(HEPATOLOGY 2011;) See Editorial on Page 1430 Two models of cirrhosis formation have developed. One hypothesis indicates that cirrhosis develops as a consequence of a progressive deposition

of collagen and scar tissue PLX3397 clinical trial induced by chronic inflammation and necrosis. Another, not mutually exclusive, hypothesis indicates that telomere shortening represents an underlying cause of cirrhosis.8 Telomeres form the ends of human chromosomes. The main function of telomeres is the maintenance of chromosomal stability. However, telomeres shorten as a consequence of cell division due to the “end replication problem” of DNA polymerase, processing of telomeres during S-phase of cell cycle, and the absence of telomerase expression in most somatic tissues.9 Telomere shortening limits the proliferative life span of human cells to 50-70 cell doublings by induction

of a permanent cell Selleckchem Silmitasertib cycle arrest (replicative senescence) in response to telomere dysfunction.10, 11 Previous studies have shown that telomere shortening also limits the life span of primary human hepatocytes.12 Studies of human cirrhosis have demonstrated that telomere shortening is a general marker of cirrhosis formation correlating with an accumulation of senescent hepatocytes.13, 14 In addition, studies on telomerase-deficient mice have provided the first experimental evidence that telomere shortening limits the regenerative response to acute and chronic liver injury, accelerating the formation of liver fibrosis and steatosis.15, 16 Together, these studies have led to the telomere model of cirrhosis formation, indicating that chronic liver diseases increase the rate of cell turnover, thus leading to accelerated telomere shortening and regenerative exhaustion.8, 17 In agreement with this hypothesis, it has been recognized that proliferative activity declines after long latencies of chronic liver disease and this decline was associated with the progressive formation of disease.18

Genetic studies have proven that mutations in telomerase are the underlying cause of accelerated telomere shortening and organ failure in some rare human diseases, including some forms of dyskeratosis congenita (DKC)19 and aplastic anemia.20 4-Aminobutyrate aminotransferase In addition, 10% of the cases of familial idiopathic lung fibrosis are associated with telomerase mutations.21, 22 In most of these cases heterozygous mutations were found in either the RNA (TERC) or protein component (TERT) of telomerase. Interestingly, familial cases of idiopathic lung fibrosis and bone marrow failure also showed an increased frequency of unexplained liver pathologies, including fibrosis, inflammation, macrovesicular steatosis, and hepatic nodular regeneration.23-25 Some of these patients carried mutations in telomerase genes.

2 However, the current mode of treatment is not equally effective for all HCV genotypes and significant Palbociclib molecular weight side effects are still observed. Efforts are currently being made to develop a combination of new direct-acting antivirals (DAAs) not leading to the emergence of escape

mutations and, if possible, free of IFN. First proofs of concept recently emerged from clinical trials demonstrating that combinations of DAAs can result in the cure of chronic HCV infection.3, 4 However, combinations of drugs targeting different steps of the viral life cycle, including virus entry, will likely improve viral response rates and therapeutic success. HCV is a small enveloped virus with a positive stranded RNA genome belonging to the Hepacivirus genus in the Flaviviridae family.5 Its genome encodes two envelope glycoproteins (E1 and E2), which play a key role in virus entry into the hepatocyte. However, as a result of its association with low- or very-low-density lipoproteins,6 the lipoprotein moiety can also play a role in the entry process of HCV particle. HCV entry is currently viewed as a complex multistep process, because a series of specific cellular entry factors have been shown to be essential in the early steps of the HCV life cycle.7 These molecules include the CT99021 scavenger receptor class B type 1 (SRB1), the tetraspanin CD81,

tight-junction proteins claudin 1 (CLDN1) and occludin (OCLN), and receptor tyrosine kinase-like epidermal growth factor receptor. After its interaction with entry factors at the cell surface, HCV particle is internalized by clathrin-mediated endocytosis.8 Importantly, as for several other viruses, HCV can also spread Ribonucleotide reductase by direct cell-to-cell transfer.9, 10 3D, three-dimensional; Ab, antibody; BVDV, bovine viral diarrhea virus; CC50, 50% cytotoxic concentration; CI, combination index; CLD, chronic liver disease; CLDN1, claudin 1; CMFDA, 5-chloromethylfluorescein diacetate; CQ, chloroquine; DAAs, direct-acting antivirals; DMEM,

Dulbecco’s modified Eagle’s medium; DMSO, dimethyl sulfoxide; FCS, fetal calf serum; ffu, focus forming unit; FQ, ferroquine; gRNA, genomic RNA; HCV, hepatitis C virus; HCVcc, hepatitis C virus produced in cell culture; HCVpp, hepatitis C virus pseudoparticle; IC50, half-maximal inhibitory concentration; IC90, 90% inhibitory concentration; IF, immunofluorescence; IFN, interferon; JFH-1, Japanese fulminant hepatitis type 1; LT, liver transplantation; mAb, monoclonal Ab; OCLN, occludin; PE, phycoerythrin; Peg-IFN-α, pegylated interferon alpha; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; RBV, ribavirin; SRB1, scavenger receptor class B type 1; YFV, yellow fever virus. Ferroquine (FQ; SSR97193) is a ferrocenic analog of chloroquine (CQ) that has been developed as a new antimalarial drug (Fig. 1A).

Methods: (1) Nude mice bearing tumor xenografts of human colon carcinoma were injected intravenously with 18.5 MBq 99Tcm-GX1, and ECT imaging were performed; (2) Immunohistochemistry and immunofluorescence were performed to evaluate the binding ability of GX1 to RMEC; (3) Antiangiogenesis ability of GX1 on RMEC were analyzed by in vitro MTT assay, migration assay, and tube formation assay. Results: (1) ECT imaging indicated that tumor on right flank could be visualized from 8 h and the activity was higher than that of heart until 24 h. The most clearly visualized imaging appeared at 18 h; (2) GX1

was observed binding specifically to RMEC with no positive staining observed in control group according to Immunohistochemistry and immunofluorescence, which indicated

GX1 could target retinal neovasculature of diabetic retinopathy; (3) GX1 significantly inhibited the proliferation, micro-tube formation and selleck products migration of RMEC or RMEC cultured with VEGF165. Conclusion: GX1 owned the ability of specific targeting of colon cancer angiogenesis in vivo, specific binding ability and antiangiogenesis to RMEC, which indicated GX1 was to be explored for effective antiangiogenesis targeting drug to tumor and diabetic retinopathy. Key Word(s): 1. GX1 peptide; 2. tumor ; 3. diabetic retinopathy; 4. antiangiogenesis; Presenting Author: YANAN HAN Additional Authors: JIPENG YIN, KAICHUN WU Corresponding Author: YANAN HAN Affiliations: Xijing Hospital of Digestive Disease Objective: Our check details group previously got a cyclic peptide GX1 which bind selectively to endothelial cells of cancer by using a Ph. D.-C7CTM Phage display peptide library. Many previous studies in vivo and in vitro showed that, GX1 could well target

to tumor and negatively regulate angiogenesis. But its receptors are still unknown.Our aim is to screen and identify the GX1 receptors by optimizing the conditions of IP, using the immortalized human umbilical vein endothelial cells (sv-HUVEC) established by our group. Methods: 1.Special marks of endothelial cell were detected by immunofluorescence; the expression and location of GX1 receptors were detected by IF and Western Niclosamide Blot.2.The candidate proteins of GX1 receptors was obtained by using IP, sliver staining, MALDI-TOF/TOF and Bioinformatics analysis.3.The expression and location of GX1 receptors and its candidate proteins were detected and compared by WB,IF, immunohistochemistry and laser scanning confocal microscope; the recognition of candidate molecules and GX1 receptor was detected by IP,WB. Results: 1.CD31 and Factor VIII expressed on sv-HUVECs, and sv-HUVEC also expressed GX1-binding proteins, which were mainly located on cytoplasm and cell membrane. WB showed that 90-130KD proteins could bind GX1 well.2.We utilized the better conditions to enrich the GX1-binding proteins, approximately a 115KD protein band.

We hypothesized that ARG might be driving the evolution to ALF, if values PI3K Inhibitor Library of ARG were lower than expected in ALF patients, suggesting a muted immune response in this setting. Methods: Serum levels of ARG-1 isotype were measured using a sandwich type ELISA employing HRP-labeled antibody in 107 HBV patients with different phenotypes: HBV-ALF (non-immunosuppressed), acute HBV with

recovery, chronic hep B (with and without flares of activity), and, as controls, 20 acetaminophen-related ALF, 10 chronic hepatitis C and 10 healthy subjects. Results: Healthy controls had median ARG of 5 ng/mL, chronic HBV and HCV ∼25-30 ng/mL (Table), while acute HBV, HBV flares and HBV-ALF median levels were 89.2, 78.4 and 69.5 ng/mL, respectively, markedly lower than APAP median level of 968 ng/mL. HBV-ALF

ARG levels were actually lower than acute or flare HBV despite comparable aminotransferase levels. Particularly low values for ARG were found in those who died of HBV-ALF (median 30.4 ng/ mL; n=5). For chronic HBV phenotypes with relatively low AST values there was poor correlation of AST with ARG (Spearman rho); only flare or APAP patients showed strong correlations (rho >0.75). Summary/Conclusions: Despite massive hepato-cyte necrosis, low ARG levels characterize HBV-ALF and, to a lesser Cobimetinib extent, acute HBV patients, supporting the postulate of ARG-driven immunomodulation in hepatitis B. A genetically mediated alteration in ARG protein might account for the low levels observed. Further understanding of the significance of ARG levels in these settings will require mechanistic or genomic studies. Median Arginase, AST Results and Correlationby Categories and Etiologies Disclosures: William M. Lee – Consulting: Eli Lilly, Novartis; Grant/Research Support: Gilead, Roche, Vertex, BI, Anadys, BMS, merck; Speaking and Teaching: Merck Background and aims: Some orthotopic liver transplantation (OLT) patients experience HBV recurrence with detectable HBV-DNA despite hepatitis B immune globulin+lamivudine

(HBIg+LAM) prophylaxis. We analyzed changes in the HBV-qua-sispecies in patients with recurrent HBV post-OLT. Methods: Twenty-nine OLT patients included in a previous study(1) to compare LAM vs. LAM+HBIg in preventing HBV recurrence AZD9291 were followed for >10 years (mean, 154.9 months [50-188]). In patients with recurrent HBV after OLT, defined as detectable HBV-DNA by real-time PCR, a region of HBV surface gene (S, codons s92-s200), including the “a” determinant, was studied by ultra-deep pyrosequencing (UDPS, GS-Junior, Roche). Results: Twelve (41%) of 29 patients had detectable HBV-DNA at some timepoint after OLT. In addition, 4 of them were HBsAg positive. Among patients with recurrent HBV, one with, and three without HBsAg had available pre- and post-OLT samples with HBV-DNA above 10E3 IU/mL and were selected for UDPS analysis (table).

Cirrhosis, either by clinical evidence or biopsy, was present in 14% of the entire cohort. The median AST was 41 IU/L (standard deviation [SD] = 22) and median ALT 56 IU/L (SD = 36). An elevated alkaline phosphatase level with normal aminotransferase levels defined by local laboratory reference

ranges was found in 4% and a positive AMA in 4% of patients. There was no association between an isolated alkaline phosphatase elevation and a positive AMA. Of those with a biopsy at any time, 54% had ≥34% steatosis, 47% had GSK1120212 ≥grade 2 lobular inflammation, 66% had ballooning, 57% met the criteria for “definite” NASH, and 31% had bridging hepatic fibrosis or cirrhosis. The major differences between those with contemporaneous liver biopsies and those without was the lower prevalence of diabetes and

hypertension, lower glucose, lower HDL cholesterol, higher triglycerides, and less advanced fibrosis in the contemporaneous biopsy group. The contemporaneous liver biopsy group included all of the PIVENS patients, who did not, by definition, have diabetes or cirrhosis. Interestingly, the prevalence of the metabolic syndrome as defined by the NCEP ATP-III criteria was similar in all groups despite the group differences in individual components that define the metabolic syndrome. Aminotransferase levels were also higher in the contemporaneous biopsy group, possibly selleckchem reflecting more patients with lower enzyme levels because Protein kinase N1 of “burnt out” NASH in the setting of advanced fibrosis in the other groups. Further analyses of the study cohort focused on the subgroup with contemporaneous

liver biopsies. Factors associated with definite NASH in patients with NAFLD and contemporaneous liver biopsies are shown in Table 2. Patients with NASH were more likely to be women, have diabetes, and meet the NCEP criteria for the metabolic syndrome; they also had significantly higher levels of AST, ALT, GGT, triglycerides, HbA1c, HOMA-IR, and lower levels of HDL cholesterol compared to those without definite NASH. Patients with NASH also had significantly more steatosis, lobular inflammation, ballooning, and fibrosis as well as higher NAFLD Activity Scores. Portal inflammation was more likely to be greater than mild in those with definite NASH. There were no differences between the two groups in age, BMI, waist circumference, acanthosis nigricans, or self-identified Hispanic ethnicity. Interestingly, autoantibodies were found more often in those without definite NASH compared to those with NASH. Overall, the same factors associated with definite NASH were also significantly associated with ballooning. This may reflect the dominant role that the presence of ballooning has in establishing a diagnosis of definite NASH. The value of using ALT levels to screen for NASH in patients with NAFLD was examined using three different cutoffs for the upper reference range.

CCl4, carbon tetrachloride; cDNA, complementary DNA; HNF-4α, hepatocyte nuclear factor 4α; NF-κB, nuclear factor κB; qPCR, quantitative polymerase chain reaction. Liver cirrhosis was induced as described beginning in 4-week-old

inbred male Lewis rats, weighing 100-130 g, using Phenobarbital (Sigma, St. Louis, MO) and carbon tetrachloride (CCl4, Sigma).16 Specific details are provided in the Supporting Information. Four-week-old male inbred Nagase analbuminemic rats (weighing approximately 100-130g) were treated with two doses of 30 mg/kg retrorsine, a pyrrolizidine alkaloid that inhibits hepatocyte proliferation,17-19 given 2 weeks apart via intraperitoneal injection. Four weeks after the last injection, a 70% partial hepatectomy was selleck compound performed to induce donor hepatocyte proliferation. Hepatectomy was performed via ligation of the median and left lateral lobes of the liver. Animals (five per group) then underwent transplantation via the spleen with primary hepatocytes isolated from normal or cirrhotic rat livers or received intrasplenic injection of 0.1 mL Dulbecco’s modified Eagle’s medium as a control. Cyclosporine was given to control rejection by daily intramuscular injection at

15 mg/kg body weight. Five million cells for each transplantation procedure were washed, resuspended in 0.1 mL of phosphate-buffered saline, and injected into the splenic pulp over 30 selleck products seconds using a 27-gauge needle. Primary

hepatocytes injected into the spleens of recipient noncirrhotic rodents are known to migrate and engraft into the liver parenchyma. Hepatocytes from four donor sources were used for these studies: 6- and 9-month-old control naïve Lewis rats (control); 6-month-old Resminostat Lewis rats treated for 14 weeks with phenobarbital and CCl4 to induce cirrhosis with normal liver function (cirrhosis without liver failure); and 9-month-old Lewis rats treated with at least 26 weeks of phenobarbital and CCl4 to induce stable cirrhosis-induced (Child-Pugh class C) liver failure (cirrhosis with chronic liver failure). All RNA samples were analyzed using an Agilent Bioanalyzer Lab-on-a-Chip Nano 6000 chip to determine the integrity and concentration of the samples. Only samples passing this quality control step with a mass ratio of the 28S to 18S RNA peaks of ≥2.0 were used for expression analysis. Twenty micrograms of total RNA was indirectly labeled using amino-allyl deoxyuridine triphosphate and an anchored oligo(dT)20 to prime reverse-transcription. Fluorescent label (CyDye, Amersham Biosciences) was coupled to the complementary DNA (cDNA) and hybridized to the PancChip version 5.0 13K cDNA microarray.

N WONG,1 S ROBERTS,1 P LEWIS,1 E PAUL,2 M KITSON,1 D ISER,1 W KEMP1 1Alfred Hospital, Department of Gastroenterology, Commercial Rd, Melbourne, Australia, 2Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia

Background: Detecting Selleck Tyrosine Kinase Inhibitor Library fibrosis progression is important in the management of chronic hepatitis C (CHC). However factors influencing the evolution of liver fibrosis in CHC using transient elastography (TE) are unclear. BMI, alcohol use and HIV co-infection are cofactors in progression of CHC although the impact on liver stiffness (LSM) progression in CHC has not been demonstrated. Aim: To determine the impact of BMI, alcohol use and HIV co-infection on fibrosis progression using TE. Methods: Patients with CHC and at least two TE assessments 12 months or more apart were identified from a prospectively maintained database. Baseline demographic, anthropometric and TE data were extracted. Data were cross-matched with information prospectively collected via patient reported questionnaire at the time of TE examination. Change in LSM (ΔLSM) was

adjusted for follow up time, and CHC treatment response. Results: From March 2010 to December 2013, 508 patients (62% Male, age 50.8 ± 10 yrs) with CHC and at least two TE examinations were identified. TE was performed on average 21 ± 9 months (range 12–41 months) apart. Overall there was no difference in LSM between the first (LSM1; median 7.1 ± 8.5 kPa) and second (LSM2; median 7.0 ± 9.2 kPa) assessments (mean ± SD ΔLSM = 0.25 ± 0.25). Neither BMI or alcohol click here use were associated with change in LSM. HIV co-infection (n = 62) was associated with a significant increase in LSM (ΔLSM = +1.84 kPa, p = 0.018). 47% of patients who underwent CHC treatment between LSM1 and LSM2 achieved an SVR (18/37). SVR was associated with a non-significant reduction in LSM (ΔLSM = −3.9 vs −1.0 kPa, p = 0.2) Conclusion: This

data supports the reproducibility of LSM but neither BMI nor alcohol intake were associated with change in LSM over a 21 month follow up. HIV co-infection was associated with significant LSM increase in this study with relatively short follow up. This supports the increased rates fibrosis progression in the HIV cohort. LT GAN,1 B SHADBOLT,2 V WONG,3 this website L ADAMS,4 T DWYER,1 H CHAN,3 N TEOH,1 S CHITTURI,1 G FARRELL1 1Liver Research Group, and 2Biostatistician, ANU Medical School and The Canberra Hospital, ACT, 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatton, Hong Kong, 4Gastroenterology and Hepatology Unit, Charles Gairdner Hospital, Perth, WA Introduction: Non-alcoholic fatty liver disease (NAFLD) affects 27% of the Hong Kong population1 with similar or higher prevalence in Australia. While ∼75% of patients do not have significant liver disease, identifying those with non-alcoholic steatohepatitis (NASH) and/or significant liver fibrosis is challenging.

infestans showed that heterothallic Phytophthora species are capable of producing antheridia and oogonia but are self-incompatible (Galindo and Gallegly 1960). Until recently, P. ramorum was known

to exist as three clonal lineages named NA1 and NA2 (from North America) and EU1 (from Europe) (Grünwald et al. 2009). In 2012, a fourth lineage (EU2) was reported in Europe (Van Poucke et al. 2013). Originally, P. ramorum mating type A2 was only present ABC294640 concentration in the US and mating type A1 was only present in Europe. In the US, this changed when EU1-A1 was first found in 2006 in a Californian nursery (Grünwald et al. 2008). In Europe, this also changed with the report of three A2 isolates (from 2002 to 2003) in Belgium (Werres and De Merlier 2003; Vercauteren et al. 2011). Molecular studies revealed that these ‘Belgian’ A2 isolates belong to the EU1 lineage and resulted probably from mutation or mitotic gene conversion (Vercauteren et al. 2011). Oospore production in pure culture of several heterothallic Phytophthora has been reported in response to fungicides (Groves and Ristaino 2000), long-term culture (Brasier 1972; Ko 1981), stimulation by compounds produced by root exudates (Jayasekera et al. 2007), bacteria (Mukerjee and Roy 1962), antagonistic fungi (Brasier 1975) Wnt inhibitor or compounds

used in growth media (Smart et al. 2000). Self-fertility

phenomena have also been reported in oospore progenies of P. ramorum (Boutet et al. 2010). Reversible mating type conversion has been described in Phytophthora parasitica (Ko 1981) and P. cinnamomi (Ann and Ko 1989). These changes, if they occur in nature, might increase the level of recombination within the population of the pathogen. This is especially the case for P. ramorum for which only a single compatibility Astemizole type could be introduced into a specific geographical area. The purpose of this study was to evaluate the mating type stability of the three Belgian EU1 A2 isolates maintained under different storage conditions for several years. The Phytophthora ramorum isolates used in this study are listed in Table 1. Four isolates (2531, 2533, 2545 and 2546) were isolated from saplings of Quercus robur, Q. petraea, Alnus glutinosa and Acer pseudoplatanus inoculated with isolate 2338 (under bark inoculation with a mycelium plug) in 2003. Routine cultures were carried out on V8 at 20–22°C in the dark. A subculture of isolate 2338 was transferred to JKI in 2003 and maintained in the JKI collection as a hyphal tip culture. The isolate was given a new name, BBA26/02. Isolate 3237 is derived from a subculture of isolate BBA26/02. It was sent to the CRAW in 2005 after subculturing isolate BBA26/02 on carrot piece agar (CPA, Werres et al. 2001) at JKI.

Conclusion: A small proportion of endoscopists do not report completeness of resection of pedunculated polyps, but the majority

of histopathology reports do not mention this.This has implications on surveillance and risk of cancer development.Surveillance endoscopies and tattooing are still not performed according to national guidelines. Key Word(s): 1. Surveillance; 2. Tattooing; 3. Polyp; 4. Pedunculated; Presenting Author: find more XIAO-JUAN LV Additional Authors: WEI-HONG WANG, XIAO-LEI WANG, SHU-JUN WANG, YUN-XIANG CHU, GUI-GEN TENG Corresponding Author: WEI-HONG WANG Affiliations: Peking University First Hospital Objective: Constipation is a common disease which affects 10% people worldwide. It has been suspected to be linked to the risk of colorectal cancer (CCR). However, epidemiological evidence is inconclusive. We examined the relation between constipation and the risk of CCR in this meta-analysis. Methods: Studies published by March 2013 were selected through a literature search in PubMed, Cochrane library and Google scholar. The reference list of the retrieved reviews was also used to identify additional relevant studies. Studies reported the bowl habit in patients with CCR and the controls

were included. We assessed the study quality MAPK inhibitor according to the Newcastle–Ottawa Scale. Pooled effect sizes were calculated using a random effects model.

An odds ratio was used to estimate the association between CRC and constipation. Results: There were 19 nested and case-control studies were included in the analysis with 242,453 participants. ID-8 Constipation was defined differently in these studies. We accepted the definitions given in each study. In 6 nested case–control studies, the incidence of CRC in constipation group was significantly lower than in controls without constipation (OR = 0.73, 95% CI 0.62–0.87). Constipation subjects had a significantly increased CCR incidence compared to non-constipation controls (OR = 1.58,95% CI 1.35–1.84) in 13 case-control studies with significant heterogeneity. Subgroup analysis of 4 nested case-control studies showed that there was no significant increase of color cancer (OR 0.58, 95% CI 0.19–1.80) and rectal cancer (OR 0.66, 95% CI 0.35–1.25) in constipation groups. Conclusion: Nested case-control studies and case-control studies indicated different outcomes for the association between constipation and CCR. This may be caused by the different definition of constipation and the study design. Key Word(s): 1. constipation; 2. colon cancer; 3.

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 Selleckchem Olaparib 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 KU-57788 nmr 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 Dapagliflozin 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.