Impact of oral anti-hepatitis B therapy on the survival of patients with hepatocellular carcinoma initially treated with chemoembolization / 癌症

<p><b>INTRODUCTION</b>Most hepatocellular carcinomas (HCC) develop in a background of underlying liver disease including chronic hepatitis B. However, the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus (HBV)-related HCC treated with chemoembolization is unclear. This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.</p><p><b>METHODS</b>A total of 224 HCC patients who successfully underwent chemoembolization were identified, and their survival and other relevant clinical data were reviewed. Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival (OS).</p><p><b>RESULTS</b>The median survival time (MST) was 15.9 (95% confidence interval [CI], 9.5-27.7) months in the antiviral group and 9.6 (95% CI, 7.8-13.7) months in the non-antiviral group (log-rank test, P = 0.044). Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS (P = 0.008). Additionally, a further analysis was based on the stratification of the TNM tumor stages. In the subgroup of early stages, MST was significantly longer in the antiviral-treatment group than in the non-antiviral group (61.8 months [95% CI, 34.8 months to beyond the follow-up period] versus 26.2 [95% CI, 14.5-37.7] months, P = 0.012). Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup (P = 0.006). However, in the subgroup of advanced stages, MST of the antiviral-treated group was comparable to that of the non-antiviral group (8.4 [95% CI, 5.2-13.5] months versus 7.4 [95% CI, 5.9-9.3] months, P = 0.219). Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.</p><p><b>CONCLUSION</b>Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC, especially in patients with early-stage tumors.</p>

Relationship and clinical significance of TGF-beta1 expression with Treg cell infiltration in hepatocellular carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>There are few studies about origins of regulatory T (Treg) cells increased in primary hepatocellular carcinoma (HCC) tissue. Studies showed that Treg cells could be induced by transforming growth factor-beta1 (TGF-beta1), but the relation between TGF-beta1 expression and Treg cell infiltration is unclear in HCC tissue. This study was to investigate the expression of TGF-beta1 and correlations with the amount of Treg cells in HCC, and to evaluate their clinical values in predicting the prognosis of HCC.</p><p><b>METHODS</b>Envision immunohistochemistry was used to detect the expression of TGF-beta1 and Foxp3 in 102 specimens of HCC tissue and paired adjacent non-tumor liver tissue.</p><p><b>RESULTS</b>Of the 102 specimens of HCC, 41 showed low TGF-beta1 expression and 61 (59.8%) showed high expression; of the 102 specimens of adjacent non-tumor tissue, 22 showed low TGF-beta1 expression and 80 (78.4%) showed high expression. The high expression rate of TGF-beta1 was significantly lower in HCC than in adjacent non-tumor tissues (P = 0.001). Average Foxp3+ cell density in HCC was 2.98 cells/HP, but there was very few or no expression of Foxp3 in adjacent non-tumor liver tissue. Expression of TGF-beta1 was positively correlated with expression of Foxp3 in HCC tissues (r = 0.228, P = 0.021). The expression of TGF-beta1 was significantly higher in HCC tissues with high preoperative AFP concentration than in those with low preoperative AFP concentration (P = 0.023). TGF-beta1 and Foxp3 expression had no correlations with tumor diameter, tumor capsule, liver cirrhosis, and so on. The 5-year survival rate was not different between HCC tissues with high and low TGF-beta1 expression (P = 0.790); however, it was significantly lower in HCC tissues with high Treg cell infiltration than in those low infiltration (25% vs. 44%, P = 0.007). Cox multivariate analysis showed that the number of Treg cells and tumor capsule were independent prognostic factors (P = 0.021, P = 0.001).</p><p><b>CONCLUSIONS</b>Expression of TGF-beta1 may relate to the infiltration of Treg cells in HCC tissues, but the relation need to be further investigated. The number of Treg cells in HCC tissues could be used as a potential immunological prognostic indicator for HCC patients after resection.</p>

Clinical significance of regulatory T cells proportion in the peripheral blood and tumor tissue in primary hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of the amount of regulatory T cells (Treg) in the peripheral blood CD4+ cells and tumor tissue in primary hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>From January 1999 to December 2000, 63 HCC patients underwent radical resection in Sun Yatsen University Cancer Center. Tregs in those patients were detected in the samples of preoperative peripheral blood by flow cytometry and also in tissue samples of the resected tumors by immunohistochemistry. All patients had been followed up till Dec 30, 2005. The correlations of Treg amount in the peripheral blood CD4+ cells and tumor tissue with clinicopathologic characteristics and prognosis of HCC were analyzed.</p><p><b>RESULTS</b>The proportion of Treg/CD4+ in the peripheral blood was significantly higher in the patients with HCC than that in those with HBsAg positive (P < 0.01) and in the normal controls (P < 0.01). The mean number of Treg in tumor tissue was (15.69 +/- 13.29)/mm2, but none or very few Treg was detected in the normal liver tissue, para-cancerous liver tissue, and HBV-infected liver tissue. The proportion of Treg/ CD4+ in the peripheral blood was significantly positively correlated with the number of Treg in tumor tissue (P = 0.024). The 5-year survival in patients with high amount of Treg in both peripheral blood and tumor tissue was significantly poorer than that in the patients with low amount of Treg (P = 0.042, 0.019). The 5-year disease-free survival rate was significantly lower in the patients with high amount of Treg in tumor tissue than that in the patients with lower amount (P = 0.001).</p><p><b>CONCLUSION</b>Regulatory T cells in the circulatory blood and tumor tissue are increased in patients with hepatocellular carcinoma. The increased amount of regulatory T cells either in peripheral blood or in the tumor tissue is pertaining to poor prognosis. Detection of regulatory T cells both in the preoperative peripheral blood CD4+ cells and tumor tissue may be used as a potential immunological prognostic indicator for the hepatocellular carcinoma patients after radical resection.</p>

The study on the 0, 12 month vaccination schedule' of Healive inactivated hepatitis A vaccine in children / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children.</p><p><b>METHODS</b>A total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose.</p><p><b>RESULTS</b>The vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml.</p><p><b>CONCLUSION</b>GMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.</p>