Our data demonstrate that miR-200a is frequently down-regulated in HCC tissues in comparison with the adjacent noncancerous hepatic tissues, a finding that is consistent with other reports.35, 36 Reduced levels of the histone H3 acetylation at the mir-200a promoter and increased levels of HDAC4 mRNA were also observed in HCCs. Because HDAC4 alone is enzymatically inactive, BYL719 purchase it may suppress the transcription of miR-200a and induce the histone H3 deacetylation at the mir-200a promoter by recruiting catalytically active HDACs into transcriptional

corepressor complexes.37 Therefore, further investigations are required to fully elucidate the nature of HDAC4-containing repressor complexes at the mir-200a promoter. In addition to miR-200a, the miR-200 family also includes miR-200b, miR-200c, miR-141, and miR-429, with miR-200b, miR-200a, and miR-429 being located on chromosome 1 and miR-200c and miR-141 being located on chromosome 12. Both clusters are encoded

as polycistronic transcripts. Our results show that HDAC4 regulates the expression of the miR-200b, miR-200a, miR-429 cluster, but does not regulate the other cluster. Other reports have demonstrated that HDAC inhibitors induce up-regulation of miR-200c,15, 17 and therefore we speculated that other HDACs may participate in the regulation of the miR-200c and miR-141 cluster. Interestingly, we observed that miR-200a, in turn, negatively regulated HDAC4 expression by directly targeting the complementary sites in the 3′-UTR selleck inhibitor of HDAC4 mRNA, generating a double negative feedback loop. Feedback loops are common in many genetic pathways involving miRNAs, and they seem to enhance the robustness of gene networks.38 A significant inverse correlation was also observed between HDAC4 and miR-200a in human HCC tissues. Copy number alterations of

miR-200a and HDAC4 were not found in HCC tissues compared with matched controls. Other proteins such as ZEB1,24 SIRT1,22 p53,39 and gata-binding factors23 can also regulate the expression of miR-200a. Therefore, there is an intricate mechanism regulating the expression of miR-200a and HDAC4 in HCCs. Further investigations are required to elucidate whether the up-regulation of HDAC4 or the down-regulation of miR-200a is the initial 上海皓元 factor of this loop in HCC. Recently, many studies have demonstrated that miRNAs may affect the epigenetic mechanism. For instance, miR-152 induced aberrant DNA methylation in HCC by targeting the DNA methyltransferase 1, as demonstrated in our previous study.40 Other miRNAs, such as miR-148a/b,41 miR-1,20 and miR-449a19, have also been reported to target epigenetic modifying enzymes and modulate the epigenetic transcriptional-regulatory process. However, whether miRNAs can affect the histone acetylation level in HCC remains largely unknown.

10 Using FRG mice, Verma and coworkers11 were able to create human chimeric liver mice without the additional step of administering a vector encoding an hepatotoxic transgene, albeit at lower levels of repopulation of 10% to 20%. In recent work, Verma and colleagues12 demonstrated robust repopulation of FAH mouse livers with human hepatocytes simply by increasing the number of transplanted human hepatocytes to 3 to 5 × 106 hepatocytes per mouse CDK inhibitor versus an inoculum of 0.2 to 1 × 106 hepatocytes administered

in their previous study.11 An average rate of chimerism with human hepatocytes of approximately 40% was achieved without any requirements for additional manipulation, with some animals demonstrating over 80% human hepatocyte chimerism.12 In addition, a strong correlation between serum levels of human albumin and the level of human hepatocyte chimerism was shown, and thus yielding a relatively noninvasive measure of reconstitution of chimeric animals for use in this model. Further experiments

demonstrated FRG human hepatocyte chimeric mice to have a capacity for productive infection by both HBV and HCV, and preliminary experiments demonstrated the feasibility of studying antiviral therapies for both HBV and HCV in this model.12 The FRG human hepatocyte chimeric model appears to hold a number of advantages over previously developed models. As noted above, treatment with NTBC can maintain the check details viability of FRG mice and therefore make the timeframe for hepatocyte reconstitution in these animals less critical. Furthermore, in contrast to previous studies using the Alb-uPA lineage, in which human hepatocyte repopulation appeared to require fresh hepatocytes,

the livers of FRG mice have been successfully reconstituted with hepatocytes up to 48 hours after harvest, and success has also been reported with cryopreserved hepatocytes10, 11; this increases the potential for more widespread use of this model. Successful serial transplantation of human hepatocytes from one FRG mouse to another FRG mouse has also been demonstrated,10 and yielding the potential for an inbred mouse lineage reconstituted with hepatocytes from a single individual in which the biology of a range medchemexpress of viral variants or the efficacy of a range of treatments may be assessed. The development of the FRG human hepatocyte chimeric model, an apparently robust and reproducible system, has exciting potential for the further study of the biology and therapeutics of HBV and HCV. Furthermore, the advent of immunodeficient mouse models reconstituted with human adaptive immune systems via the transfer of CD34-positive progenitors13 raises the possibility of this model being combined with such systems; a small animal model may result in which the immunopathogenesis of HBV and HCV14 and the potential immunomodulatory effects of candidate therapies can be studied.

10 Using FRG mice, Verma and coworkers11 were able to create human chimeric liver mice without the additional step of administering a vector encoding an hepatotoxic transgene, albeit at lower levels of repopulation of 10% to 20%. In recent work, Verma and colleagues12 demonstrated robust repopulation of FAH mouse livers with human hepatocytes simply by increasing the number of transplanted human hepatocytes to 3 to 5 × 106 hepatocytes per mouse Y-27632 ic50 versus an inoculum of 0.2 to 1 × 106 hepatocytes administered

in their previous study.11 An average rate of chimerism with human hepatocytes of approximately 40% was achieved without any requirements for additional manipulation, with some animals demonstrating over 80% human hepatocyte chimerism.12 In addition, a strong correlation between serum levels of human albumin and the level of human hepatocyte chimerism was shown, and thus yielding a relatively noninvasive measure of reconstitution of chimeric animals for use in this model. Further experiments

demonstrated FRG human hepatocyte chimeric mice to have a capacity for productive infection by both HBV and HCV, and preliminary experiments demonstrated the feasibility of studying antiviral therapies for both HBV and HCV in this model.12 The FRG human hepatocyte chimeric model appears to hold a number of advantages over previously developed models. As noted above, treatment with NTBC can maintain the Selleckchem BMS-777607 viability of FRG mice and therefore make the timeframe for hepatocyte reconstitution in these animals less critical. Furthermore, in contrast to previous studies using the Alb-uPA lineage, in which human hepatocyte repopulation appeared to require fresh hepatocytes,

the livers of FRG mice have been successfully reconstituted with hepatocytes up to 48 hours after harvest, and success has also been reported with cryopreserved hepatocytes10, 11; this increases the potential for more widespread use of this model. Successful serial transplantation of human hepatocytes from one FRG mouse to another FRG mouse has also been demonstrated,10 and yielding the potential for an inbred mouse lineage reconstituted with hepatocytes from a single individual in which the biology of a range MCE公司 of viral variants or the efficacy of a range of treatments may be assessed. The development of the FRG human hepatocyte chimeric model, an apparently robust and reproducible system, has exciting potential for the further study of the biology and therapeutics of HBV and HCV. Furthermore, the advent of immunodeficient mouse models reconstituted with human adaptive immune systems via the transfer of CD34-positive progenitors13 raises the possibility of this model being combined with such systems; a small animal model may result in which the immunopathogenesis of HBV and HCV14 and the potential immunomodulatory effects of candidate therapies can be studied.

In our current study, in contrast, we analyzed Selleck BMS-777607 a far larger cohort than any other previous report, and evaluated a comprehensive panel of clinical and pathological parameters in relation to the N-glycan profile in HCC. Tang et al.35 also described some HCC-specific glycans in their previous study that we did not find to be significant in our current analyses. This is likely due to the fact that the patient number in their study was smaller than ours, and the fact that the N-glycome profile in serum is gender- and age-dependent.36 In this

study, the mean age and the distribution of gender and infection of hepatitis B and C virus were the difference between NC and HCC patients. However, the selected 14 serum N-glycans were quantified by our MALDI-TOF MS analysis and compared with NC by ROC analysis. These were statistically different between HCC and NC with respect to the quantity. Because these 14 serum N-glycans of which the AUC values were greater than 0.80 were

revealed learn more to be specific for HCC, they had a high discriminating ability to differentiate HCC from NC. Further analyses are required to determine whether G2890 and G3560 are elevated in patients with hepatitis B, hepatitis C, and/or cirrhosis without HCC. The most important adverse prognostic factor for liver resection and transplantation in HCC has been found to be microscopic venous invasion.5 However, microscopic portal invasion is not diagnosed preoperatively, and is revealed only by pathological examination. New biomarkers that are more strongly associated with prognosis and recurrence of HCC than medchemexpress AFP, AFP-L3, or PIVKA-II are therefore highly desirable. Our current data show that the N-glycans G2890 and G3560 correlate closely with well-known tumor-related prognostic and recurrent factors such as tumor number, size, microscopic portal vein invasion, microscopic hepatic vein invasion, differentiation, macroscopic vascular invasion, stage, AFP, AFP-L3, and PIVKA-II (Table 6). Moreover,

when G2890 and G3560 were simultaneously included in multivariate analysis for PS and DFS with AFP, AFPL3 and PIVKA-II, P-values of G2890 and G3560 were lower than AFP, and AFPL3, and PIVKA-II were not selected as valuables by AIC. We demonstrate that these are novel independent prognostic factors for HCC that are related to the survival and recurrence of this disease and that show a lower P-value than other established tumor factors. Hence, we predict that G2890 and G3560 will prove to be markers that can preoperatively predict HCC tumor malignancy including microscopic portal vein invasion, and the PS and DFS rates more accurately and with more potency than the more well-known biomarkers.

These patients intriguingly shared some biochemical features with WD patients. It is noteworthy that WD patients 23 and 24 (Table 2) were siblings who showed

features very similar to those of CDG patients included in the control group, but in both CDG was excluded on the basis of a normal transferrin isoelectric focusing profile. Their serum aminotransferase levels normalized after 20 or 4 months of penicillamine treatment. The features of our series are remarkably different from those of other pediatric reports, which in most cases have included WD children with either acute or chronic symptomatic liver disease or liver failure.3, 6-9, 13 In fact, all the WD patients evaluated click here in the present study were referred for raised aminotransferases and could be considered asymptomatic or presymptomatic. Therefore, this population represents a valuable specimen for assessing the appropriateness of the

WD diagnostic criteria in children with mild liver disease. The present study has highlighted different peculiarities of these patients with respect to WD children reported elsewhere.6-9, 13 The measurement of ceruloplasmin serum levels is also a first-step test for the diagnosis of WD in children with mild liver disease, as demonstrated by the good sensitivity and acceptable specificity of this test at the cutoff of 20 mg/dL in the studied population. Obviously, low levels of ceruloplasmin are MCE公司 not always indicative of a copper storage disorder because both heterozygotes for WD and patients with other disorders may share this feature.20-23 Furthermore, as see more reported elsewhere, ceruloplasmin serum levels are also influenced by the ATP7B genotype.24, 25 As for basal daily urinary copper

excretion, on the basis of our results, the diagnosis of WD should be considered when this test produces a value > 40 μg/24 hours. This cutoff value has also been recently stressed by AASLD guidelines,2 although its diagnostic accuracy has not yet been defined. There is only one report describing a sensitivity of 68% at the cutoff value of 40 μg/24 hours in an adult population.26 Among the adult series, the sensitivity of basal urinary copper excretion at the cutoff value of 100 μg/24 hours is 59% to 88%.7, 26, 27 As for the pediatric series, urinary copper levels have exceeded 100 μg/24 hours in 81% to 94% of cases.5, 9, 28 In symptomatic and asymptomatic children, the sensitivity for basal cupriuria at the cutoff value of 63.5 μg/24 hours is approximately 95% and 70%, respectively.3, 9 No data are available about the specificity of this test because the cutoff value of 40 μg/24 hours has never been evaluated; our results suggest that this is the optimal threshold both as a single test and in the context of the WD scoring system in children with mild liver disease suspected of having WD.

These patients intriguingly shared some biochemical features with WD patients. It is noteworthy that WD patients 23 and 24 (Table 2) were siblings who showed

features very similar to those of CDG patients included in the control group, but in both CDG was excluded on the basis of a normal transferrin isoelectric focusing profile. Their serum aminotransferase levels normalized after 20 or 4 months of penicillamine treatment. The features of our series are remarkably different from those of other pediatric reports, which in most cases have included WD children with either acute or chronic symptomatic liver disease or liver failure.3, 6-9, 13 In fact, all the WD patients evaluated Protein Tyrosine Kinase inhibitor in the present study were referred for raised aminotransferases and could be considered asymptomatic or presymptomatic. Therefore, this population represents a valuable specimen for assessing the appropriateness of the

WD diagnostic criteria in children with mild liver disease. The present study has highlighted different peculiarities of these patients with respect to WD children reported elsewhere.6-9, 13 The measurement of ceruloplasmin serum levels is also a first-step test for the diagnosis of WD in children with mild liver disease, as demonstrated by the good sensitivity and acceptable specificity of this test at the cutoff of 20 mg/dL in the studied population. Obviously, low levels of ceruloplasmin are MCE公司 not always indicative of a copper storage disorder because both heterozygotes for WD and patients with other disorders may share this feature.20-23 Furthermore, as BGJ398 mw reported elsewhere, ceruloplasmin serum levels are also influenced by the ATP7B genotype.24, 25 As for basal daily urinary copper

excretion, on the basis of our results, the diagnosis of WD should be considered when this test produces a value > 40 μg/24 hours. This cutoff value has also been recently stressed by AASLD guidelines,2 although its diagnostic accuracy has not yet been defined. There is only one report describing a sensitivity of 68% at the cutoff value of 40 μg/24 hours in an adult population.26 Among the adult series, the sensitivity of basal urinary copper excretion at the cutoff value of 100 μg/24 hours is 59% to 88%.7, 26, 27 As for the pediatric series, urinary copper levels have exceeded 100 μg/24 hours in 81% to 94% of cases.5, 9, 28 In symptomatic and asymptomatic children, the sensitivity for basal cupriuria at the cutoff value of 63.5 μg/24 hours is approximately 95% and 70%, respectively.3, 9 No data are available about the specificity of this test because the cutoff value of 40 μg/24 hours has never been evaluated; our results suggest that this is the optimal threshold both as a single test and in the context of the WD scoring system in children with mild liver disease suspected of having WD.

PI anaemia was observed in 61% and 33% required BT during the first 12 weeks of treatment. ITPase deficiency was associated with less PI anaemia (40.7% vs 68.2%, p = 0.001). No association between week 4 Hb decline and gender, age <45 yrs, fibrosis stage, treatment history or IL28B genotype was observed. The proportion of patients requiring BT was lower in those with ITPase deficiency (7.4% vs 21%). A multivariable model including ITPase activity, gender, age, fibrosis stage, and RBV dose (mg/kg) was used to determine factors associated with BT requirement. Both gender and ITPase activity were independent predictors of requiring a BT (male

gender OR 0.2, p = 0.003; wild-type ITPase activity OR 3.3, p = 0.04). Conclusions: Baseline ITPA genotype predicts the development of early and significant anaemia during PI therapy for HCV and identifies patients who are at higher Ivacaftor cost risk for requiring a blood transfusion during therapy. Fellay J, Thompson AJ, Ge D, et al. ITPA gene variants protect against anaemia in Selleckchem BAY 80-6946 patients treated for chronic hepatitis C. Nature 2010; 464:405–408. JA HOLMES,1,2 S BONANZINGA,3 MK SANDHU,1 YH KIA,1 M CONGIU,2 SJ BELL,1 T NGUYEN,1 DM ISER,1 KL MELLOR,1 K VISVANATHAN,2,5 W SIEVERT,5,6 DS BOWDEN,3 PV DESMOND,1,2 AJ THOMPSON1,2,3 1Department of Gastroenterology;

St Vincent’s Hospital; Fitzroy; Australia, 2Department of Medicine, University of Melbourne; St Vincent’s Hospital; Fitzroy; Australia, 3Victorian Infectious Diseases Reference Laboratory; North Melbourne; MCE Australia, 4Department of Medical Imaging; St Vincent’s Hospital; Fitzroy; Australia, 5Infectious Diseases Department; Monash Medical Centre; Monash University; Clayton; Australia, 6Department of Gastroenterology; Monash Medical Centre; Monash University; Clayton; Australia, 7Department of Gastroenterology; Duke University Medical Centre; Duke Clinical Research Institute; Durham; USA Background: In 2009, IL28B genotype (gt) was identified as the strongest baseline predictor of peg-interferon and ribavirin (PR) response for HCV-1. In 2013, a novel dinucleotide

variant in interferon-lambda-4 (IFNL4, ss469415590, ΔG/TT), in high linkage disequilibrium (LD) with IL28B polymorphism, was proposed to be the causal variant. IFNL4 gt was reported to be a better predictor of sustained virological response (SVR). We have performed the first independent validation study of the association between IFNL4 variation, IL28B variation, and PR treatment outcomes in a large cohort of Australian HCV-1/3 patients. Methods: HCV-1/3 patients who received PR were included. IL28B (rs12979860) and IFNL4 (ss469415590) gts were determined from serum (TaqMan allelic discrimination kit, custom designed primers where testing unsuccessful). IFNL4 gt was correlated with rapid virological response (RVR) and SVR, and compared to IL28B gt using logistic regression modeling and LD calculation.

PI anaemia was observed in 61% and 33% required BT during the first 12 weeks of treatment. ITPase deficiency was associated with less PI anaemia (40.7% vs 68.2%, p = 0.001). No association between week 4 Hb decline and gender, age <45 yrs, fibrosis stage, treatment history or IL28B genotype was observed. The proportion of patients requiring BT was lower in those with ITPase deficiency (7.4% vs 21%). A multivariable model including ITPase activity, gender, age, fibrosis stage, and RBV dose (mg/kg) was used to determine factors associated with BT requirement. Both gender and ITPase activity were independent predictors of requiring a BT (male

gender OR 0.2, p = 0.003; wild-type ITPase activity OR 3.3, p = 0.04). Conclusions: Baseline ITPA genotype predicts the development of early and significant anaemia during PI therapy for HCV and identifies patients who are at higher HDAC inhibitor review risk for requiring a blood transfusion during therapy. Fellay J, Thompson AJ, Ge D, et al. ITPA gene variants protect against anaemia in Selleckchem Tamoxifen patients treated for chronic hepatitis C. Nature 2010; 464:405–408. JA HOLMES,1,2 S BONANZINGA,3 MK SANDHU,1 YH KIA,1 M CONGIU,2 SJ BELL,1 T NGUYEN,1 DM ISER,1 KL MELLOR,1 K VISVANATHAN,2,5 W SIEVERT,5,6 DS BOWDEN,3 PV DESMOND,1,2 AJ THOMPSON1,2,3 1Department of Gastroenterology;

St Vincent’s Hospital; Fitzroy; Australia, 2Department of Medicine, University of Melbourne; St Vincent’s Hospital; Fitzroy; Australia, 3Victorian Infectious Diseases Reference Laboratory; North Melbourne; medchemexpress Australia, 4Department of Medical Imaging; St Vincent’s Hospital; Fitzroy; Australia, 5Infectious Diseases Department; Monash Medical Centre; Monash University; Clayton; Australia, 6Department of Gastroenterology; Monash Medical Centre; Monash University; Clayton; Australia, 7Department of Gastroenterology; Duke University Medical Centre; Duke Clinical Research Institute; Durham; USA Background: In 2009, IL28B genotype (gt) was identified as the strongest baseline predictor of peg-interferon and ribavirin (PR) response for HCV-1. In 2013, a novel dinucleotide

variant in interferon-lambda-4 (IFNL4, ss469415590, ΔG/TT), in high linkage disequilibrium (LD) with IL28B polymorphism, was proposed to be the causal variant. IFNL4 gt was reported to be a better predictor of sustained virological response (SVR). We have performed the first independent validation study of the association between IFNL4 variation, IL28B variation, and PR treatment outcomes in a large cohort of Australian HCV-1/3 patients. Methods: HCV-1/3 patients who received PR were included. IL28B (rs12979860) and IFNL4 (ss469415590) gts were determined from serum (TaqMan allelic discrimination kit, custom designed primers where testing unsuccessful). IFNL4 gt was correlated with rapid virological response (RVR) and SVR, and compared to IL28B gt using logistic regression modeling and LD calculation.

PI anaemia was observed in 61% and 33% required BT during the first 12 weeks of treatment. ITPase deficiency was associated with less PI anaemia (40.7% vs 68.2%, p = 0.001). No association between week 4 Hb decline and gender, age <45 yrs, fibrosis stage, treatment history or IL28B genotype was observed. The proportion of patients requiring BT was lower in those with ITPase deficiency (7.4% vs 21%). A multivariable model including ITPase activity, gender, age, fibrosis stage, and RBV dose (mg/kg) was used to determine factors associated with BT requirement. Both gender and ITPase activity were independent predictors of requiring a BT (male

gender OR 0.2, p = 0.003; wild-type ITPase activity OR 3.3, p = 0.04). Conclusions: Baseline ITPA genotype predicts the development of early and significant anaemia during PI therapy for HCV and identifies patients who are at higher Target Selective Inhibitor Library concentration risk for requiring a blood transfusion during therapy. Fellay J, Thompson AJ, Ge D, et al. ITPA gene variants protect against anaemia in Dinaciclib ic50 patients treated for chronic hepatitis C. Nature 2010; 464:405–408. JA HOLMES,1,2 S BONANZINGA,3 MK SANDHU,1 YH KIA,1 M CONGIU,2 SJ BELL,1 T NGUYEN,1 DM ISER,1 KL MELLOR,1 K VISVANATHAN,2,5 W SIEVERT,5,6 DS BOWDEN,3 PV DESMOND,1,2 AJ THOMPSON1,2,3 1Department of Gastroenterology;

St Vincent’s Hospital; Fitzroy; Australia, 2Department of Medicine, University of Melbourne; St Vincent’s Hospital; Fitzroy; Australia, 3Victorian Infectious Diseases Reference Laboratory; North Melbourne; MCE公司 Australia, 4Department of Medical Imaging; St Vincent’s Hospital; Fitzroy; Australia, 5Infectious Diseases Department; Monash Medical Centre; Monash University; Clayton; Australia, 6Department of Gastroenterology; Monash Medical Centre; Monash University; Clayton; Australia, 7Department of Gastroenterology; Duke University Medical Centre; Duke Clinical Research Institute; Durham; USA Background: In 2009, IL28B genotype (gt) was identified as the strongest baseline predictor of peg-interferon and ribavirin (PR) response for HCV-1. In 2013, a novel dinucleotide

variant in interferon-lambda-4 (IFNL4, ss469415590, ΔG/TT), in high linkage disequilibrium (LD) with IL28B polymorphism, was proposed to be the causal variant. IFNL4 gt was reported to be a better predictor of sustained virological response (SVR). We have performed the first independent validation study of the association between IFNL4 variation, IL28B variation, and PR treatment outcomes in a large cohort of Australian HCV-1/3 patients. Methods: HCV-1/3 patients who received PR were included. IL28B (rs12979860) and IFNL4 (ss469415590) gts were determined from serum (TaqMan allelic discrimination kit, custom designed primers where testing unsuccessful). IFNL4 gt was correlated with rapid virological response (RVR) and SVR, and compared to IL28B gt using logistic regression modeling and LD calculation.

Conclusions:  VX-770 chemical structure There was no significant difference in delta polyp size between the examinees with gallbladder polyps and cholelithiasis and those with gallbladder polyps only. Hence, a small proportion of subjects with gallbladder polyps and cholelithiasis, such as those with thickened gallbladder walls and an interval increase in the size of the gallbladder polyps are candidates for prophylactic cholecytectomy. “
“Transient elastography (TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis. The present study was designed to provide

a definitive characterization of the “confounding” increase in liver stiffness (LS) following a standardized meal in a consecutive population of 125 patients with chronic HCV infection at different stages of fibrotic evolution. LS values were obtained after overnight fasting and 15, 30, 45, 60, and 120 minutes following the onset of a standardized liquid meal (400 mL, 600 Kcal, 16.7% protein, 53.8% carbohydrates, 29.5% fat). An evident increase in LS values was observed 15 to 45 minutes after the onset of the meal with return to baseline premeal

levels within 120 minutes in all patients. The peak postmeal delta increase in LS was progressively more marked with increasing stages of fibrosis (P < 0.001), becoming maximal in patients with cirrhosis. However, the probability of identifying the Metavir stage BMS-777607 of fibrosis, the Child-Pugh class, or the presence/absence of esophageal MCE公司 varices with the postmeal delta increase in LS was inferior to that obtained with baseline LS values. Conclusion: The results of the present study provide definitive evidence of the confounding effect of a meal on the accuracy of LS measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggest that a fasting period of 120 minutes should be observed before the performance of TE. (HEPATOLOGY 2013;) Transient elastography

(TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis.1 In this clinical setting, TE has been shown to be able to discriminate between at least three stages of fibrotic evolution: the absence of significant fibrosis, the presence of advanced fibrosis/cirrhosis, and an intermediate stage, often defined as a “gray area.” This distinction is useful in everyday practice for directing the need of liver biopsy,2 and overall, the use of TE, alone or in association with other noninvasive means, considerably reduces the number of liver biopsies necessary for correct patient management.