Progressive increase of serum circulating immune complexes and its significance in patients during the progression from chronic hepatitis B to hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the significance of increasing circulating immune complex (CIC) in patients during the progression from chronic hepatitis B to hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Serum levels of CIC from 20 hospitalized patients diagnosed by pathology with primary HCC, and 13 with hepatic hemangioma, and from 45 subjects with chronic HBV infection who finally developed into HCC (45 cases), and age- and gender-matched 45 subjects who kept the chronic HBV infection after consecutively followed up for 10 - 13 years by June of 2009 were quantified by ELISA. The serum levels of anti liver-kidney microsomal (anti LKM-1) antibodies were also measured by ELISA, and that of HBV-DNA were quantified by Taqman probe-based real time PCR in the followed up chronic HBV infection subjects. In the 45 chronic HBV subjects who finally developed into HCC and the 45 controls, serum samples were collected and determined at 3 time points: the baseline when the subjects were recruited, the middle point during the follow-up, and the end of follow-up.</p><p><b>RESULTS</b>The serum level of CIC was significantly higher in the 20 HCC patients than that in the 13 hemangioma cases (P < 0.001). When HCC was diagnosed, the CIC concentration was significantly higher than that in the baselines (P < 0.001) in the 45 chronic HBV subjects who finally developed into HCC after the consecutively follow-up for 5 - 13 years. Of them, 36 patients (80.0%) showed progressively increased CIC during the follow-up (P < 0.001). In the controls, the CIC levels were kept relatively stable during the follow-up. Among them, 17 patients (37.8%) showed CIC slightly increased (P = 0.046). Kaplan-Meier survival analysis indicated that elevated serum CIC during the follow-up increased cumulative HCC incidence (HR = 2.77, 95%CI 1.47 - 5.22). In addition, the serum levels of anti-LKM-1 and HBV-DNA were also significantly higher in the patients who finally progressed into HCC than that in the controls and maintained at a high level during the follow-up tested at all the 3 time points. Further analysis indicated that the serum level of CIC was correlated with that of serum HBV-DNA only when HCC was diagnosed (r = 0.344, P = 0.026).</p><p><b>CONCLUSION</b>Progressive increase of serum CIC level may be one of risk factors reflecting HCC development from chronic HBV infection.</p>

The association of hepatitis B virus genotype and the basal core promoter mutation in Qidong, China / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the prevalence of hepatitis B virus (HBV) genotypes and the association with hepatocellular carcinoma (HCC) or basal core promoter (BCP) mutation in Qidong, China.</p><p><b>METHODS</b>The whole genome of HBV or X gene sequences were obtained from serum samples of HBV infected patients by using PCR and direct sequencing methods. Phylogenetic tree was constructed to determine the genotypes or subgenotypes of HBV.</p><p><b>RESULTS</b>According to the phylogenetic tree constructed from full-length sequence of HBV, genotype C2 was predominant in Qidong area. It was prevalent in 44 out of the 48 cases (91.7%), whereas genotype B2 only existed in 4 cases (8.3%). No other genotypes or recombinant types were found in Qidong patients. The result of genotyping based on X gene sequence confirmed the above observation. In a total of 182 samples, 169 (92.9%) showed genotype C2 and 10 (5.5%) showed genotype B2. There were 3 (1.6%) patients showed a coinfection with C2 and B2. The infection rate of genotype C in Qidong was significantly higher than that in neighboring city Shanghai (chi(2) = 12.252, P less than 0.01). There was no significant difference of genotype distribution between HCC and chronic hepatitis groups (P is more than 0.05). The frequency of T1762/A1764 double mutation in genotype C2 (70.3%) was significantly higher than that in genotype B2 (30.8%, P less than 0.05). The other two types of point mutation which also occurred in BCP, i.e. T1766 and A1768, were only seen in genotype C2.</p><p><b>CONCLUSION</b>(1) Genotype C2 is the predominant genotype in Qidong, China. (2) There is no association between genotype C and HCC in Qidong. (3) Genotype C has a higher prevalence of BCP mutation than genotype B.</p>