Analysis of the relationship between hepatitis B virus precore and basal core promoter mutations and acute-on-chronic liver failure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the relationship between hepatitis B virus (HBV) precore (PC) and basal core promoter (BCP) mutations and HBV-related acute-on-chronic liver failure (HB-ACLF).</p><p><b>METHODS</b>Forty-four patients with HB-ACLF and 28 patients with chronic hepatitis B (CHB; used as controls) were enrolled and venous blood samples were collected from all individuals. The PC and BCP gene fragments were amplified by nested PCR. HBV genotype and BCP/PC mutations were determined by direct sequencing and analysis by BioEdit (version 7.0.9.0). Ten of the HB-ACLF patients were selected for follow-up (range: 2-8 weeks), which included once weekly sera collection to determine the relation of mutations and treatment response. Serum levels of HBV DNA were measured by real-time PCR assay, and alanine aminotransferase, total bilirubin, creatinine and albumin were measured by standard biochemical assay and used to determine the MELD score.</p><p><b>RESULTS</b>All 44 HB-ACLF patients were infected with HBV genotype C. In the CHB group, 26 patients were infected with genotype C and two with genotype B. Single mutations (A1762T, G1764A, T1753V, G1896A, and G1899A) and combined mutations (A1762T + G1764A, G1896A + G1899A, T1753V+ A1762T + G1764A, G1896A + G1899A + A1762T + G1764A, and A1762T + G1764A + G1896A) were more frequently detected in HB-ACLF patients than in CHB patients (P less than 0.05). A significantly higher proportion of PC/BCP wild-type sequences was found in patients with CHB than in patients with HB-ACLF (17.9% vs. 2.3%; x² = 5.440, P = 0.020). The proportion of patients carrying both PC and BCP mutations was significantly higher in HB-ACLF patients than in CHB patients (79.6% vs. 39.3%; x² = 12.021, P = 0.001). The proportion of patients carrying only BCP mutation was 42.9% in the CHB group and 20.5% in the HB-ACLF group (x² = 4.157, P = 0.041). No occurrences of only PC mutation were detected in either the CHB or HB-ACLF group. The combined mutations were present in all 10 of the HB-ACLF follow-up patients. Mutations G1899A, T1753V, and A1846T were correlated with disease recovery. Significant decreases in the MELD score were accompanied by decreases in the A1846T mutation.</p><p><b>CONCLUSION</b>Significantly more HB-ACLF patients carried HBV with mutations in the PC and BCP than CHB patients. Moreover, more HB-ACLF patients carried HBV with PC + BCP combined mutations and PC mutation only. The G1899A, T1753C, and A1846T mutations were associated with HB-ACLF response to treatment and improvement in liver function.</p>

The discrepancy of HBsAg titre and HBV DNA in patients with chronic hepatitis B, HBV-related liver cirrhosis and hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>HBsAg 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>HBsAg 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.</p>