For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

Endoscopic approach has the potential to be a first-line therapy for the management of biliary complications after LDLT.

No abstract

Three tumor markers for hepatocellular carcinoma (HCC) are available in daily practice in Japan: alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). To elucidate the predictability of these tumor markers on HCC recurrence after curative ablation, we enrolled 416 consecutive patients with naïve HCC who had been treated by percutaneous ablation at our department from July 1997 to December 2002. Tumor marker levels were determined immediately before and 2 months after the treatment. Complete ablation was defined on CT findings as nonenhancement in the entire lesion with a safety margin. Tumor recurrence was also defined as newly developed lesions on CT that showed hyperattenuation in the arterial phase with washout in the late phase. We assessed the predictability of recurrence via tumor markers in multivariate analysis, using proportional hazard regression after adjusting for other significant factors in univariate analysis. Until the end of follow-up, tumor recurrence was identified in 277 patients. Univariate analysis revealed the following factors to be significant for recurrence: platelet count; size and number of tumors; AFP, AFP-L3, and DCP preablation; and AFP and AFP-L3 postablation. Multivariate analysis indicated that AFP >100 ng/mL and AFP-L3 >15%, both pre-and postablation, were significant predictors. The positivity of AFP and AFP-L3 preablation that turned negative postablation was not significant. In conclusion, tumor markers pre-and post-ablation were significant predictors for HCC recurrence and can complement imaging modalities in the evaluation of treatment efficacy. (HEPATOLOGY 2006;44:1518-1527 H epatocellular carcinoma (HCC) is a common malignancy worldwide, and its incidence is increasing in the United States and elsewhere. 1,2 Current options for the treatment of this cancer consist of surgical resection, orthotropic liver transplantation, transcatheter arterial embolization, and percutaneous ablation therapy. Although surgical resection is usually the first choice for treatment, 3,4 it is frequently contraindicated by underlying chronic liver disease based on hepatitis B or C virus infection. 5,6 Orthotopic liver transplantation is a strategy that can treat both cancer and liver dysfunction, and indeed has shown an excellent survival rate in patients at an early stage of the cancer (e.g., single nodule measuring Յ5 cm in diameter or fewer than three nodules measuring Յ3 cm in diameter). 7,8 However, in countries such as Japan, where cadaveric donor organs are scarce, application of liver transplantation is limited. Percutaneous ablative methods-including percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy, and radiofrequency ablation-can achieve high local cure without deteriorating background liver function 9-15 and have played an important role in the treatment of HCC.Alpha-fetoprotein (AFP) has served as a diagnostic test for HCC since the 1970s, when most patients wit...