Multiple hepatitis virus infections in chronic HBsAg carriers in Naples

Summary.  In order to determine the prevalence of multiple infections with hepatitis viruses in chronic HBsAg carriers in Naples, to assess the interaction between HBV, HDV and HCV infections and to evaluate the influence of multiple virus hepatitis infections on the clinical presentation, we studied 198 HBsAg chronic carriers observed consecutively from 1971 to 1988 at our Liver Unit. Of the 198 HBsAg chronic carriers, 171 had undergone percutaneous liver biopsy. The presence of HBcAg or HDAg in the liver biopsy was considered a marker of HBV or HDV replication, respectively; the presence of anti-HCV was considered a marker of HCV infection. Anti-HCV was observed in 13.6% of the 22 subjects with normal liver, in 27.7% of the 47 patients with minimal chronic hepatitis, in 40% of the 50 with mild chronic hepatitis, in 70.6% of the 17 with moderate hepatitis, in 66.7% of the 3 with severe chronic hepatitis and in 65.6% of the 32 with active cirrhosis. Anti-HCV positive cases were antiHD positive more frequently than the anti-HCV negative (59.2% vs. 43%, p=0.05). HDV infection exerted a clear inhibition on the HBV genome. Among the 171 HBsAg chronic carriers, the finding of an active chronic hepatitis (moderate chronic hepatitis+severe chronic hepatitis+active cirrhosis) is less frequent in subjects with HBV replication alone than in those with HDV replication or HCV infection. Patients with both HBV replication and HCV infection and those with both HDV replication and HCV infection showed a very high prevelance of active chronic hepatitis.     

Differential effect of chronic hepatitis D virus infection on intrahepatic expression of hepatitis B viral antigen.

AIMS: To determine how chronic hepatitis D virus (HDV) infection affects intrahepatic hepatitis B virus (HBV) antigen expression. METHODS: Ninety eight liver biopsy specimens from 68 patients seropositive for total antibody to HDV were studied by immunohistochemistry, and the amount of HBV antigens was also quantified by radioimmunoassay in 12 patients and compared with 30 patients with chronic HBV infection. RESULTS: Forty nine of the 68 patients were positive for intrahepatic HDV antigen and only five were positive for HBV core antigen (HBcAg). HBV surface antigen (HBsAg) was present in 55 (80.9%) patients and was always cytoplasmic in distribution. Hepatic pre-S1 and pre-S2 expressions paralleled that of HBsAg, and were detected in 53 (77.9%) and 54 (79.4%) patients, respectively. There was no relation between the intrahepatic expression of HDV antigen and HBsAg/pre-S1/pre-S2. Follow up biopsy specimens in 25 patients showed either static or deteriorating histology while intrahepatic HDV antigen remained the same or fell. The patients with intrahepatic expression of HBcAg had either absent or noticeably decreased expression of HBcAg in their follow up biopsy specimens (median two years). In contrast, HBsAg/pre-S1/pre-S2 were the same or increased (p less than 0.001). Quantification of intrahepatic HBsAg in patients with chronic HDV infection (0.61 pg/hepatocyte, range: 0.05-1.08, n = 12) showed no difference with patients with chronic HBV infection alone (0.64 pg/hepatocyte, range: 0.02-1.02, n = 30, p = NS). CONCLUSION: These data indicate that chronic HDV infection suppresses intrahepatic expression of HBcAg but not HbsAg and pre-S antigens, suggesting a differential effect of chronic HDV infection on HBV gene expression.     

Hepatitis B virus antigens in liver resections from patients with hepatocellular carcinoma

A high rate of hepatitis B virus (HBV) antigen carriers among patients with hepatocellular carcinoma (HCC) has been recorded from areas of endemic HBV infections in Africa and Asia, but there are only rare and contradictory data for Europe. 12 specimens of resected liver tissue were immunohistologically investigated for hepatitis B surface antigen (HBsAg) as well as for hepatitis B core antigen (HBcAg). HBsAg was contained in non-tumorous liver tissue in 66 per cent of these cases. In two cases detection of HBcAg in the liver provided evidence to replication of the virus. HBcAg plus HBsAg were present in tumour tissue in one case. All of the HBV antigen carriers did not have chronic hepatitis. On the other hand, all patients with chronic hepatitis had HBV antigens in their liver tissue. HBV antigens were detectable in 7 non-cirrhotic livers, but were contained in only one of two cirrhotic livers. These results are likely to suggest a possible relevance of HBV infection to the aetiology of HCC even in central Europe without customary liver cirrhosis.     

Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C.

BACKGROUND: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy. OBJECTIVES: our aim was to evaluate the prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C. STUDY DESIGN: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were further studied histologically, with morphometric analyses and immunostaining techniques. Twenty-five were treated with alpha Interferon and ribavirin and followed for at least 18 months. RESULTS: HBV DNA was detected in 29.4% of liver tissue specimens and in only one (1.9%) serum sample. Three liver specimens were positive for surface gene, nine for core gene, three for both and none for the X gene. No significant difference in mean transaminase values, HCV viral titre, HCV genotype, or grading and staging and morphometric analysis was observed in patients with or without HBV DNA. Moreover, all 51 liver specimens were negative for both HBsAg and HBcAg. Sustained response to combination therapy was achieved in 40% of patients with and in 53% of patients without HBV DNA in the liver specimens (P=NS). CONCLUSIONS: HBV DNA is frequently found in the liver of patients with chronic hepatitis C. However, the lack of any significant impact on HCV viral titre, liver enzymes, histological parameters and response to therapy, suggests that in most cases HBV DNA detected in the liver by PCR may be either an integrated or low level replicative form.     

Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C

Although occult hepatitis B virus (HBV) infections in individuals without detectable hepatitis B surface antigen (HBsAg) may occur and have been reported to be common in patients with chronic hepatitis C, the clinical relevance remains controversial. We searched for serum HBV DNA in 210 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (110 patients with chronic hepatitis, 50 patients with cirrhosis, and 50 patients with hepatocellular carcinoma) by PCR. Most of the patients had detectable antibodies to HBsAg or HBV core antigen. All of the 110 chronic hepatitis C patients were treated with a combination therapy consisting of interferon plus ribavirin. In addition, 100 HBsAg-negative healthy adults served as controls. Thirty-one of the 210 patients (14.8%) had HBV DNA in their sera, as did 15 of the 100 healthy controls (15%). HBV DNA was not detected in the sera of those negative for serological markers of HBV infection. In patients with chronic HCV infection, the prevalence of occult HBV infection did not parallel the severity of liver disease (14.5% in patients with chronic hepatitis, 8% in patients with liver cirrhosis, and 22% in patients with hepatocellular carcinoma). In addition, the sustained response to combination therapy against hepatitis C was comparable between patients with and without occult HBV infection (38 versus 39%). In conclusion, these data suggest that occult HBV infection does not have clinical significance in chronic hepatitis C patients residing in areas where HBV infection is endemic.     

Occult hepatitis B virus and hepatitis C virus infections

Occult HBV infection is a well-recognised clinical entity characterised by the detection of HBV-DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). Occult HBV infection has been described not only in patients who have resolved an acute or chronic HBV infection but also in patients without any serological markers of a past HBV infection. Occult HBV infection in patients with chronic HCV infection may induce more severe liver disease and lower response rate to interferon treatment. The existence of occult HCV infections has been also reported more recently. Occult HCV infection is characterised by the presence of HCV-RNA in liver and peripheral blood mononuclear cells in the absence of detectable serum HCV-RNA. Occult HCV infection may occur under two different clinical situations: in hepatitis C antibody-(anti-HCV) negative and serum HCV-RNA-negative patients with abnormal liver function tests and in anti-HCV-positive patients who have no detectable serum HCV-RNA and who have normal liver enzymes. The clinical relevance of occult HCV infections is still under investigation.     

Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.     

Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease.

BACKGROUND: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known. METHODS: With the polymerase chain reaction, we searched for HBV DNA in liver and serum samples from 200 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). One hundred of the patients had detectable antibodies to the HBV core antigen (anti-HBc); 100 were negative for all HBV markers. Eighty-three were treated with interferon alfa. We also studied 50 patients with liver disease who were negative both for HBsAg and for HCV markers. In six patients found to have occult HBV infection, we evaluated possible genomic rearrangements through cloning or direct sequencing procedures. RESULTS: Sixty-six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C (14 percent, P=0.01). Among the 66 patients, 46 were anti-HBc-positive and 20 were negative for all HBV markers (P<0.001). Twenty-two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent, P=0.04). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective (P=0.06). None of the sequenced HBV genomes had changes known to interfere with viral activity and gene expression. CONCLUSIONS: Occult hepatitis B infection occurs frequently in patients with chronic hepatitis C liver disease and may have clinical significance.     

Prevalence of hepatitis B and hepatitis C virus coinfection in chronic liver disease

Coinfection with HBV and HCV may lead to serious consequences. The present study was done to find out the prevalence of coinfection in patients with chronic liver disease. From patients with hepatitis and chronic liver disease 1673 samples were received and analysed for HBsAg by ELISA. 1342 samples were analysed for anti HCV by third generation ELISA. 493 samples positive for HBsAg were also analysed for Anti HCV to see the prevalence of coinfection. 15(3.0%) were found positive for both HBsAg and anti HCV. Out of 15 patients with coinfection 4 (26.6%) had HCC. Prevalence of HCC in patients with coinfection was higher than either infection alone i.e. HBV-9.1% and HCV-16.5%.     

Prevalence of hepatitis B virus and hepatitis C virus in patients with human immunodeficiency virus infection in central China

Co-infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has an adverse effect on liver disease progression. This study investigated the prevalence of HBV and/or HCV co-infection in HIV-infected patients in Central China. A total of 978 HIV-infected patients from Hunan Province were enrolled. HBV serum markers, anti-hepatitis-C-virus antibody (anti-HCV), HBV DNA, and HBV genotypes were analyzed. The prevalence of hepatitis B surface antigen (HBsAg) and anti-HCV in HIV-infected patients was 19.4 % and 62.4 %, respectively. The prevalence of anti-HCV in HIV-positive intravenous drug users was 93.6 %. Among HBsAg-positive patients, 88.1 % were found to have at least one HBV serum marker. The rates of HIV mono-infection, HBV/HIV dual infection, HCV/HIV dual infection, and HBV/HCV/HIV triple infection were 30.4 %, 7.2 %, 50.2 %, and 12.2 %, respectively. Antibody to HBsAg (Anti-HBs) was more common in anti-HCV-positive than anti-HCV-negative patients (53.3 % vs 40.2 %, P = 0.000), but isolated hepatitis B core antibody (anti-HBc) was more common in anti-HCV-negative than anti-HCV-positive patients (24.2 % vs 12.3 %, P = 0.000). Hepatitis B e antigen (HBeAg) and sexual transmission were independent risk factors for active HBV replication. Intravenous drug use and male sex were independent risk factors, but old age and presence of HBeAg were independent protective factors for anti-HCV. Co-infection of HBV and/or HCV with HIV infection is common in central China. HCV status is associated with anti-HBs and isolated anti-HBc in co-infected patients.     

HBV抗原在乙型肝炎肝硬化患者脑组织中的表达及意义

目的 探讨惭型肝炎肝硬化患者脑组织中乙型肝炎病毒（HBV）感染的状况及意义。方法 应用免疫组织化学链霉菌亲生物素蛋白-过氧化物酶连接法（S-P法）对70例乙型肝炎肝硬化死亡患者脑组织进行了HBsAg、HBcAg检测，分析HBV抗原的表达与临床、病理的关系。结果 HBV抗原患者30例（42.89%)，其中HBsAg阳性24例（34.29%)，HBcAg阳性18例（25.71%)。抗原主要定位于细胞质，分布于神经元、神经胶质细胞及血管内皮细胞内，阳性细胞呈单个霰 在或灶性、小片状分布。HBV抗原的表达与血清HBV水平无关，而与肝性脑病（HE）的有无及HE患者脑组织病理损害的程度相关。结论 乙型肝炎肝硬化患者脑组织中存在HBV感染。并可能存在复制，脑组织中HBV感染，可能对乙型肝炎肝硬化患者HE的发生发展具有重要作用。     

Concurrent hepatitis C virus and hepatitis delta virus superinfection in patients with chronic hepatitis B virus infection.

Since hepatitis C virus (HCV) and hepatitis delta virus (HDV) are transmitted by the same routes as hepatitis B virus (HBV), simultaneous or concurrent HCV and HDV infection in patients with chronic HBV infection may occur. To test this hypothesis and to examine the clinicohistological and immunopathological presentations of such multiple hepatitis virus infections, acute and/or convalescent serum specimens from 86 patients with acute HDV superinfection were tested by enzyme immunoassay for antibodies to HCV. Of the 86 patients, 18 (20.9%) were associated with HCV infection. Although patients with early mortality cannot be evaluated by the HCV markers used in this study, the results showed that the clinical and histologic features were similar except that patients with HCV infection were older than those without HCV infection (P less than 0.01). Immunopathological studies carried out within 2 months after the onset of acute HDV superinfection demonstrated that hepatitis B core antigen (HBcAg) was not detected in any patient and HDV antigen was detected in 18.2% of the patients with HCV infection whereas HBcAg and HDAg were found in 7% and 65.1%, respectively, of those without HCV coinfection (P less than 0.02). It is concluded that concurrent HCV and HDV superinfections can and do occur in patients with chronic HBV infection. In these triple viral infections, HCV may even transiently suppress HDV and HBV.     

Hepatitis B-DNA replication and histological patterns in liver biopsy specimens of chronic HBsAg positive patients with and without hepatitis delta virus superinfection.

The role of active hepatitis B virus (HBV) infection in chronic HBsAg positive hepatitis with and without hepatitis delta virus (HDV) superinfection was analysed in percutaneous liver biopsy specimens from 50 patients. Each specimen was divided into two--one part for histological evaluation and for the detection of HBcAg and delta antigen; the other part was tested for HBV-DNA using Southern blotting. Ten cases were of chronic lobular hepatitis, 10 of chronic persistent hepatitis, and 30 of chronic active hepatitis. Ten cases were delta antigen positive and showed high grade lobular activity but no evidence of HBV-DNA episomal forms or HBcAg reactivity. Twenty one cases showed HBV-DNA replicative intermediate forms; 19 had high grade lobular activity, which occurred in five cases without evidence of free viral DNA. Of the 21 biopsy specimens with HBV-DNA episomal forms, 14 were positive for HBcAg; only one of the 19 cases without detectable viral DNA was positive for such antigen. These data indicate that the presence of HBV or HDV active infection correlates with the histological finding of prominent lobular necrosis. Moreover, intrahepatic HBV-DNA seems to be a more sensitive marker than the presence of viral antigens for indicating HBV replication.     

Flowcytometric quantitation of hepatitis B viral antigens in hepatocytes from regular and fine-needle biopsies

The aim of the study was to investigate the use of flow cytometry, as an alternative for immunohistochemistry, for the detection of viral antigens in the liver of patients with chronic hepatitis B virus (HBV) infection. Hepatocytes were obtained from regular- and fine-needle biopsy from HBV positive (n=17) and negative (n=7) patients and quantified by flow cytometry for intracellular hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). Number of HBsAg positive hepatocytes ranged from 0 to 83%. A significant correlation was found between the percentage of infected hepatocytes and the intracellular expression level of HBsAg (R=0.841, p<0.001). The specificity and sensitivity of flow cytometry was similar to immunohistochemistry. Of the patients on anti-viral treatment with undetectable serum HBV DNA (<400 copies/ml), two had high HBsAg expression in the liver. HBcAg staining was found in 3 out of 15 patients, with 2-3% positive hepatocytes. The results obtained with fine-needle aspiration biopsy (n=12) were comparable to regular biopsy. In conclusion, flowcytometric quantitation of HBV antigens is sensitive and provides relevant information on the course of infection. The minimally invasive fine-needle biopsy provides a useful alternative for regular-needle biopsy for monitoring intrahepatic antiviral responses during therapy.     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.     

Polymerase chain reaction detects hepatitis B virus DNA in paraffin-embedded liver tissue from patients sero- and histo-negative for active hepatitis B

Summary The polymerase chain reaction (PCR) was used to analyse tissues from paraffin blocks of liver needle biopsies retrospectively. Biopsies of 29 patients with proven HBsAg and HBcAg expression in liver tissue and of 8 healthy volunteers served as positive (group 1) and negative tissue controls (group 2), respectively. These were compared with 16 patients with proven HBsAg expression in liver but lack of HBcAg (group 3), with 23 patients with anti-HBc as the only hepatitis B virus (HBV)-related marker (group 4) and with 21 patients with liver disease and without HBV markers in tissue or serum (group 5). PCR detected HBV sequences in all cases of the positive control group and in 94% of group 3, in 65% of group 4, and in 71.4% of group 5, whereas all healthy volunteers were negative. Our data show that PCR is able to detect HBV-DNA sequences in virtually all patients with active viral antigen expression but also in a high proportion of hepatitic patients who are silent for active HB but may or may not show signs of a contact with the HBV. Thus, PCR for HBV-DNA in paraffin sections might become a useful tool for identifying patients carrying HBV-DNA but not expressing HBV antigens.     

Evaluation of the pre-S (pre-S(1)Ag/pre-S(2)Ab) system in hepatitis B virus infection.

The diagnostic and prognostic value of pre-S(1)Ag and pre-S(2)Ab was investigated in 69 HBsAg surface antigen positive patients--14 with acute hepatitis B, 30 with chronic liver disease (six chronic persistent hepatitis, 14 chronic active hepatitis, 10 with cirrhosis) and in 25 asymptomatic carriers. Pre-S(1)Ag was found in all patients with chronic hepatitis B virus (HBV) infection regardless of viral replication. In contrast, pre-S(2)Ab was not detected in any patients. Acute hepatitis was studied sequentially with periodic controls at 20 day intervals. Pre-S(1)Ag cleared before HBsAg in six of 14 (43%) patients who progressed favourably, and the two antigens cleared simultaneously in eight of 14 (57%) cases. Patients with early clearance of pre-S(1)Ag progressed favourably, thus indicating the prognostic value of this test, which, however, is still of limited practical application given the small temporal difference between the moment of clearance of the two antigens. The first markers to clear, however, were HBeAg and DNA-HBV, which showed significant differences with respect to the clearance of HBsAg. Moreover, pre-S(2)Ab appeared before HBsAb in 57.1% of our patients and was found in some patients before pre-S(1)Ag and HBsAg had cleared (42.8%), thus allowing complete viral clearance and acute HBV infection to be predicted earlier.     

In situ hybridization study of HBV DNA in chronic active hepatitis

Liver biopsies from 50 patients with chronic active hepatitis B were analysed immunohistochemically for HBcAg and HBsAg, and with in situ hybridization for HBV DNA. Double labelling technique for detecting HBV DNA and viral antigens simultaneously was also performed in some of these cases. The results showed that localization of HBV DNA in hepatocytes could be classified into whole cytoplasmic, submembranous, nucleic and intermembranous types. The last type suggests that HBV DNA might be transmitted directly to the adjacent hepatocytes through the cell membrane. By double labelling technique, it was disclosed that most hepatocytes with high level of HBV replication did not contain HBcAg or HBsAg. Conversely and most liver cells strongly positive for HBAg have low or negligible level of viral replication. Additionally, in a few cases, HBV DNA was found in the cytoplasm of bile ductule epithelia and sinusoidal endothelia.     

Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease

Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C virus (HCV)-infected patients and it increased with increasing severity of the liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was 16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone positive patients compared to only 7.1% in healthy controls who were also anti-HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with increasing severity of the liver disease, but this increase was only marginally significant and, perhaps, could have been significant if more patients were involved in the study. Although Lebanon is an area of low endemicity for both HBV and HCV, occult HBV infection is common in HCV-infected patients. The presence of HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV detection methods are not used.     

Significance of serum IgM anti-HBc in chronic hepatitis B virus infection.

Because of widely differing reports on the significance of IgM anti-HBc in chronic hepatitis B virus (HBV) infection, paired sera and liver biopsies from 49 patients with chronic HBV infection were analysed for serum IgM anti-HBc, HBsAg titre, HBeAg/anti-HBe, HBV DNA, serum aspartate transaminase, intrahepatic HBcAg expression, and liver histology. High levels of IgM anti-HBc, in the diagnostic range of acute hepatitis B (greater than 1.2), were detected in seven patients (14.3%) and a total of 34 patients (69.6%) had an index of more than 0.2. No correlation was found between IgM anti-HBc and the serum markers of active viral replication or HBsAg titre but it correlated significantly with intrahepatic expression of cytoplasmic HBcAg (r2 = 0.165, P = 0.002). IgM anti-HBc also correlated with active liver histology (P = 0.015) but there was a considerable overlap of the IgM anti-HBc index values between the various disease groups, indicating a poor specificity. Serial assessment of IgM anti-HBc in eight patients treated with interferon-alpha (four responders) showed an increase in IgM anti-HBc in three out of four patients corresponding to the e-seroconversion period followed by a drop in IgM anti-HBc levels. However, an increase in IgM anti-HBc was also seen in one non-responder, indicating that this feature is not unique to interferon-alpha responders. These data indicate that serum IgM anti-HBc cannot be used alone as a certain diagnostic measure of HBV replication nor in the prediction of liver histology.