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Recent data suggest that non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in Asia, with an updated population prevalence of 34%. In parallel, NAFLD-associated hepatocellular carcinoma (HCC) is also on the rise. In this review, we describe the changing epidemiology of HCC in Asia over the past 30 years. While traditional risk factors for HCC (older age, male sex and metabolic factors) are also important in Asia, the PNPLA3 gene polymorphism is particularly prevalent in East Asia and may increase the risk of HCC. NAFLD among non-obese individuals is also commonly described in Asia. Because NAFLD is often undiagnosed, few patients receive HCC surveillance, and the target surveillance population beyond patients with cirrhosis remains poorly defined. As a result, NAFLD-associated HCC is often diagnosed at an advanced stage, rendering curative treatment impossible. Finally, despite around 20-30 years of universal vaccination, chronic HBV infection remains prevalent in Asia, and emerging evidence highlights the importance of metabolic factors and concomitant hepatic steatosis on HCC development in infected patients. Future studies should explore the role of metabolic treatments in HCC prevention among patients with hepatic steatosis and concomitant liver diseases., Competing Interests: Conflicts of interests Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen and Roche. Vincent Wong has served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Inventiva, Merck, Novartis, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions, and Terns; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a grant from Gilead Sciences for fatty liver research. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) remains a severe health issue worldwide, especially in Asia. To date, molecular classifications proposed for the overall survival (OS) or recurrence-free survival (RFS) prediction of Asian HCC patients after hepatectomy are quite few and limited in clinical practice. Here, we established a molecular subtyping system for Asian HCC to facilitate prognosis evaluation. Firstly, differentially expressed genes (DEGs) (FDR [false discovery rate] <0.05) between different types of liver cancer and non-tumor tissue were screened. Among the DEGs solely between HCC and non-tumor samples, 185 genes simultaneously significantly associated with the OS and RFS were identified as HCC-characteristic genes. The molecular subtypes were developed based on the expression profiles of the 185 genes in the training dataset (TCGA [The Cancer Genome Atlas] dataset) using non-negative matrix factorization (NMF) clustering method. Patients were then classified into Subtype1 and Subtype2 groups denoting unfavorable and favorable clinical outcome respectively. The robustness and effectiveness of the molecular subtype was confirmed in another independent dataset (GSE14520) by the same clustering approach and Kaplan-Meier analyses. Moreover, functional prediction analysis revealed that the identified molecular signature was involved in chemotaxis, apoptosis and cell development associated pathways. Besides, the molecular signature was closely related to the clinical characteristics including TNM stage, preoperative alpha-fetoprotein (AFP) level and TP53 mutation. Furthermore, integration of the molecular subtype and TNM stage was demonstrated to improve risk stratification. Taken together, our molecular subtyping system exhibited great utility and potential in prognosis prediction and therapeutic decision making of Asian HCC patients.

The incidence of hepatocellular carcinoma (HCC) is rising sharply in the United States and deaths from HCC have increased at the highest rate of all cancers. Though Asians have the highest incidence of HCC of all ethnicities in the US, racial/ethnic minorities, including Asians, have worse survival from HCC. We sought to identify barriers to care in treatment of HCC among affected individuals in the NYC Chinese immigrant community. We held focus groups with Chinese immigrant patients in NYC with HCC. 29 individuals participated in the focus groups. We analyzed focus group data using grounded theory methodology. Barriers to care identified included insurance, money, time, language, residency status, and stigma. The impact of provider bias and culture were also discussed. Knowledge gathering with minority patients with HCC is essential for us to fully comprehend the barriers to healthcare experienced by this community. Future policy and intervention efforts must be founded in this reality.

Background: Historically, the benefit of liver resection for non-colorectal, non-neuroendocrine (NCNN) liver metastases has been controversial. This study aims to determine the preoperative prognostic factors of liver resection for NCNN liver metastases and validate the Adam score in an Asian population., Methods: Consecutive patients who underwent liver resection for NCNN liver metastases were identified retrospectively from a prospective liver resection database of the single institution between 2001 and 2014. Univariate Cox regression models were used to identify associations with outcome variables. Recurrence-free interval and overall survival were determined using the Kaplan-Meier method and compared using log-rank test., Results: Seventy-eight consecutive patients were identified, which met the study criteria. Univariate analysis demonstrated that adenocarcinoma histology of primary cancer, disease-free interval and number of nodules were significant predictors of survival. Four of the six components of Adam score were significant predictors of survival. These were the presence of extrahepatic metastases, R2 resection, disease-free interval and type of a primary tumour. The total Adam score was also a significant predictor of survival., Conclusion: Liver resection for NCNN liver metastases is a safe and viable treatment option in carefully selected patients. Significant preoperative prognostic factors include adenocarcinoma primary tumours, disease-free interval and number of nodules. The total Adam score was a good predictor of overall survival and can be used to risk stratify patients undergoing hepatic resection for NCNN liver metastases.

Aim: To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in Singapore., Methods: One thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31 st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank test., Results: The median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort ( P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG ( P < 0.001), higher Child-Pugh status ( P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups by BCLC and HKLC were 6.1 and 2.6 years respectively ( P < 0.001). When only patients receiving curative treatment were analyzed, BCLC still predicted overall median survival better than HKLC (7.1 years vs 5.5 years, P = 0.037)., Conclusion: BCLC performs better than HKLC in our multiethnic Asian population in allocating patients to curative treatment in a real-life situation as well as in predicting survival., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Background: Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC., Methods: We investigated 1200 patients with CHB who were treated with NAs for at least four years and evaluated the association of the variables ALT, HBsAg, HBV DNA, age and platelet count with the occurrence of HCC. We used multivariable analysis to identify independent risk factors for the development of HCC., Results: HCC developed in 153 NA-treated patients. Serum HBV DNA levels of 18.17% (218/1200) patients were>2000IU/mL. The median level of liver stiffness measurement (LSM) of all patients was 8.3±6.7kPa vs. 19.8±10.1kPa in patients with HCC. Advanced age, lower platelet counts, positive HBV DNA load, lower ALB concentration and relatively advanced liver disease were associated with an increased risk of developing HCC. Further, TGF-β and IFN-γ levels were higher and lower in patients with HCC or CHB, respectively., Conclusions: Hepato-carcinogenesis occurred more frequently in patients with a positive HBV DNA load and relatively advanced liver disease. Therefore, it is important to administer antiviral therapy to patients with CHB before they develop HBV-related cirrhosis., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The Wnt/β-catenin pathway plays a vital role in initiating and sustaining hepatocellular carcinoma (HCC). However, few studies have investigated polymorphisms in the Wnt/β-catenin signaling pathway genes in the Chinese Han population. The aim of the present retrospective study was to investigate the correlations between polymorphisms of the Wnt/β-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression.Twenty tagging single nucleotide polymorphisms were chosen from HapMap data and genotyped in 320 patients with HCC, 320 chronic hepatitis B virus (HBV)-infected patients without HCC (N-HCC, including 95 liver cirrhosis, 164 chronic hepatitis B, and 61 asymptomatic HBV carriers), and 320 healthy controls. Associations between polymorphisms in the 2 Wnt/β-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression were investigated.Genotype AA (P = 0.002, odds ratio [OR] = 2.524) and allele A (P = 0.0003, OR = 1.613) of the WNT2 rs4730775 polymorphism were associated with HCC susceptibility compared with healthy controls. Genotype GA (P = 0.001, OR = 0.567) and allele A (P = 0.002, OR = 0.652) of rs3864004, and genotype AG (P = 0.0004, OR = 0.495) and allele G (P = 0.001, OR = 0.596) of rs11564475 in the CTNNB1 gene were correlated with HCC compared with N-HCC patients. These findings were consistent in dominant and recessive models. Multidimensionality reduction analysis revealed that interactions among rs3864004, rs11564475, and rs4730775 were significantly associated with HCC compared with N-HCC patients. The polymorphism rs4135385 of CTNNB1 genotype GA was associated with a higher risk for Stage III + IV HCC (modified Union for International Cancer Control) (P = 0.001, OR = 2.238).Genetic polymorphisms in the WNT2 and CTNNB1 genes were closely associated with HCC risk and progression in a Chinese Han population.

Background: Liver cancer exhibits geographic and ethnic differences in its prevalence and biology, which implies that it is impractical to develop universal guidelines for all patients. Thus, a meta-analysis was conducted to identify the accuracy of apparent diffusion coefficients (ADCs) for discriminating malignant from benign liver lesions in Asians., Methods: Eligible studies published in PubMed, Ovid, and Embase/Medline were updated onto October 2014. STATA 12.0 and Meta-Disc 1.4 were used to perform this meta-analysis., Results: Eight studies comprising 661 benign liver lesions and 598 malignant liver lesions fulfilled all the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.88 (95% confidence interval [CI] 0.75-0.95), 0.93 (95% CI 0.86-0.97), 12.42 (95% CI 6.09-25.31), 0.13 (95% CI 0.06-0.29), and 95.58 (95% CI 35.29-258.89), respectively. Overall, the area under the summary receiver-operating characteristic curve was 0.96 (95% CI 0.94-0.98). Heterogeneity was found to originate potentially from the type of benign lesion. A subgroup analysis showed that differentiating between hemangiomas, cysts, and malignant liver lesions produced a significantly higher diagnostic accuracy than that of solid liver lesions., Conclusion: Our meta-analysis indicated that ADC could be promising for characterizing liver lesions among Asians, indicating that the ADC value is a promising diagnostic criterion candidate. Meanwhile, the use of dual b values could be sufficient for liver lesion characterization. However, large-scale, high-quality trials should be conducted to identify specific standards, including cut-off values for further development of diffusion-weighted imaging as a routine clinical application among Asian populations., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To investigate the relationship between microRNA-149 (rs2292832), microRNA-499 (rs2292832) polymorphism and hepatocellular carcinoma susceptibility by meta-analysis., Methods: We used"hepatocellular carcinoma/HCC","miRNA-149/miR-149/microRNA-149", and"miRNA-499/miR-499/microRNA-499"as key words to search papers in databases including China National Knowledge Internet (CNKI), Chinese BioMedical Literature (CBM), Vip Citation Databases (VIP), Wanfang, PubMed and Web of Science databases, and collected the case-control studies on the association of rs2292832 or rs3746444 and the susceptibility to hepatocellular carcinoma from updated to May 31st 2015. Data were extracted by two independent reviewers and pooled OR with 95% CI was calculated. A bioinformatics analysis was further conducted., Results: A total of 13 research papers were collected, and 5 studies for rs2292832 and 12 studies for rs3746444. 1 096 cases and 1 701 controls were included for rs2292832 and 3 117 cases and 4 126 controls were included for rs3746444. Meta-analysis failed to detect associations between rs2292832, rs3746444 and susceptibility to hepatocellular carcinoma under each genetic model tested and alleles of OR(95% CI) were 0.99(0.78-1.28) and 1.11(0.88-1.40). However, subgroup analysis showed that rs3746444 C allele seem to be associated with an increased hepatocellular carcinoma risk in both researches which had more than 400 samples and which used more accurate genotyping methods, and OR(95%CI) were 1.32(1.02-1.70) and 1.34(1.09-1.66), respectively. Furthermore, bioinformatics analysis also showed that the expression of both SNPs were down-regulated in HepG2 cells and indicated possible functional effects on gene transcription. Cochran's Q test indicated that there was the heterogeneity among the studies included., Conclusions: No significant association was found between rs2292832, rs3746444 and susceptibility to hepatocellular carcinoma, but subgroup study indicated C allele might be associated with increased hepatocellular carcinoma risk for rs3746444. Bioinformatics analysis indicated that the two SNPs might have possible influence on gene transcription.

Objective: To understand the association between two single-nucleotide polymorphism (HLA-DQ rs28567185 and rs9275572) and different outcomes of hepatitis B virus (HBV) infection., Methods: A total of 825 HBV infection related cases were enrolled, and peripheral blood samples were collected from them for DNA extraction. The single-nucleotide polymorphism in HLA-DQ region were genotyped by using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Logistic regression analysis was conducted to evaluate the association between HLA-DQ gene polymorphism and different outcomes of hepatitis B virus infection., Results: Our study indicated that cases with HLA-DQ rs2856718G (524 cases) and rs9275572A (369 cases) had reduced susceptibility to HBV infection (OR=0.702, 95%CI: 0.558-0.856, P=0.001; OR=0.548, 95%CI:0.365-0.847, P=0.005) and higher HBV natural clearance (OR=0.589, 95%CI: 0.478-0.892, P=8.81 × 10(-3); OR=0.673, 95%CI: 0.457-0.860, P=0.014). Moreover, rs9275572A was also associated with the lower risk of the development of hepatocellular carcinoma (OR=0.759, 95%CI: 0.538-0.914, P=0.041)., Conclusion: Our study suggested that HLA-DQ loci might be associated with the different outcomes of HBV infection in Chinese in Han ethnic group in northern China, rs2856718G and rs9275572A might be protective factors for HBV infection, HBV natural clearance and HBV-related disease progress.

Objective: HJURP (Holliday Junction-Recognizing Protein) plays dual roles in DNA repair and in accurate chromosome segregation during mitosis. We examined whether the single nucleotide polymorphisms (SNPs) of HJURP were associated with the risk of occurrence of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers from well-known high-risk regions for HCC in China., Methods: Twenty-four haplotype-tagging SNPs across HJURP were selected from HapMap data using the Haploview software. We genotyped these 24 SNPs using the using Sequenom's iPLEX assay in the Fusui population, consisting of 348 patients with HCC and 359 cancer-free controls, and further investigated the significantly associated SNP using the TaqMan assay in the Haimen population, consisting of 100 cases and 103 controls. The genetic associations with the risk of HCC were analyzed by logistic regression., Results: We observed an increased occurrence of HCC consistently associated with A/C or C/C genotypes of the non-synonymous SNP rs3771333 compared with the A/A genotype in both the Fusui and Haimen populations, with a pooled odds ratio 1.82 (95% confidence interval, 1.33-2.49; P = 1.9 × 10-4). Case-only analysis further indicated that carriers of the at-risk C allele were younger than those carrying the A/A genotype (P = 0.0016). In addition, the expression levels of HJURP in C allele carriers were lower than that in A/A genotype carriers (P = 0.0078 and 0.0010, for mRNA and protein levels, respectively)., Conclusion: Our findings suggest that rs3771333 in HJURP may play a role in mediating the susceptibility to HCC among Chinese.

Aim: To investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea., Methods: Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC., Results: None of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323)., Conclusion: Although no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.

Aim: To investigate the relationship between interleukin-21 (IL21) gene polymorphisms and chronic hepatitis B virus (HBV) infection in a Chinese population., Methods: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma (HCC; n = 94) and non-HCC (n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012. In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis. Two hundred eight unrelated healthy controls were also included. Genomic DNA was extracted from peripheral blood. Single nucleotide polymorphisms (SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaPshot SNP technique., Results: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBV-infected patients and control subjects. Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group. However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls (OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model (AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group. IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls (OR = 1.809, 95%CI: 1.043-3.139; P = 0.035). In the haplotype analysis, the ATA haplotype (rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group (0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863)., Conclusion: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onset in a Chinese population.

Aim: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB)., Methods: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested., Results: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity., Conclusion: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.

Background: Mannose-binding lectin2 (MBL2) is implicated in the host immune response, but there are limited data about MBL2 polymorphisms and hepatocellular carcinoma (HCC) risk. This study aimed to investigate the relationship between the MBL2 rs7096206 polymorphism and HCC risk in a Chinese Han population., Methods: A population-based case-control study of 220 HCC patients and 220 age- and gender-matched healthy control subjects from a Chinese Han population was conducted. Genomic DNA was extracted from blood samples, and the presence of the MBL2 polymorphism rs7096206 was assessed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Conditional logistic regression was performed to assess the risk of HCC by determining odds ratios and 95% confidence intervals (CIs)., Results: The odds of HCC among carriers of CG and GG genotypes were 7.33 (95% CI, 2.53-21.29) and 12.48 (95% CI, 2.08-74.90), respectively. In the dominant genetic model, GG+CG carriers had an approximately 8-fold increased risk (95% CI, 2.83-22.62) compared with those with the CC genotype. The G allele was significantly associated with elevated HCC risk, with an odds ratio of 6.83 (95% CI, 2.90-16.10)., Conclusions: Our findings suggest that the MBL2 polymorphism rs7096206 is associated with HCC susceptibility and has the potential to serve as a biomarker to detect populations at increased HCC risk.

Background: The aim of the present study was to evaluate the influence of tumor necrosis factor-alpha (TNF-α) -308 G > A polymorphism on hepatocellular carcinoma (HCC) risk., Methods: The present case-control study was conducted in a Han Chinese population consisting of 753 HCC patients and 760 controls from May 2010 to March 2013. The -308 TNF-a promoter polymorphisms were detected. Conditional logistic regression was performed to analyze the association between TNF-α -308 G > A polymorphism and the risk of HCC, which were estimated by odds ratios (ORs) and their 95% confidence intervals (95% CIs)., Results: The genotypic frequencies in the cases were not similar to that of the controls, differences being statistically significant (P = 0.002). Using the GG genotype as the reference genotype, AA was significantly associated with increased risk of HCC (adjusted OR = 5.12, 95% CI = 2.31-7.82). Similarly, AG + AA genotype showed 5.59-fold increased HCC risk in a dominant model. Furthermore, we found A allele was significantly associated with increased risk of HCC, compared with G allele (OR = 4.18, 95% CI = 1.76-6.97)., Conclusion: The present study showed that TNF-α -308 G > A polymorphism was associated with increased HCC risk in a Han Chinese population. Further prospective studies on large and different ethnic populations will be necessary to confirm our findings and elucidate the underlying molecular mechanism for the development of HCC., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000&#95;2014&#95;199.

Aim: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers., Methods: The end-stage liver disease samples [n = 93, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis] and trimmed normal Chinese donor livers (n = 35) from The Institute of Organ Transplantation in Beijing, China. Total RNA was extracted, purified, and subjected to real-time RT-PCR analysis., Results: For cytochrome P450 enzymes 1 (CYP1) family, the expression of CYP1A2 was decreased 90% in HCC, 80% in alcoholic cirrhosis, and 65% in severe cirrhosis. For CYP2 family, the expression of CAR was decreased 50% in HCC, but increased 50% in peri-HCC tissues. Similar decreases (about 50%) of CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 were observed in HCC, as compared to peri-HCC tissues and normal livers. CYP2C19 were decreased in all end-stage liver diseases and CYP2E1 also decreased in alcoholic cirrhosis and severe cirrhosis. For CYP3 family, the expression of PXR was decreased 60% in HCC, together with decreases in CYP3A4, CYP3A5, and CYP3A7. In contrast, the expression of CYP3A7 was slightly increased in HBV cirrhosis. The expression of CYP4A11 was decreased 85% in HCC, 7% in alcoholic cirrhosis and severe liver cirrhosis, along with decreases in PPARα. The 93 end-stage livers had much higher inter-individual variations in gene expression than 35 normal livers., Conclusion: The expression of CYP enzyme genes and corresponding nuclear receptors was generally decreased in end-stage liver diseases, and significant differences in gene expression were evident between peri-HCC and HCC.

Runt-related transcription factor 3 (RUNX3) is a potential tumor suppressor that is frequently hypermethylated in hepatocellular carcinoma (HCC). The present meta-analysis of case-control studies was carried out to determine whether RUNX3 hypermethylation is associated with HCC. The PubMed, Embase, and Chinese National Knowledge Infrastructure databases were searched for all relevant studies published between May 2000 and May 2012. A total of 11 studies were identified, and 8 studies involving 491 patients with HCC and 409 patients without tumors were found to satisfy the inclusion criteria for the meta-analysis. All tissue samples were from Asian populations. There was significant heterogeneity between the studies. Over the entire sample, the odds ratio (OR) of RUNX3 promoter methylation was 18.5 [95% confidence interval (CI), 11.6-29.6] for HCC tissues relative to control tissues. The ORs of RUNX3 methylation were 16.6 (95%CI = 6.5-42.4) for tumor tissues relative to tumor-adjacent tissues in patients with HCC, 67.3 (95%CI = 13.0-348.5) for tumor tissues from patients with HCC relative to liver tissues from patients with non-neoplastic liver diseases, and 3.26 (95%CI = 1.54-6.90) for tissues from patients with hepatitis C virus (HCV)- related HCC relative to liver tissues from patients with HCC unrelated to HCV. There was no association between RUNX3 methylation and age, gender, pathological stage, or hepatitis B virus infection in HCC tissues. Methylation of the RUNX3 promoter strongly correlated with HCC in Asian populations, especially in individuals with HCV-related HCC, and may be a useful marker for HCC diagnosis in these populations.

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

Backgrounds/aims: Increasing evidence supports the contribution of the pro-/anti-inflammatory cytokine balance and genetic factors to hepatocellular carcinoma (HCC). Here, we investigated whether genetic interferon gamma polymorphisms were associated with HCC in Korean patients with chronic hepatitis B., Methodology: We genotyped a single nucleotide polymorphism (SNP, rs2430561, +874A/T) and a microsatellite (rs3138557, (CA) (n) repeat), located in the first intron of the interferon gamma gene, by direct sequencing and the gene scan method. A population-based case-control study of HCC was conducted and included 170 patients with chronic hepatitis and HCC, and 171 with chronic hepatitis B patients without hepatocellular carcinoma in a Korean population., Results: Genotype and allele distributions of the interferon gamma gene SNP were associated with HCC. The frequencies of the AA genotype and the A allele were significantly increased in hepatocellular carcinoma subjects (p < 0.05). Combined analysis using the genotype of rs2430561 and the number of microsatellites revealed that the frequencies of AT-CA12, and TT-CA12 increased significantly in hepatocellular carcinoma subjects (p < 0.0001)., Conclusions: Our results suggest that the interferon gamma gene may be a susceptibility gene and a risk factor for HCC in the Korean population.

Background: No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk., Design: Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population., Results: During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06-2.51] and women (HR = 1.64, 95% CI 1.03-2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P(trend) < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors., Conclusions: T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens., (© 2013 John Wiley & Sons A/S.)

Background/aims: The mean age of hepatocellular carcinoma (HCC) patients has increased (=65 years old). We want to identify the recent trend of the clinical features of HCC patients due to hepatitis C virus (HCV) (HCV-HCC)., Methodology: From 2000 to 2009, 855 naive HCC patients were admitted. HCV-HCC patients were divided into two groups, first period group (2000-04, n=270) and second period group (2005-09, n=343) and the clinical features of HCV-HCC were investigated., Results: There was no difference in gender, TNM stage and percentages of HCV-HCC between the periods. On the other hand, the ratio of HCV-HCC patients with worse liver function (Child-Pugh B or C), elderly (=75 years old) and the population of patients treated with low invasive radiofrequency ablation were increased (30.0% to 42.0%, 17.2% to 35.8% and 25.1% to 36.2%, respectively; p<0.01). The 1y-, 3y- and 5y-survival rate of HCV-HCC did not show differences (82.1%, 60.5% and 44.7% vs. 81.8%, 56.9% and 37.7%, respectively; p=0.219)., Conclusions: The ratio of aged HCV-HCC as well as HCV-HCC patients with worse liver function was increased. The less invasive treatment for HCC in these patients and the quick anti-viral treatment for HCV patients should be considered to avoid occurrence of HCC in Japan.

The host genetic compound plays a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease. In this report, we explored whether the intronic polymorphism rs3820998 of the TANK gene was associated with outcomes of HBV infection by binary logistic regression analysis. A total of 1305 unrelated Han Chinese patients recruited from Wuhan, including 180 acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients, 331 HBV-related liver cirrhosis (LC) patients, 308 HBV-related hepatocellular carcinoma (HCC) patients, and 486 asymptomatic HBV carriers (AsC) were genotyped using the TaqMan probe method. Logistic analysis revealed that the single-nucleotide polymorphism (SNP) rs3820998 was significantly associated with susceptibility to ACLF-HBV (dominant model, OR 0.643, 95% CI 0.428,0.964, p=0.033; additive model, OR 0.640, 95% CI 0.414,0.990, p=0.045), and LC (recessive model, OR 0.398, 95% CI 0.164,0.966, p=0.042; additive model, OR 0.379, 95% CI 0.155,0.928, p=0.034). These results indicate that the G > T variant is a protective factor in the development of ACLF-HBV and LC, and that the SNP rs3820998 in the TANK gene may play a role in mediating susceptibility to ACLF-HBV and LC in a Chinese Han population.

Objectives: Routine screening for hepatocellular carcinoma (HCC) is recommended in chronic hepatitis B (HBV) patients with cirrhosis and select non-cirrhotic HBV populations including Asian males ages 40 and older and females ages 50 and older. However, many younger HBV patients develop HCC and there have been few studies examining this group. Additionally, studies of HCC in the Asian immigrant population in the United States have been limited. The objective of this study was to determine the associated risk factors for the development of early-onset (males and females under ages 40 and 50, respectively) and late-onset HCC in immigrants with chronic HBV in the United States., Methods: Clinical, demographic, and laboratory data were retrospectively collected on all Asian immigrants with HBV at Bellevue Hospital Center from 2003 to 2009. Patients with HCC were identified within this cohort. Features of early-onset and late-onset HCC cases were compared with age-matched HBV controls without HCC., Results: We identified 168 cases of HCC in Asians with HBV. In all, 74% (124/168) of cases were late-onset, and 26% (44/168) were early-onset. When comparing the 124 late-onset HCC cases with 199 age-matched HBV controls, gender (odds ratio (OR)=4.4; P<0.05) and cirrhosis (OR=9.6; P<0.05) or surrogate labs (i.e., platelets, international normalized ratio, total bilirubin, albumin) were found to be associated with HCC development. When comparing the 44 early-onset HCC cases with 432 age-matched HBV controls, family history of HCC (OR=2.7; P<0.05), and smoking history (OR=3.4; P<0.05) were independently associated risk factors in addition to gender (OR=2.7; P<0.05), and cirrhosis (OR=19.5; P<0.05) or surrogate labs. In all, 54.8% of late-onset HCC cases were cirrhotic and 29.5% of early-onset HCC cases were cirrhotic., Conclusions: HCC occurs in Asian immigrant HBV patients younger than currently recommended screening guidelines. A large majority of these early-onset patients did not have cirrhosis at the time of their HCC diagnosis; therefore, factors other than cirrhosis need to be considered when evaluating HCC risk in young patients. Factors associated with HCC development across all ages include cirrhosis and male gender, while family history and smoking history may identify younger Asian immigrant HBV patients at risk for HCC. Prospective validation, including cost-effectiveness evaluation, is necessary, but our results suggest that younger Asian HBV patients, especially those with a smoking history or family history of HCC, appear to have an increased risk for HCC and should be considered for enrollment in early screening programs regardless of their age.

Background and Aim: To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population., Methods: Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included., Results: A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC., Conclusions: The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Chronic hepatitis B is the leading cause of liver cancer and the largest health disparity between Asian/Pacific Islanders (APIs) and the general US population. The Hep B Free model was launched to eliminate hepatitis B infection by increasing hepatitis B awareness, testing, vaccination, and treatment among APIs by building a broad, community-wide coalition. The San Francisco Hep B Free campaign is a diverse public/private collaboration unifying the API community, health care system, policy makers, businesses, and the general public in San Francisco, California. Mass-media and grassroots messaging raised citywide awareness of hepatitis B and promoted use of the existing health care system for hepatitis B screening and follow-up. Coalition partners reported semi-annually on activities, resources utilized, and system changes instituted. From 2007 to 2009, over 150 organizations contributed approximately $1,000,000 in resources to the San Francisco Hep B Free campaign. 40 educational events reached 1,100 healthcare providers, and 50% of primary care physicians pledged to screen APIs routinely for hepatitis B. Community events and fairs reached over 200,000 members of the general public. Of 3,315 API clients tested at stand-alone screening sites created by the campaign, 6.5% were found to be chronically infected and referred to follow-up care. A grassroots coalition that develops strong partnerships with diverse organizations can use existing resources to successfully increase public and healthcare provider awareness about hepatitis B among APIs, promote routine hepatitis B testing and vaccination as part of standard primary care, and ensure access to treatment for chronically infected individuals.

Objective: Lipiodol transcatheter arterial chemoembolization (TACE) is widely used to treat hepatocellular carcinoma (HCC). Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. The purpose of this study was to compare the efficacy and safety of intra-arterial injection of DEB loaded with doxorubicin versus conventional, Lipiodol-based TACE regimens in Asian patients with HCC., Methods: The study was designed as a case-control, single-institution clinical trial. Twenty patients with HCC who received DEB loaded with 50 mg doxorubicin ('cases') were matched with 20 patients who had undergone conventional TACE ('controls'). The primary efficacy endpoint was tumor response at 1 month according to modified Response Evaluation Criteria in Solid Tumors. The primary safety endpoint was liver toxicity., Results: The rate of objective response by modified Response Evaluation Criteria in Solid Tumors was 85% (17 of 20 patients) in the DEB arm versus 30% (six of 20 patients) in the conventional TACE arm (P=0.001). Subgroup analyses conducted in patients with large (>5 cm) or multinodular tumor confirmed significantly higher objective response rates in patients receiving DEB as compared with those treated with conventional TACE (P=0.003 and P=0.005, respectively). At the dose of 50 mg doxorubicin, there was no statistically significant difference in liver toxicity between DEB and conventional TACE (P>0.05)., Conclusion: In Asian patients with HCC, transcatheter treatment with DEB loaded with doxorubicin offers a distinct advantage in objective tumor response rate as compared with conventional, Lipiodol-based TACE regimens.

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems., Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor-node-metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared., Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow-up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child-Pugh-stage, alpha-fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3-month survival while CLIP performed better in predicting the outcome of 6- and 12-month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance., Conclusion: We have validated CUPI in a population composed of predominant HBV-related HCC. CUPI is an appropriate staging system for HBV-related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Hepatocellular adenoma (HCA) is a benign liver neoplasm with a risk of spontaneous bleeding and malignant transformation. The aim of this review article is to review all the case reports and case series of patients with HCA from 1998 to 2008 in China and other parts of the world in order to compare clinical presentation, surgical management and outcomes. A search for all reports of HCA in the world literature from 1998 to 2008 was performed. A total of 356 patients were identified, including 191 patients from China, 104 from Europe, 46 from North America, and 15 from South-East Asia. A female predominance was not observed in Chinese patients in contrast to the other regions. Acute/chronic abdominal pain was the main clinical presentation in all regions. Twenty patients were diagnosed with coexistent hepatocellular carcinoma (HCC), and hepatitis B virus infection (HBV) was found among six of them. The management of HCA consisted of resection in most cases. The clinical presentation of HCA in China differed from other parts of the world regarding male predominance and a higher incidence of coexistent HCC in China. This might be the result of the birth control policy in China, limited oral contraceptive use, and the higher incidence of HBV., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Secreted frizzled-related protein 1 (sFRP1) is a new tumor suppressor based on recent researches, but the correlation of the genetic instability of sFRP1 gene with the clinicopathologic features of the hepatocellular carcinoma (HCC) has not been studied in Chinese people. In this study, 42 pairs of paraffin-embedded HCC and adjacent non-carcinoma tissues were examined for the loss of heterozygosity (LOH) and microsatellite instability (MSI) of two microsatellite markers D8S532 and D8S1722 located in the vicinity of the sFRP1 gene. Envision immunohistochemistry was used to assess the expression of sFRP1. We found that the reduced expression of the sFRP1 protein was frequently observed in Chinese patients with HCC, which may at least partially result from the genetic instability, especially LOH. The LOH-associated sFRP1 downregulation may play an important role in the development of HCC.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents., (© 2010 John Wiley & Sons A/S.)

Corticotropin-releasing hormone receptor 2 (CRHR2) plays a role in both the central nervous system (CNS) and the peripheral nervous system. CRHR2 together with its ligands, urocortins (Ucns) and corticotropin-releasing hormone (CRH), functions as a mediator of inflammatory response and inhibitor of angiogenesis. Recently, it has been reported to be expressed in many human cancers. An association between rs2267716 polymorphism in the CRHR2 gene and susceptibility to hepatocellular carcinoma (HCC) was found in patients with chronic hepatitis C virus (HCV) infection. In the present study we analyzed, using a polymerase chain reaction-ligation detection reaction (PCR-LDR), the rs2267716 polymorphism in 364 hepatitis B virus (HBV)-related HCC patients, 196 non-HCC patients with HBV infection, and 404 healthy controls. The aim was to detect the possible association of this single-nucleotide polymorphism (SNP) with susceptibility to HBV-related HCC. Significant differences of rs2267716 allele were detected between HBV-related HCC patients and healthy controls (OR = 1.55, 95% CI 1.13-2.15, P = 0.007) or non-HCC patients with HBV infection (OR = 1.61, 95% CI 1.13-2.31, P = 0.009). These results suggest that the rs2267716 polymorphism in the CRHR2 gene might influence the risk of developing HCC in patients with HBV infection in Chinese population.

Background: The Western Pacific region has the highest level of endemic hepatitis B virus (HBV) infection in the world, with the Chinese representing nearly one-third of infected persons globally. HBV carriers are potentially infectious to others and have an increased risk of chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. Studies from the U.S. and Canada demonstrate that immigrants, particularly from Asia, are disproportionately affected by liver cancer., Purpose: Given the different health care systems in Seattle and Vancouver, two geographically proximate cities, we examined HBV testing levels and factors associated with testing among Chinese residents of these cities., Methods: We surveyed Chinese living in areas of Seattle and Vancouver with relatively high proportions of Chinese residents. In-person interviews were conducted in Cantonese, Mandarin, or English. Our bivariate analyses consisted of the chi-square test, with Fisher's Exact test as necessary. We then performed unconditional logistic regression, first examining only the city effect as the sole explanatory variable of the model, then assessing the adjusted city effect in a final main-effects model that was constructed through backward selection to select statistically significant variables at alpha=0.05., Results: Survey cooperation rates for Seattle and Vancouver were 58% and 59%, respectively. In Seattle, 48% reported HBV testing, whereas in Vancouver, 55% reported testing. HBV testing in Seattle was lower than in Vancouver, with a crude odds ratio of 0.73 (95% CI = 0.56, 0.94). However after adjusting for demographic, health care access, knowledge, and social support variables, we found no significant differences in HBV testing between the two cities. In our logistic regression model, the odds of HBV testing were greatest when the doctor recommended the test, followed by when the employer asked for the test., Discussion: Findings from this study support the need for additional research to examine the effectiveness of clinic-based and workplace interventions to promote HBV testing among immigrants to North America.

The outcome of liver transplantation in China remains speculative. From 1998 to 2007, 177 adult Hong Kong patients underwent liver transplantation in China and were subsequently followed up at Queen Mary Hospital, Hong Kong. One hundred six (59.9%) patients had hepatocellular carcinoma (HCC). The grafts were probably derived from uncontrolled non-heart-beating donors. The 1-month mortality rate was 4.0%. The 1-, 3-, and 5-year overall survival rates were 73.9%, 59.0%, and 53.9%, respectively. The 5-year overall survival rates for non-HCC, HCC, HCC (within the Milan criteria), and HCC (beyond the Milan criteria) patients were 66.3%, 44%, 58%, and 26.2%, respectively. The long-term survival was compromised by the high incidence of HCC recurrence and graft failure secondary to diffuse intrahepatic biliary strictures. The overall survival rate of the entire group was lower than that of the patients receiving deceased donor liver grafts at Queen Mary Hospital in the same period. For non-HCC patients, however, the 5-year survival rate of 66.3% was comparable to that of recent reports from the Western world.

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, there is no general consensus as to which staging system is the most reliable for predicting the survival of patients with HCC. The aims of this study were to compare commonly-used staging systems in a cohort of Chinese HCC patients undergoing curative resection., Methods: From January 1991 to June 2002, 234 Chinese patients undergoing curative resection for HCC from one medical center were evaluated. All patients were classified by the Okuda, Cancer of the Liver Italian Program (CLIP), tumor node metastasis (TNM) (6th edition) and the Chinese University Prognostic Index (CUPI) staging systems. Survival curves were calculated using the Kaplan-Meier method and were examined using log-rank testing. The overall predictive power for patient survival with each staging system was evaluated by the area under the receiver operating characteristic (ROC) curve., Results: The overall median survival of the entire cohort was 24.9 months (95% confidence interval (CI) 18.15-31.65 months) and the estimated survival rates at 1, 3, and 5 years were 69.66% 3.01%, 41.02% 3.31%, and 29.08% 3.55%, respectively. In our patient cohort, the log-rank test demonstrated that the TNM and Okuda staging systems gave better results than the other staging systems in the prognosis stratification. The prognostic predictive powers of the TNM staging for survival, evaluated by ROC curve areas, was also superior., Conclusions: For HCC patients undergoing curative resection, the TNM staging system (6th edition) proved the best for prognostic stratification and prognosis prediction.

Background & Aims: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance., Methods: We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression., Results: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages >or=50 years compared with those with HBsAg seroclearance at ages <50 (P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement (P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5-10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels., Conclusions: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.

Aim: To study the relationship between nm23H1 gene genetic instability and its clinical pathological characteristics in Chinese digestive system cancer patients., Methods: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze the microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was employed to detect the expression of nm23H1., Results: The MSI was higher in TNM stage I + II than in stage III + IV of gastric, colonic and gallbladder carcinomas. The LOH was higher in TNM stage III + IV than in stage I + II of gastric, colonic and hepatocellular carcinomas. Lymphatic metastasis was also observed. The expression of nm23H1 protein was lower in TNM stage III + IV than in stage I + II of these tumors and in patients with lymphatic metastasis.The nm23H1 protein expression was higher in the LOH negative group than in the LOH positive group., Conclusion: MSI and LOH may independently control the biological behaviors of digestive system cancers. MSI could serve as an early biological marker of digestive system cancers. Enhanced expression of nm23H1 protein could efficiently inhibit cancer metastasis and improve its prognosis. LOH mostly appears in late digestive system cancer.

Patient-centered approaches to health-care delivery have increased interest in patient satisfaction with care. However, there is no instrument currently available which takes into account the specific concerns of Chinese patients. This study aimed to evaluate the psychometric properties of the Nine-Item Chinese Patient Satisfaction Questionnaire (ChPSQ-9) in a Chinese hepatocellular carcinoma (HPC) sample. A total of 222 Chinese patients with primary HPC completed the ChPSQ-9, the Medical Interview Satisfaction Scale (MISS), and eating satisfaction measures. The principal component analysis yielded two factors in the ChPSQ-9, named 'doctor' and 'nurse' subscales, which explained 79% of the total variance. The instrument also possessed good internal consistency (Cronbach alpha = 0.93) and concurrent validity with MISS. The divergent validity was indicated by inverse relationships between the ChPSQ-9 and eating satisfaction. The current results support the use of the ChPSQ-9 as a self-report measure of patient satisfaction among Chinese HPC populations and suggest that a caring orientation was highly valued by these patients., ((c) 2007 John Wiley & Sons, Ltd)

Background: To the authors' knowledge, no previous U.S. study has examined time trends in the incidence rate of liver cancer in the high-risk Asian/Pacific Islander population. In this study, liver cancer incidence trends were evaluated in Chinese, Filipino, Japanese, Korean, and Vietnamese men and women in the Greater San Francisco Bay Area of California between 1990 and 2004., Methods: Populations at risk were estimated by using the cohort-component demographic method. Annual percentage changes (APCs) in age-adjusted incidence rates of primary liver cancer among Asians/Pacific Islanders in the Greater Bay Area Cancer Registry were calculated by using joinpoint regression analysis., Results: The incidence rate of liver cancer between 1990 and 2004 did not change significantly in Asian/Pacific Islander men or women overall. However, the incidence rate declined, although the decline was not statistically significant, among Chinese men (APC, -1.6%; 95% confidence interval [95% CI], -3.4-0.3%), Japanese men (APC, -4.9%; 95% CI, -10.7-1.2%), and Japanese women (APC, -3.6%; 95% CI, -8.9-2%). Incidence rates remained consistently high for Vietnamese, Korean, and Filipino men and women. Trends in the incidence rate of hepatocellular carcinoma were comparable to those for liver cancer. Although disparities in liver cancer incidence between Asians/Pacific Islanders and other racial/ethnic groups diminished between the period from 1990 through 1994 and the period from 2000 through 2004, the disparities among Asian subgroups increased., Conclusions: Liver cancer continues to affect Asian/Pacific Islander Americans disproportionately, with consistently high incidence rates in most subgroups. Culturally targeted prevention methods are needed to reduce the high rates of liver cancer in this growing population in the U.S., ((c) 2007 American Cancer Society)

Background: Little is known about hepatitis B (HBV) and liver cancer control in Chinese in Canada. Liver cancer, a significant health problem in Asia, is preventable and can be controlled through HBV blood testing, vaccination, and community education about HBV., Objective: The overall goal was to increase HBV testing and vaccination in Chinese adult Canadians. The objective was to present findings on HBV testing, vaccination and knowledge in Chinese immigrants., Methods: 504 randomly selected Chinese adult immigrants residing in Vancouver responded to the survey which examined HBV blood testing and vaccination practices, HBV knowledge levels and socio-demographic characteristics. Face-to-face interviews were conducted in Cantonese, Mandarin, or English., Results: 57% of participants reported that they had received HBV blood testing, 38% had been vaccinated, and 6% were known HBV carriers. There were gender differences, with lower rates of testing and vaccination, and higher chronic carrier rates, among men. Over 80% knew that HBV can be spread by asymptomatic persons and can cause cirrhosis and liver cancer. However, confusion existed about the routes of HBV transmission., Interpretation: A sizeable proportion of Chinese adult immigrants in Vancouver have not been tested or vaccinated for HBV. Knowledge level, especially about routes of HBV transmission, was low. This is a concern, given that chronic HBV infection is the most common cause of liver cancer in Asian North Americans. To improve knowledge, reduce risk of infection and the burden of chronic infection and its sequelae in immigrant populations, continuing educational efforts are needed.

Patients undergoing treatment for cancer have reported a variety of work-related problems. The aim of this study was to investigate the impact of a cancer diagnosis on employment status, and to identify relevant associated factors. This prospective cohort study was conducted at the National Cancer Center in Korea. Male patients newly diagnosed with stomach, liver, or colorectal cancers were recruited. Patients were interviewed and asked to complete an employment questionnaire every 3 months for 24 months. Clinical, sociodemographic and work-related factors were assessed. There were 305 male patients who had a primary diagnosis of cancer and underwent appropriate treatment. Of the 305 male patients who were employed at the time of diagnosis, 53% lost their job, and of these 23% later reemployed. In a multivariate Cox regression analysis, job loss was significantly associated with years of education, job characteristics and disease stage. Reemployment was significantly associated with disease stage and cancer site. Change of employment was common among cancer patients in Korea. With an understanding of the factors involved, it should be possible to reduce unnecessary work cessation, and increase the rate of employment of cancer survivors., (Copyright 2006 John Wiley & Sons, Ltd.)

Background: Liver cancer, a significant health problem in Chinese, can be controlled through HBV blood testing, vaccination, and community education about HBV. The PRECEDE framework has been very helpful in identifying factors associated with health practices., Objectives: The objective was to identify factors associated with HBV testing in Chinese Canadians, using the PRECEDE framework., Methods: Five hundred and thirty-three randomly selected Chinese Canadian adults were interviewed about HBV blood testing practices. Factors were grouped as predisposing, reinforcing and enabling., Results: Fifty-five percent had received HBV blood testing. Several predisposing factors, all reinforcing factors and one enabling factor were associated with HBV testing in bivariate analysis. A physician's recommendation for testing was the strongest factor associated with testing in multiple logistic regression analysis (OR=4.4, p<0.0001)., Interpretation: Many Chinese Canadian adults in Vancouver have not been tested for HBV. Continuing educational efforts are needed and the PRECEDE framework can inform the development of health education interventions.

Background: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study., Methods: The polymorphisms of IL-10 promoter region were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way., Results: Polymorphisms of T/C or T/N on -872 site occurred frequently in Han ethnic population. Polymorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the polymorphisms was inserting base A between -1058 and -1057., Conclusion: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.

Aim: To evaluate the risk factors for primary liver carcinoma (PLC) in Chinese population., Methods: Chinese Biomedical Literature Database, China Hospital Knowledge Database and MEDLINE were searched. All the related literatures were screened, and the risk factors for PLC in Chinese population were studied. Heterogeneity was evaluated by odds ratio (OR) q test. Combined OR and its 95% confidence interval (95%CI) were calculated, the association between the investigated risk factors and PLC was determined. Validity and bias of the findings were evaluated by sensitivity analysis and funnel plot analysis respectively., Results: Fifty-five of one hundred and ninety identified studies were accepted according to the inclusive criteria. Ten factors related to PLC were demonstrated by sensitive analysis and funnel plot analysis. They were cirrhosis (OR = 11.97, P = 0.000), HBV infection (OR = 11.34, P = 0.000), HCV infection (OR = 4.28, P = 0.000), family history of liver cancer (OR = 3.49, P = 0.000), unstable emotion (OR = 2.20, P = 0.000), depressed characters (OR = 3.07, P = 0.000), aflatoxin (OR = 1.80, P = 0.000), alcoholic (OR = 1.88, P = 0.000), intake of musty food (OR = 1.87, P = 0.000) and drinking contaminated water from pond (OR = 1.77, P = 0.003)., Conclusion: The main risk factors for PLC in China are liver diseases, family history of liver carcinoma, poor psychic status, aflatoxin, and some unhealthy behaviors.

Aim: To investigate the occurrence of cellular src (c-src) activating mutation at codon 531 in colorectal cancer patients from Chinese mainland., Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay followed by sequencing and single-strand conformation polymor-phism analysis were carried out to screen 110 samples of primary colorectal cancer and 20 colorectal liver metastases., Results: Only one sample showed PCR-RFLP-positive results and carried somatic codon 531 mutations. No additional mutation of c-src exon 12 was found., Conclusion: c-src codon 531 mutation in colorectal cancer is not the cause of c-src activation.

Background: The aim of this research was to determine the hepatitis B surface antigen (HBsAg) carrier prevalence among cases of hepatocellular carcinoma (HCC), and the population attributable risk of HBsAg carriage for HCC, by ethnicity in New Zealand., Methods: The hospital notes of HCC cases registered with the New Zealand Cancer Registry, for the years 1987-1994 inclusive, were viewed to determine the HBsAg status. Results The HBsAg status was determined for 193 cases of HCC. The HBsAg carrier prevalence for non-Europeans with HCC was markedly higher than that for Europeans, being 76.7% for Maori, 80.0% for Pacific Island people, and 88.5% for Asians, compared to 6.0% for Europeans. In addition to the effect of ethnicity, HCC cases aged <60 years were more likely to be HBsAg carriers than those aged > or = 60 years. The estimated population attributable risk of HBsAg for HCC, within each ethnic group, was only marginally less than the HBsAg prevalence due to the high relative risk of HBsAg carriage for HCC. The standardized incidence rate ratios of HCC for Maori, Pacific Island people and Asians compared to Europeans were 9.6, 20.4, and 22.3, respectively. Hepatocellular carcinoma attributable to HBsAg carriage explained 79%, 83%, and 92% of the excess standardized rate of HCC, compared to Europeans, for Maori, Pacific Island people, and Asians, respectively. Conclusions The HBsAg carrier prevalence in non-European cases of HCC in New Zealand is between 75% and 90%. HBsAg carriage explains the majority of the excess rate of HCC in non-Europeans compared to Europeans in New Zealand.