Carcinoma, Hepatocellular ; blood ; complications ; virology ; Glycomics ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; Humans ; Liver Cirrhosis ; blood ; complications ; virology ; Liver Neoplasms ; blood ; complications ; virology ; Neoplasm Staging

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

OBJECTIVETo investigate the discrepancy of HBsAg titre and correlation of HBV DNA levels among patients with chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC).

METHODSHBsAg titre and HBV DNA in serum samples were measured among 47 CHB, 72 LC and 54 HCC cases using Abbott chemiluminescence and fluorescence quantitative PCR, respectively. Statistical analyses among multiple groups, between two groups and about the correlation were performed using Kruskal-Wallis test, Mann-Whitney U test and Spearman test, respectively.

RESULTSThe median HBsAg titre level in serum samples decreased from 2361.10 IU/ml in CHB cohort to 1001.64 IU/ml in LC cohort and 594.35 IU/ml in HCC cohort, suggesting a statistically significant difference (x2 = 24.394, P less than 0.05). Moreover, HBsAg titre in CHB group was significantly higher than that in LC group ( Z = -3.754, P less than 0.05). CHB patients had significantly higher HBsAg titre than HCC cases ( Z = -4.630, P less than 0.05). However, there was no statistically significant difference in HBsAg titre between LC and HCC group. Among HBeAg positive patients, HBsAg titre decreased from 3259.83 IU/ml in CHB group to 1077.30 IU/ml in LC group and 789.72 IU/ml in HCC group, indicating a significant difference (x2 = 15.643, P less than 0.01). Among HBeAg negative patients, HBsAg titre declined from 1669.00 IU/ml in CHB group to 1001.64 IU/ml in LC group and 582.05 IU/ml in HCC group, suggesting of a significant difference (x2 = 6.423, P less than 0.05). Positive correlation between HBsAg titre and HBV DNA was found in CHB ( r = 0.297, P less than 0.05), LC (r = 0.346, P less than 0.05) and HCC (r = 0.452, P less than 0.05), respectively.

CONCLUSIONHBsAg titre level in serum decreased progressively from CHB to LC and HCC group. There were positive correlations between HBsAg titre and HBV DNA level in CHB, LC and HCC.

Adult ; Carcinoma, Hepatocellular ; blood ; virology ; DNA, Viral ; blood ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; Humans ; Liver Cirrhosis ; blood ; virology ; Liver Neoplasms ; blood ; virology ; Male ; Middle Aged

Adult ; Aged ; Carcinoma, Hepatocellular ; blood ; pathology ; virology ; DNA, Viral ; blood ; Female ; Hepatitis B ; blood ; virology ; Hepatitis B virus ; genetics ; Humans ; Liver ; pathology ; virology ; Liver Neoplasms ; virology ; Male ; Middle Aged

OBJECTIVEBy 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.

METHODSAsCs 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.

RESULTSIn 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.

CONCLUSIONDifferent 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

Carcinoma, Hepatocellular ; blood ; virology ; Female ; Hepatitis B virus ; physiology ; Humans ; Liver Neoplasms ; blood ; virology ; Male ; Middle Aged ; NF-kappa B ; blood ; Virus Replication

No abstract available.
Antiviral Agents/*therapeutic use ; Carcinoma, Hepatocellular/*virology ; Female ; Hepatitis B Surface Antigens/*blood ; Hepatitis B, Chronic/*blood/*drug therapy ; Humans ; Liver Neoplasms/*virology ; Male

OBJECTIVETo establish a culture system of HBV positive serum infected Hep G2 cells in vitro.

METHODSHep G2 cells were seeded into six-well cluster dishes, at 1 x 10(-6) cells per well and incubated with 3 ml 10% fetal calf serum/ Dulbecco's modified Eagle's medium (10% FCS/DMEM) at 37 degrees in 5% CO2 air. At 24 h after plating, infection group Hep G2 cells were cultured with 0.5 ml HBV positive serum, in control group HBV negative serum was used, 24 h later the inoculums was removed. The cells were then extensively washed with 0.01 mol/L phosphate-buffered saline (PBS). After washing with PBS, 4 ml 2% FCS/DMEM were added to each well and the medium was collected every 12 h. ELISA method was used to detect HBsAg in culture medium. HBV DNA in cells and culture medium was detected by PCR.

RESULTSIn infection group, HBsAg could be detected from cell culture medium from 12 h (after PBS washed) to 84 h. HBV DNA could be detected by PCR in culture medium and cells.

CONCLUSIONInfection of Hep G2 cells by HBV positive serum is feasible.

Carcinoma, Hepatocellular ; pathology ; virology ; Cell Line, Tumor ; DNA, Viral ; genetics ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; blood ; virology ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B virus ; genetics ; growth & development ; immunology ; Humans ; Liver Neoplasms ; pathology ; virology ; Polymerase Chain Reaction ; Serum ; virology

BACKGROUND/AIMS: Serum alpha fetoprotein (alpha-FP) measurement has a limitation to detect hepatocellular carcinoma (HCC) because it is elevated in various liver diseases. Therefore, we studied the sensitivity and specificity of high alpha-FP in the diagnosis of HCC. METHODS: We studied 253 patients with HBsAg positive liver cirrhosis prospectively. We analyzed incidence of HCC related cut-off values of serum alpha-FP levels. During the follow-up period, we analyzed sensitivity and specificity of cut-off values of alpha-FP for the diagnosis of HCC, and alpha-FP elevation rate in relation to mass size. RESULTS: One hundred and twenty-five patients had a transient elevation of alpha-FP levels above 20 ng/mL. The corresponding incidences of HCC were 27.2% (34/125) and 15.6% (20/128 patients without elevation of alpha-FP), respectively with a statistically significant difference (p=0.03). Among 54 patients with HCC, 18 patients (33.0%) had levels of alpha-FP below 20 ng/mL on the time of diagnosis of HCC. When we defined cut-off values of serum alpha-FP as 20, 100 and 500 ng/mL, the corresponding sensitivity and specificity for HCC were 62.9% and 24.0%, 7.4% and 54.2%, 77.3% and 91.9%, respectively. We studied sensitivity according to cut-off values of alpha-FP defined as 20, 100, 200, 500 ng/mL in patients with small HCC below 2 cm. The corresponding sensitivity were 50.0%, 43.7%, 25.0%, 18.7%, respectively. In patients with levels of serum alpha-FP below 20 ng/mL, percentages of mass size less than 2 cm, 2~3 cm, 3~5 cm and more than 5 cm were 50.0%, 25.0%, 28.5% and 25.0%, respectively. CONCLUSIONS: We suggested that in order to detect HCC, careful periodic monitoring with alpha-FP, ultrasonography and abdominal computed tomography is needed in patients with HBsAg positive liver cirrhosis and whose serum level of alpha-FP is above 20 ng/mL.
Adult ; Aged ; Carcinoma, Hepatocellular/complications/*diagnosis/virology ; English Abstract ; Female ; Hepatitis B Surface Antigens/*blood ; Humans ; Liver Cirrhosis/*complications/virology ; Liver Neoplasms/complications/*diagnosis/virology ; Male ; Middle Aged ; Sensitivity and Specificity ; Tumor Markers, Biological/analysis ; alpha-Fetoproteins/*analysis

Adult ; Carcinoma, Hepatocellular ; epidemiology ; pathology ; virology ; DNA, Viral ; blood ; genetics ; Female ; Genotype ; Hepatitis B ; epidemiology ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; epidemiology ; pathology ; virology ; Male ; Middle Aged ; Neoplasm Staging ; Polymerase Chain Reaction ; methods