<b>OBJECTIVEb>To explore the clinical significance of hepatitis B virus large envelope protein (HBV-LP) in diagnosing viral replication, we detected the HBV-LP and HBV DNA in the serum of the patients infected with HBV.

<b>METHODSb>Serum HBV DNA was detected by fluorescent quantitative PCR (FQ-PCR). HBV-LP was analyzed by enzyme linked immunosorbent assay (ELISA).

<b>RESULTSb>(1) No significant difference between the detectable rate of HBV DNA and HBV-LP was found in the HBeAg negative patients without of anti-virus treatment. Of all HBeAg negative patients without of anti-virus treatment, the copies of HBV-DNA was related positively to the absorbency HBV-LP. (2) There was significant diference between the detectable rate of HBV DNA and HBV-LP in the HBeAg negative patients after anti-virus treatment.

<b>CONCLUSIONb>There is a perfect correlation between the positive rate of HBV-LP and HBV DNA in the HBeAg negative patients.The HBV DNA is a reliable serological marker that can reflect the replication of HBV in the HBeAg negative patients.

Adult ; Aged ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; diagnosis ; virology ; Humans ; Male ; Middle Aged ; Viral Envelope Proteins ; blood ; Young Adult

<b>OBJECTIVEb>By means of observing the clinical development of asymptomatic chronic HBsAg carriers (AsC) to explore the clinical rule of development of chronic hepatitis B (CHB) to liver cirrhosis (LC) to hepatocellular carcinoma (HCC) and to seek effective method for blocking the procedure.

<b>METHODSb>AsCs were selected from health examination according to the diagnostic standard from the National Program for Prevention and Treatment of Viral Hepatitis, by periodical or non-periodical conventional examination of liver diseases, mixed infection of HCV was excluded. A 16-year systematic observation on clinical process of HBV infection series was completed.

<b>RESULTSb>In the 217 AsCs observed, 21 cases (9.68%) with the HBsAg negatively converted, the average year negative conversion rate being 0.58%, among them, 13/21 cases (61.9%) had production of anti-HBs antigen; 20 cases were clinically cured; 1 case transferred to HCC; 124 cases (57.14%) remained asymptomatic carriers; 73 transferred to chronic liver disease, showing a tendency of gradually developing from CHB to LC to HCC, the year transferring rate from AsC to LC and HCC being 1.04% and 0.40%, respectively. Fifteen patients died of liver diseases, in which one died of severe CHB, 3 of LC and 11 of HCC.

<b>CONCLUSIONb>Different clinical end-results may reveal in AsCs according to their age and regulation on immune response to HBV. Few of the HCC and LC patients were HBeAg (e+) positive, they often reveal HBeAg (e-) negative or anti-HBe positive. HCC always develops on the basis of liver fibrosis or cirrhosis, which are the prophase of HCC, and patients with liver fibrosis or cirrhosis are the high risk group of developing HCC. HCC is not only the terminal pathologic stage of hepatopathy, but also one of the most important factors that causes death of chronic hepatopathy. From the viewpoint of integrative medicine in typing hepatopathy to observe the clinical speciality of AsC developing to CHB, LC and HCC, it is considered that the degree of blood stasis is in accordance with the development of hepatopathy.

Carcinoma, Hepatocellular ; virology ; Carrier State ; virology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; virology ; Male ; Medicine, Chinese Traditional

OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular ; blood ; diagnosis ; virology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; blood ; diagnosis ; virology ; Mass Spectrometry ; Metabolome ; Metabolomics ; ROC Curve

<b>OBJECTIVEb>To study the relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B.

<b>METHODSb>One hundred and fifty-seven patients with chronic hepatitis B were included in the study, 49 patients among them were diagnosed as early cirrhosis by liver biopsy. Serum HBV DNA levels were determined using fluorescent quantitative PCR, and serum hepatic fibrosis markers including hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III precollagen (P III P) and type IV collagen (IV-C) were determined by radioimmunity assay. The relationship between serum HBV DNA levels and hepatic fibrosis markers were analyzed. Serum HBV DNA levels and hepatic fibrosis markers of 49 patients with early cirrhosis were compared with those of 108 non-cirrhotic patients.

<b>RESULTSb>There was no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B (P>0.05). Patients with early cirrhosis had much higher hepatic fibrosis markers together with lower HBV DNA levels than non-cirrhotic patients (P<0.05).

<b>CONCLUSIONSb>There were no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in patients with chronic hepatitis B.

Adult ; Biomarkers ; analysis ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; complications ; virology ; Humans ; Liver Cirrhosis ; diagnosis ; virology ; Male ; Middle Aged

BACKGROUND/AIMS: Acute exacerbation (AE) of chronic hepatitis B (CHB) can occur spontaneously, and may be followed by HBeAg clearance. HBeAg seroconversion often coincides with the normalization of liver biochemical tests and clinical remission. The purpose of this study was to identify the etiology and the clinical consequence of severe AE in Korean patients with CHB. METHODS: The medical records of CHB patients with severe AE (defined by the sudden increase of ALT above 400 IU/L) who were admitted to Kyung Hee University Hospital between January 1992 and December 2001, were reviewed retrospectively. Forty-four patients were included in the severe AE group. RESULTS: The most common etiology of severe AE was spontaneous exacerbation (77%). Drugs (16%), alcohol (5%), and HCV coinfection (2%) were suspected of causing AE in the remaining patients. HBeAg seroconversion at 12, 18, and 24 months following severe spontaneous AE was 18.5%, 40.7%, and 48.1%, respectively. These were significantly higher compared to CHB patients without AE (4.3%, 4.3%, and 10.9%, respectively). Seroconversion within 3 months, however, occurred in only 15% of CHB patients with AE. There was a tendency to progress to liver cirrhosis more frequently in the patients with AE as compared to the patients without AE (17.6% vs. 5.5%, P<0.08). CONCLUSIONS: Severe AE in patients with CHB is mainly caused by spontaneous exacerbation. Although HBeAg seroconversion occurs frequently in these patients, the rates are relatively low compared to those reported in other countries and early seroconversion is expected only in a small proportion. Further studies will be warranted to determine the efficacy of the early use of antiviral agents at the time of AE.
Acute Disease ; Adult ; Alanine Transaminase/blood ; English Abstract ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*complications/diagnosis/virology ; Humans ; Male ; Middle Aged

<b>OBJECTIVESb>To identify serologic markers that may indicate the early presence of hepatocellular carcinoma (HCC), and analyze their significance in the pathogenesis of chronic hepatitis B.

<b>METHODSb>Hepatitis B x antigen (HBxAg) positive and negative HepG2 cells were subjected to PCR select cDNA subtraction to identify differentially expressed genes that may precede the development of HCC. These included the up-regulated genes URG4, URG7, URG11, and VEGFR3, and the down-regulated gene, Sui1. Specific ELISAs were constructed to measure differentially expressed antigens and their corresponding antibodies to determine whether they had prognostic and/or diagnostic value. The study population consisted of 730 people. Among them, 416 were HBsAg(-) and 298 were HBV carriers with chronic liver disease and/or HCC. In addition, 16 patients had non-viral hepatitis. Among these, serial serum samples from 53 HBsAg(+) patients with cirrhosis were collected and studied.

<b>RESULTSb>Antibodies to multiple differentially regulated genes were detectable in serum samples from patients with HBV associated cirrhosis and HCC, but not in serum samples from uninfected individuals (P < 0.01). Antibodies were undetectable in serum samples from HBV patients without liver disease and in serum samples from patients with other tumor types, and among those with non viral hepatitis. Among patients at high risk of developing HCC, these antibodies were found to be independent of nationality and ethnicity. Statistical analysis of the 28 HBsAg(+) patients with HCC showed that anti-URG11 and anti-VEGFR3 were the most frequently detected antibodies. These antibodies were found to coexist in 16 (P < 0.05). In contrast, among the 25 HBsAg(+) patients without HCC, anti-Sui1 and anti-URG7 were the most prevalent antibodies. These antibodies coexisted in 11 (P < 0.05). In addition, HCC patients with four or more antibodies detected before the appearance of HCC had a poorer survival outcome.

<b>CONCLUSIONb>These antibodies can be detected in serum samples several months to several years before the appearance of HCC. This suggests that they may be preneoplastic markers that may help to distinguish which HBV carriers with cirrhosis are most likely to progress and develop HCC.

Adult ; Aged ; Biomarkers ; blood ; Biomarkers, Tumor ; Carcinoma, Hepatocellular ; diagnosis ; virology ; Female ; Hep G2 Cells ; Hepatitis Antibodies ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; complications ; Humans ; Liver Neoplasms ; diagnosis ; virology ; Male ; Middle Aged ; Precancerous Conditions ; Prognosis ; Young Adult

<b>OBJECTIVEb>To explore the relationship between the syndrome types in traditional Chinese medicine (TCM) and serum HBV DNA load in chronic HBV carriers positive for HBeAg.

<b>METHODSb>According to the TCM syndrome types, 185 chronic HBV carriers with HBeAg positivity were classified into single syndrome group (liver Qi depression, kidney Qi deficiency, spleen Qi deficiency, and kidney Yang deficiency), compound syndrome group, and unidentifiable syndrome group; based on the nature of the condition in TCM terms, the patients were classified into excess syndrome group, deficiency syndrome group and comorbidity syndrome group. The serum HBV DNA levels in these cases were analyzed in relation to the TCM syndrome types and disease nature.

<b>RESULTSb>HBV DNA levels showed no significant difference among the patients with single syndrome, compound syndromes and unidentifiable syndrome (F=0.910, P=0.404), nor among the patients with the 5 different single TCM syndromes (χ²=4.672, P=0.323) or those with different disease nature (F=0.631, P=0.596).

<b>CONCLUSIONb>Serum HBV DNA level can not be considered as the evidence for syndrome differentiation in chronic HBV carriers with positive HBeAg.

Adolescent ; Adult ; Carrier State ; blood ; diagnosis ; Child ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; diagnosis ; virology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Young Adult

BACKGROUND/AIMS: HBeAg-negative chronic hepatitis B (CHB) has a poor long-term prognosis. Since no precise clinically relevant HBV thresholds are known in HBeAg-negative CHB, the decision to treat is difficult. The aim of this study was to evaluate the levels of serum HBV DNA and transaminase and to investigate the correlation of these values in patients with HBeAg-negative CHB. METHODS: The study analyzed the sera from 82 patients with HBeAg-negative CHB, 61 men and 21 women. The mean age was 45 years. The patients were divided into two groups according to serum ALT levels: the patients with lower ALT level (n=52, UNL < ALT < 2 X UNL) and higher level (n=30, ALT >or= 2 X UNL). The level of serum HBV DNA was determined by the Cobas Amplicor HBV Monitor(TM) (Roche). RESULTS: The median serum HBV DNA level was 2.7 X 10(5) copies/mL in patients with HBeAg-negative CHB. The median serum HBV DNA level of patients with a higher ALT level (1.0 X 10(6) copies/mL) was significantly higher than that of patients with a lower ALT level (5.6 X 10(4) copies/mL)(p<0.001). The serum ALT level was correlated with serum HBV DNA levels in patients with HBeAg-negative CHB (r=0.416, p<0.001). The serum level of HBV DNA in patients with cirrhosis (median 2.0 X 10(5) copies/mL) did not differ from patients without cirrhosis (median 4.7 X 10(5) copies/mL). CONCLUSIONS: The level of serum HBV DNA was higher in patients with higher serum ALT level than it was in patients with lower serum ALT, and it was closely correlated with serum ALT levels in HBeAg-negative CHB.
Alanine Transaminase/*blood ; DNA, Viral/*blood ; English Abstract ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B virus/*genetics/isolation & purification ; Hepatitis B, Chronic/blood/diagnosis/*virology ; Humans ; Lamivudine/*therapeutic use ; Male ; Middle Aged

<b>OBJECTIVb>To investigate the potential value of urine hepatitis B virus (HBV) DNA as a new noninvasive diagnostic indicator for HBV-associated glomerulonephritis (HBV-GN).

<b>METHODSb>A total of 152 patients including 66 with HBV-GN, 66 with non-HBV-GN, and 20 with chronic hepatitis B (CHB) without renal disease were examined for serum and urine HBV DNA levels using polymerase chain reaction (PCR) and for 5 serum HBV markers using enzyme-linked immunosorbent assays.

<b>RESULTSb>Twenty-two patients (33%) in the HBV-GN group, but none in the other two groups, were found positive for urine HBV DNA. In the diagnosis of HBV-GN, urine HBV DNA had a high specificity (0.98), a good positive predictive value (PPV, 0.96), and a modest negative predictive value (NPV, 0.60). Urine HBV DNA, alone or in combination with serum HBeAg, was superior in the diagnosis of HBV-GN to the combination of urine HBV DNA with serum HBV DNA, hepatitis B surface antigen and the hepatitis B e antigen.

<b>CONCLUSIONb>Urine HBV DNA may be one of the new noninvasive diagnostic criterion for HBV-GN.

Biomarkers ; blood ; urine ; DNA, Viral ; blood ; urine ; Enzyme-Linked Immunosorbent Assay ; Glomerulonephritis ; diagnosis ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; complications ; Humans ; Polymerase Chain Reaction ; Predictive Value of Tests ; Sensitivity and Specificity

BACKGROUND/AIMS: The post-treatment relapse patterns and efficacy of lamivudine re-treatment for relapsed patients have not been clarified. The aims of this study were to evaluate the relapse patterns after discontinuing therapy and the effects of lamivudine re-treatment for relapsed patients after HBeAg seroconversion. METHODS: Therapy was discontinued after HBeAg seroconversion in 121 patients. Sixty-six patients were relapsed and included in this study. The duration of lamivudine re-treatment therapy was from 6-35 (mean: 16) months. Post-retreatment monitoring continued for 1-40 (mean: 8.9) months. RESULTS: Among the relapsed 66 patients, 50 (75.8%) had HBeAg reappearance while 16 (24.2%) remained HBeAg negative and anti-HBe positive. The cumulative relapse rates at 3, 6, 12 and 24 months were 27%, 47%, 60% and 66%, respectively. Forty-two relapsers received lamivudine re-treatment. Among them, 33 were HBeAg positive and 9 were HBeAg negative and anti-HBe positive, Response was achieved in 31 of the 42 patients (73.8%). The cumulative response rates at 6, 9 and 12 months were 62%, 69% and 72%, respectively. Six patients (14.3%) developed viral breakthrough. All patients were HBeAg positive chronic hepatitis B. The duration of lamivudine re-treatment was the only predictable factor for response of lamivudine re-treatment. Therapy was discontinued after response in 21 patients. Eleven patients were relapsed, including 6 who were HBeAg positive and 5 who were HBeAg negative. Predictive factors for post-retreatment relapse were age and the duration of additional lamivudine therapy after response. CONCLUSIONS: The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The breakthrough and relapse rates, however, were similar in both initial and retreated lamivudine therapy.
Adult ; Antiviral Agents/*therapeutic use ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/diagnosis/*drug therapy/virology ; Humans ; Lamivudine/*therapeutic use ; Male ; Recurrence ; Retreatment