On multivariate analysis, segmental small bowel involvement (OR 0.104 (95% CI0.022–0.50)) and mural stratification (OR 0.02 (95% CI0.003–0.26) were independent predictors of CD. After adding CTE findings to colonoscopic parameters, the accuracy of diagnosing either CD or

ITB increased from 66.7% (70/105) to 95.2% (100/105) (P < 0.001). Conclusion: CTE seems to add unique information to colonoscopy in differential diagnosis between CD and ITB. Correct diagnosis can be made in most patients when combining colonoscopy and CTE findings. Key Word(s): 1. Crohn's BMS-777607 purchase disease; 2. Colonoscopy; 3. tuberculosis; 4. CT enterography; Presenting Author: REN MAO Additional Authors: MIN-HU CHEN PD0332991 cell line Corresponding Author: REN MAO Affiliations: The first affiliated hospital of Sun Yat-sen University Objective: Risk factors of surgery for structuring Crohn’s disease (CD) are not well characterized. Methods: 86 CD patients with strictures detected by endoscopy between 2004 and 2012 were evaluated. The primary outcome was surgery. Results: The median follow-up was 366 days. Factors associated with higher rates of surgery included smoking (hazard ratio (HR) 2.72; 95% confidence interval (CI), 1.35–5.5, P = 0.005),

disease duration at first detection of stricture <3 years (HR 2.73; 95%CI, 1.3–5.75, P = 0.008), stricture located in upper gastrointestinal tract (HR 2.91; 95%CI, 1.07–7.95, P = 0.037), complicated with obstructive symptoms (HR 2.74; 95%CI, 0.33–5.61, P = 0.006) and CDAI > 220 (HR 2.44; 95%CI, 1.18–5.08, P = 0.016). After adjustment for other variables, independent

risk factors predicting surgery was smoking (HR 5.49, 95%CI,2.32–13.02, P = 0.000), disease duration <3 years (HR3.89; 95%CI, 1.6–9.5, P = 0.003), complicated with obstructive symptoms (HR 2.68; 95%CI, 1.24–5.78, P = 0.012) and CDAI > 220 (HR 2.68; 95%CI, 1.22–5.90, P = 0.015). Gender, age at first detection of stricture on endoscopy, location of stricture, ESR, and hs-CRP did not influence outcome. Conclusion: smoking, disease duration at first detection of stricture <3 years, complicated with obstructive symptoms and CDAI > 220 are Flucloronide independent risk factors of surgery for structuring CD. Key Word(s): 1. Crohn’s disease; 2. Endoscopy; 3. stricture; 4. Surgery; Presenting Author: REN MAO Additional Authors: MIN-HU CHEN Corresponding Author: REN MAO Affiliations: The first affiliated hospital of Sun Yat-sen University Objective: Both CD and MG are autoimmune diseases which are complex disorders caused by combination of environmental factors and genetic susceptibility. An association between CD and MG has been previous reported in few cases. Methods: We report a case of CD patients who deveopled MG. Literature review was done to suggest potential association between MG and CD.

All liver sections were scored by two board-certified pathologists who were blinded to the identity of the samples. Lobular

necrosis was evaluated in liver sections stained with hematoxylin-eosin.25 Lobular necrosis Inhibitor Library in vitro was scored as follows: −, 0 foci; +/−, <2 foci; +, 2-4 foci; ++, >4 foci.25 Sections were examined in a coded fashion by BX-51 light microscopy (Olympus, Tokyo, Japan) equipped with a camera. We measured (1) the percentage of cholangiocyte apoptosis by semiquantitative terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling kit (Apoptag; Chemicon International, Inc.); (2) cholangiocyte proliferation by evaluation of the percentage of small and large cholangiocytes positive Selleckchem Adriamycin for PCNA5; and (3) intrahepatic bile duct mass (IBDM)5 of small (<15 μm)1 and large (>15 μm)1 bile ducts. IBDM was measured as the area occupied by cytokeratin-19–positive bile

duct/total area × 100. Proliferation was evaluated by immunoblots20 for PCNA in protein (10 μg) from lysate from spleen (positive control) and large cholangiocytes from WT and SR−/− BDL mice. Blots were normalized by β-actin.5 The intensity of the bands was determined by way of scanning video densitometry using the Storm 860 and the ImageQuant TL software version 2003.02 (GE Healthcare, Little Chalfont, Buckinghamshire, England). These experiments were performed in large cholangiocytes from WT and knockout 7-day BDL mice, a period where a marked ductal hyperplasia is observed.2, 12 We evaluated basal and secretin-stimulated cAMP levels (a functional parameter of cholangiocyte growth)13, 18 by commercially available RIA kits20; and phosphorylation of ERK1/2 by immunoblots in protein (10 μg) from cholangiocyte lysate. The intensities of the bands were determined by scanning video densitometry using a phospho-imager. Our small (negative control) and large cholangiocytes8 were treated at 37°C with 0.2% bovine serum albumin (BSA) (basal) or secretin (100 nM) for 48

hours in the absence or presence of preincubation (1 hour) with H89 (protein kinase A [PKA] Suplatast tosilate inhibitor, 30 μM) or PD98059 (mitogen-activated protein kinase kinase [MEK] inhibitor, 10 nM) before evaluating proliferation by CellTiter 96 Cell Proliferation Assay20 (Promega Corp., Madison, WI). Absorbance was measured at 490 nm on a microplate spectrophotometer (Molecular Devices, Sunnyvale, CA). Data were expressed as the fold change of treated cells compared with vehicle-treated controls. In separate experiments, large cholangiocytes were treated with 0.2% BSA (basal) or secretin (100 nM) for 6 hours in the absence or presence of H89 (30 μM) or PD98059 (10 nM) before evaluating PCNA expression by way of immunoblotting,5 PKA activity,20 and phosphorylation of ERK1/2 by way of immunoblotting.5 The intensity of the bands was determined as described above.

The study was approved by the Institutional Review Board of Mayo Foundation and the Ethics Committee of the Korean National Cancer Center. The HCC lesions were characterized by cross-sectional radiographic characteristics, which included (1) the number of tumor nodules, (2) the diameter of the largest nodule, (3) vascular invasion (enhancing vascular tumor thrombi), and (4) extrahepatic metastasis. Based on these radiographic information and laboratory data at entry into the study, individual patients were staged according to the BCLC, the CLIP score, and the JIS score. The original MELD score (before

modification for the purpose of organ allocation) was calculated as published.18 For survival analysis, patients were followed from the first visit date for HCC assessment TAM Receptor inhibitor forward until July 22, 2010 and September 1, 2004 in the derivation and validation cohorts, respectively. To ascertain complete capture of all decedents, a proprietary information source (Accurint) was used to supplement information in the medical records in the derivation cohort and the National Cancer Registry data in the validation

cohort. Death from any causes was considered an event in this analysis. In the base-case analysis, liver transplantation was not considered an event, whereas a subsequent sensitivity analysis was conducted censoring liver transplantation. Patient survival probability was estimated using the Kaplan-Meier PD0325901 method. The main tool for survival analysis was the proportional hazards model. Based on variables with univariate significance (P < 0.10) and clinical relevance, multivariate models were created. The output of the model was expressed as coefficients, which were used to compute hazard ratios. In addition, the coefficients were used to calculate

a risk score, which, in turn, was used to predict survival. In the derivation cohort, cross-validation was used to examine the reproducibility of the survival model. The data were Sucrase randomly divided into four equal subsets and the coefficients were recalculated after removing one subset of the data at a time. The concordance (c)-statistic was computed using the new coefficients in the remainder of the data. The c-statistic from each of the four subsets was compared to one another. In testing the accuracy of the model prediction in the validation cohort, patients were divided into three groups at the 25th and 75th percentiles of the risk score. The observed survival in the validation cohort was compared with survival estimated by the survival model. The goodness-of-fit of the models was assessed using the c-statistics.

Peak mean induction was observed by Day 3 (48 hours) with return to baseline values by Day 8. No increase in serum IFNα was observed. No clinically significant changes in HBsAg levels or HBV DNA were observed. Conclusions: Oral administration of GS-9620 stimulates a pre-systemic immune response without clinical significant systemic Fluorouracil mouse adverse events associated with IFNα in chronic hepatitis B patients. Baseline characteristics   Treatment naϊve N=25 SAD 0.3 mg (N=6) 1 mg

(N=6), 2 mg (N=6) MAD 0.3 (N=6), 1 mg (N=1) Virologically suppressed N=22 SAD 0.3 (N=6), 1 (N=6), 2 mg (N=4) MAD 0.3 (N=6) Age, mean years 40     44 Male, % 68     96 HBeAg positive, % 16     36 IL28B genotype, CC % 44     59 HBsAg, mean IU/mL 7169     5768 HBV DNA, mean log10 IU/mL 4.15     <1.46 ISGl5an d CCL8 mRNA inductioi

> 2 fold change from baseline n of patients   ISG15 INK 128 nmr CCL8 ISG15 CCL8 SAD 0.3 mg [min, max induction] 3/5 [2-12] 5/5 [2-10] 2/5 [3-18] 3/5 [2-610] SAD 1 mg [min, ma, Inc,Mont 3/5 [3-36] 4/5 [3-9] 3/5 [2-9] 4/5 [2-17] SAD 2 mg [min, max induction] 2/5 [2-16] 5/5 [2-164] 1/3 [3-13] 1/3 [3-186] Placebo [min, max induction] 0/3 1/3 [2] 0/3 1/3 [2] Disclosures: Edward J. Gane – Advisory Committees or Review Panels: Roche, AbbVie, Novar-tis, Tibotec, Gilead Sciences, Janssen Cilag, Vertex, Achillion; Speaking and Teaching: Novartis, Gilead Sciences, Roche Stuart C. Gordon – Advisory Committees or Review Panels: Tibotec; Consulting: Merck, CVS Caremark, Gilead Sciences, BMS; Grant/Research Histone demethylase Support: Roche/Genentech, Merck, Vertex Pharmaceuticals, Gilead Sciences, BMS, Abbott, Intercept

Pharmaceuticals, Exalenz Sciences, Inc. Stuart K. Roberts – Board Membership: Jannsen, Roche, Gilead, BMS Carla S. Coffin – Grant/Research Support: BMS, Gilead Sciences, Roche Paul Y. Kwo – Advisory Committees or Review Panels: Abbott, Anadys, Novartis, Merck, Gilead, BMS, Janssen; Consulting: Vertex; Grant/Research Support: Roche, Vertex, GlaxoSmithKline, Merck, BMS, Abbott, Idenix, Vital Therapeutics, Gilead, Vertex, Merck, Idenix; Speaking and Teaching: Merck, Merck Barbara A. Leggett – Advisory Committees or Review Panels: MSD, MSD, MSD, MSD; Speaking and Teaching: Roche, Roche, Roche, Roche, Gilead Daryl Lau – Advisory Committees or Review Panels: Gilead, BMS; Consulting: Roche; Grant/Research Support: Gilead, Merck Stefan Pflanz- Employment: Gileadn Sciences Benedetta Massetto – Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead Sciences, Inc Mani Subramanian – Employment: Gilead Sciences John G.

Targeting CD147 function during liver injury using mAb, siRNA or genetic knockout in mice significantly reduced hepatocyte MMP production, reduced total ECM production, and resulted in a net reduction in fibrotic ECM, but it also reduced leukocyte aggregation and the extent of the injury. Conclusion: Although leukocyte aggregation is well described as occurring in inflammation, we have uncovered a new CD147 dependent mechanism by which this occurs and impacts on the severity of injury. We furthermore demonstrated that hepatocytes produce active MMPs capable of ECM remodelling in liver fibrosis. And we have shown that this process is regulated by CD147.

CD147 is a powerful player in liver injury and is also found to be highly increased in HCC. A detailed understanding of CD147 function is therefore required for the selective targeting of those processes and has the Daporinad in vivo potential to lead to new therapeutic agents. E ARFIANTI, SS LEE, D HEYDET, C LARTER, V BARN, NC TEOH, GC FARRELL Liver Research Group, ANU Medical School at The Canberra Hospital, ACT Background: Obesity and type 2 diabetes both promote the development of hepatocellular buy Staurosporine carcinoma (HCC), which is an increasingly recognized complication of obesity/diabetes-related non-alcoholic fatty liver disease. We recently reported early onset of diethylnitrosamine (DEN)-induced HCC in obese and diabetic foz/foz NOD.B10 mice which

was associated with hyperinsulinemia, hyperglycemia and perturbed Teicoplanin serum adipokine levels, rather than inflammation [JGH 2011; 26 (Suppl):6]. The mammalian target of rapamycin (mTOR), a nutrient-sensitive protein kinase, is abberantly activated in up to 50% of HCC cases. In the present study, we investigate the role of Akt/mTOR signalling pathways during the early (premalignant) stage of hepatocarcinogenesis. Methods Male foz/foz and non-obese heterozygous (foz+/−) littermates

were injected with DEN (10 mg/kg i.p.) at 12–15 days of age; controls were injected with vehicle (saline). At 12 weeks post-DEN injection, dysplastic hepatocytes were identified by glutathione S-transferase pi (GST-pi) immunohistochemistry (IHC). Protein expression of Akt/mTOR signalling intermediates in liver lysates were analysed by immunoblotting and IHC. We also determined the growth inhibitory effect of rapamycin on primary HCC cell culture using cells derived from foz/foz mice using MTT assays. Results: DEN-treated foz/foz mice exhibited a higher number of GST-pi-positive cells compared to respective lean mice (3.7 ± 0.68% vs. 1.6 ± 0.20 %, P < 0.05), reflecting enhanced growth of dysplastic hepatocytes. DEN increased proliferative and apoptosis markers in obese mice, corresponding to the up-regulation of positive cell cycle regulators (cyclins D1, E) and pro-apoptotic Bax, respectively. Interestingly, Akt phosphorylation, an important mediator of insulin signalling, was enhanced in livers from DEN-injected obese mice.

However, our original report of kangaroo dry-sheep-equivalents

(DSE) of 0.42 based on DMI was an overestimate. Using the correct values for the gross DMIs needed to satisfy the FMRs of a standard 25-kg red kangaroo and standard 45-kg sheep, we estimate a kangaroo DSE to be 0.37 (Corrigendum Table 5). The authors sincerely apologise for any inconvenience this may have caused. A.J. Munn, School of Biological Sciences, The University of Wollongong, Australia T.J. Dawson, click here School of Biological, Earth and Environmental Sciences, The University of New South Wales, Australia S.R. McLeod, Industry & Investment New South Wales, Orange Agricultural Institute, New South Wales, Australia “
“Quantifying bird song variation can be an important tool for ensuring accurate species identification and can provide a significant basis for understanding the evolutionary processes that shape phenotypic diversity. This study describes variation in the songs of rattling cisticolas Cisticola chiniana across sub-Saharan Africa. For many cisticola species, learned songs are the most obvious phenotypic indicators of

species affiliation and may also function selleck chemicals llc to indicate individual quality. We examined 957 songs recorded from 61 individuals and archived in sound libraries. To assess the diversity of syllable and song types, we examined patterns of syllable use. We also measured vocalization frequency and time parameters and assessed how they vary through space. Results indicated that rattling cisticola songs are highly variable, but also have features that are species-specific. Examined songs had a relatively fixed structure containing one of three characteristic introductory note types, followed by an end phrase. Two of the introductory note types were sung across the species’ range (some 4500 km), whereas the third was only recorded check details in south-western Africa. End phrases generated most of the diversity in songs and appeared to have an unlimited number

of forms. End-phrase characteristics showed a strong geographic variation, but did not vary with elevation. Song features varied individually and geographically in ways that are consistent with evolution due to multiple selective pressures, including stabilizing selection for species recognition on the introductory notes and diversifying selection on the end phrases. This pattern of lability in some song features coupled with stability in others may be a common feature of cisticola songs as it has also been found in Cisticola erythrops, a congener with a similarly broad range. The songs of birds vary spatially and temporally in a multitude of different ways (Podos & Warren, 2007; Catchpole & Slater, 2008). Songs are often used as a species-identifying characteristic, but may not be effective if the range of song features for any one species is not well-described.

19 This led us to evaluate the potential role of β2SP in mouse and human liver regeneration

and, specifically, the activation of hepatic progenitor cells. Our initial analysis reveals that β2SP expression demonstrates a clear spatial and temporal Kinase Inhibitor Library solubility dmso variation as regeneration proceeds and has a reciprocal relationship with the expression of several progenitor cell markers. Reduced β2SP is also associated with an expanded population of hepatic progenitor cells following two-thirds partial hepatectomy that are likely activated by impaired hepatocyte proliferation and activated Wnt signaling in β2SP+/− mutant mice. β2SP, β2-Spectrin; DDC, 3,5-diethoxycarbonyl-1.4-dihydrocollidine; ES, embryonic stem; HCC, hepatocellular carcinoma; Oct3/4, octamer 3/4; PH, plekstrin homology; STAT3, signal transducer Liproxstatin-1 purchase and activator of

transcription 3; TBRII, TGF-β type II receptor; TGF-β, transforming growth factor beta; TRITC, tetramethyl rhodamine isothiocyanate. Formalin-fixed and paraffin-embedded human postliving donor transplant liver biopsy specimens were obtained from the Department of Pathology, Georgetown University Medical Center, Washington, DC. Liver biopsies from 10 living donor transplant recipients were collected at 1 week (two specimens), 6 weeks (five specimens), and 12–16 weeks (three specimens) posttransplant as part of a standardized protocol to rule out liver pathology following living donor transplantation. Zero specimens were collected to evaluate for suspected rejection. All human tissue procedures were approved by the Institutional Review Board of Georgetown University Medical Center, Washington, almost DC. Wild-type

and β2SP+/− 129 SvEv Black Swiss mice 8–16 weeks of age were subjected to two-thirds partial hepatectomy as described by Mitchell and Willenbring20 and then sacrificed at 0, 24, 48, 72, and 168 hours after hepatectomy (n ≥ 3). Liver tissue was then collected for immunohistochemical, protein, and RNA analysis. Generation of β2SP+/− knockout mice was as described.16 Whole-cell lysates were prepared from pooled livers from each experimental group with a radioimmunoprecipitation assay buffer (Sigma) containing fresh protease and phosphatase inhibitor cocktails. The primary antibodies used in this study were rabbit anti-β2SP (1:1000) and rabbit anti-actin (1:2500). Details of anti-β2SP antibody have been described.16 Horseradish peroxidase-conjugated secondary antibodies (Santa Cruz Biotechnology) were used at 1:5000 dilution.

Fluorescent microscope was employed

to observe the transfection results. At 48 hours after transfection, RNAs and proteins AP24534 datasheet were extracted; Then the expressions of XPD, DNp73 and GADD45β were detected by RT-PCR and Western blotting, respectively. The cell proliferation was assessed by MTT assay. The changes in cell apoptosis were evaluated by flow cytometry. Results:  Green Fluorescent Protein (GFP) was expressed in SMMC-7721-pEGFP-N2-XPD group cells and SMMC-7721-pEGFP-N2 group cells. In contrast, GFP was undetectable in Lip group and Blank group cells by fluorescent microscope. Compared with Blank group, Lip group and N2 group, the expression of DNp73 mRNA decreased significantly in XPD group (P < 0.01), but the expressions of XPD and GADD45β mRNAs were enhanced obviously in XPD group (P < 0.01). There was no statistical diffirences of XPD, DNp73 and GADD45βmRNAs expressions among Blank group, Lip group and N2 group (P > 0.05). The trend of XPD, DNp73 and GADD45β proteins detected by Western blotting were consistent with the trend of their mRNAs. The proliferation of SMMC-7721 cells

was markedly inhibited (P < 0.01) and the apoptosis of SMMC-7721 cells was increased after transfected by XPD (P < 0.01). Conclusion:  The wild-type XPD as an tumor suppressor gene plays an inhibitory role in the carcinogenesis of HCC. The expression Talazoparib solubility dmso of DNp73 decreased and the expression of GADD45βincreased with the overexpression of XPD, suggests that both of them may play a key role in the mechanism of XPD inhibiting the carcinogenesis of HCC. Key Word(s): 1. Hepatoma; 2. XPD gene; 3. DNp73 gene; 4. GADD45b gene;

Presenting Author: ANILK JOHN Additional Authors: MADIHAEMRAN SOOFI, SAADAL KAABI, ESRAMOHD AL ADHAL, SALWA KANDATH, MOUTAZ DERBALA, MT BUTT, RAFIE YAKOOB, SPTLC1 MUNEERA MOHANNADI, HAMID WANI Corresponding Author: ANILK JOHN Affiliations: Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation; Hamad Medical Corporation Objective: Percutaneous liver biopsy is the standard of care for obtaining hepatic tissue for histopathological assessment of parenchymal liver disease. Today percutaneous liver biopsies are mostly performed under real time ultra sound guidance by radiologists. We prospectively audited our practice of blind outpatient liver biopsies, performed without image guidance by gastroenterologists for its safety and adequacy, in this era of high tech imaging. Methods: All patients who underwent blind percutaneous liver biopsies without image guidance by gastroenterologists for grading and staging of chronic hepatitis B/C were audited prospectively for the safety of the procedure and the adequacy of tissue samples for proper grading and staging.

Opioids.  The endogenous opioid system in the skin has two components: the first component consists of peptides such as enkephalins and endorphins and the second component comprises opioid receptors (mu, kappa and delta) to which these peptides bind.23 Mu and kappa opioid receptors may act as modulators of itch in the central nervous system of animals. Mu agonists are pro-pruritogens, while kappa agonists

are antipruritic.24 www.selleckchem.com/products/nivolumab.html It has been recognized that an imbalance between these receptors may initiate itch through systemic and peripheral pathways.25 Mu receptor agonists and a peripherally restricted opioid agonist, loperamide, induced a pruritic reaction in mice. On the other hand, selective delta opioid agonists did not illicit a similar reaction.26 This pruritic response, however, was not replicated in human studies. Intradermal application of mu opioid agonists even at highest concentrations did not produce itch or mast cell degranulation.27 On the other hand, opioid levels are increased in patients with chronic liver disease and increased opioidergic neurotransmission in cholestasis is thought to mediate pruritus.28,29 Rat models demonstrated that the liver

may act as a source of endogenous opioids, namely proenkephalin-derived opioids. These opioids when present at elevated concentrations induce pruritus.30 Several studies oppose the role of opioids in cholestatic pruritus. Patients with intrahepatic cholestasis selleck chemicals of pregnancy show similar mu opioid activity as controls. Furthermore, patients with primary biliary cirrhosis having pruritus had similar opioid levels when compared to patients without pruritus.14 In patients with primary biliary cirrhosis, opioid concentrations were elevated in late

(stage 3–4) disease, which usually exhibits an improvement of symptoms such as pruritus.31 The role of opioids in cholestatic pruritus is controversial and requires further investigation. Histamine.  Fenbendazole Histamine is responsible for many allergic reactions and is also thought to have a role in cholestatic pruritus. In a study by Gittlen et al. involving patients with PBC and PSC, histamine levels were elevated in patients complaining of pruritus. Histamine levels were significantly higher (P < 0.01) in pruritic (319 [132] pg/mL) (X [SD]) versus non-pruritic (227 [75] pg/mL) patients with chronic cholestatic liver disease.32 Despite the above evidence, several issues weaken the role of histamine as a mediator of pruritus. Patients with cholestatic pruritus do not exhibit dermatologic reactions seen in patients with elevated histamine levels and as discussed later in the management section, patients with cholestatic pruritus do not appear to benefit from antihistamines.

Randomized, controlled trials have thus far been negative. New therapeutic directions may be proposed Palbociclib clinical trial by investigating yet unexplored pathophysiologic processes. Tabibian et al. turned their attention to cellular senescence. Their results reveal that cholangiocytes of PSC patients express proteins and proinflammatory markers of senescence, in contrast to cholangiocytes of healthy controls. The researchers established an in vitro model of lipopolysaccharide-induced senescence of normal human cholangiocytes.

With this model, they could demonstrate induction of senescence in bystander cholangiocytes by senescent cholangiocytes. The researchers found that this senescence depends on N-ras and can be prevented by an N-ras inhibitor. These are provocative results. We are eager to know whether they can be translated into a benefit for patients with

PSC. (HEPATOLOGY; 2014;59:2263–2275.) The patatin-like phospholipase domain-containing learn more 3 (PNPLA3) gene is a hot topic in hepatology. A single-nucleotide polymorphism (SNP) located in this gene has been consistently associated with progression of liver diseases, such as NASH, alcoholic liver disease (ALD), and CHC. This SNP has been associated with inflammation and fibrosis, two important features predisposing to hepatocellular carcinoma (HCC). In order to investigate whether this PNPLA3 SNP is also associated with HCC, Trépo et al. performed a meta-analysis based on 2,503 European patients with cirrhosis. Methodologically, check details they were able to access the individual participant data. Their results indicated an association between the PNPLA3 SNP and HCC. The association was stronger in patients with ALD, but also significant in patients with CHC after adjustment for age, sex, and body mass index. However, the magnitude of the association is not sufficient to provide a biomarker for HCC surveillance based on this SNP. That said, the mechanism should be further investigated, especially for a gene whose function is still controversial. (HEPATOLOGY; 2014;59:2170–2177.) Transplantation is an excellent option for eligible patients with

HCC. These recipients are cured from the tumor and from cirrhosis. With the implementation of surveillance programs, more and more patients with HCC are listed. Wong et al. used the United Network for Organ Sharing registry to provide accurate numbers and proportions over a decade. From 2002 to 2012, the number of patients transplanted for HCC increased 10-fold, which represents a percentage increase from 3% to 23%. Not surprisingly, HCV was the leading etiology. NASH was the second etiology, but it was the most rapidly growing indication. It is only a matter of time for NASH to become the leading cause of HCC in transplanted patients, which is likely to come sooner with the development of new treatments against HCV. (HEPATOLOGY; 2014;59:2188–2195.