Biomedical subjects

C M Chu

Publications and source records attributed to C M Chu.

At least 73 records · Page 4Linked to original sources

PubMed1997

Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers.

The authors conducted a study to assess the importance of underlying liver cirrhosis in the development of hepatocellular carcinoma (HCC) and the multifactorial etiology of liver cirrhosis in chronic carriers of hepatitis B virus (HBV). Between November 1980 and May 1990, all male hepatitis B surface antigen (HBsAg) carriers who routinely attended a clinic for asymptomatic HBV carriers at the Liver Unit of Chang-Gung Memorial Hospital, Taiwan, were enrolled in the study (n = 1,506). The authors used this cohort to investigate prospectively for liver cirrhosis and HCC at 6-month intervals by means of ultrasonography and clinical assessment. There were 16 incident cases of HCC and 89 cases of liver cirrhosis (78 of whom were detected during follow-up) identified after an average follow-up of 7.1 years. Subclinical liver cirrhosis diagnosed by ultrasonography was significantly associated with the risk for HCC (multivariate-adjusted relative risk (RR) = 11.8, 95% confidence interval (CI) 3.9-35.8). By multivariate analysis, the significant risk factors found for liver cirrhosis in HBsAg carriers were age, hepatitis B e antigen (HBeAg) carrier status, chronic hepatitis manifested by sustained elevated serum aminotransferase levels for > or = 6 months, cigarette smoking, non-A blood types, and low educational levels. Habitual alcohol drinking was not independently related to liver cirrhosis. However, the risk of liver cirrhosis associated with smoking was more striking among drinkers than nondrinkers (> or = 20 cigarettes/day vs. nonsmokers: drinkers, RR = 9.3, 95% CI 1.1-78.8; nondrinkers, RR = 1.85, 95% CI 0.98-3.51), which suggests a possible modification effect of alcohol drinking on the liver cirrhosis risk of cigarette smoking. The authors observed synergistic effects on liver cirrhosis development for cigarette smoking with HBeAg carrier status and chronic hepatitis.

Adult↗

PubMed1997

Quantitative assessment of hepatitis C virus RNA by polymerase chain reaction and a digoxigenin detection system: comparison with branched DNA assay.

A method for quantifying hepatitis C virus (HCV) RNA in serum using reverse transcription-polymerase chain reaction (RT-PCR) followed by slot-blot hybridization with a specific, digoxigenin-labeled probe was developed. Using RNA synthesized from cloned HCV cDNA as a standard, serum concentration of HCV RNA above 10 copies/ml can be quantitatively determined. To compare this method with branched DNA (bDNA) assay, 45 serum samples from 26 patients with newly acquired acute hepatitis C (n = 16) or hepatitis C with acute exacerbation (n = 10) were submitted to both assays. HCV RNA in 30 (67%), 12 (27%) and three (6.7%) samples can be quantitatively determined by both, either and none of the two assays, respectively. Using a standardized qualitative HCV RNA detection test (Amplicor HCV test) as a reference, 1 and 0 false positive results were found by bDNA and this assay, respectively. This quantitative assay using RT-PCR and a digoxigenin detection system was comparable to bDNA assay. Since a false positive result was rarely found, this technique can be used as a first line test to screen a large number of samples rapidly and economically.

Acute Disease↗

PubMed1997

Response of patients with dual hepatitis B virus and C virus infection to interferon therapy.

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.

Adult↗

PubMed1997

Molecular cloning of a defective hepatitis C virus genome from the ascitic fluid of a patient with hepatocellular carcinoma.

A defective hepatitis C virus (HCV) genome in the ascitic fluid of a patient with hepatocellular carcinoma was cloned and sequenced up to the 3' poly(U) stretch. When compared with the published Taiwanese HCV sequence, this defective genome contained deletions of single nucleotides at eight sites, double nucleotides at two sites, triple nucleotides at four sites, quadruple nucleotides at one site and replacement of a short stretch of sequence at one site. For comparison, the corresponding regions containing these mutations were also cloned from a serum sample from this patient. Except for deletions of two triple nucleotides in the hypervariable region, the reading frames of all serum-derived clones were intact. The defective HCV genome encoded a truncated core protein with 90 amino acid residues (the last 20 amino acid residues came from a different reading frame), whereas the serum-derived genome encoded a full-length core protein. When expressed in Huh-7 cells, these two proteins were localized to the nucleus and cytoplasm, respectively. Using specific primer-sets, ascites- and serum-derived genomes were each detected alone in ascitic fluid and serum samples, respectively, whereas both sequences were present in ascitic mononuclear cells. The defective sequence thus constituted the major virus population in the ascitic fluid whereas a putative helper genome coexisted with it inside the ascitic mononuclear cells. This sequence is possibly a defective and interfering genome.

Amino Acid Sequence↗

PubMed1997

Natural history of chronic hepatitis B virus infection: an immunopathological study.

Three clinicopathological phases of chronic hepatitis B virus (HBV) infection are identified. First, is immune tolerance of HBV. High levels of viraemia are associated with normal alanine aminotransferase (ALT) levels and minimal histological lesions. More than 30-40% of hepatocytes have the hepatitis B core antigen (HBcAg), predominantly in their nuclei. Maternally derived hepatitis B e antigen (HBeAg) crossing the placenta may result in the elimination of T helper cells responsive to HBeAg/HBcAg. This phase can last for periods ranging from a few weeks to 10 or more years until the immune tolerance is lost. Second, is the immune clearance of HBV. Intermediate levels of viraemia are associated with fluctuating ALT levels and active and ongoing hepatitis. Approximately 20-30% of hepatocytes have HBcAg, predominantly in their cytoplasm. Expression of pre-core defective HBV mutants during chronic HBV infection may lead to a reduction in the secretion of HBeAg and may trigger the beginning of the immuno-elimination phase. The mechanism of intrahepatic shift of HBcAg from the nucleus to the cytoplasm and the decreased levels of viraemia in this phase may be, at least in part, secondary to liver damage and regeneration. Third, is latent infection with residual integrated HBV. Undetectable viraemia is associated with normal ALT levels and no virus-induced liver damage. With regard to hepatocyte expression of HBsAg in chronic HBV infection, membrane staining of HBsAg on hepatocytes has been shown to correlate well with the presence of viraemia. The degree of cytoplasmic hepatitis B surface antigen (HBsAg) expression inversely correlates with the level of viraemia. Therefore, HBsAg carriers with high levels of viraemia have low levels of cytoplasmic hepatitis B surface antigen (HBsAg) expression, while those with low levels of viraemia have high levels of cytoplasmic HBsAg expression. However, several exceptions have been identified. High levels of viraemia associated with high levels of cytoplasmic HBsAg expression were recognized in patients with fibrosing cholestatic hepatitis. In contrast, low levels of viraemia associated with low levels of cytoplasmic HBsAg expression were recognized in patients with hepatitis C virus but not hepatitis D virus superinfection.

Cell Cycle↗

PubMed1997

The degrees of hepatocyte nuclear but not cytoplasmic expression of hepatitis B core antigen reflect the level of viral replication in chronic hepatitis B virus infection.

Although immunodetection of hepatitis B core antigen (HBcAg) in the liver has long been recognized as a marker of active hepatitis B virus (HBV) replication, the correlation between the level of viral replication and the degrees of expression of HBcAg in hepatocytes remains to be established. In this study, we examined the semiquantitative relationship between the level of HBV DNA in serum and the degree of expression of HBcAg in the hepatocyte nucleus or cytoplasm in 80 adults with chronic hepatitis B. Expression of HBcAg in hepatocytes was studied by the avidin-biotin immunoperoxidase method, and the results were scored on a scale of 0 to 4, values corresponding to the positivity of 0, 1 to 10, 11 to 25, 26 to 50, and > 50%, respectively, of hepatocytes examined. Serum HBV DNA was tested by a liquid hybridization assay, and the results were scored on a scale of 0 to 5, values corresponding to undetectable levels and levels of < or = 50, 51 to 100, 101 to 150, 151 to 200, and > 200 pg/ml, respectively. The results revealed a highly significant, positive correlation between the level of HBV DNA in serum and the degree of expression of HBcAg in nuclei (Spearman rank correlation coefficient [rs] = 0.653, P < 0.001). The mean scores (95% confidence intervals) of levels of HBV DNA in sera of patients whose levels of expression of HBcAg in nuclei received a score of 0 (n = 33), 1 or 2 (n = 35), and 3 or 4 (n = 12) were 1.3 (1.1 to 1.5), 2.5 (2.1 to 2.9), and 3.9 (3.1 to 4.7), respectively. However, no correlation between the level of HBV DNA in serum and the degree of expression of HBcAg in the cytoplasm was noted (rs = 0.026, P > 0.8). In conclusion, the degree of expression of HBcAg in the hepatocyte nucleus but not the cytoplasm can accurately reflect the level of viral replication in patients with chronic hepatitis B.

Adult↗

PubMed1996

Distinct composition of viral quasispecies between ascites and serum samples from patients with late stage chronic hepatitis C.

By performing single-strand conformation polymorphism and PCR-cloning followed by sequencing, the amino acid composition of hepatitis C virus hypervariable and variable regions were analyzed in ascites and serum samples from two patients with late stage chronic hepatitis C. In patient-LC, the major ascitic clone was constituted by a minor serum-derived clone, while the major serum derived clone was absent in the ascites. In patient-HCC, the major ascitic clone was defective and genetically different from all the serum-derived clones. In addition, anti-genomic HCV RNA was detected in the ascitic mononuclear cells from patient-LC. These results argued that the peritoneal cavity served as a relatively isolated environment for evolution of distinct composition of viral quasispecies.

Aged↗

PubMed1996

Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.

In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.

Adult↗

PubMed1996

Characterization of nuclear localization of a hepatitis B virus precore protein derivative P22.

Both of hepatitis B virus core protein and a precore protein derivative, named P22, have been shown to localize in the nucleus. Although P22 has ten additional amino acid residues at its amino-terminus, both proteins contain the same nuclear localization signal. In order to understand the mechanism that regulates the activity of this signal, we have studied the nuclear localization of P22 and compared it with that of core protein. It was found that both cytosolic and nuclear fractions of P22 were phosphorylated but to a lesser extent when compared with cytosolic core protein. This distinction was likely attributed to different conformations between these two proteins since the density gradient analysis revealed a different particle formation for P22 in the cytosol. When expressed in Vero cells synchronized by serum deprivation, P22 remained in the cytosol during G0 and G1 phases, accumulated gradually in the nucleus during S phase, and largely localized in the nucleus when cells were confluent. On the other hand, the core protein was transported into the nucleus during mid-G1 phase, shuttled back to the cytosol in S phase and again accumulated in the nucleus when cells were confluent. Interestingly, when aphidicolin was used to arrest the cells in late G1 phase, both proteins were found to accumulate in the nuclei. These results indicated that although both P22 and core proteins possessed the same nuclear localization signal, the cellular regulation of their nuclear transport was not identical and might involve different molecular mechanisms.

Animals↗

PubMed1996

Acute exacerbations in chronic hepatitis C: a clinicopathological and prognostic study.

BACKGROUND/METHODS: To examine the incidence, predisposing factors, clinicopathological characteristics and implications of acute exacerbations in chronic hepatitis C, a consecutive series of 194 biopsy-verified, anti-HCV-positive and hepatitis B surface antigen-negative patients were followed up and studied for the events of acute exacerbations, sustained biochemical resolution and development of cirrhosis. RESULTS: During a mean period of 6.2 +/- 3.5 (1.0-14.0) years, 151 episodes of acute exacerbations were recorded in 78 patients (40.2%). The estimated annual incidence of acute exacerbations was 11.9%. Fifty-five percent of acute exacerbations were asymptomatic. Histological study of acute exacerbations showed mild to moderate lobular inflammatory activities without bridging hepatic necrosis in all and periportal piecemeal in 23 (42.6%). The clinicopathological features of acute exacerbations in patients with chronic hepatitis C were less severe than those in patients with chronic hepatitis B. The route of infection, sex, age, mode of clinical presentation and the initial histology did not influence the occurrence of acute exacerbations. Only those with alanine aminotransferase > or = 300 U/l at entry tended to develop acute exacerbations more frequently (p < 0.001, odds ratio = 3.6, 95% confidence interval: 1.9-6.5). Acute exacerbations per se did not influence the subsequent development of cirrhosis or sustained biochemical resolution. Cirrhosis developed more frequently in patients with chronic active hepatitis at entry (p < 0.001, odds ratio = 6.5, 95% confidence interval: 2.6-16.0). Compared with baseline HCV-RNA level, HCV-RNA increased in 61% of acute exacerbations but the genotype remained unchanged in 75%. CONCLUSIONS: These results suggest that acute exacerbations also occur frequently in patients with chronic hepatitis C. They are clinically indolent, histologically less severe and not likely to be followed by sustained remission or development of cirrhosis.

Adult↗

PubMed1996

A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients.

BACKGROUND: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients. METHODS: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis. RESULTS: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P < 0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P-value of 0.057. CONCLUSIONS: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.

Adult↗

PubMed1996

Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: incidence and risk factors.

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trails were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to INF alpha-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P < 0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3-6.6; P < 0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2-32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.

Adult↗

PubMed1996

Precore mutant of hepatitis B virus prevails in acute and chronic infections in an area in which hepatitis B is endemic.

By using an amplification-created restriction site method, the precore TAG mutant of hepatitis B virus was detected in 6 (75%) of 8 acute fulminant hepatitis B patients, 7 (58%) of 12 acute self-limiting hepatitis B patients, 35 (81%) of 43 hepatitis B virus surface antigen carriers with fulminant hepatitis, and 42 (70%) of 60 hepatitis B virus surface antigen carriers with chronic hepatitis. The precore TAG mutant prevails in acute and chronic hepatitis B of various severity in this area where hepatitis B is endemic.

Acute Disease↗

PubMed1995

A single serine mutation on the nuclear localization signal of hepatitis B virus core protein abolishes the inhibition of nuclear transport by surface proteins.

The nuclear localization signal of hepatitis B virus core protein contained three SPRRR motifs. Substitution of a single serine residue on the third SPRRR motif enhanced significantly the nuclear localization of core protein. By performing immunofluorescence staining assays and subcellular fractionation experiments, it was demonstrated that although nuclear transport of the wild type core protein was markedly suppressed by co-expression of hepatitis B virus surface proteins, nuclear transport of this serine mutant protein was not affected. These results indicated that the serine residue in the SPRRR motifs played an important role in regulating the nuclear transport of core protein and the interaction between core and surface proteins.

Animals↗

PubMed1995

Serum carboxy terminal propeptide of type I procollagen to amino terminal propeptide of type III procollagen ratio is a better indicator than each single propeptide and 7S domain type IV collagen for progressive fibrogenesis in chronic viral liver diseases.

Twenty chronic viral hepatitis patients, mainly with hepatitis B related with progression to liver cirrhosis were included for an assay of serum collagen markers: PICP (carboxy terminal propeptide of type I procollagen), PIIINP (amino terminal propeptide of type III procollagen), and 7S-IV (7S-domain type IV collagen). PICP is increased in 20% of chronic hepatitis patients with a mean of 190.3 ng/ml, which is not different from that of the follow-up concentration in liver cirrhosis, where 35% of cases were abnormal with a mean of 220.5 ng/ml. The serum level and percent of abnormality of PIIICP in chronic hepatitis and in liver cirrhosis are 23.5 ng/ml vs 14.8 ng/ml and 90% vs 100%, respectively (P > 0.05). PICP/PIIINP is significantly higher during liver cirrhosis (15.11 vs 10.08, P < 0.05). PICP during chronic hepatitis is not related to serum biochemical changes, while PICP during liver cirrhosis and PIIINP are correlated with hepatic enzymes. 7S-IV in chronic hepatitis and in liver cirrhosis is 14.0 ng/ml vs 10.9 ng/ml, respectively; both were positively correlated with hepatic enzymes. These results suggest that PICP/PIIINP is a better indicator of hepatic fibrogenesis than either PICP or PIIINP alone in viral hepatitis. A ratio of more than 12 is suggestive of liver cirrhosis.

Adult↗

PubMed1995

Prevalence and prognostic significance of bacterascites in cirrhosis with ascites.

The prevalence and prognostic significance of bacterascites (BA) were prospectively studied in 443 predominantly HBsAg-positive cirrhotic patients with ascites. Spontaneous bacterial peritonitis (SBP), culture-negative neutrocytic ascites (CNNA), and BA were identified in 12.4%, 8.4%, and 10.8%, respectively. Of these, 67%, 70%, and 71%, respectively, had peritonitis-related signs or symptoms. Among patients with SBP or CNNA, the clinical and laboratory data showed no significant difference between the symptomatic and asymptomatic groups. In contrast, among the patients with BA, the symptomatic group had significantly higher levels of serum total bilirubin and prolonged prothrombin time and significantly lower levels of ascitic fluid total protein than the asymptomatic group. Furthermore, the clinical and laboratory data were relatively similar between patients with asymptomatic BA and those with sterile ascites. In contrast, patients with SBP, CNNA, or symptomatic BA exhibited significantly more severe degrees of liver disease and significantly lower levels of ascitic fluid total protein than those with sterile ascites. There was no statistically significant difference between SBP and bacterascites regarding flora. All patients with SBP, CNNA, or symptomatic BA received antibiotic treatment immediately after paracentesis, as did six of the 14 patients with asymptomatic BA for concurrent respiratory or urinary tract infection, while the remaining eight patients with asymptomatic BA were followed clinically without treatment. Repeated paracentesis in the latter revealed no evidence of SBP or CNNA. The in-hospital mortality for sterile ascites was 22.8%, significantly lower than the 54.5% for SBP, 43.2% for CNNA, and 50% for symptomatic BA, but similar to the 21.4% for asymptomatic BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗

PubMed1995

Serum levels of interferon-alpha and -gamma in acute and chronic hepatitis B virus infection.

To evaluate the potential implication of in vivo interferon production in the pathogenesis of different forms of acute and chronic hepatitis B virus infection, serum levels of interferon-alpha and -gamma were measured using immunoassay techniques in 20 patients with acute hepatitis B who subsequently cleared the virus (group Ia), 8 patients with acute hepatitis B who became HBsAg carriers (group Ib), 55 patients with chronic hepatitis B (group II), and 15 healthy controls. None of the controls had interferon-alpha or -gamma detectable in serum, while 15% and 100% of group Ia patients, 25% and 100% of group Ib patients, and 22% and 15% of group II patients, had raised serum levels of interferon-alpha and -gamma, respectively. Serum interferon-gamma was detected significantly more frequently in group Ia and Ib patients than in controls and in group II patients. Among patients with acute hepatitis B, serum levels of interferon-alpha and -gamma showed no significant difference between group Ia and group Ib patients. Among patients with chronic hepatitis B, interferon-alpha was detected significantly more frequently in patients with serum HBV-DNA (31.4% or 11/35) than in those without (5% or 1/20), whereas interferon-gamma was detected significantly more frequently in patients with chronic active hepatitis (28% or 7/25) than in those with chronic persistent hepatitis (3.3% or 1/30). In conclusion, in acute hepatitis B, serum levels of interferon-alpha and -gamma did not show a significant difference between patients who subsequently cleared the virus and those who became HBsAg carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Subcellular localization of hepatitis B core antigen in relation to hepatocyte regeneration in chronic hepatitis B.

BACKGROUND & AIMS: To test whether the dominant cytoplasmic expression of hepatitis B core antigen (HBcAg) in active chronic hepatitis B is secondary to liver damage and regeneration, the relationship between subcellular localization of HBcAg, liver inflammatory activity, and hepatocyte regeneration in chronic hepatitis B was studied. METHODS: Correlation of the clinical and laboratory data with the topographical distribution of HBcAg was studied in 30 patients. The subcellular localization of HBcAg in relation to hepatocyte cell cycles was studied by double immunostaining of HBcAg and proliferating cell nuclear antigen. RESULTS: Patients with predominant cytoplasmic HBcAg had significantly higher levels of biochemical and histological activities and proliferating cell nuclear antigen expression than patients with predominant nuclear HBcAg. The levels of proliferating cell nuclear antigen expression correlated positively with biochemical and histological activities and degrees of cytoplasmic HBcAg expression but negatively with degrees of nuclear HbcAg expression. Proliferating cell nuclear antigen expression was shown in 49% of hepatocytes with cytoplasmic HBcAg but in only 2% of hepatocytes with nuclear HBcAg. CONCLUSIONS: These findings suggested that, following liver damage, the regeneration of surviving hepatocytes might cause the shift of intracellular HBcAg from nucleus to cytoplasm. As a result, the extent of nuclear HBcAg expression reduces with concomitant increase in cytoplasmic HBcAg expression.

Adolescent↗