Comparison of class and subclass distribution of antibodies to the hepatitis B core and B e antigens in chronic hepatitis B

The IgG subclasses IgM and IgA1 of antibodies to hepatitis B core antigen (anti-HBc) and hepatitis B e antigen (anti-HBe) were assayed in sera from 82 patients with chronic hepatitis B utilising class/subclass-specific enzyme immunoassays (EIA). The solid-phase was either recombinant hepatitis B core antigen (rHBcAg) or rHBcAg converted to HBeAg by addition of 0.1% SDS with remaining HBcAg antigenicity blocked with monoclonal anti-HBc. Anti-HBc IgG1 was detected in 81 sera at a geometrical mean titre (GMT) of 296,110 x divided by 2.9. Anti-HBc IgG2 was not detected in any of the sera, and anti-HBc IgG3 and IgG4 were detected in 50 and 37 sera, respectively. Anti-HBc IgM and IgA1 were both significantly correlated to the presence of HBV DNA. The predominant antibody to HBeAg was found to be IgG1, being detected in 45 sera with a GMT of 1,035 x divided by 3.3. Anti-HBe IgG2 was not detected in any serum, while anti-HBe IgG3 and IgG4 were found in 8 and 23 sera, respectively. Anti-HBe IgG1, IgG3, and IgG4 were mainly detected in sera positive for anti-HBe in RIA (Abbott). No patient was found positive for anti-HBe IgA1 or IgM. Thus, in contrast to HBcAg, HBeAg does not trigger a persistent IgM and IgA1 response in chronic hepatitis B. The levels of anti-HBe IgG1 and IgG3 were much lower than the levels of anti-HBc IgG1 and IgG3. The presence of anti-HBe IgG4 was significantly correlated to that of anti-HBc IgG4.(ABSTRACT TRUNCATED AT 250 WORDS)     

HBeAg/anti-HBe seroconversion during and after protracted immunosuppressive treatment in type B chronic hepatitis

Seventy-seven consecutive HBeAg-positive chronic hepatitis patients were studied from 1971 to 1983 to establish the seroconversion rate in the e system. Patients with less than a year of follow-up were not included in the study. Fifty-six patients with chronic active hepatitis (CAH) received immunosuppressive treatment (corticosteroids combined with azathioprine). The remaining twenty-one patients received no treatment, nine of them with chronic persistent hepatitis (CPH) and 12 with CAH. A retrospective study was performed with stored sera samples: HBeAg and anti-HBe were determined by RIA, and results were correlated with alanine aminotransferase (ALAT) levels in the same samples. The linearized seroconversion rate from HBeAg to anti-HBe was expressed as percent per patient-year. It was 9.6% in CPH patients and 8.8% in CAH patients without treatment. In CAH patients under immunosuppressive drugs it was as low as 1.1% and increased to 28.7% when treatment was withdrawn. ALAT levels were significantly lower in total seroconverted patients when compared with nonseroconverted (NS) patients, but no difference was found between partial seroconverted (PS) and NS patients. The results suggest that although immunosuppressive drug withdrawal may enhance seroconversion rate in type B CAH, delayed seroconversion and reported side effects during treatment stand against protracted usage of these drugs.     

Natural seroconversion from hepatitis Be antigen to antibody among hepatitis B virus carriers in Okinawa Islands

In the Okinawa Islands, the great majority of hepatitis B surface antigen (HBsAg) carriers have already acquired antibody to hepatitis Be antigen (anti-HBe) by the age of 30 years (preliminary cross-sectional data). To elucidate natural seroconversion from hepatitis Be antigen (HBeAg) to anti-HBe among HBsAg carriers found in the islands of Okinawa Prefecture, 34 HBeAg-positive HBsAg carriers were followed for 1-6 years with serial measurements of aminotransferase levels, HBeAg, and anti-HBe. The 34 subjects included 24 patients with chronic hepatitis (group 1) and ten asymptomatic HBsAg carriers (group 2). During the follow-up period, HBeAg disappeared from 14 subjects in group 1 with the cumulative clearance rate of HBeAg of 56.3% within the first 2 years and with 10 of the 14 subsequently developing anti-HBe. Moreover, the aminotransferases in 12 of the 14 spontaneously seroconverted fell into the normal range. The annual clearance rates of HBeAg among group 1 and group 2 were 25.6% and 9.3%, respectively. The tendency for early disappearance of HBeAg during a carrier's life time or in the course of chronic hepatitis may lead to the low death rate from hepatocellular carcinoma (HCC) particularly HCC associated with hepatitis B virus infection in this area.     

High frequency of hepatitis B virus DNA in anti-HBe positive sera on longitudinal follow-up of patients with renal transplants and chronic hepatitis B

Hepatitis B virus (HBV) markers were determined in 821 patients receiving renal allografts and undergoing immunosuppressive therapy during 1970-1986. Twenty-four of the patients with a renal transplant functioning for longer than 1 year originally were or became chronic carriers of hepatitis B surface antigen (HBsAg). These patients remained carriers during the follow-up period, which lasted until death or until the end of 1986. Follow-up time was 1.2-15.3 years (mean 9.1 years). A total of 301 samples from the HBsAg-positive patients were tested for HBV DNA and HBeAg/DNA and HBeAg/anti-HBe. Nine patients who were constantly positive for HBeAg also remained positive for HBV DNA. Reactivation of HBV replication occurred in 11 patients. Among these, HBV DNA and HBeAg varied in parallel in six patients, three patients developed anti-HBe, and two patients were constantly positive for anti-HBe. Another four of the 24 patients seroconverted to anti-HBe, and two of these also lost HBV DNA. Three of 12 deceased patients died from liver failure during follow-up. None of these three had been constantly positive for HBeAg or HBV DNA, but they had had reactivations of HBV; two were also positive for HBV DNA in serum specimens available from their terminal month. HBV DNA was demonstrated in 99% of HBeAg-positive and 53% of anti-HBe-positive sera and in at least two samples from each of the 24 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a new radioimmunoassay for detecting hepatitis B e antigen and its antibody

A new commercially available radioimmunoassay (RIA) (Abbott-HBe^TM) was used for determination of hepatitis B e-antigen (HBeAg) and its antibody (anti-HBe). Serial serum samples from 20 transiently HBsAg-positive patients with acute hepatitis were tested. In nearly all patients HBeAg could be shown for a short period with subsequent development of antiHBe. From 24 chronic HBsAg carriers serial serum samples collected during several years were tested. In 18 of 19 initially HBeAg-positive patients the HBeAg was lost after 6 months to 6 years; in 14 anti-HBe developed. A correlation was seen between the seroconversion and normalization of elevated alanine transferase levels. From another 22 chronic HBsAg carriers single serum samples were assayed. These samples were selected because neither HBeAg nor anti-HBe could be detected by the immunodiffusion (ID) technique. They had previously been examined for HBV-associated DNA-polymerase activity. In 20 patients HBeAg or anti-HBe could be detected by RIA. Those who were DNA-polymerase negative had anti-HBe, and 3 of 4 who were DNA-polymerase positive had HBeAg. When compared to earlier results by ID in these materials a higher frequency of HBeAg and, in particular, anti-HBe was detected by the RIA. By this test, HBeAg or anti-HBe was found in nearly all patients. The usefulness of HBeAg/anti-HBe in the evaluation of infectivity and prognosis in hepatitis B has been limited by the low sensitivity of the earlier test systems. Thus, this new RIA is a valuable addition to the diagnostic tests for patients with hepatitis B.     

Relative functional affinity of specific anti-core IgG in different categories of hepatitis B virus infection

While resolution of hepatitis B virus (HBV) infection occurs in most cases, a carrier state can exist in which the HBV surface antigen (HBsAg) persists. Some carriers are also positive for the HBV “e” antigen (HBeAg), indicative of high viral replication. Others are HBV “e” antibody (anti-HBe)-positive carriers in whom there appears to be a fall in the level of viral replication with the appearance of antibodies against the “e” antigen. The former group of carriers is considered to be at a higher risk of transmitting HBV infection than the latter. In order that a carrier state may occur, some degree of tolerance to the infectious agent must exist. A study of the rate of increase of specific antibody avidity following infection provides a means of assessing the maturity of the immune response to an infectious agent. Since antibodies specific for the HBV core antigen (HBcAg) are produced in almost all cases of HBV infection and the HBeAg and HBcAg share a large number of amino acids and some B- and T-cell epitopes, the increase in the avidity of antibodies against the HBV core antigen (anti-HBc) in cases of acute, resolving HBV infection and in HBV carriers has, therefore, been studied. An increase in the avidity of specific antibody, similar to that seen in other viral infections, was observed following acute, resolving infection. However, low avidity antibody persisted longer in carriers who remained positive for HBeAg, whereas in cases where there were antibodies specific for HBeAg, the anti-HBc antibody was of high avidity. Analysis of sequential sera from carriers who seroconverted from HBeAg-positive to anti-HBe-positive showed that an increase in anti-core avidity could predate seroconversion from HBeAg-positive to anti-HBe-positive status. Thus, anti-HBc avidity studies may be of diagnostic and prognostic significance. J. Med. Virol. 51:189–197, 1997. © 1997 Wiley-Liss, Inc.     

Virus receptors for polymerized human albumin: A prognostic marker in HBeAg-positive chronic hepatitis type B?

Seventeen out of 30 patients with chronic hepatitis type B with hepatitis B e antigen (HBeAg) in serum remained persistently positive for e antigen, while 13 seroconverted to antibody (anti-HBe) when followed over a period of one to five years. Initial levels of serum hepatitis B virus (HBV) markers, such as the hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA polymerase (HBV-DNAP) were similar in the two groups of patients, while initial titres of the HBsAg-associated receptor for polymerized human serum albumin (pHSA), recently identified on HBV particles, were significantly higher in the patients who remained HBeAg positive (mean titre +/- SD = 2(-7.00) +/- 2(-3.2)) compared to the cases who eventually seroconverted to anti-HBe during the follow-up (2(-2.54) +/- 2(-2.14) P less than 0.001). A receptor titre above 1:64 by haemagglutination was highly predictive of persistence of HBeAg, suggesting that in patients with HBeAg-positive chronic hepatitis testing for the HBsAg-associated pHSA receptor may be useful in predicting the duration of HBe antigenaemia, with relevant clinical and prognostic implications.     

Perinatal transmission of hepatitis B virus in Thailand

Perinatal transmission of hepatitis B virus (HBV) from asymptomatic HBsAg carrier mothers to their infants was studied in 78 mother-infant pairs by determination of HBsAg, HBeAg and anti-HBe both in the mothers and in their infants at regular intervals for those children up to the time when they reached at least one year of age. Twenty-five out of the 78 (32.1%) infants born to these mothers were HBsAg-positive 2-6 months after birth and they remained so throughout the observation period of at least one year or more. Perinatal HBV transmission occurred only in infants born to HBsAg carrier mothers who were HBeAg-positive (92.6%) but not in those born to HBsAg carrier mothers who had no detectable HBeAg. This study suggests that preventive measures against HBV transmission during the perinatal period should be taken only for infants born to HBsAg carrier mothers who are HBeAg-positive. In addition, the active immune response to HBV was studied in 75 non-HBsAg carrier infants born to HBsAg carrier mothers by determination of anti-HBs at one year of age or older. Forty-three of these infants were treated with HBIG at birth and 32 infants received no treatment. It was found that infants born to HBsAg carrier mothers who were HBeAg-positive had a better active immune response (84.2% positive for anti-HBs) than infants born to HBsAg carrier mothers who had no detectable HBeAg or anti-HBe (14.3% and 20.4% positive for anti-HBs respectively).     

Detection of HBeAg and anti-HBe in acute hepatitis B by a sensitive radioimmunoassay

A solid-phase radioimmunoassay using anti-HBe-coated polysterene beads and iodine-¹²⁵-labeled anti-HBe of human origin was developed for the detection of HBeAg. Anti-HBe could be determined by a blocking test. Both assays were about 500-fold more sensitive than immunodiffusion. Few nonspecific positive results for HBeAg could be recognized in the anti-HBe test by increase in cpm over that of the negative control. HBeAg was not found in acute hepatitis A and non A-non B heptatis or in a control group of accident patients. On admission to the hospital 12 of 48 (25%) acute hepatitis B patients from Greece and 17 of 20 (85%) acute hepatitis B patients from Germany were HBeAg-positive. All 39 initially HBeAg negative sera were already anti-HBe positive. Tests of the acute stage and follow-up sera of the 20 German patients indicated that HBeAg is regularly present in the incubation period and early acute phase of hepatitis B. After onset of disease the antigen is cleared from the serum very rapidly in uncomplicated cases and is usually followed by the appearance of anti-HBe. Like anti-HBe, anti-HBe. can serve as a tool for the diagnosis of hepatitis B after the disappearance of HBsAg.     

Longitudinal study of hepatitis activity and viral replication before and after HBeAg seroconversion in chronic hepatitis B patients infected with genotypes B and C

The aims of this study were to compare chronic hepatitis B (CHB) patients with genotypes B and C for the probability of HBeAg seroconversion, hepatitis activity, and viral replication before and after HBeAg seroconversion and to compare the prevalence of core promoter and precore mutations. A total of 180 asymptomatic Chinese patients with CHB were monitored for a median of 53.8 months, and 38 patients with cirrhosis-related complications were studied. Hepatitis B virus (HBV) DNA levels were measured in 16 patients with HBeAg seroconversion at 3 months before, during, and 3 months after HBeAg seroconversion and in all patients at the last follow-up. Hepatitis B genotypes and core promoter and precore mutations were determined. Compared to patients with genotype C (n = 109), patients with subtype Ba (n = 69) had a higher rate of anti-HBe positivity on presentation (P = 0.05). HBeAg-positive patients with subtype Ba had a higher cumulative rate of HBeAg seroconversion than patients with genotype C (P = 0.02). However, there were no differences between the two groups with regard to the median HBV DNA levels before, during, and after HBeAg seroconversion; the probability of having persistently normal or elevated aminotransferase levels; and the median HBV DNA levels and liver biochemistry at the last follow-up. There was no difference in the prevalence of genotypes and core promoter and precore mutations between patients with and without cirrhosis-related complications. Though patients with subtype Ba had earlier HBeAg seroconversion, the liver biochemistry, HBV DNA levels in different phases of the disease, and the probability of development of cirrhosis-related complications were the same with genotypes Ba and C.     

Identification of different states of hepatitis B virus infection with a quantitative PCR assay

The level of hepatitis B virus (HBV) DNA in serum reflects the replicative activity of HBV. To compare serum HBV DNA levels in different states of hepatitis B, 47 sera of patients with HBeAg-positive chronic hepatitis B, 4 sera of patients with HBeAg-negative chronic hepatitis B, 40 samples of patients after HBeAg seroconversion during alpha interferon treatment, 57 sera of inactive HBsAg carriers, and 42 sera of patients who had recovered from chronic hepatitis B more than 12 months prior to blood collection were checked for the presence of HBV DNA with the Amplicor HBV Monitor Test. In patients with HBeAg-positive chronic hepatitis B, the median of serum HBV DNA levels (8.3 x 10(8) copies/ml) was significantly higher than that for patients after HBeAg seroconversion (6.2 x 10(3) copies/ml) and than that for inactive HBsAg carriers (5.6 x 10(3) copies/ml). None of the patients who had recovered from hepatitis B had detectable HBV DNA in serum. Quantitative PCR proved to be a valuable tool for identification of different states of HBV infection. This technique was found to be a good method for determination of serum HBV DNA levels both for patients with HBeAg seroconversion and for inactive carriers who showed low viremia not detectable by conventional hybridization assays.     

Conservation of precore and core sequences of hepatitis B virus in chronic viral carriers

Mutations in the precore region of hepatitis B virus (HBV) have been associated with failure of expression of HBV e-antigen (HBeAg), however, the prevalence of these and other mutations in HBV carriers without overt chronic liver disease remains uncertain. Homosexual or bisexual males (n = 65) with chronic HBV infection attending The Middlesex Hospital, London were studied, of whom two had clinical evidence of chronic liver disease. HBV DMA was amplified from 62 of 65 serum samples using nested and double nested polymerase chain reaction (PCR) assays. Direct sequencing of the PCR products was employed to investigate sequence variation. HBV-DNA from all available HBeAg-negative (n = 9) and selected HBeAg-positive (n = 33) sera were sequenced in the entire precore gene, the 3′ terminal portion of the X gene (aa128–154), and the 5′ terminus of the core gene (aa18–73). Sequences were highly conserved in all regions studied. Samples from two anti-HBe-seropositive patients contained mutations in the precore region. In one, a single mutation in the first amino acid resulted in a change to leucine, which would prevent translation of this region and therefore HBeAg expression. Wild type sequences were also detected in this sample. In the other sample from a patient with overt chronic liver disease, a mutation of precore amino acid 28 changed a tryptophan residue to a stop codon which would also prevent HBeAg expression. Although few such patients were studied, precore mutations may be uncommon in anti-HBe-seropositive patients without overt chronic liver disease. Possibly such mutations are not related to HBeAg to anti-HBe seroconversion, but rather they may arise in patients who remain anti-HBe seropositive for prolonged periods and they may be causally associated with the development of chronic liver disease. © 1994 Wiley-Liss, Inc.     

Semiquantitative anti-HBc IgM detection in children with chronic hepatitis B: A long-term follow-up study

Serum anti-HBc IgM titres were monitored monthly by a semiquantitative method in 14 children with HBeAg positive chronic hepatitis B followed up for 18-65 months. All patients, but one, were treated with alfa-interferon (IFN) at different times. On the whole, 12 flare-up episodes were observed and 7 patients cleared HBV-DNA and seroconverted to anti-HBe. Seroconversion occurred only in patients with pretreatment anti-HBc IgM index greater than 0.15 and serum HBV-DNA concentration below 100 pg/ml; the pretreatment alanine aminotransferase (ALT) value was not predictive of response. Combining anti-HBc IgM results and serum HBV-DNA levels observed during the pre-IFN period allowed a precise identification of patients who were likely to respond to IFN therapy. Patients who seroconverted to anti-HBe showed a progressive reduction in serum anti-HBc IgM titres within 6 months. Interestingly, one child, in whom HBV-DNA reappeared andwho reconverted to HBeAg 7 months after treatment, showed no anti-HBc IgM decrease afterthe transient clearance of HBV-DNA and anti-HBe seroconversion. Semiquantitative anti-HBcIgM detection is a useful tool in the decision making process for children with chronic hepatitis B. © 1995 Wiley-Liss, Inc.     

Hepatitis may precede the occurrence of precore region mutation in hepatitis B virus genome during infection in young carriers

To understand when the mutation with a stop codon of precore region in hepatitis B virus genome occurs, the prevalence of the mutation of viral DNA clones propagated from sera of school-age carriers was investigated with respect to hepatitis B e antigen (HBeAg)/anti-HBe and sequential changes of mutants along HBeAg seroconversion were analyzed. Of 32 carriers aged 8–18 years, 14 HBeAg(+) patients had 2.2% mutant clones, whereas 8 patients with low titer anti-HBe had a higher rate of 18.1% (P < 0.01) and the highest rate of 61.3% was found in 10 patients with high anti-HBe titer (P < 0.001). By contrast, the amount of viral DNA decresed significantly in patients with anti-HBe. Sequential analysis in six cases revealed three types of seroconversion with time difference of the emergence and increase of mutant clones. It is concluded that mutation occurs at a relatively young age and increases along time and/or HBeAg seroconversion. Hepatitis might precede or accelerate the emergence and increse of mutant population which might be predictive of sustained resolution of the disease.     

Small and large forms of hepatitis B e antigen in the serum: determination by two-site sandwich radioimmunoassay with monoclonal antibodies.

Serum samples containing hepatitis B e antigen (HBeAg) were subjected to electrophoresis in agarose, and fast-migrating 'small' HBeAg and slow-migrating 'large' IgG-associated HBeAg were pooled separately. HBeAg of each category was determined by a two-site radioimmunoassay that sandwiched HBeAg between monoclonal antibody (anti-HBe) against one epitope of HBeAg, fixed on a solid support, and anti-HBe against another epitope, labelled with radioiodine. Eighteen sera in which small HBeAg dominated revealed activities of hepatitis B surface antigen-associated DNA polymerase significantly higher than 14 sera in which large HBeAg dominated (logarithm of ct/min, mean +/- s.e. 3.36 +/- 0.08 versus 2.14 +/- 0.11, P less than 0.01). Shift from small HBeAg to large HBeAg was observed, along with the disappearance of DNA polymerase, in the serum from two carriers who seroconverted to anti-HBe.     

Enzyme-linked immunosorbent assay for detection of receptors for polymerized human serum albumin on hepatitis B surface antigen particles

An enzyme-linked immunosorbent assay (ELISA) was developed to detect the polymerized human serum albumin (pHSA) receptor on hepatitis B virus surface antigen (HBsAg) particles. The receptor values on particles from HBeAg-positive patients were significantly higher than those from anti-HBe-positive and HBeAg-, anti-HBe-negative patients. In patients' sera with moderate to high receptor values, there was significant correlation between the values obtained in the ELISA and serum DNA-polymerase activity (P less than 0.005), but not with HBeAg titer. During a 1-year follow-up of 47 HBeAg-positive patients with chronic hepatitis, termination of active viral replication, as evidenced by seroconversion from HBeAg to anti-HBe-positive, was observed in 1 of 26 with high initial receptor values, 2 of 12 with moderately high values and 6 of 9 with low receptor values. The results suggest that the ELISA described, which detects pHSA receptors on HBsAg particles, might be of value as a prognostic test in HBeAg-positive chronic hepatitis type B.     

Correlation between HBV DNA detection by polymerase chain reaction and Pre-S1 antigenemia in symptomatic and asymptomatic hepatitis B virus infections

The presence of hepatitis B virus (HBV) genome in sera from 73 symptomatic and asymptomatic HBsAg carriers was studied by the polymerase chain reaction (PCR) with primers specific for the S and C regions. Pre-S proteins of the HBV envelope were detected in serum by a specific monoclonal antibody in a double immunoradiometric assay. Out of twenty-five symptomatic patients with chronic active hepatitis (14 with HBeAg and 11 with anti-HBe), all were positive for HBV DNA by PCR, while 14/14 HBeAg and 2/11 (18%) of the anti-HBe patients were positive by dot blot hybridization. All but one anti-HBe patient (96%) carried Pre-S1 proteins. Among the asymptomatic HBsAg carriers, HBV DNA was detected by PCR in 14/14 (100%) HBeAg positive patients and in 25/34 (73%) anti-HBe positive patients. Pre-S1 proteins were found, respectively, in 14/14 (100%) and 11/22 (50%) of the same cases tested in parallel. The 20 healthy blood donors devoid of HBV markers and with normal transaminases tested were found negative for HBV DNA using PCR. Out of 12 patients who recovered from acute hepatitis B, all were found negative by PCR analysis after a mean follow up of 1 year after seroconversion to anti-HBs. When serial samples from 2 patients (one with acute hepatitis B, the other with chronic hepatitis B) were tested for the presence of HBV DNA and of Pre-S1 proteins, both markers showed parallel development.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoglobulin isotypes of anti-HBc and anti-HBe and hepatitis B virus (HBV) DNA elimination in acute hepatitis B

Antibodies to hepatitis B core antigen (anti-HBc) and e antigen (anti-HBe) were assayed in 46 sera from ten patients with acute hepatitis B utilizing immunoglobulin class- and subclass-specific enzyme immunoassays (EIAs). The sera were sampled 1 to 512 days after onset of hepatic symptoms. Four patients cleared HBsAg rapidly, within 24 days, and six patients cleared HBsAg slowly, within 27-74 days after the onset of symptoms. In three of the patients with rapid clearance of HBsAg, hepatitis B virus (HBV) DNA was not detected in sera tested during the first week after onset. The fourth patient was not tested until 12 days after onset and was then found to be negative for HBV DNA. In four of the patients with slow clearance of HBsAg, HBV DNA was present during the first week of illness. In the other two patients, HBV DNA was not detected in the first serum, 11 and 17 days after the onset of illness. Anti-HBc IgM and IgA1 were detected in all patients, with maximum titers shortly after onset. Anti-HBc IgG1 was present in all sera tested. Anti-HBc IgG2 was not detected in any of the sera. Anti-HBc IgG3 and IgG4 were detected in all patient sera, with IgG3 paralleling IgG1, and IgG4 mainly in sera long after onset. Anti-HBe IgG1, IgG3, and IgG4 were detected in three, two, and two patients, respectively. Anti-HBe IgG2, IgM, IgA1, or IgA2 was not found in any patient. The time required for maximum titer of anti-HBc IgG1 was shorter in the patients with rapid clearance of HBsAg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of hepatitis B virus-specific markers in asymptomatic hepatitis B surface antigen carriers.

A study was undertaken to assess the state of hepatitis B virus infection in a group of asymptomatic hepatitis B surface antigen (HBsAg) carriers. This study confirmed that the presence of hepatitis B e antigen (HBeAg) in serum was closely associated with serum HBsAg-specific deoxyribonucleic acid polymerase activity, hepatitis B core antigen (HBcAg) in serum and liver cell nuclei, and a histological picture of chronic hepatitis. No HBsAg-specific deoxyribonucleic acid polymerase activity or HBcAg was detected in highly concentrated anti-HBe-positive sera. In addition, liver biopsy specimens from carriers with anti-HBe were negative for HbcAg by immunofluorescence, and the liver histology was either normal or revealed only fatty changes. These data indicate that the anti-HBe-positive sera contained either no Dane particles or, if present, at least a 500-fold-lower concentration of Dane particles than that found in HBeAg-positive sera.     

Development and validation of a model for hepatitis B e antigen seroconversion in entecavir-treated patients with chronic hepatitis B

Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg-positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5-years ETV therapy in patients with CHB.