Results: Skin biopsy of leg ulcer showed vasculitis. Gastroscopy result showed erosive gastritis and colonoscopy result showed multiple ulcer in colon. Result of biopsy of gastric showed find more the presence of vasculitis which patohological anatomic result revealed signs of erythrocyte

extravacation. He was given methyl prednisolon at immunosuppresant dose, oral anticoagulant with prophylactic dose, proton pump inhibitor and acyclovir. The ulcers were resolved after one month follow up. Conclusion: We reported a 48 year old man with gastrointestinal manifestation of systemic vasculitis presented with chronic gastritis Key Word(s): 1. Systemic vasculitis; 2. Chronic gastritis; 3. Gastrointestinal; Presenting Author: XUEFENG LUO Additional Authors: XIAO LI Corresponding Author: XUEFENG LUO Affiliations: westchina hospital Objective: The purpose of this study was to evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) placement in the management

of portal hypertension in non-cirrhotic patients with portal cavernoma. Methods: From June 2005 to December 2011, 15 non-cirrhotic patients with portal cavernoma treated with TIPS placement via a transjugular approach alone in our hospital were followed until last clinical evaluation. There were 4 women and 11 men with a mean age click here of 29.1 years. Technical success of TIPS placement, complications and follow-up

results were evaluated. Results: TIPS placement was successful in 11 out of 15 patients (technical success rate, 73.3%). Procedure-related complication was postprocedural hepatic encephalopathy in one patient. In patients with successful shunt placement, the portosystemic pressure gradient decreased from 25.8 ± 5.7 to 9.5 ± 4.2 mmHg (p < 0.001). TIPS dysfunction occurred in two patients during a median follow-up time of 45.2 months. Revision was not performed in one patient as there was not adequate outflow to keep the stent patent. The other patient died of massive gastrointestinal bleeding in a local hospital. The remaining nine patients all had functioning shunts until the last MCE evaluation. Conclusion: TIPS is a safe and effective therapeutic option in the treatment of non-cirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma. Key Word(s): 1. TIPS; 2. non-cirrhotic; 3. portal cavernoma; 4. PVT; Presenting Author: PÉTER NAGY Additional Authors: SAGA JOHANSSON, STEPHEN SWEET Corresponding Author: PÉTER NAGY Affiliations: AstraZeneca; Research Evaluation Unit, Oxford PharmaGenesis Ltd Objective: Some pharmacokinetic and pharmacodynamic studies have reported that proton pump inhibitors (PPIs), in particular omeprazole and esomeprazole, reduce the antiplatelet activity of clopidogrel by competitively inhibiting its conversion from a prodrug to an active metabolite.

Conclusion: Nrf2 supports

compensatory liver hypertrophy after PVBL. This finding is particularly intriguing, because the primary effect of PVBL is limited to the alteration of bloodstream; this effect is much milder than changes resulting from hepatectomy, in which intrahepatic bloodstream and bile production cease. Our results suggest that premedication with an Nrf2 inducer may be a promising strategy to improve the outcome of PVE; this approach expands Erlotinib price the indication of hepatectomy to patients with poorer liver function. (Hepatology 2014;59:2371–2382) “
“Hemorrhoids are cushions of vascular tissue normally present in the anal canal. They present as painless rectal bleeding and/or prolapsing tissue. The diagnosis is confirmed by anoscopy. Treatment includes high-fiber diet, increased water intake, office procedures such as infrared coagulation, rubber band ligation, sclerotherapy, stapled hemorrhoidopexy, and hemorrhoidectomy. Anal fissure is marked by severe pain during evacuation, which may last from minutes to hours after defecation. The diagnosis is confirmed by inspection and treatments include topical glyceryl trinitrate, diltiazem,

or botulinum toxin type A injection along with supportive care. The most effective treatment is surgical sphincterotomy. Anorectal abscesses and fistulas are caused by infection of the anal glands. The treatment for abscesses is incision and drainage. Fistulas are managed selleck chemicals by fistulotomy or fistulectomy if minimal amount of sphincter is involved or mucosal advancement flap, seton, fibrin glue or collagen plug in the case of high transsphincteric fistulas, anterior fistulas in women, and in patients with Crohn’s disease. “
“This chapter contains sections

titled: Background Epidemiology of travelers’ diarrhea Etiology of travelers’ diarrhea Evidence-base evaluation Prevention of medchemexpress travelers’ diarrhea Historical considerations Immunoprophylaxis Effectiveness of chemoprophylaxis and immunoprophylaxis in the prevention of TD Current practice and recommendations Future research in prevention of travelers’ diarrhea Treatment of travelers’ diarrhea Evidence-based review of travelers’ diarrhea treatment Current practice and recommendations Future research for treatment of travelers’ diarrhea Conclusions Acknowledgments References “
“Aim:  The impact of serological HBsAg− and anti-HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti-HBc positivity imposes any effect on the course of HCV-related chronic liver disease. Methods:  We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow-up of all cohort studies.

As shown in Fig. 1A, HEV RNA appeared in the culture medium of A549 cells www.selleckchem.com/products/ly2835219.html inoculated with HEV genotype 3 stool suspension containing 3.14 × 106 copies of HEV RNA on day 40 after inoculation. The levels of HEV RNA in the culture medium were 1.98 × 102 copies/mL; these levels continued to increase thereafter, reaching a maximum level of 4.35 × 105 copies/mL on day 100 after inoculation. No CPE was observed in HEV-A549 cells. To determine whether HEV was stably generated from HEV-A549 cells, the cells were split for subsequent passage at a ratio of 1:3 when HEV RNA reached the peak titer of 4.35 × 105 copies/mL in culture

medium. Figure 1B illustrates that HEV RNA could be detected in the culture medium harvested from HEV-A549 cells at the second passage. The viral titers were maintained at approximately 3-4 × 104 copies/mL up to the 16th day of passage. IFA showed that ORF2 protein was detectable in the cytoplasm of the HEV-A549 cells (Fig. 1C,D). HEV-A549 cells generating an HEV RNA titer of 4.16 × 104 copies/mL into the culture medium were treated with increasing concentrations of human IFN-α (10, 50, 100, 250, 500, and 1000 U/mL). As shown in Fig, 2, the average reduction rates (as a percentage of the rate

of the control) of the HEV RNA in culture supernatants were only about 10%, 20%, and 50% in the presence of IFN-α at concentrations of 250, 500, and 1000 U/mL, respectively, after 72 hours of incubation. Lower doses of IFN-α (10, 50, and 100 U/mL) did not result in any appreciable reduction in HEV RNA levels (data not shown). Furthermore, subsequent experiments showed that BGB324 mouse HEV replication was not completely inhibited by IFN-α even at a concentration of 5000 U/mL (approximately 50% reduction, data not shown). To investigate how HEV resists IFN-α–mediated responses, three IFN-stimulated response element–controlled cellular genes, PKR, MxA, and 2′,5′-OAS, were analyzed by real-time PCR in both HEV-A549 cells and A549 cells with and without IFN-α. In the absence of stimulation by IFN-α, no significant difference was found in the expression

of any of these genes in A549 cells compared with HEV-A549 cells (Fig. 3). Addition of IFN-α resulted in a significant induction of PKR (∼126-fold increase) and 2′,5′-OAS (∼20-fold). Similarly, an increase in induction of PKR and 2′,5′-OSA was observed after IFN-α treatment of HEV-A549 cells that was MCE significantly weaker than observed in A549 cells (P < 0.005). The difference in activation of MxA was not significant between A549 cells and HEV-A549 cells with and without IFN-α treatment. Many viruses inhibit IFN-α signaling by interfering with the normal activities of STAT1 in the Jak/STAT signal transduction pathway.21 Therefore, steady-state protein level and phosphorylation of STAT1 in response to IFN-α in uninfected A549 cells were determined and compared with HEV-infected HEV-A549 cells. As shown in Fig. 4, STAT1 levels were markedly increased in HEV-A549 cells compared with A549 cells.

The present standard of care (SOC) for patients infected with HCV genotype 1, the most prevalent global genotype, is pegylated interferon (PEG IFN) combined with ribavirin (RBV) for 48 weeks.[4] However, sustained virological response (SVR), defined as the reduction of serum HCV RNA to undetectable levels 24 weeks after the completion

of therapy, is achieved in only 42–52% of patients.[5-7] Moreover, response rates are influenced by patient factors such as sex, age and ethnicity,[8-10] as well as virological factors such as genotype and viral load.[11] SVR rates remain unsatisfactorily low (22%) in women aged 50 years or more who are infected with HCV genotype 1 in Japan.[12] Hence, there is a pressing need to improve the efficacy of antiviral treatment in such patients. Recently, a new class of drugs, with a mechanism based on inhibition of the NS3/NS4 protease of the HCV polyprotein,

Selleckchem Pexidartinib has been investigated for the treatment of chronic hepatitis C. Of the drugs in this class, telaprevir www.selleckchem.com/small-molecule-compound-libraries.html has been selected as a clinical candidate for further development.[13] Telaprevir combined with PEG IFN and RBV has shown potent antiviral activity in phase II[14, 15] and III clinical trials;[16, 17] SVR rates of approximately 70% have been reported in patients infected with HCV-1. Similarly, in Japan, a phase III study was conducted in patients with HCV-1 to compare the efficacy and safety of the telaprevir regimen with those of the current SOC in treatment-naïve patients,[18] and to assess

the efficacy and safety of the telaprevir regimen in relapsers medchemexpress and non-responders after previous IFN-based therapy.[19] However, the high efficacy was offset by treatment-induced anemia: early hemoglobin levels during triple therapy decreased by up to 4 g/dL, whereas decreases with SOC were not higher than 3.0 g/dL.[14, 15] Additionally, we have previously reported that the factors associated with decreases in hemoglobin levels during triple therapy included female sex and age of more than 50 years.[20] Japanese patients infected with HCV genotype 1b with high viral loads are, on average, much older than Western patients infected with the same genotype, owing to a widespread HCV infection that occurred in Japan approximately 20 years ago.[21] Therefore, we considered that triple therapy would be highly effective when combined with careful monitoring of hemoglobin levels and prompt modification of RBV dose. Consequently, in this study, we evaluated the effectiveness and safety of telaprevir-based triple therapy, administrated at an initial telaprevir dose of 2250 or 1500 mg/day, in the retrospective matched control study of 120 Japanese patients with chronic HCV-1 infection with high viral loads.

2A; Supporting Fig. 1F). Twenty-three of twenty-seven cases of HCCs (85%) showed a decreased Rnd3 expression, when compared to peritumor tissue. Mean tumor/nontumor ratio www.selleckchem.com/products/CP-690550.html was 0.68 ± 0.08 (P = 0.0005). Using IHC, Rnd3 expression in peritumor tissue varied from faint to intense and was predominantly localized to the cytoplasm of hepatocytes (Fig. 2B). In contrast, low or no expression was observed in tumor samples (Fig. 2B). Rnd3 protein expression was also determined in healthy primary human hepatocytes as well as in the tumor cell lines, Huh6, Huh7, SNU398, SNU475, Hep3B,

and HepG2. Results showed that Rnd3 expression was reduced in all tumor cell lines tested, as compared to primary hepatocytes (Fig. 2C). Because RND3 expression showed a strong correlation with the presence of satellite nodules in HCC, we analyzed the effect of changes in RND3 expression level on cell invasion in the

Hep3B HCC cell line. Lentiviral transduction led to a 6-fold overexpression of Rnd3, which was associated with a 4.5-fold reduction in cell ability to invade Matrigel (Fig. 3A). On the other hand, transient Rnd3 knockdown using two different siRNAs led to decreased expression of Rnd3 protein by 95% (S1) or 75% (S3) (Fig. 3B) and resulted in a significant increase in invasion (Fig. 3B). The increase was more drastic with S1 than S3, which is in agreement with their silencing efficacy. While performing invasion assays, we also analyzed cell growth and found that Rnd3 knockdown led to an inhibition of HCC cell growth (Fig. 3C). Thus, our results demonstrate that Rnd3 expression levels learn more inversely regulate HCC cell-invasion and growth properties. Because of our initial observation that down-regulation of Rnd3 was associated with evidence of an invasive phenotype in patients, and to better characterize Rnd3 involvement in HCC progression, we focused our study on the invasion mechanism. Because loss of the cell-junction protein, E-cadherin, is associated 上海皓元 with HCC cell invasiveness,23, 24 we evaluated E-cadherin

expression in Rnd3-depleted cells. Rnd3 silencing in Hep3B (Fig. 4A,B) using both siRNAs led to a significant decrease in E-cadherin mRNA expression, whereas a significant down-regulation of E-cadherin protein was only observed with S1. However, decrease of E-cadherin protein expression was significantly observed with both siRNAs in Huh7 cells (Supporting Fig. 2A). IF analyses confirmed that E-cadherin expression was strongly reduced at cell-cell contacts in Rnd3-silenced cells (Supporting Fig. 2B). These results suggest that Rnd3 depletion affected the integrity of adherens junctions. We then sought to analyze E-cadherin protein levels in the 27 HCCs previously used for measuring Rnd3 expression. E-cadherin expression was down-regulated in 16 of 27 HCCs, as compared to peritumor tissue (Supporting Fig. 3).

Transfection of nonsusceptible human hepatoma cell lines with an expression plasmid of human NTCP rendered Huh-7 and HepG-2 cells permissive to infection with HBV and HDV. Furthermore, sequence swapping of nine amino acids in the NTCP taken from nonsusceptible monkeys with the corresponding sequence from the human form of this protein converted the monkey NTCP into a functional receptor for both viruses. These results have implications for the mouse

hepatocytes and other animal data presented by the Urban group cited above, and further studies are required to clarify these observations. The discovery of NTCP as a receptor for HBV and HDV is an important step p38 MAPK pathway forward in our attempts to control and eliminate HBV/HDV, but there are some caveats. Transfection of Huh-7/Hep G-2 with NTCP did render them susceptible to HBV/HDV infection in vitro, but only 10% of the cell cultures

were positive, and the extracellular yield of virus and subviral particles was disappointingly low. This is in stark contrast to clinical HBV and HDV IWR-1 mw infection, where nearly 100% of hepatocytes can be infected and the cells express extremely high titers of viral nucleic acids and proteins. As discussed by Schieck et al.,7 host components or conditions that permit efficient viral infection and replication or block any restriction factors in vivo have yet to be identified fully. Together, these landmark studies herald an exciting and vibrant new era in HBV virology, cell biology, and pathogenesis and should accelerate the discovery and development

of a new class of HBV and HDV inhibitors. Hopefully, the eradication of both viruses and the curing of patients will now become a very real possibility. “
“Hilar medchemexpress cholangiocarcinoma (HCCA) is one of the most common types of hepatobiliary cancers reported in the world including Asia–Pacific region. Early HCCA may be completely asymptomatic. When significant hilar obstruction develops, the patient presents with jaundice, pale stools, dark urine, pruritus, abdominal pain, and sometimes fever. Because no single test can establish the definite diagnosis then, a combination of many investigations such as tumor markers, tissue acquisition, computed tomography scan, magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasonography/intraductal ultrasonography, and advanced cholangioscopy is required. Surgery is the only curative treatment. Unfortunately, the majority of HCCA has a poor prognosis due to their advanced stage on presentation. Although there is no survival advantage, inoperable HCCA managed by palliative drainage may benefit from symptomatic improvement. Currently, there are three techniques of biliary drainage which include endoscopic, percutaneous, and surgical approaches. For nonsurgical approaches, stent is the most preferred device and there are two types of stents i.e. plastic and metal.

6% [95% CI 1.3% to 1.9%]; validation cohort: 0.9% [95% CI -0.1% to 8.6%]). Moreover, it added marginally more discriminative ability than did the Charlson index (nationwide cohort: 0.4% [95% CI 0.2% to 0.7%]; validation cohort: 0.2% [95% CI -0.9% to 1.2%]). PLX4032 research buy Conclusions: Comorbidity

is prevalent and increases mortality, so it must be described, quantified, and controlled for in studies of cirrhosis patients. The CirCom score is specifically designed for these tasks, and it is much simpler and slightly better than the Charlson index. Comorbidities included in the final CirCom score. Comorbidity Adjusted hazard ratio Severity weight Chronic obstructive pulmonary disease 1.22 (1.13 to 1.32) 1 Acute

myocardial infarction 1.26 (1.08 to 1.47) 1 Peripheral arterial disease 1.28 (1.15 to 1.44) 1 Epilepsy 1.32 (1.17 to 1.49) 1 Substance abuse other than alcoholism 1.38 (1.25 to 1.54) 1 Heart failure 1.39(1.28to 1.52) 1 Non-metastatic or hematologic cancer 1.43(1.31 to 1.55) 1 Chronic kidney disease 1.91 (1.49 to 2.45) 3 Metastatic cancer 1.99 (1.64 to 2.42) 3 Disclosures: Timothy L. Lash – Advisory Committees or Review Panels: European Crop Protection Agency The following people have nothing to disclose: Peter Jepsen, Hendrik V. Vilstrup Purpose: Immune dysfunction contributes to liver disease progression and infection risk in alcoholic cirrhosis (AC). The purpose of the study is to better characterize liver injury biomarkers, Dabrafenib insulin resistance/adipokines, and immune function in subjects enrolled in an NIH-funded, placebo-controlled, clinical trial of zinc sulfate for alcoholic cirrhosis (ZAC). Methods: Baseline data and fasting blood samples of 17 consenting subjects with (Child-Pugh class A or B) AC were evaluated

and compared to 8 non-drinking, healthy controls. Plasma adipokines and whole blood ex vivo lipopolysacharide-stimu-lated (LPS) and phytohemagglutinin-stimulated (PHA) cytokine production were measured by Luminex. Plasma cytokeratin 18 (CK18, M30 and M65) were measured by ELISA. Differences between the means (AC vs. controls) were evaluated by t-test using GraphPad-Prism 上海皓元医药股份有限公司 and statistical significance was set at p<0.05. Results: The mean age (55.0±10.1 years) and BMI (26.2±3.9 kg/m2) in AC were similar to controls. The mean Child-Pugh and MELD scores in AC were (6.0±1.4 and 9.0±3.5). 6 AC subjects were still drinking alcohol and 3 had type 2 diabetes. Mean plasma CK18 M30 and M65 were significantly increased in AC compared to controls (p<0.05). Mean insulin levels were significantly increased in AC (p<0.05) while mean glucose levels were similar. There were non-significant trends towards higher adiponectin, leptin, PAI-1, and resistin in AC. Un-stimulated whole blood ex vivo production of IL-6, IL-8, IL-10, and TNF-α were significantly increased in AC (p<0.05).

Therefore, a new strategy to delay or prevent disease progression in PBC patients with an incomplete response to UDCA is urgently required. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells capable of differentiating into multiple lineages.[10-13] MSCs have been used as a therapeutic strategy for tissue regeneration and repair, and their potential immunomodulatory capacity has also raised significant clinical interest.[14-17] Although these properties are not completely understood, emerging evidence from animal and human studies makes MSCs a promising

therapeutic tool for autoimmune disease. The umbilical cord-derived MSC (UC-MSC) is of particular Talazoparib datasheet interest because of its relatively easy accessibility and abundant source,[18] making it a good substitute for MSC in future clinical Z-IETD-FMK cost studies. Recently, transfusion of UC-MSCs has been reported to significantly improve symptoms in patients with severe autoimmune diseases, such as severe and refractory systemic lupus erythematosus,[19] therapy-resistant rheumatoid arthritis,[20] and immune thrombocytopenia patients,[21] with few adverse effects. Recently, our

own 上海皓元医药股份有限公司 research has indicated that UC-MSC therapy is well tolerated and has the potential to

improve liver function, and reduce ascites and mortality in hepatitis B virus-associated patients with decompensated liver cirrhosis[22] and liver failure,[23] respectively. The goal of the present pilot study was to evaluate the safety and initial efficacy of UC-MSC transplantation in PBC patients with an incomplete response to UDCA therapy. Seven PBC patients with an incomplete response to UDCA were enrolled in the study between May 6, 2010 and March 5, 2011 in Research Center for Biological Therapy/Beijing 302 Hospital. These patients (ages between 33 and 58 years) were diagnosed with PBC based on the presence of an antimitochondrial antibody (AMA) titer > 1 : 40, and serum alkaline phosphatase (ALP) at least twice the upper limit of normal in the absence of biliary obstruction, which was in accordance with the American Association for the Study of Liver Diseases practice guidelines.[1] Additionally, enrolled patients did not have a normalization of their ALP after a minimum of six months of treatment with adequate doses of UDCA.[8, 24, 25] The exclusion criteria were as follows: pregnancy; coexisting liver disease (hepatitis A, hepatitis B, and hepatitis C, etc.

15 Whole-cell extracts from cultured cells or tissues were prepared and subjected to western blot. For immunodetection, the following antibodies were used: anti–Bcl-xL antibody and anti-human Mcl-1 antibody from Santa Cruz Biotechnology (Santa Cruz, CA); anti-mouse Mcl-1 antibody from Rockland (Gilbertsville, PA); anti-Bid antibody, anti-Bax antibody, and anti-cleaved caspase-3 antibody from Cell Signaling Technology (Beverly, MA); anti-Bak antibody from Millipore (Billerica, MA); anti-Bim antibody from Assay

Design (Ann Arbor, MI); anti-ubiquitin-specific peptidase 9, X-linked (USP9X) antibody from Abnova (Taipei, Taiwan); and anti–beta actin selleck chemical antibody from Sigma-Aldrich (St. Louis, MO) or Cell Signaling Technology. To produce a xenograft tumor, 3 × 106 to 5 × 106 Hela–Bcl-xLTet-on clone A or Huh7 cells were subcutaneously injected to Balb/c nude mice. For induction of HA–Bcl-xL, the mice that

were injected with Hela–Bcl-xLTet-on clone A cells were fed with water containing 100 μg/mL doxycycline. For anticancer therapy, ABT-737 was administered as described.17 Sorafenib tablets were crushed and orally administered with water containing 12.5% Cremophor EL (Sigma-Aldrich) and 12.5% ethanol. We estimated the volume of the xenograft tumor using the following formula: tumor volume = π/6 × (major axis) × (minor axis)2. Hepatoma cell lines were transfected with Stealth select RNAi (set of three oligonucleotides, Invitrogen) Cell Cycle inhibitor RNA interference (RNAi) directed against Mcl-1 or USP9X. A Stealth RNAi negative control kit (set of three oligonucleotides, Invitrogen) was used as a control for sequence-independent 上海皓元医药股份有限公司 effects following Stealth RNAi delivery. The transfections were carried out using Lipofectamine RNAiMAX (Invitrogen) according to the reverse transfection protocol. Real-time reverse-transcription

PCR (RT-PCR) was performed as previously described.15 Mcl-1 messenger RNA (mRNA) expressions were measured using TaqMan Gene Expression Assays (Assay ID: Hs03043899_m1) and were corrected with the quantified expression level of beta actin mRNA measured using TaqMan Gene Expression Assays (Assay ID: Hs99999903_m1). Data are presented as mean ± standard deviation. Differences between two groups were determined using the Student t test for unpaired observations unless otherwise noted. Multiple comparisons were performed by analysis of variance followed by Scheffe post hoc correction. P < 0.05 was considered statistically significant. Research has shown that Bcl-xL overexpression confers resistance to apoptosis in a variety of tumor cells. To examine its impact on tumor growth in vivo, we generated the Hela–Bcl-xLTet-on cell line which expresses the modified tetracycline repressor molecule (rtTA) and Bcl-xL under control of tetracycline-responsive cis-elements.

7 The same group also performed a second GWAS, with an increased sample size of 458 Japanese persistent HBV infection cases and 2,056 controls for additional GWA scan, and they found

such an association with another two SNPs (rs2856718 and rs7453920) in HLA-DQ.8 However, in these two GWAS studies, the data on HBV exposure of controls were unknown, which may have introduced information bias in the results. Quizartinib mouse To further test the association of HLA-DP/DQ variants with risk of both HBV clearance and HCC development, we genotyped these four SNPs in 1,300 HBV-positive HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance in Southeast Han Chinese populations. CD, cluster of differentiation; χ2, chi-square test; CI, 95% confidence

interval; GWA, genome-wide association; GWAS, genome-wide association study; anti-HBc, antibody against hepatitis B core antigen; anti-HBs, antibody against hepatitis B surface antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; anti-HCV, HCV antibody; HCC, hepatocellular carcinoma; HLA, human leukocyte antigen; LD, linkage disequilibrium; OR, odds ratio; SNPs, single-nucleotide polymorphisms; WT, wild type. This study was approved by the Institutional Review Board of Nanjing Medical MK-2206 cost University (Nanjing, China). Briefly, HCC patients were consecutively recruited between January 2006 and December 2010 at the Nantong Tumor Hospital (Nantong, China), Qidong Liver Cancer Institute (Qidong, MCE China), and the First Affiliated Hospital of Nanjing

Medical University without restrictions of age and sex. The diagnosis of HCC was confirmed by a pathological examination and/or alpha-fetoprotein elevation (>400 ng/mL) combined with imaging examination (i.e., magnetic resonance imaging and/or computerized tomography). Because HCV infection is rare in Chinese populations, we excluded patients with HCC with HCV infection. As a result, 1,300 HBV-positive HCC cases consented to participate in the study and provided blood samples. Two groups of controls were used in the current study: one was the HBV persistent carrier group and the other was a group of subjects with HBV natural clearance. Overall, the controls from two cities in Jiangsu Province (9,720 subjects from Changzhou and 48,422 subjects from Zhangjiagang) were screened for the HBV/HCV (hepatitis C virus) markers in 2004 and 2009. All participants were self-reported Han Chinese and more than 30 years old. HBV persistent carriers were those who were positive for both HBsAg and antibody against hepatitis B core antigen (anti-HBc), but negative for HCV antibody (anti-HCV); subjects with HBV natural clearances were those who were negative for HBsAg and anti-HCV, but positive for both antibodies against hepatitis B surface antigen (anti-HBs) and anti-HBc.