IgM antibody to hepatitis B core antigen in Korean patients with hepatocellular carcinoma

Primary hepatocellular carcinoma (PHC) has been linked etiologically to persistent hepatitis B virus (HBV) infections by epidemiologic, serologic and molecular lines of evidence. To evaluate the frequency of IgM antibody to the viral core antigen (IgM anti-HBc) detected by a highly sensitive radioimmunoassay, we compared 110 Korean patients with PHC to a group of 63 age- and sex-matched control patients with other tumors. Results were correlated with those of commercially available HBV assays. IgM anti-HBc was found in 74 of 110 PHC patients (67%), but only 1 of 63 (1.6%) control patients. Although HBsAg was found in a larger percentage of PHC patients (81%), it was also present in more control patients (14%). Thus, IgM anti-HBc was more specifically associated with PHC than was the presence of HBsAg. IgM anti-HBc was found in 91% of PHC patients with detectable HBeAg and 74% of PHC patients with positive anti-HBe tests (p less than 0.04). The frequency of IgM anti-HBc was similar among HBsAg-positive PHC patients with and without anti-HBs, or those with low or high levels of serum alpha-fetoprotein. In 18 patients with PHC, IgM anti-HBc was further characterized by rate-zonal centrifugation of sera, all were found to have 19S IgM anti-HBc although 6 also had greater or equal IgM anti-HBc reactivity in the low molecular weight region. The presence of IgM anti-HBc in adult Korean HBsAg carriers may indicate an especially high risk for the development of PHC, and this should be evaluated in prospective studies.     

Serologic markers of hepatitis B virus (HBV) and hepatitis D virus infection in carriers of hepatitis B surface antigen who are frequently exposed to HBV

Serum hepatitis B e antigen (HBeAg) and HBV DNA are indicators of active replication of HBV, whereas IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to chronic HBV infection. Fifty-eight carriers of hepatitis B surface antigen (HBsAg) who had frequent parenteral exposures were studied for the presence of HBeAg, HBV DNA, IgM anti-HBc and hepatitis delta virus (HDV) serologic markers. Active replication of HBV was detected in 36.2% (25% of drug addicts, 16.7% of thalassemia patients, and 46.9% of hemodialysis patients) and seropositivity for IgM anti-HBc in 55.2% of the HBsAg carriers. Among the 39 HBsAg carriers who were negative for HBeAg, IgM anti-HBc was detected significantly more frequently than HBV DNA (46.1% vs. 5.1%, p less than 0.001). Serologic evidence of HDV infection was detected in 35% of drug addicts, 50% of thalassemia patients and in 9.4% of hemodialysis patients. These data revealed that continued replication of HBV was more frequent in hemodialysis patients than in drug addicts and thalassemia patients who are HBsAg carriers and the opposite was true for the prevalence of HDV infection.     

Significance of IgM antibody to hepatitis B core antigen in a Greek population with chronic hepatitis B virus infection

IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti-HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti-HBc was detected more frequently than HBV DNA in this population (50% vs 34, p less than 0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti-HBe) (48% vs 22%, p less than 0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti-HBc in 64% of the cases (p less than 0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti-HBc and HBV DNA than in patients positive only for HBV DNA (p less than 0.001) irrespective of their HBeAg or anti-HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.     

Fluctuations in viremia,aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations

We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg+) followed up for 12–20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase→ALT flare→IgM anti-HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV-DNA baseline levels before flares were lower in anti-HBe+ (3.9±1.2 pg/ml) than in HBeAg+ patients (35.3±5.4 pg/ml) (p<0.0001) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations (p< 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV-DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B.     

Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.     

A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.     

A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years.

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.     

Hepatitis B virus DNA in hepatitis B surface antigen-positive blood donors: relation to the hepatitis B e system and outcome in recipients

The presence of hepatitis B virus (HBV) DNA was investigated in 26 hepatitis B surface antigen-positive blood donors. Three donors (12%) were concordantly positive for HBV DNA and hepatitis B e antigen (HBeAg) and had IgM antibody to hepatitis B core antigen (anti-HBc). Two donors (8%) had HBV DNA without HBeAg; both were positive for antibody to HBeAg and lacked IgM anti-HBc. Twenty-one HBV DNA-negative donors had antibody to HBeAg, and all were negative for HBeAg and IgM anti-HBc. Blood units from 16 donors were transfused. A sufficient serological and clinical follow-up was available for 10 HBV-susceptible recipients. Three recipients of HBV DNA-positive blood units were infected irrespective of HBeAg status or presence of IgM anti-HBc. Six (86%) of seven recipients of HBV DNA-negative blood units developed HBV infection. Thus all hepatitis B surface antigen-positive blood donors should still be considered infectious irrespective of status with regard to HBeAg, HBV DNA, and IgM anti-HBc.     

Hepatitis B virus (HBV) markers and HBV-DNA in serum and liver tissue of patients with acute exacerbation of chronic type B hepatitis

We analysed the serum samples and the liver biopsies of six consecutive chronic HBsAg/anti-HBe carriers admitted to hospital because of an episode of acute hepatitis. The six patients became positive for IgM anti-HBc and negative for HBeAg, hepatitis Delta virus (HDV) markers, IgM anti-hepatitis A virus (HAV), anti-cytomegalovirus (CMV) and anti-Epstein-Barr virus (EBV). Two patients showed positivity for hepatitis B virus (HBV)-DNA in serum obtained on admission, with no positivity in the subsequent weeks; the results of the other four patients were always negative for seric HBV-DNA. The Southern-blot analysis of the DNA extracted from the liver tissue of four subjects showed the presence of HBV-DNA in the form of replicative intermediates; focal positivity of HBcAg was detected in the liver of only one. The liver biopsies of the last two patients were negative for HBV-DNA and for HBcAg. The analysis of HBV-DNA in the liver extracts and the demonstration of an increase of the IgM anti-HBc titre at the time of the abrupt elevation of the aminotransferase levels seem to be the most useful tools in revealing HBV activation as a cause of acute hepatitis in chronic HBsAg carriers, overall when the phase of viremia is transient.     

Replication of hepatitis B virus in adult carriers in an endemic area

We have examined serological markers of replicative and nonreplicative infection in 124 adult, black South African carriers of hepatitis B virus (HBV), in whom this infection is predominantly acquired in early childhood. The mean age of the group was 36 years. Antibody to hepatitis B e antigen (anti-HBe) was present in the serum of 93.5% of these carriers. Only 25.8% of the carriers were positive for HBV DNA in serum, and in the majority of these only trace amounts were detectable. IgM antibody to hepatitis B core antigen (IgM anti-HBc) was negative in 54% of the carriers, and only 26% had IgM anti-HBc in high titer. A significantly greater proportion of carriers who were positive for anti-HBe were positive for IgM anti-HBc (43.1%) than were positive for HBV DNA (24.5%). Serum aminotransferases were less than twofold elevated in 90.3% of the carriers. Only one carrier has thus far developed hepatocellular carcinoma. These results suggest that there is an inexorable progression to predominantly nonreplicative infection in the majority of southern African adult, black carriers, an occurrence that may take several decades. In areas endemic for HBV infection, antiviral agents effective against replicative HBV will have to be administered in childhood.     

Studies of HBV replication during acute hepatitis followed by recovery and acute hepatitis progressing to chronic disease

The serologic and viral profiles of 24 patients who presented with acute hepatitis B virus (HBV) infection were studied. Although in rare cases, HBV-DNA was detectable before hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), in the majority the viral proteins appeared first. In acute hepatitis followed by recovery, as IgM anti-HBc (hepatitis B core antigen) titres rose, the level of HBV replication fell and serum transaminases became elevated. In patients progressing to chronic HBV infection, IgM anti-HBc titres rose early, viral replication was initially low but continued to rise as the serum transaminase levels became elevated. 7S IgM anti-HBc, although present in the phase of established chronic HBV infection, was not found in the early phase of the chronic infection. Thus this antibody appears to be a consequence of, rather than a causative factor in, chronic HBV infection.     

Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection

OBJECTIVES: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single baseline serum HBV DNA measurement by a quantitative polymerase chain reaction (PCR) assay in this setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. RESULTS: HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000 copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it was <30,000 copies/ml in all inactive carriers (undetectable in 14). In particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000 copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or 100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg-negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed better by correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels evaluated by sensitive quantitative PCR assays can be used for differentiation between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface antigen carrier state, but the cut-off level should be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.     

Are alanine aminotransferase,hepatitis B virus DNA or IgM antibody to hepatitis B core antigen serum levels predictors of histological grading in chronic hepatitis B?

Abstract: Paired sera and liver biopsies from 105 patients with chronic hepatitis B virus infection (34 HBeAg positive and 71 anti-HBe positive) were studied to investigate the relation between the degree of histological activity and alanine aminotransferase (ALT), hepatitis B virus DNA (HBV-DNA) or IgM antibody to hepatitis B core antigen (IgM anti-HBc) levels. ALT levels were significantly higher in patients with piecemeal necrosis (155±124 vs 75±42, p=0.0017), but there were no differences in the ALT values of patients with or without intralobular necrosis. ALT values were within normal range in 29% of 31 patients without versus 15% of 65 with piecemeal necrosis (p=0.19). Serum HBV-DNA levels were not related to the grade of lobular or portal/periportal activity in HBeAg-positive patients. Anti-HBe-positive subjects with piecemeal necrosis had higher HBV-DNA levels (34±93 vs 4±6, p=0.01). IgM anti-HBc indexes were significantly higher in patients with intralobular necrosis (0.635±0.600 vs 0.356±0.367, p=0.0005) or piecemeal necrosis (0.671 ±0.633 vs 0.321 ±0.219, p=0.0002). In summary, since serum IgM anti-HBc-IMx indexes can reflect the grade of histological activity, the quantitative assessement of this antibody could be useful for non-invasive monitoring of hepatocellular damage in chronic hepatitis B.     

Anti-HBc of IgM-class,HBeAg and anti-HBe in acute and chronic hepatitis B

ABSTRACT— The presence and persistence of IgM antibody against hepatitis B core antigen (anti-HBc IgM) and the correlation with other HBV markers were studied in 42 patients, all of whom had acute HBsAg-positive hepatitis but whose subsequent diseases differed. All patients initially had anti-HBc IgM. In 13 out of 15 patients with uncomplicated acute hepatitis, anti-HBc IgM disappeared within 6 months after onset of the disease. In five out of 12 patients, who in spite of transient HBsAg developed chronic liver disease, the anti-HBc IgM persisted for more than 2 years. Among 15 patients with persistent HBsAg, anti-HBc IgM was present from 7 months to more than 8 years. Seroconversion from HBeAg to anti-HBe was observed in seven patients and in five of these anti-HBc IgM disappeared during the follow-up period. These results indicate that anti-HBc IgM can be used as a serological marker of recent or ongoing HBV infection.     

Is anti-HBc IgM a useful clinical test in patients with HBsAg-positive chronic hepatitis or primary hepatocellular carcinoma?

Seventy HBsAg-positive patients, including 24 with primary hepatocellular carcinoma, 34 with chronic active hepatitis, 12 with chronic persistent hepatitis and 30 asymptomatic healthy hepatitis B virus carriers were tested for anti-HBc IgM using the Corzyme-M test. Anti-HBc IgM was detected in 50% of the primary hepatocellular carcinoma patients, 26.5% of the chronic active hepatitis patients, 25% of the chronic persistent hepatitis patients, but in none of the healthy hepatitis B virus carriers. There was no correlation between the presence of anti-HBc IgM and HBeAg, hepatitis B virus DNA, ALT or alpha-fetoprotein levels in either the chronic active hepatitis or chronic persistent hepatitis patients. However, a significantly higher positive rate of anti-HBc IgM was noted in the HBeAg-positive or HBV DNA-positive primary hepatocellular carcinoma patients than in those with negative markers of viral replication, but no correlation was noted between the presence of anti-HBc IgM and serum ALT or alpha-fetoprotein levels in these primary hepatocellular carcinoma patients. Also, no differences in positivity for HBeAg, HBV DNA or levels of serum ALT were noted when patients with high titers of anti-HBc IgM were compared to those with low titers. Thus, anti-HBc IgM cannot distinguish between HBsAg-positive patients with chronic active hepatitis, chronic persistent hepatitis or primary hepatocellular carcinoma, does not correlate with serum ALT or alpha-fetoprotein levels and is only associated with markers for viral replication in primary hepatocellular carcinoma patients. Based on this, anti-HBc IgM appears to have a limited usefulness for diagnosis of either chronic hepatitis B or primary hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

19S and 7-8S forms of IgM antibody to hepatitis B core antigen in acute icteric hepatitis superimposed on hepatitis B surface antigen carriage

Summary The 19S and 7-8S forms of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were separated by rate-zonal centrifugation from the serum of 20 Greek hepatitis B surface antigen (HBsAg) carriers with a superimposed acute icteric hepatitis positive for IgM anti-HBc by a radioimmunoassay. Serological markers of hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections were detected with radioimmunoassays and serum HBV DNA was detected with molecular hybridization techniques. Eighteen of the 20 carriers showed a predominance of one or the other form of IgM anti-HBc. Low molecular weight (7-8S) IgM anti-HBc was observed more frequently in HDV superinfection (5/9) and was related to a low mortality (1/9). In contrast, 19S IgM anti-HBc was observed more frequently in reactivation of chronic hepatitis B (6/9) and was related to a high mortality (5/9). These preliminary data show that in HBsAg carriers with a superimposed acute icteric hepatitis, predominance of 19S IgM anti-HBc is frequently associated with a severe clinical course; the opposite is true for predominance of 7-8S IgM anti-HBc.

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19S und 7-8S IgM-Antikörper gegen Hepatitis B Virus Core-Antigen bei Hepatitis B Virus Oberflächenantigen-Trägern mit akuter ikterischer Hepatitis

Zusammenfassung Aus dem Serum von 20 griechischen HBsAg-Trägern mit akuter ikterischer Hepatitis wurden mittels Radioimmunassay anti-HBc IgM-Antikörper nachgewiesen; diese Antikörper wurden durch Gradientenzentrifugierung in 19S- und 7-8S-Formen aufgetrennt. Der Nachweis der serologischen Marker für Hepatitis A Virus (HAV), Hepatitis B Virus (HBV) und Hepatitis D Virus (HDV) erfolgte mit Radioimmunassays; HBV DNA wurde durch molekulare Hybridisierung nachgewiesen. Bei 18 der 20 Carrier überwog die eine oder andere Form des anti-HBc IgM. Anti-HBc IgM mit niederem Molekulargewicht (7-8S) fand sich häufiger bei HDV Superinfektion (5/9), wobei ein Patient dieser Gruppe verstarb. Bei reaktivierter chronischer Hepatitis überwog die 19S-Form des anti-HBc IgM (6/9); die Sterblichkeit war mit 5/9 hoch. Diese vorläufigen Ergebnisse weisen darauf hin, daß ein Überwiegen der 19S-Form des anti-HBc IgM bei akuter ikterischer Hepatitis, die sich auf chronisches HBsAg Trägertum aufpfropft, häufig mit einem schweren klinischen Verlauf einhergeht, im Gegensatz zu Fällen, bei denen die 7-8S-Form des anti-HBc IgM überwiegt.

     

Diagnosis and management of pre-core mutant chronic hepatitis B

Chronic hepatitis due to pre-core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with pre-core stop codon mutation at nucleotide 1896 (mainly selected in non-A HBV genotypes), but also with other pre-core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre-core mutants can be detected both in patients with HBeAg-negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV-DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow-up of aminotransferase activity and viraemia levels, although the cut-off level of serum HBV DNA has not been definitely determined. IgM anti-HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon-alpha (IFN-alpha) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg-negative CHB. A 12-month course of IFN-alpha achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long-term outcome of this subset. A 12-month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long-term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30% of patients remaining in remission in the third year of therapy. Several other antiviral agents are currently being evaluated in this setting with combined regimens being the most reasonable step for the near future.     

Hepatitis B virus markers in the population of Dar es Salaam, Tanzania

A total of 542 serum samples from healthy adults (medical students and medical staff, blood donors and pregnant women) residing in or near the city of Dar es Salaam, Tanzania were examined for markers of hepatitis B virus (HBV) infection. Of these samples, 95 (17.5%) were not found to contain any HBV marker when examined by enzyme-linked immunoassay for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). HBsAg was demonstrated in 52 (9.6%) samples of which 7 (13.5%) were positive for hepatitis Be antigen (HBeAg) and 17 (32.7%) were positive for anti-HBc IgM. None of 9 HBsAg positive pregnant women were carriers of HBeAg. These results show that hepatitis B infection is very common in this country. The relatively low prevalence of HBeAg among HBsAg carriers may indicate that transmission of hepatitis B at birth is not of major importance.     

乙型肝炎病毒e抗原阳性慢性乙型肝炎病毒感染者5年随访结果

目的 了解HBeAg阳性慢性HBV感染者的转归情况.方法 对168例HBeAg阳性慢性HBV感染者进行为期5年的临床症状、肝组织活检及血清学检查的动态观察研究,率的比较采用χ~2检验.结果 在5年随访期间.168例HBeAg阳性慢性HBV感染者中有23例出现乙型肝炎活动,占13.7%,其中肝脏病理有明显炎性反应(≥G2)者乙型肝炎活动率为24.1%(21/87例),而原肝组织炎症活动度分级为G0～G1者活动率为2.5%(2/81例),两者比较差异有统计学意义(X~2=14.88,P<0.01).43例感染者行2次肝组织活检,原肝组织正常者几年内相对稳定,病理很少变化,原病理炎性反应较重者不易恢复,但可在小范围内波动.45例发生HBeAg血清转换,HBeAg年转阴率为5.4%.14例HBsAg转阴,年转阴率为1.67%.结论 HBeAg阳性慢性HBV感染者乙型肝炎活动与肝脏炎症活动度分级密切相关.     

Chronic carriers of hepatitis B virus in Bangladesh: a comparative analysis of HBV-DNA,HBeAg/anti-HBe,and liver function tests

Serological markers of hepatitis B virus (HBV), liver function tests and quantitative estimation of HBV-DNA are important in the assessment of the state of infection and prognosis following treatment for hepatitis B. This study aimed to determine whether low-cost assays, eg hepatitis B e antigen (HBeAg) and liver function tests, could be used for the assessment of infectivity as an alternative to HBV-DNA estimation. We tested 125 hepatitis B carriers for HBeAg, antibody to HBeAg (anti-HBe), and serum HBV-DNA; we also carried out a range of standard liver function tests. Seventy-three subjects were positive and 52 were negative for HBeAg. Of the HBeAg positive cases, 3 were also positive for anti-HBe; of the HBeAg negative cases, 5 were also negative for anti-HBe. Of these 8 cases, 7 had no detectable HBV-DNA. Most of the HBeAg positive but anti-HBe negative subjects were positive for HBV-DNA (74.3%; 52/ 70) whereas most of the HBeAg negative and anti-HBe positive subjects (93.6%; 44/47) were also negative for HBV-DNA. Of 56 HBV-DNA positive individuals, alanine transaminase (ALT) was found to be raised in 69.6% (p=0.066) and aspartate transaminase (AST) was raised in 66.1% (p=0.011), while 67.9% had normal alkaline phosphatase (ALP) (p=0.054). HBeAg (p=0.018) and raised ALT (p=0.008) were found to be independent predictors for HBV-DNA positivity among HBV carriers. This study suggests that HBeAg positive and anti-HBe negative hepatitis B carriers with raised ALT and AST are likely to be positive for HBV-DNA; the combination of routine serology and biochemical tests may be considered as an alternative to HBV-DNA in evaluating the state of chronic HBV infection. However, HBV-DNA should be specifically assessed if discordance is observed between seromarkers and transaminases.