The prevalence of family history of T2DM was also significant. STAT inhibitor Table 2 shows the age-adjusted and multivariate odds ratios with underlying fatty liver for IFG and T2DM. After adjustment for the potential confounders, fatty liver was a significant risk factor for IFG and T2DM in both men and women. The impact did not differ with the sex. The odds ratios (OR) were significantly larger among those with lower BMI. We thus found significant decrease of OR with

fatty liver for IFG and T2DM, that is 0.92 (95% confidence interval [CI] 0.86–0.99) in men and 0.90 (95% CI 0.81–0.99) in women, for one increment of BMI. The present study demonstrated that fatty liver as assessed by ultrasonography is an independent risk factor for IFG and T2DM in Japanese subjects undergoing health checkups. The incidence of newly diagnosed IFG or T2DM over the 5-year period was significantly higher in the participants Buparlisib with fatty liver than without fatty liver in both sexes. In addition, a significant interaction between fatty liver and BMI was observed and risk was higher among the leaner participants. It has been demonstrated that fasting hyperglycemia,

systolic blood pressure, BMI, family history of DM and visceral adiposity are risk factors for T2DM.12–14 Elevation of liver enzymes, including γ-glutamyltransferase and alanine aminotransferase is associated

with the metabolic syndrome and is an independent predictor of T2DM.15–18 In most cases, elevation is due to fatty liver.12,16,17,20 Indeed, it has been shown that NAFLD is a risk factor for impaired glucose metabolism and T2DM,2–4,21 as confirmed for both sexes in the present study. It is well established that obesity is a strong risk factor for T2DM and a link has been found with increased BMI even within non-obese levels.34 Insulin resistance and hyperinsulinemia 上海皓元医药股份有限公司 appear closely associated with NAFLD in the subjects with normal bodyweight24–26 and there may be increased risk of cardiovascular diseases.26,35 Indeed, we demonstrated herein that the impact of fatty liver on the risk factor of IFG or T2DM was stronger in leaner participants of both sexes. Taken together with the previous reports, we conclude that non-obese participants with fatty liver should be advised to make appropriate lifestyle changes. The mechanisms by which fatty liver might lead to IFG or T2DM could not be elucidated in the present study. However, it is widely accepted that there is a close association with insulin resistance.7–10,20 Hepatic lipid accumulation causes impaired insulin clearance and defects in insulin suppression of glucose production which results in increased fasting serum glucose.

Early diagnosis and treatment have reduced in-hospital mortality from approximately 80% to 15–20%. “
“Abnormal metabolism of non-esterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), a LD-binding protein, regulates the storage and see more hydrolysis of TG in LD. However,

its roles and underlying mechanisms in the liver remain unknown. Here, we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression Proteasome inhibitor and activity of PPARα stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically,

we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. Conclusion: We revealed Plin5 as an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis, which provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. (Hepatology 2014;) “
“A 68-year-old male with liver cirrhosis and hepatocellular

carcinoma treated by radiofrequency ablation was hospitalized for right hepatic hydrothorax and ascites. Perflubutane injected into the peritoneal cavity after an ultrasonography contrast agent revealed jet-like flow from the ascites to a pleural effusion, indicating a diaphragmatic defect. A hepatic hydrothorax was sutured under thoracoscopy and did not recur. An intraperitoneal injection of perflubutane enables a less-invasive 上海皓元医药股份有限公司 diagnosis of a diaphragmatic defect. (HEPATOLOGY 2012;) CEUS, contrast-enhanced ultrasonography; HCC, hepatocellular carcinoma; RFA, radiofrequency ablation; US, ultrasonography A 68-year-old male with chronic hepatitis B and C was admitted during April 2009 with hepatocellular carcinoma (HCC). We performed ultrasonography (US)-guided radiofrequency ablation (RFA) using a 2-cm cool-tip electrode (Radionics, Burlington, MA) to treat a 1.5-cm HCC nodule adjacent to the diaphragm in segment VIII (Fig. 1A, arrow). One year later, a 1.0-cm localized tumor progression (Fig.

Early diagnosis and treatment have reduced in-hospital mortality from approximately 80% to 15–20%. “
“Abnormal metabolism of non-esterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), a LD-binding protein, regulates the storage and Trichostatin A hydrolysis of TG in LD. However,

its roles and underlying mechanisms in the liver remain unknown. Here, we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression buy Metformin and activity of PPARα stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically,

we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. Conclusion: We revealed Plin5 as an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis, which provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. (Hepatology 2014;) “
“A 68-year-old male with liver cirrhosis and hepatocellular

carcinoma treated by radiofrequency ablation was hospitalized for right hepatic hydrothorax and ascites. Perflubutane injected into the peritoneal cavity after an ultrasonography contrast agent revealed jet-like flow from the ascites to a pleural effusion, indicating a diaphragmatic defect. A hepatic hydrothorax was sutured under thoracoscopy and did not recur. An intraperitoneal injection of perflubutane enables a less-invasive medchemexpress diagnosis of a diaphragmatic defect. (HEPATOLOGY 2012;) CEUS, contrast-enhanced ultrasonography; HCC, hepatocellular carcinoma; RFA, radiofrequency ablation; US, ultrasonography A 68-year-old male with chronic hepatitis B and C was admitted during April 2009 with hepatocellular carcinoma (HCC). We performed ultrasonography (US)-guided radiofrequency ablation (RFA) using a 2-cm cool-tip electrode (Radionics, Burlington, MA) to treat a 1.5-cm HCC nodule adjacent to the diaphragm in segment VIII (Fig. 1A, arrow). One year later, a 1.0-cm localized tumor progression (Fig.

Our observations for a major find more proinflammatory function of IL-32 in chronic HCV are in accordance

with those presented by Joosten et al.13 demonstrating that IL-32 was specifically up-regulated in synovial tissue of patients with rheumatoid arthritis (but not in patients with osteoarthritis) and correlated with markers of systemic and synovial inflammation. In patients with COPD, IL-32 staining of fixed lung tissues correlated with disease severity and the level of TNF-α and MAPK p38 expression, again strongly highlighting the association of IL-32 with inflammation and the expression of other proinflammatory cytokines.14 In primary cultured human endothelial cells from the umbilical veins, IL-32 is constitutively expressed and increases upon stimulation with IL-1β.15 In our study, we observed that IL-32 is also constitutively expressed in hepatoma cell lines and increases upon exposure to IL-1β or TNF-α. Moreover, there is a marked synergistic effect of TNF-α plus IFN-α in increasing IL-32 in these cells which can be efficiently blocked by NF-κB and/or Jak/STAT inhibition. IFN-α is a pleiotropic cytokine that exerts numerous antiviral, antiproliferative, and antiinflammatory functions.38 IFN-α alone did not affect IL-32 expression, even at rather high nonphysiologic concentrations such Selleck ICG-001 as 1,000 or 2,500

U/mL, suggesting that such an effect might not be functional in vivo. In contrast, 上海皓元 the synergistic effect on TNF-induced

IL-32 induction in both hepatocytes and especially in CD14+ monocytes may be clinically relevant because this would result in augmented inflammation in the infected liver of these patients. In mice expressing human IL-32β as a transgene, there is greater inflammation with a second stimulus. In fact, it appears that IL-32β expression in transgenic mice increases lipopolysaccharide (LPS) lethality.16 Very recently, Nold et al.20 reported that recombinant IL-32 controls HIV-1 replication in human peripheral blood mononuclear cells (PBMCs). Mechanistically, the authors demonstrated that the antiviral effect was due to IFN-α because antibody to the type I interferon receptor or a neutralizing soluble type I interferon receptor abrogated IL-32′s antiviral capacity.20 We found that type I interferon modulates TNF-induced IL-32 expression. Therefore, we asked whether IL-32 might affect HCV infection. Of note, IL-32 immunoreactivity was significantly higher in patients infected with HCV genotype 3 compared with patients with HCV genotype 1. Antiviral activity has been reported for several proinflammatory cytokines such as IL-1β, IL-12, and TNF-α, and suppression of these cytokines is a well-known mechanism of HCV immune escape.39-41 Using HCV luciferase reporter viruses, we did not observe any antiviral capacity for IL-32 employing two different experimental models. Importantly, however, we demonstrated that HCV infection of Huh-7.

Depending on the anatomy

of the targeted SPSS and preference of the interventional radiologist, the approach and occlusive type of intervention was determined. In case of recanalized paraumbilical veins, the approach was mainly percutaneous (occasionally transhepatically) and under local anesthesia, whereas for SRS, mesenterico-renal, or -caval shunts, the access was primarily transhepatically or less frequently by way of the femoral vein and under general anesthesia. In any case, the SPSS was first confirmed and evaluated by way of conventional angiography. Embolization was subsequently performed using either check details coils, amplatzer plugs or matrix, or a combination of these latter. Occlusion was angiographically confirmed at the end of the procedure. In patients fulfilling inclusion and lacking exclusion criteria, medical history, demographic and biochemical characteristics, drug history, specifics of the SPSS, details of the embolization procedure including potential associated complications, immediate and long-term outcome, and survival were reconstructed and completed according to medical records and clinical databases and/or by contacting the general physician KU-57788 research buy in charge

of the patient. The data were retrieved per center by way of a standardized case-report form and centrally processed. Efficacy was evaluated by direct (primary) and indirect (secondary) outcome parameters. MCE The primary outcome measure was to evaluate the number of patients free of HE within 100 days pre- and postintervention (short-term efficacy) and during overall time of follow-up pre- and postintervention (long-term efficacy). Secondary parameters involved assessment

of the worst grade of encephalopathy, number and days of hospitalizations because of HE, changes in medical therapy, and the degree of disability on a short- and long-term basis, as defined above. The degree of disability or dependence in daily activities was assessed through the modified Rankin Scale (mRS).20 Safety was assessed by evaluating immediate postprocedural complications (bleeding, thromboembolic events, infection, anaphylaxis, hypotension, etc.) and in the long-term by monitoring portal hypertensive complications: de novo occurrence or aggravation of preexisting gastroesophageal varices or portal hypertensive gastropathy (with or without bleeding), ascites (with or without need of paracentesis), or spontaneous bacterial peritonitis. Changes in liver function were assessed by alterations in the MELD score. Statistical analysis was performed using MedCalc Statistical Software. Data are given as mean ± standard error of the mean (SEM) or as range between brackets.

6%). FBD experience multiple bleeding symptoms and obstetrical-gynaecological morbidity. The female UDC is the first prospective, longitudinal surveillance in the US focusing on FBD and has the potential to further

identify complications and reduce adverse outcomes in this population. “
“The therapeutic plasma levels of factor VIII (FVIII) or factor IX (FIX) in various clinical situations are reasonably well known and the methods to achieve, maintain, and monitor these levels are well established. The aim of this chapter is to review the pharmacokinetics of FVIII and FIX, with a description of methods and parameters, and in addition to give a brief outline of clinical applications to optimize the treatment of hemophilia. The pharmacokinetics of FVIII and FIX in the applicable populations of patients has been studied extensively and some information Selleck GSK1120212 has

been obtained on relationships with observable patient characteristics. Dose adjustment, or dose tailoring, of coagulation factor treatment must however be based on measurements and clinical observations in the individual. Applied pharmacokinetics has become an established tool to aid dosing in the treatment of hemophilia. FK228 nmr “
“The aim of this study was to evaluate the capability of thromboelastometry (ROTEM) and thrombin generation assay (TGA) to monitor the treatment response of bypassing agent (BPA) therapy and to study whether one method is superior to another. In a prospective crossover study haemophilia A patients

with high titre MCE公司 inhibitors were included to receive a dose of 75 U kg−1 activated prothrombin complex concentrates (aPCC) intravenously. Blood sampling was performed at baseline, 15, 30 min, 1, 2, 3 and 4 h post-infusion for TGA and ROTEM analysis. After a washout period of 14 days the subjects received recombinant FVIIa (rFVIIa) at a dose of 90 μg kg−1 and similar blood sampling was performed. Healthy subjects were used as controls. Six haemophilia A patients with inhibitors were included. We found that TGA parameters endogenous thrombin potential (ETP) and peak thrombin increased 2–3 folds from baseline 15–30 min after infusion. ROTEM parameters MaxVel and maximum clot firmness increased to a level comparable to that of healthy controls. An individual difference in response was observed for different parameters among participants. ETP and peak thrombin were almost two-fold greater following aPCC infusion compared to rFVIIa, whereas ROTEM parameters showed no difference in response between the two products. The study showed that ROTEM and TGA have a great potential to evaluate the effect of BPA in haemophilia patients with inhibitors. TGA seemed to be more sensitive than ROTEM in reflecting the difference in treatment response between aPCC and rFVIIa. Additional prospective clinical studies are needed to clarify which assay and what parameters are clinically predictive.

Results: The total number of esophageal cancer related hospitalizations remained stable with 12,230 admissions in 2000 to 13,672 in 2009 (p trend – NS). The proportion of inpatients being discharged to home care increased from 17.9% to 30.2% (p trend < 0.01) while those with routine discharge decreased from 49.25% to 38.5% (p trend < 0.05) (See figure). Per capita charges for inpatient hospitalizations more than doubled from $ 33,984 in 2000 to $73,884 in 2009, with a $2904/ year increase on linear regression (p < 0.01). These trends coincided with an increase in associated conditions

like dysphagia or malnutrition from 19.1% to 29.1% (p trend < 0.01). However the rates of aspiration pneumonia (2.5% in 2000 and 2.6% in 2009, p – NS) and procedures like esophagectomy (2.7% in 2000 vs 5.7%

in 2009, p- NS) STA-9090 remained stable. There is a decrease Temsirolimus order in the mortality rate from 13.9% to 10.3% (p trend < 0.05) Conclusion: The rates of inpatient admissions for esophageal cancer have remained stable but there has been a significant increase in hospitalization costs. Despite a significant improvement in patient mortality over the past decade, there continues to be a 10% in-hospital mortality rate with increasing number of these patients being discharged to home care. Future studies are needed to determine if efforts to prevent hospitalization of these patients can reduce disease mortality and costs. Key Word(s): 1. Esophageal Cancer; 2. Inpatients;

3. Outcomes; Presenting Author: ZHONG GAO WANG Additional Authors: ZHI WEI HU, JI MIN WU, JIAN JUN LIU, SHU RUI TIAN, FENG JI, ZHI TONG LI Corresponding Author: ZHONG GAO WANG Affiliations: Center for GERD, General Hospital of Second Artillery; Center for GERD, The First Affiliated Hospital of Zhengzhou University Objective: GERD may cause extra-esophageal symptoms (ES) such as asthma, chronic cough and hoarseness. A Center for GERD was established especially for ES by us in 2006. In addition to apply adjusting life habit and medical treatment, so far, 3158 patients has been admitted with full documents, with 1423 Patients treated by Stretta radiofrequency and 1310 by fundoplication. This study is to investigate the effectiveness of interventional treatment for ES. Methods: atients medchemexpress with medication refractory ES and/or typical GERD were admitted, diagnosis was established on GERD symptom score questionnaire, endoscopy, reflux monitoring and manometry. Patients were followed up 12 months after they received radiofrequency or fundoplication with the questionnaire. Results: Among the 3158 patients, 2016 have already been collected in the database. There were 1032 (51.2%) males and 984 females (48.8%). The age was from 7 to 85 with an average of 49.8 ± 12.6. The illness course was from 0.5 to 70 years with an average of 14.6 ± 8.0. 111 patients (5.

In our population, it also seems to have a greater influence on treatment response. IL28B’s mechanism of action is likely effected through ISG expression. These results indicate that patient’s native IL28B genotype has a greater influence than donor genotype on relevant ISG expression, and consequently on treatment response. Disclosures: Richard Gilroy – Advisory Committees

or Review Panels: FDA GIDAC; Speaking and Teaching: Salix, Vertex, Gilead The following people have nothing to disclose: Zoe Raglow, Chuanghong Wu, Winston Autophagy Compound Library supplier Dunn, Yu-Jui Y. Wan BACKGROUND & AIMS MicroRNAs (miRNAs) are an important class of small non-coding RNA molecules that bind to their complementary sequence on their target mRNAs, resulting in translational repression. MiRNAs play major

roles in development, metabolism, infection, and cancer. The diagnosis of cholangiocarcinoma is sometimes difficult due to the lack of a specific tumor marker and limited sampling for histological evaluation. In this study, we analyzed miRNA expression in bile to identify predictive miRNAs for hepatobiliary malignancy. METHODS MiRNAs were obtained from bile samples taken from 25 patients with benign hepatobiliary disease and 34 patients with malignant hepatobiliary disease, including cholangiocarcinoma and gallbladder cancer. Expression of 328 miRNAs was determined with the TaqMan real-time PCR detection system using a MicroRNA Assays Human Panel. MiRNAs were functionally selleck compound evaluated in cholangiocarcinoma cell lines (Huh28, Hucct1, and KMBC) following the overexpression or knocking down of specific miRNAs using mimic-miRNA or anti-miRNA. RESULTS Among the 328 miRNAs tested, 16 were differentially expressed between the bile of patients with malignant hepatobiliary disease and those

with benign hepatobiliary medchemexpress disease (p<0. 05). From these 16 miRNAs, we focused on the two—miR-451 and miR-486—that were most significantly increased in malignant hepatobiliary disease. The area under the curve of the receiver operating characteristic curve for the prediction of malignant hepatobiliary disease using these miRNAs was 0. 85, which was equivalent to that of the tumor marker CA19-9. Univariate analysis using multiple clinical parameters, including tumor markers (CEA and CA19-9) and a liver function test, revealed serum ALT and T-Bil, miR-451, and miR-486 as significant variables. Multivariate analysis identified CEA, CA19-9, and miR-486 as significant variables. Functional analysis of these miRNAs showed that miR-451 had tumor suppressive and anti-inflammatory properties by decreasing the expression of PDGFRα, KRT7, IL1, and IL6, while miR486 was tumorigenic by increasing the expression of PDGFRα, N-cadherin, and p38MAPK. CONCLUSIONS We identified two predictive miRNAs, miR-451 and −486, in bile for the diagnosis of malignant hepatobiliary disease.

As a result, a “rule-of-two” was defined that predicted Selleck Lumacaftor hepatotoxicity more reliably when compared with dose alone. Applying the rule-of-two to the drug development process and to clinics will likely reduce

risk for DILI particularly in complex comedication. ADMET, absorption, distribution, metabolism, excretion, toxicity; ATC, Anatomical Therapeutic Chemical; CCR, correct classification rate; DILI, drug-induced liver injury; FDA, Food and Drug Administration; LTKB-BD, liver toxicity knowledge base benchmark data set; OR, odds ratio; OTC, over-the-counter; WHO, World Health Organization. Two publicly available drug databases were used to test for the relationship between lipophilicity, daily dose, and risk for DILI. The first data set is the liver toxicity knowledge base benchmark data set (LTKB-BD) recently published by selleckchem our group17 that is available from the US Food and Drug Administration’s web site.18 It contains

287 drugs with the potential to cause liver injury as defined by the FDA-approved drug labels. Drugs were divided into three categories: most-DILI-concern, less-DILI-concern, and no-DILI-concern. The most-DILI-concern group contains drugs that were either withdrawn from the market due to hepatotoxicity or were assigned a black box warning for their potential to cause liver injury, or had a warnings and precautions section that specified concern about DILI that has a greater than moderate severity. The less-DILI-concern group contains drugs that specify a DILI concern in the warnings and precautions section with low severity or in an adverse reactions MCE section, while the no-DILI-concern group comprised drugs with no DILI description mentioned in the labels. In the present study, we considered the most-DILI-concern (n = 116) and no-DILI-concern drugs (n = 48) (Supporting Table 1 and Supporting Fig. 1A). A second data set published

by Greene et al.19 was analyzed. The authors classified drugs into four groups, of which two groups were selected: those with evidence of hepatotoxicity in humans (hepatotoxic-positive) and those with no evidence of hepatotoxicity in any species (hepatotoxic-negative). Despite a difference in the approach to annotate a drug’s hepatotoxic potential, the concordance between the two data sets is high (∼90%).17 After removing drugs which overlapped with the LTKB-BD and mapping to the Anatomical Therapeutic Chemical (ATC) database of the World Health Organization (WHO), a total of 179 oral drugs remained of which 115 drugs were hepatotoxic positives and 64 negatives. The flowchart for drug inclusion is shown in Supporting Fig. 1B, and a full list of drugs is given in Supporting Table 2. Daily doses were retrieved from the WHO’s ATC database (http://www.whocc.no/atc_ddd_index), supplemented with FDA-approved drug labels (http://dailymed.nlm.nih.gov/dailymed/about.cfm) and literature searches.

Soft agar colonies were stained with 0.5 μM of calcein-AM solution (Life Technologies) and counted 5-14 days after plating with an Acumen eX3 multiplate reader (TTP LabTech Ltd., Melbourn, UK). Data were derived from five independent experiments. Percent inhibition was defined as percent Ku-0059436 order reduction in average number of colonies formed

in siBCL9 or siMTDH cells, relative to siControl cells (set to 100%), in each assay. P values between siControl and siBCL9 or siMTDH samples were calculated using a two-sample t test. To characterize the genomic landscape of HCC, we compiled a collection of snap-frozen tumor and adjacent nontumor liver tissues from 286 patients who were treated with surgical resection (Table 1). Both RNA and DNA were isolated from all samples and profiled on the Illumina Human HT-12 v4 BeadChips and Human Omni1-Quad SNP genotyping arrays (Illumina), respectively.

Based on the SNP genotyping array data, we derived the somatic copy number profiles of the 286 HCCs using their matched nontumor liver tissue as references. On average, there are 200 somatic copy number gain events and 247 somatic copy number loss events per HCC, accounting for 12.0% and 11.3% of the genome, respectively. A genome-wide view of the segmented copy numbers revealed that most chromosome arms have undergone large-scale copy number gains or losses, with frequent gains observed on 1q, 6p, 7p, 7q, 8q, 13q, and 17q and frequent losses on 1p, 4q, 8p, 9p, 9q, 13p, 16p, and 16q (Fig. 1A). We also GSK2126458 price devised a CIN score, which is a single metric that summarizes the extent of CNAs in individual tumors (see Patients and Methods). We found that the CIN scores were positively associated with various features of tumor progression, such as American Joint Committee on Cancer (AJCC) stage, Edmondson grade, and tumor size, in agreement with our understanding of somatic CNAs as a cumulative process as a tumor

advances (Table 1). On the other hand, the CIN scores were negatively associated with patients’ 上海皓元 age, the Child-Pugh score, and cirrhosis, which reflect overall liver function and pathological state of the non-HCC liver (Table 1). In addition to clinical HCC samples, we also profiled 30 HCC cell lines on the same gene expression and SNP genotyping array platforms. Overall, the spectrum of CNAs in HCC cell lines recapitulates primary HCCs (Fig. 1A). To assess the extent to which somatic CNAs in HCC drive downstream transcriptional programs, we calculated the correlation between a gene’s somatic copy number and its mRNA expression in cis across our patient cohort. Overall, there were 3,152 genes for which at least 10% (i.e., correlation coefficient ≥0.316) of their expression variation can be explained by their own copy number changes, whereas by chance only one gene was expected at the same level of correlation (FDR = 3.17 × 10−4) (Supporting Fig. 1A).