A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (< or = 3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) > or = 400 ng/mL, HBV DNA level > or = 4 log(10) copies/mL, prolonged prothrombin time, tumor size > or = 2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-alpha) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level > or = 4 log(10) copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP > or = 400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-alpha treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level > or = 4 log(10) copies/mL. Patients with persistent HBV DNA level > or = 4 log(10) copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level > or = 4 log(10) copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-alpha treatment significantly decreased the recurrence risk after resection.

Two SNPs (rs1800562 of HFE and rs2279744 of MDM2) were associated with HCC with moderate epidemiological evidence and deserve further study and additional biological and clinical assessment.

BackgroundHereditary hemochromatosis (HH) is an autosomal recessive disorder mainly associated with homozygosity for the C282Y and H63D mutations in the hemochromatosis (HFE) gene. The reports about the C282Y and H63D mutations and hepatocellular carninoma (HCC) were controversial. To clarify the relationship between C282Y and H63D mutations and HCC, a meta-analysis including nine studies (1102 HCC cases and 3766 controls, mainly came from European populations) was performed.MethodsThe association was measured using random-effect (RE) or fixed-effect (FE) odds ratios (ORs) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.ResultsMeta-analysis of nine studies showed that Y allele of C282Y was associated with HCC risk: RE OR reached 1.50 (95%CI: 1.05-2.14, p for heterogeneity = 0.02, I2 = 0.57). Subgroup analysis of seven studies also showed Y allele was associated with HCC risk in healthy populations: RE OR reached 1.61 (95%CI: 1.08-2.39, p for heterogeneity = 0.04, I2 = 0.55). We further did subgroup analysis in alcoholic liver cirrhosis (LC) patients of four studies (224 cases and 380 controls) and found that both the dominant model and Y allele of C282Y were associated with HCC risk (FE OR reached 4.06, 95%CI: 2.08-7.92 and 3.41, 95%CI: 1.81-6.41, respectively). There was no distinct heterogeneity among the studies (I2 = 0). Sensitivity analyses showed the results were robust in the subgroup analysis of alcoholic LC patients.ConclusionsC282Y mutation was associated with HCC in European alcoholic LC patients.