摘要:

AbstractTwo types of clinical events, acute exacerbation and uneventful course, precede spontaneous HBeAg serocon‐version to its antibody (anti‐HBe) in chronic type B hepatitis. To examine the possible mechanism responsible for these two types of clinical events, serial serum specimens from 75 patients who underwent spontaneous HBeAg seroconversion were assayed for hepatitis B virus DNA by slot blot hybridization with32P‐labeled cloned hepatitis B virus DNA as probe. Of these 75 patients, 47 (62.7%) had episodes of acute exacerbation (ALT>300 IU per liter) within 3 months prior to HBeAg seroconversion. All of these 47 patients had high hepatitis B virus DNA levels (>1,000 pg per ml) at the onset of acute exacerbation. Their serum hepatitis B virus DNA disappears shortly before or simultaneously with the HBeAg clearance in 27 patients (57.4%) and persisted but with decreasing levels for 2 to 40 months in 20 patients. Most of these patients had high α‐feto‐protein levels or evidence of bridging hepatic necrosis. In contrast, the serum hepatitis B virus DNA was undetectable for a minimum of 3 (3–17) months in the 28 patients who had an uneventful course before HBeAg seroconversion. Twenty of these 28 patients had well‐documented episodes of acute exacerbation with high hepatitis B virus DNA levels, but with normal α‐feto‐protein and little evidence of extensive necrosis as far back as 6 to 27 months before HBeAg seroconversion. The data might suggest that all spontaneous HBeAg seroconversion in chronic type B hepatitis was preceded by acute exacerbation as a result of immune clearance of hepatitis B virus, and the clinical events occurred within 3 months before HBeAg seroconversion were related to the serum hepatitis

ISSN:0270-9139    

DOI:10.1002/hep.1840070102

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe reactivity of sera was examined in patients with autoimmune chronic active hepatitis and other liver diseases by immunoblotting. Polypeptides and glycolipids of liver plasma membrane, liver‐specific lipoprotein and kidney membrane were separated and probed with sera from patients and from a rabbit immunized with mouse liver plasma membrane. Chronic active hepatitis sera reacted with a number of polypeptides in the liver plasma membrane preparations; similar but weaker reactivity was observed with sera from patients with other diseases and in some healthy subjects. Chronic active hepatitis sera did not react with glycolipids from liver plasma membrane. The immune rabbit serum reacted with two polypeptides of 180 kd present in liver plasma membrane but absent from kidney membrane, with two polypeptides of 50 kd which were nonliver‐specific but species‐specific, and with three major glycolipid components of liver plasma membrane: this reactivity thus differed markedly from that of the chronic active hepatitis sera. In studies using dot‐blotting, it was found that solubilization of liver plasma membrane in detergents resulted in a marked reduction of the reactivity to liver plasma membrane of chronic active hepatitis sera, but little change in the reactivity of the immune rabbit antiserum. Analysis of the reactivity of chronic active hepatitis and other sera with liver‐specific lipoprotein by immunoblotting indicated that liver‐specific lipoprotein consisted of constituents of liver plasma membrane together with intracellular proteins. While conditions utilized for electrophoretic separation of components of liver plasma membrane prior to immunoblotting do allow identification of some polypeptide‐directed reactivities in chronic active hepatitis sera, these were not dis

ISSN:0270-9139    

DOI:10.1002/hep.1840070103

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe course after hepatitis B virus infection seems to be determined by the host's immune response, which in turn may be regulated by the major histocompatibility complex. In order to find a possible relationship between the course of disease and the phenotype frequency of HLA determinants, we studied 396 Dutch subjects of northern European local race. Six groups of individuals with various courses after hepatitis B virus infection were compared to healthy controls. The hepatitis B patients were grouped according to standard criteria: (i) 47 had recovered from acute symptomatic hepatitis B virus infection; (ii) 60 had recovered from asymptomatic hepatitis B virus infection; (iii) 26 were asymptomatic hepatitis B surface antigen carriers; (iv) 16 had chronic persistent hepatitis B; (v) 37 had chronic active hepatitis B, and (vi) 10 had chronic active hepatitis after elimination of hepatitis B antigens. Twenty‐nine Class I and 13 Class II HLA antigens were assayed by standard microlymphocytotoxicity tests.The phenotype frequency of the Class II antigen DQw1 appeared to be significantly lower in patients with chronic active hepatitis B virus infection. Some other HLA specificities showed deviations from control values, but they were not statistically significant after correction for the number of antigens tested.In conclusion, we have found no evidence that the elimination of hepatitis B virus is related to HLA phenotype. DQw1, however, may affect the morphologic type of chronic hepatitis B infection, since its presence may protect against chronic active hepatiti

ISSN:0270-9139    

DOI:10.1002/hep.1840070104

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractIn order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty‐eight chronic HBsAg carriers with HBeAg, including 16 non‐specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication.When the detection pattern of HBeAg subtypes was examined during serial follow‐up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2, Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepa

ISSN:0270-9139    

DOI:10.1002/hep.1840070105

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe incidence, clinicopathological features and etiology of acute exacerbation occurring in patients with chronic type B hepatitis were assessed prospectively among 385 patients who had HBeAg and 279 who had anti‐HBe in serum. During an average follow‐up of 23.5 months, acute exacerbations occurred in 197 HBeAg‐positive patients and in 56 anti‐HBe positive patients, with a calculated annual incidence of 28.6 and 10.3%, respectively (p<0.001). The clinical and laboratory findings of acute exacerbations were similar in the HBeAg‐positive and anti‐HBe positive patients. The mean serum bilirubin and α‐fetoprotein levels were higher in anti‐HBe positive patients (p<0.01), but actual differences were small. The histologic features of acute exacerbations were also similar in the HBeAg‐positive patients and anti‐HBe positive patients. Lobular alterations were the main histologic findings; in addition, one‐fourth of patients had bridging necrosis and one‐fourth had piecemeal necrosis. Spontaneous reactivation of hepatitis B was the major cause of these exacerbations in both HBeAg‐positive patients (91.5%) as well as anti‐HBe positive patients (62.5%). Hepatitis delta virus superinfection accounted for a higher percentage of exacerbations in anti‐HBe positive patients (14.3%) than in HBeAg‐positive cases (6.5%). Hepatitis A and possibly non‐A, non‐B virus superinfections also contributed to some episodes of exacerbation. Thus, acute exacerbations of disease occurred more frequently in HBeAg‐positive patients than in anti‐HBe positive patients with chronic type B hepatitis, but the clinicopathologi

ISSN:0270-9139    

DOI:10.1002/hep.1840070106

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractAdenine arabinoside is an antiviral agent which has been used in a number of clinical studies for the treatment of chronic infections with hepatitis B virus. In order to better understand its effects and mode of action, we treated ducks chronically infected with duck hepatitis B virus with a 2‐week course and monitored the effects of the drug on viral replication by studying duck hepatitis B virus DNA in liver and serum using molecular biological techniques. We found the drug to be effective in ducks only at much higher doses than those used in humans. At high doses, adenine arabinoside had a dose‐related inhibitory effect on viral replication during treatment, but there was a rapid return toward baseline values soon after the cessation of treatment. The supercoiled form of viral DNA was found to be most resistant to adenine arabinoside therapy, and the drug had a disproportionate inhibitory effect on viral plus (noncoding) strand synthesis. We conclude that adenine arabinoside likely exerts its effect in hepadna virus infections predominantly through inhibition of viral DNA polymerase. On the basis of our current study and previous trials in hepatitis B virus‐infected patients, we predict that adenine arabinoside will not efficiently eliminate viral replication in chronic hepadna virus infection, when used as the sole therapeutic modality. Adenine arabinoside may have a role to play as an adjunct to immunomodulation or interferon therapy in chronic hepatitis B virus infection i

ISSN:0270-9139    

DOI:10.1002/hep.1840070107

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractA sequential study was performed to investigate the occurrence and localization of duck hepatitis B virus in the liver of domestic ducks utilizing the indirect immunoperoxidase method and electron microscopy. Seventeen ducklings were injected intravenously with duck hepatitis B virus‐positive serum within 24 hr after hatching and were subsequently sacrificed on the 2nd, 3rd, 4th, 5th, 27th and 44th day after injection. Nine ducklings were not injected and were used as a negative control.Duck hepatitis B virus DNA by spot hybridization using a [32P]‐labeled probe occurred in trace amounts on the 2nd day and in large amounts on the 4th day after inoculation. Immunoreactivity for DHBV was seen in the hepatocytes, sporadically on the 2nd day and diffusely on the 4th day, and also in the biliary epithelial cells on the 27th day. Both kinds of cells revealed staining in the cytoplasm but not in the nucleus.Virus particles were recognized by electron microscopy in the hepatocytes beginning on the 4th day. The hepatocytes had many incomplete virus particles, 40 to 61 nm in diameter, and a few complete virus particles, 40 nm in diameter, in the cisternae of the rough and smooth endoplasmic reticula. Such particles and the endoplasmic reticulum showed reaction products for duck hepatitis B virus by immunoelectron microscopy. There were clusters of core particles, 27 nm in diameter, in the hyaloplasm around peroxisomes where an assembly of cores appeared to occur. No conspicuous virus particles were recognized in the biliary epithelial cells. The similarities and differences in virus localization between duck hepatitis B virus and hepatitis B virus are discus

ISSN:0270-9139    

DOI:10.1002/hep.1840070108

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe presence of antibodies to HTLV‐III and markers of active hepatitis B virus replication was examined in a longitudinal study of 33 consecutive male homosexual HBsAg carriers. The mean follow‐up time was 37 months (range = 4 to 109 months). All patients were initially hepatitis B virus DNA‐positive and HBeAg positive. Antibodies to HTLV‐III were detectable in eight patients while they were positive for both of these markers. One of them cleared hepatitis B virus DNA and seroconverted from HBeAg to anti‐HBe. This corresponds to an annual clearance/seroconversion rate of 4% (95% confidence limits = 0 to 15%). In two patients, antibodies to HTLV‐III appeared after clearance of hepatitis B virus DNA and HBeAg, and in one of them, hepatitis B virus DNA reappeared. Among the 25 patients negative for HTLV‐III antibodies, the annual hepatitis B virus DNA clearance rate was 20% and HBeAg to anti‐HBe seroconversion rate was 11% (95% confidence limits = 11 to 31% and 4 to 20 % respectively). The observed hepatitis B virus DNA clearance rates in the two groups were significantly different (p<0.05). Disease activity, as determined by transaminase levels, was significantly lower in HTLV‐III infected individuals as compared to individuals without HTLV‐III infection (p<0.05). Infection with HTLV‐III may extend the period of active viral replication or even reactivate hepatitis B virus replication and seems to diminish inflammatory disease activity in c

ISSN:0270-9139    

DOI:10.1002/hep.1840070109

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe presence of hepatitis B virus DNA and anti‐δ was examined in a longitudinal study of 24 patients known to be δ‐infected during the course from acute to chronic hepatitis B virus infection. Fifteen patients (63%) were hepatitis B virus DNA positive in the first serum sample. Eleven of 14 patients, who cleared hepatitis B virus DNA, did so following or at the same time as onset of δ‐infection. Duration of hepatitis B virus DNA positivity in these 11 patients was shorter than in 11 anti‐δ‐negative controls matched according to duration of preceding hepatitis B virus DNA positivity, but the difference was not statistically significant. Considering only patients positive for IgM anti‐δ in the last serum sample (eight patients), a statistically significant shorter duration of hepatitis B virus DNA positivity was found in δ‐infected patients than in the controls (p<0.02). The study indicates that the δ‐agent may have the capacity to inhibit hepatitis B virus replication and that a chronic δ‐infection may lead to a termination of the period of

ISSN:0270-9139    

DOI:10.1002/hep.1840070110

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractTwenty pediatric patients with primary hepatocellular carcinoma in Taiwan were tested for HBsAg, and all were found to be positive. The youngest case was 8 months of age, five cases occurred between 9 and 10 years of age, and 14 cases occurred between 11 and 16 years of age. The serum α‐fetoprotein was elevated in all 20 primary hepatocellular carcinoma patients, and the average survival of these cases after diagnosis was 4.7 months.Seventy per cent of the mothers of the pediatric primary hepatocellular carcinoma cases and 52.9% of their siblings who were tested also were positive for HBsAg. In addition, two families had clustering of primary hepatocellular carcinoma cases.The occurrence of primary hepatoceullar carcinoma in the pediatric age group suggests the need for close follow‐up of young HBsAg‐positive carriers. Also, prevention of perinatal transmission of hepatitis B virus by immunoprophylaxis will significantly decrease both the hepatitis B virus carrier rate and the incidence of primary hepatocellular carcinoma in the asian popu

ISSN:0270-9139    

DOI:10.1002/hep.1840070111

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY