Detection of virus antigens: hepatitis B antigen

Hepatitis B virus is the infectious agent that causes hepatitis of the long incubation variety and frequently is transmitted by blood transfusions. Hepatitis B antigen (HB Ag, Australia antigen) is an immunologic marker of hepatitis B virus and is found in serum of patients with acute hepatitis and in chronic carriers. Transfusion of blood containing HB Ag frequently leads to hepatitis in the recipient. Many methods have been developed for detection of HB Ag. None of these methods are capable of detecting the minimum dose required to transmit hepatitis to humans. Radioimmunoassay methods were applied to measurement of HB Ag and hepatitis B antibody (HB Ab). Two general approaches have been used for measurement of HB Ag. The first is competitive radioassay using radioiodinated HB Ag and the second is a direct system using labeled HB Ab. Both methods offer considerably higher sensitivity than other common detection systems. However, preliminary studies suggest that donor screening for HB Ag by radioimmunoassay will not eliminate all HB Ag-associated transfusion hepatitis. Measurement of HB Ab by use of double-antibody radioimmunoassay has revealed evidence of prior exposure to HB Ag in a high proportion of the adult population, especially in lower socioeconomic groups. Evidence is accumulating that circulating HB Ab is associated with immunity to hepatitis B.     

Second-Generation Hepatitis C Elisa Antibody Tests Confirmed by the Four-Antigen Recombinant Immunoblot Assay Correlate Well with Hepatitis C Viremia and Chronic Liver Disease in Swedish Blood Donors

Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2^nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by ‘nested’ polymerase chain reaction (PCR) based on primers from a 5′-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2^nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2^nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1^st-gen Elisa positive but 2^nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference <0.7 μkat/1) was found in 26 2^nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2^nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.     

Antibody to hepatitis C virus and liver disease in volunteer blood donors

OBJECTIVE: To evaluate the specificity of antibodies to hepatitis C virus (anti-HCV) and their relation to liver disease in blood donors. DESIGN: Case series of consecutive blood donors found positive for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Patients were evaluated for antibody specificity using a recombinant immunoblotting assay (RIBA) and were evaluated for biochemical evidence of liver disease. Patients showing increased alanine aminotransferase (ALT) levels had a liver biopsy. SETTING: University hospital. PARTICIPANTS: Fifty consecutive blood donors found to be anti-HCV positive on both an initial and repeat ELISA. Inclusion criteria were as follows: an absence of hepatitis B surface antigens and non-organ-specific autoantibodies; a daily alcohol intake of less than 50 g; no history of recent hepatotoxic drug use; and normal serum levels of alpha 1 antitrypsin, ceruloplasmin, and copper. MAIN RESULTS: Anti-HCV positivity was confirmed by RIBA in only 13 of 50 donors (26%) who had positive ELISA results. These 13 donors had an elevated ALT level and histologic evidence of chronic hepatitis, which was active in 8 patients (62%) and had already produced cirrhosis in 2 patients (15%). In contrast, the 17 donors with an intermediate RIBA pattern had only mild and often nonspecific histologic liver abnormalities. The 20 patients with a negative RIBA result had normal ALT levels. CONCLUSION: In blood donors, the anti-HCV RIBA is not only more specific than the anti-HCV ELISA, but is also useful in identifying patients who have an underlying chronic liver disease.     

Follow-up Studies on Liver Disease Associated with HBS Ag Carriers

Summary: Follow-up studies on liver disease associated with HB_sAg carriers. T. D. Bolin, A. E. Davis and A. G. Liddelow, Aust. N.Z. J. Med., 1976, 6, pp. 539–542.
Eight male subjects who were initially studied in 1972 with liver biopsy because of HB_sAg carrier status were re-studied two years later with liver biopsy, clinical examination and standard liver function tests. Three of the eight subjects remained antigen positive and had continuing liver disease, this being either chronic active hepatitis or chronic persistent hepatitis. Two subjects became HB_s Ag negative and their liver biopsies returned to normal. One subject became HB_s Ag negative but his biopsy disclosed chronic active hepatitis with cirrhosis in the presence of normal liver function tests. While persistence of the antigenaemia is associated with persisting liver disease, the converse is not true in that the disappearance of the antigen does not necessarily imply an improvement in liver disease. Liver biopsy remains the only reliable means of assessing liver disease as biochemical tests of liver function and the clinical finclings may be of little value.     

A clinical, epidemological, laboratorial, histological and ultrasonographical evaluation of anti-HCV EIA-2 positive blood donors

Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83. 5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathological exams of the anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.     

A follow-up study of an outbreak of non-A, non-B hepatitis in a plasmapheresis unit

A cluster of acute non-A, non-B hepatitis comprising 12 blood donors was diagnosed in a plasmapheresis unit. Nine cases were followed-up for 2-5.5 years and seven out of them progressed to chronicity, as judged by biochemical abnormalities. In six, liver biopsy was performed 1 year after the acute disease revealing chronic active hepatitis in two, chronic persistent hepatitis in two, chronic lobular hepatitis in one and normal liver in one. Repeated biopsies showed progression to cirrhosis in one case of chronic active hepatitis, and resolution of the disease in another one, while in the remaining patients liver morphology remained unchanged. Circumstantial epidemiologic evidence suggests a single agent being the cause of the outbreak, which resulted in a broad spectrum of liver disease.     

Detection of Antibody to Hepatitis-Associated Antigen in Hemophilia Patients and in Voluntary Blood Donors

Abstract. The sera from 385 hemophilia patients and 360 normal voluntary blood donors were tested by a variety of methods for antibodies against the hepatitis- associated or hepatitis B antigen (HB Ag). Anti-HB Ag was detected in 79.8% of the hemophilia sera and 7.5% of the normal blood donor sera by a 'sandwich' solid-phase radioimmunoassay (RIA) method. The RIA method was compared with other serologic methods (agar-gel diffusion, counterelectrophoresis, complement fixation and passive hemagglutination [PHA]) and found to be significantly more sensitive than all methods except PHA. The RIA and PHA methods were approximately equal in sensitivity as judged both by endpoint titrations and tests on the 745 sera for antibodies. The RIA method is also applicable to HB Ag detection.     

肝组织中丙型肝炎病毒抗原的表达及其临床意义

目的研究肝炎患者肝组织中丙型肝炎病毒抗原的表达及其临床意义。     

An International Proficiency Survey for the Detection of Hepatitis B Antigen and Antibody in Blood Donations by Counterimmunoelectrophoresis

Abstract. A panel of ten selected human plasma samples containing low or high concentrations of hepatitis B antigen (HB Ag) or antibody (HB Ab) – as determined by the use of various techniques in two reference laboratories – was tested by counterimmunoelectrophoresis (CIEP) in 40 laboratories located in different parts of the world. As a result of replicate tests, the average proficiency of these laboratories in obtaining the predetermined results ranged from 32 to 100%, with a median value of 65%. It is desirable that the efficiency of CIEP, particularly for the detection of low levels of HB Ag and HB Ab in blood donations, should be improved.     

Hepatitis C virus RNA and liver histology in blood donors reactive to a single antigen by second-generation recombinant immunoblot assay

The clinical significance of single band reactivity (indeterminate pattern) at anti-hepatitis C virus (HCV) second-generation recombinant immunoblot assay (RIBA-2) was investigated in symptomless subjects with normal liver function tests to obtain data for their counseling and clinical management. Serum and hepatic HCV RNA were determined by the nested polymerase chain reaction, and liver histology was evaluated in 40 symptomless blood donors with stable indeterminate RIBA-2 pattern, including 38 reactive to c22-3. All but one had normal alanine aminotransferase (ALT) levels. Two new immunoblot tests, RIBA-3 and INNO-LIA HCV Ab III (LIA-III), which incorporate additional HCV antigens, were also done to assess whether they could identify the viremic subjects. Ten cases (25%, confidence interval 12 to 38) were HCV RNA positive. Three of the HCV RNA-positive and none of the HCV RNA-negative subjects had chronic hepatitis. RIBA-2 strong intensity of reaction (score >2+) was observed in all the HCV RNA-positive and in 12 HCV RNA-negative subjects. RIBA-3 and LIA-III gave positive results in 9 of 10 and 10 of 10 HCV RNApositive, but also in 8 of 30 and 24 of 30 HCV RNAnegative subjects. A c-22-3 reactivity score of 4+ by RIBA-3 and E2/NS1 reactivity by LIA-III were both strongly associated with HCV RNA (P < .001). Based on relatively high prevalence of chronic hepatitis in our series (30%), apparently healthy subjects with stable indeterminate RIBA-2 pattern and HCV RNA positivity should be considered for liver biopsy independently of ALT profile. Reactivity to particular HCV antigens by third-generation tests helped to identify the subjects with current infection.     

Genotypic variation, clinical and histological characteristics of chronic hepatitis C detected at blood donor screening

Summary. Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV-positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty-three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty-three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal-portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype.
In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent infection.     

High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus.

OBJECTIVE: To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. DESIGN: Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. SETTING: Liver unit of a referral-based university hospital. SUBJECTS: Of 30,231 consecutive donors, 368 (1.2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. CONCLUSIONS: In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.     

Chronic persistent hepatitis: hepatitis B virus markers and histological follow-up.

Twenty-six untreated patients with chronic persistent hepatitis were followed prospectively for one to 17 years (mean 5.6 years). The patients developed no clinical features of chronic liver disease. Raised serum transaminase levels were usually, but not consistently, the only biochemical abnormality; gamma globulin values were normal. Serum markers of past or present hepatitis B infection were found initially in 14 patients: another two developed markers during their follow-up. Nine patients progressed to a mild or moderate chronic active hepatitis as shown by serial needle liver biopsies but there was no evidence of cirrhosis. This progression was not associated with any clinical or biochemical deterioration. Seven of these patients had presented with insidious symptoms, seven had serum markers of hepatitis B infection, and the four who were HBsAg positive had relatively lower serum HBsAg concentrations than did those patients who continued with chronic persistent hepatitis.     

Liver disease and cell-mediated immunity in hepatitis-associated antigen (HAA) carriers

As the incidence of liver disease in hepatitis-associated antigen (HAA) carriers has not been defined and it has been postulated that continuing liver disease is associated with incompetence of the cell-mediated immune system, a prospective study was undertaken to examine both these points.

An increased incidence of HAA carriers was found in a prison population (1·3%). Eighteen of these subjects gave informed consent to further study with liver function tests, liver biopsy, and testing of cell-mediated immunity with dinitrochlorobenzene (DNCB) skin sensitization.

Liver function tests were normal in 10 subjects, mildly abnormal in six (SGPT < 100 IU/litre), and abnormal in two. Serum proteins were normal in all.

Liver biopsy showed that five subjects had chronic aggressive hepatitis, three of whom had normal liver function tests. Eight subjects had persistent hepatitis, three with normal liver function tests. The remainder had acute hepatitis (1), evidence of residual hepatitis (1), or non-specific changes (2). Only one subject had normal histology. Drug addicts, who comprised 56% of the group, had more severe liver disease then those who were not addicts.

The hypothesis that persisting liver disease is associated with impaired cell-mediated immunity was not confirmed in that nine of the 12 subjects with persistent or chronic aggressive hepatitis had a positive response to dinitrochlorobenzene skin sensitization, thus implying normal cell-mediated immunity. The findings of this study suggest that in the presence of continuing antigenaemia liver biopsy is mandatory in order to disclose treatable liver disease.

     

Detection by immunofluorescence of a new “core-like” Ag/Ab system in liver and serum of patients with NANB hepatitis

ABSTRACT— Using direct immunofluorescence, a nuclear antigen was found in liver of chronic hepatitis patients with circulating NANBe Ag or anti-NANBe, and selected sera from either group were used as source of conjugates. The new Ag/Ab system was designated NANBc Ag and anti-NANBc since it behaved like the core Ag of HBV. N ANBc Ag was detected in coded frozen liver biopsies from patients with chronic persistent 15/25 (60 %) or active 27/50 (54 %) hepatitis and cryptogenic cirrhosis 16/30 (53.3%) devoid of HBV markers. Only 2/30 alcoholic cirrhosis cases (7%) used as controls were positive (p≤0.001). The homologous anti-NANBc antibody was always detectable by indirect immunofluorescence in the patients' serum when N ANBc Ag was found in the liver. It was also found in 11/135 (8%) additional cases without any other NANB marker. A correlation was observed between coded detection of the NANBc Ag/Ab system by immunofluorescence and demonstration of NANBe Ag or anti-NANBe by immunodiffusion. In acute post-transfusion NANB hepatitis, anti-NANBc was first detectable 14 days after transfusion and persisted as long as ALT remained elevated, or longer. IgM anti-NANBc present at onset became associated with an increasing proportion of IgG after the 28th day. The prevalence of anti-NANBc in sporadic NANB hepatitis (11/50 = 22%) was significantly lower (p≤0.001) than in cases with parenteral exposure such as post-transfusion, occupational or drug addict hepatitis (47/72 = 65%). Immunofluorescent tests for NANBc Ag and Ab are promising assays for the serological diagnosis of NANB hepatitis.     

Immunoglobulin and autoantibody response in acute and chronic liver disease

Serum immunoglobulin and nonorgan-specific autoimmune responses (autoantibody response) were studied in 269 patients with a variety of acute and chronic liver disease. A majority of patients with hepatitis B antigen (HB Ag)-positive and HB Agnegative acute viral hepatitis showed a mild elevation in total globulin, gamma globulin, immunoglobulin G (IgG) levels and a moderate elevation in immunoglobulin M (IgM) levels during the first 2 weeks of illness; these levels began to subside by the 8th week of illness and were completely normal by the 12th week, concomitant with the return of normal transaminase values. Serum complement (C₃) levels were low in 20 per cent of the patients with acute viral hepatitis, during the first 2 weeks of illness and returned to normal thereafter. Of the 80 patients with acute viral hepatitis, 42.5 per cent had smooth muscle antibody (SMA), 20.5 per cent had mitochondrial antibody (MA), 10 per cent had rheumatoid factor (RA), and none had antinuclear antibody (ANA); these nonorgan-specific autoimmune markers were only transiently present (mean, 2 weeks) and became undetectable as the patient's condition improved. There was no difference in these immunologic responses between patients with HB Ag-positive and HB Ag-negative acute viral hepatitis. High levels of gamma globulin and IgG were seen in chronic active liver disease, either of viral or alcoholic etiology. Serum immunoglobulin A (IgA) levels were elevated only in those with alcoholic liver disease, whereas IgM levels were high in those with liver disease associated with an active hepatocellular damage either of alcoholic or viral etiology. HB Ag-positive blood donors with asymptomatic mild liver disease had normal immunochemistry values.     

Chronic liver disease in asymptomatic hepatitis C antibody positive blood donors

:The risks of acquisition of hepatitis C infection, the histological spectrum of liver disease, and the presence of viraemia were investigated in anti-hepatitis C virus (HCV) antibody positive blood donors. All 357 (0.64%) blood donors to the South Australian Red Cross Transfusion Service found to have anti-HCV antibody during the first seven months of testing in 1990 were assessed, and 70 (19.6%) were found to have elevated alanine transaminase levels. These subjects were referred for participation in the study; 31 presented for enrolment.
Sixteen (52%) of the 31 patients had previously used intravenous drugs, four (13%) had been transfused, two (6%) had a history of occupational exposure to blood, and three (10%) had tattoos and ear-piercing as possible risk factors for acquisition of hepatitis C. There was no history of parenteral exposure in six (16%). None of these donors had clinical evidence of liver disease, but in all 24 of the 31 who had a liver biopsy there was histological evidence of significant liver damage. Twelve had evidence of chronic active hepatitis. All 24 subjects biopsied were viraemic as judged by the presence of HCV RNA in serum. (Aust NZ J Med 1993; 23: 176–180.)     

The significance of the Australia antigen (HBsAg) persistent healthy carrier "status": a long-term follow-up study of 34 cases

Thirty-four persistent healthy carriers of HBsAg (serum HBsAg detectable for longer than 3 months with normal liver function tests and normal liver histology or slight aspecific abnormalities) were discovered by routine testing of household relatives of B virus hepatitis patients. The carriers were followed-up for 11 to 37 months by clinical control, liver function tests and liver needle biopsy. None carrier had previous jaundice. During the follow-up period, in 17 of the 34 subjects, was there no evidence of deterioration in either clinical state, liver function of pathological findings. In 5 of the 34 carriers, HBsAg disappeared from serum after a period ranging from 6 to 12 months. The remaining 12 cases developed clinical and histological picture of acute viral hepatitis after 6 to 29 months (mean 12 months). Of these 12 patients, 6 recovered and become HBsAg; 2 remained HBsAg healthy carriers despite normalization of biochemical and histological abnormalities; 3 progressed from the acute stage to antigen positive CAH. The remaining one case could not be followed-up after the acute hepatitis. Our data indicate that the outcome of the HBsAg carrier state is unpredictable and stress the need of long-term follow-up surveillance.     

乙型肝炎前S2抗原／抗体的检测与其病毒标志物的关系及临床意义

目的:探讨乙型肝炎患者前S_2抗原、前S_2抗体与乙型肝炎病毒标志物(HBV M)之间的关系及临床意义。方法:对176例乙型肝炎患者用ELISA法检测前S_2抗原、前S_2抗体及HBV M;用聚合酶链反应(PCR)法检测乙型肝炎病毒HBV-DNA。结果:急性肝炎、慢性肝炎、肝硬变患者前S_2抗原检出率分别为11.11％、73.73％、75%;前S_2抗体在上述患者中的检出率分别为77.78％、11.02％、5％。前S_2抗原在HBV-DNA、HBeAg阳性病例中的检出率明显高于阴性组(P<0.001)。前S_2抗体阳性病例中,HBV-DNA、HBeAg均为阴性。结论:前S_2抗原的检出意味着病毒有复制或有传染性。前S_2抗体的出现标志着病毒被清除,在慢性肝病中检出并不意味着病情稳定,同时发现该抗体可以在急性乙型肝炎的急性期及血清乙肝病毒标志物全部阴性的患者中检出。     

Hbc ag, anti-HBC, and DNA polymerase activity in transfused recipients followed prospectively.

Hepatitis B core antigen, antibody to core antigen, and DNA polymerase activity were measured in sera from a select group of post-transfusion hepatitis B patients who had been followed prospectively following blood transfusion. Preliminary results of this study have revealed (1) that RIA testing of blood would not eliminate but would reduce post-transfusion hepatitis B infections by about 50 per cent; (2) that infection with HB virus is modified or aborted in the presence of pre-existing antibody to HB surface antigen; and (3) that transfusion of blood containing anti-HBs does not increase the risk of post-transfusion hepatitis B. HBc Ag and/or DNA polymerase activity were observed in the sera of all recipients tested who developed liver enzyme abnormalities along HBs Ag and anti-HBc. DNA polymerase activity usually occurred in the early stages of incubation before the transaminase became abnormal, whereas HBc Ag was more often associated with increasing enzymatic evidence of liver damage, suggesting release of core structures from the hepatocytes. The presence of DNA polymerase without detectable HBc Ag may be due to the presence of intact Dane particles in the sera, preventing recognition of the core antigen. No serological evidence of hepatitis B was observed in the sera of 24 other recipients who developed abnormal transaminases. Immunoelectron microscopy of these same sera revealed evidence of exposure to hepatitis A antigen following transfusion in at least two recipients.