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Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis.

ABSTRACT: Assessment of intrahepatic hepatitis B virus (HBV) DNA levels in patients with chronic hepatitis B is important in understanding the natural history of the disease and designing antiviral therapy regimens. However, there is no standardized method for the measurement of intrahepatic HBV DNA levels. We describe a convenient novel method for the measurement of intrahepatic HBV DNA levels based on a modified COBAS Amplicor HBV Monitor test for HBV DNA measurement and real-time PCR beta-actin gene detection for human genomic DNA (hgDNA) quantitation. Fifteen hepatitis B e antigen (HBeAg)-positive patients, 26 patients positive for antibody to HBeAg (anti-HBe), and 8 control patients were recruited. The mean between-run coefficient of variation for the beta-actin real-time PCR assay was 15.4%. All eight control patients had undetectable intrahepatic and serum HBV DNA levels. All chronic hepatitis B patients had detectable intrahepatic HBV DNA levels, and all but one anti-HBe-positive patient had detectable serum HBV DNA levels. HBeAg-positive patients had higher median intrahepatic and serum HBV DNA levels than anti-HBe-positive patients (6,950 versus 676 HBV DNA copies/ng of hgDNA, respectively [P < 0.001] and 184 x 10(6) versus 6.65 x 10(6) copies/ml, respectively [P < 0.001]). The intrahepatic HBV DNA levels correlated strongly with the serum HBV DNA levels (r = 0.842; P < 0.001) and with the degree of fibrosis (P = 0.014). We conclude that the method that we describe is reliable and convenient for the measurement of intrahepatic HBV DNA levels and has potential clinical significance.

SUBMITTER: Wong DK

PROVIDER: S-EPMC516337 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

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Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis.

Wong Danny Ka-Ho DK Yuen Man-Fung MF Tse Eric E Yuan HeJun H Sum Simon Siu-Man SS Hui Chee-Kin CK Lai Ching-Lung CL

Journal of clinical microbiology 20040901 9

Assessment of intrahepatic hepatitis B virus (HBV) DNA levels in patients with chronic hepatitis B is important in understanding the natural history of the disease and designing antiviral therapy regimens. However, there is no standardized method for the measurement of intrahepatic HBV DNA levels. We describe a convenient novel method for the measurement of intrahepatic HBV DNA levels based on a modified COBAS Amplicor HBV Monitor test for HBV DNA measurement and real-time PCR beta-actin gene de ...[more]

PMID: 15364969

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Project description:The purpose of this study was to explore the correlations of serum hepatitis B core-related antigen (HBcrAg) with intrahepatic Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV total DNA in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Serum HBcrAg and other parameters, including HBV DNA, HBV RNA, HBeAg, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were quantitatively measured at baseline and follow-up time points. Intrahepatic HBV cccDNA and total DNA were quantitatively detected at baseline and 96?weeks. Grading of liver necroinflammation and staging of hepatic fibrosis were assessed at baseline and 96?weeks. Correlations between serum HBcrAg and other parameters were analyzed by Pearson's correlation analysis. The results showed that pretreatment HBcrAg correlated significantly with HBV total DNA levels (r?=?0.328, P? =?0.003) in 82 CHB patients, and, after removing three outliers, with intrahepatic HBV cccDNA (r?=?0.323, P? =?0.004; n?=?79). Serum HBcrAg correlated better with HBV cccDNA in patients with lower levels of serum HBV DNA (stratified by 7?log IU/ml of HBV DNA; r?=?0.656, P? =?0.003 versus r?=?-0.02, P = 0.866). Significant inverse correlations were found between HBcrAg and grade of liver necroinflammation (r?=?-0.245, P? =?0.037), stage of hepatic fibrosis (r?=?-0.360, P? =?0.002) at baseline. Serum HBcrAg presented significant correlation with intrahepatic HBV cccDNA in patients with HBeAg seroconversion at 96?weeks (r?=?0.622, P? =?0.006). The decrease in HBcrAg showed significant correlation with the decrease in HBV cccDNA after 96-week NA therapy (r?=?0.282, P? =?0.043). Serum HBcrAg also correlated significantly with other serum markers at baseline and 96 weeks of NA therapy. In conclusion, baseline HBcrAg and its decreased value were significantly correlated with the corresponding intrahepatic HBV cccDNA.

Project description:ObjectiveThe objective was to develop a multiparametric CT algorithm to stage liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.Materials and methodsAbdominal CT and laboratory measures in 469 patients with HCV (340 men and 129 women; mean age, 50.1 years) were compared against the histopathologic Metavir fibrosis reference standard (F0, n = 49 patients; F1, n = 69 patients; F2, n = 102 patients; F3, n = 76 patients; F4, n = 173 patients). From the initial candidate pool, nine CT and two laboratory measures were included in the final assessment (CT-based features: hepatosplenic volumetrics, texture features, liver surface nodularity [LSN] score, and linear CT measurements; laboratory-based measures: Fibrosis-4 [FIB-4] score and aspartate transaminase-to-platelets ratio index [APRI]). Univariate logistic regression and multivariate logistic regression were performed with ROC analysis, proportional odds modeling, and probabilities.ResultsROC AUC values for the model combining all 11 parameters for discriminating significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.928, 0.956, and 0.972, respectively. For all nine CT-based parameters, these values were 0.905, 0.936, and 0.972, respectively. Using more simplified panels of two, three, or four parameters yielded good diagnostic performance; for example, a two-parameter model combining only LSN score with FIB-4 score had ROC AUC values of 0.886, 0.915, and 0.932, for significant fibrosis, advanced fibrosis, and cirrhosis. The LSN score performed best in the univariate analysis.ConclusionMultiparametric CT assessment of HCV-related liver fibrosis further improves performance over the performance of individual parameters. An abbreviated panel of LSN score and FIB-4 score approached the diagnostic performance of more exhaustive panels. Results of the abbreviated panel compare favorably with elastography, but this approach has the advantage of retrospective assessment using preexisting data without planning.

Dataset Information

Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis.

Publications

Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis.

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