated by older women. Age is not a contraindication to breast preservation.     

DNA-based immunization against hepatitis B surface antigen (HBsAg) in normal and HBsAg-transgenic mice

Hepatitis B virus (HBV) remains a serious worldwide health problem and the possibility to control it will depend on the availability of safe, effective and affordable vaccines. Recombinant protein or plasma-derived vaccines containing HBV surface antigen (HBsAg) are safe and generally efficacious, however, they are too expensive for widespread use in areas of HBV endemicity and are only partially effective for treatment of HBV chronic carriers. Immunization of mice by injection of HBsAg-expressing plasmid DNA results in rapid induction of strong and long-lasting humoral and cell-mediated immune responses. Here we report optimization of the humoral response with the use of necrotizing agents, co-expression of cytokines or co-stimulatory molecules and formulation of the DNA with cationic liposomes. DNA-based immunization of HBsAg-transgenic mice can also overcome non-response to HBsAg. Thus, DNA vaccines against HBV may be useful for both prophylactic and therapeutic purposes.     

Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection

24 consecutive AIDS patients with wasting, and who had never received anabolic therapies, were evaluated to determine their profile of sex hormones and whether transformation of testosterone (T) to the nuclear androgen, dihydrotestosterone (DHT), was impaired. Eleven (46%) patients had normal testosterone and DHT (group I), 10 (42%) had normal testosterone but low DHT (group II), and 3 (12%) had low testosterone and low DHT (group III). Age, prior opportunistic complications, symptoms, serum albumin, hemoglobin levels, and CD4 lymphocyte counts were similar in the groups. DHT was significantly lower (22.2 +/- 6.8 microg/dl) in group II compared with group I (50.8 +/- 15.3 microg/dl). The ratio of T/DHT, a measure of the conversion of testosterone to DHT, in group I was 15.1 +/- 3.5, which was within the range for eugonadal young men. In group II, the ratio was 22.3 +/- 1.5, indicating a defect in generation of DHT. Patients in group II had lost 9.2 +/- 3.5 kg compared with 5.6 +/- 2.6 kg in group I (p = .015). Thus, a syndrome of low DHT with normal testosterone was associated with significantly greater weight loss than in patients with normal testosterone and DHT. Further studies are needed to clarify whether low DHT is a result of AIDS wasting or is causally related to weight loss and whether androgen therapy in the form of DHT could reverse some of the metabolic changes associated with AIDS wasting.     

GB virus C/hepatitis G virus infection in autoimmune liver diseases

Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.     

The intrahepatic expression of the hepatitis B virus in chronic delta hepatitis

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.     

Immunohistochemical evidence of immunopathogenetic mechanisms in chronic hepatitis C recurrence after liver transplantation

Viremia and genotype are implicated in a rapid course of posttransplant hepatitis C virus (HCV) infection recurrence, but the role played by host immune reactions has not yet been evaluated. We correlated the degree of liver injury with the intrahepatic expression of molecules involved in immune response. The study included 32 biopsies of 30 liver transplant recipients. Recurrence of viremia was detected by Amplicor assay. Genotype was tested by Inno-Lipa. Cryostat sections were assessed by immunohistochemistry, using a wide panel of monoclonal antibodies. Correlations between histological-immunohistochemical semiquantitative evaluation and levels of viremia were performed. In severe hepatic inflammation, high numbers of activated cytotoxic T cells were found, along with marked hepatocellular expression of beta 2-microglobulin (beta 2-MG) and intercellular adhesion molecules. Likewise, a strong vascular adhesion molecule expression was observed mainly in those areas that were more inflamed. A striking endoglin reactivity was detected in enlarged portal tracts, and the presence of neoformed microvessels was also noteworthy. By contrast, in mild hepatic inflammation only a few activated T cells were detected, together with a weaker reactivity for all molecules studied. The level of viremia did not correlate with the degree of liver damage. The severe forms of post-transplant HCV infection recurrence are associated with a marked and aberrant intrahepatic expression of molecules involved in antigen recognition, and intercellular and vascular adhesion, decisive in regulating the recruitment and activation of cytotoxic T lymphocytes.     

丙肝病毒感染者血清乙肝病毒标志物与肝功能情况分析

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)是引起慢性肝病的主要致病因子,并与肝硬变、肝癌的发生密切相关[1].由于这两种病毒具有相似的传播途径,所以HBV和HCV的合并感染比较常见,流行率约10%～15%[2,3].