Our data suggest that APAP treatment leads to GSH depletion, protein adduct formation, mitochondrial dysfunction, and oxidant

stress and eventually oncotic www.selleckchem.com/products/BKM-120.html necrosis in HepaRG cells, similar to what has been observed in primary mouse hepatocytes but not in typical human hepatoma cells. The basis for this behavior is that HepaRG cells are capable of differentiating into two subpopulations: one with hepatocyte-like morphology and gene expression and one with the appearance of biliary epithelial cells.22, 24 The hepatocyte-like cells express a nearly complete complement of drug-metabolizing enzymes, including most of the cytochrome P450 enzymes.25, 26 HepaRG cells also possess many other characteristics unique to adult differentiated hepatocytes, including hepatocyte-specific transporter expression,25, 33 iron-loading capacity,34 and inducibility of CYPs and other proteins.33, 35 Thus, these cells have the potential to be a useful tool to study mechanisms of drug hepatotoxicity in a human system. The distinct advantage of the HepaRG cell line over primary human hepatocytes is the unlimited availability of identical cells. Nevertheless, they are hepatoma-derived selleck chemical and there is the

possibility that certain intracellular signaling mechanisms might be different. It is therefore important to study mechanisms of cell death induced by known hepatotoxicants in these cells. Acetaminophen hepatotoxicity in rodents depends on the formation of the reactive metabolite NAPQI, which can be detoxified by glutathione. However, after depletion of GSH in the cell, NAPQI binds to cellular proteins, which is considered the initiating event in the toxicity.2, 36 Our experiments with HepaRG cells identified depletion of cellular GSH and the formation of protein

adducts as the earliest detectable events. This is consistent with mouse studies of APAP hepatotoxicity.18, 37 Evidence for increased GSH turnover and detection of APAP-protein adducts in human plasma after APAP exposure suggests that these events also MCE公司 occur in humans.38, 39 Although our data agree with the general hypothesis of reactive metabolite formation, GSH depletion and protein adduct formation as early response to APAP exposure, the sequence of events is not as previously assumed. Our data clearly show that protein adduct formation occurs parallel to GSH consumption and does not require extensive GSH depletion. In fact, protein adducts were detected in HepaRG cells and in HepG2 cells before significant effects on GSH levels and well before any evidence of mitochondrial dysfunction and cell death. This suggests that small amounts of protein binding per se does not initiate toxicity and probably a certain level needs to be reached to trigger the early mitochondrial effects. More recently, mitochondrial dysfunction and the MPT have emerged as central to the mechanism of APAP-induced cell death in cultured rodent hepatocytes10-12 and in vivo.

S1). A median-joining network was drawn including all the New Zealand mtDNA control region haplotypes and considering the putative population subdivision (Fig. 2). The network shows a complex structure Atezolizumab with a central core of missing (unsampled or extinct) haplotypes and no clear clustering based on population origin. A total of 84 individuals for the mtDNA data set and 79 for the microsatellite data set was examined to test for possible differentiation among putative Oceanic, Coastal, and Hauraki Gulf populations. The program

STRUCTURE was used to test population structure without a priori sample assignment to a specific population. The most likely number of clusters was found to be two (K = 1, LnP = −4,269.93; K = 2, LnP = −4,261.49; K = 3, LnP = −4,565.97; K = 4, LnP = −4,381.87, K = 5, LnP = −4,449.32, K = 6, LnP = −4,632.84). The application of the Evanno method also identified K = 2 as the most likely number of cluster (K = 2, ΔK= 70.89; K = 3, ΔK = 10.19; K = 4, ΔK = 4.45; K = 5, ΔK = 2.18). However, the clusters do not identify any population as previously assigned based on the sample origins (Oceanic, Coastal or Hauraki Gulf) (Fig. 3). The Principal Component check details Analysis

(PCA) was also performed and the first two principal components

explained MCE 64.42% of the total variation (Fig. 4). Along both components, the Coastal population appears slightly differentiated from the others. FST values, based on the mtDNA data, suggested small but significant genetic differentiation between the putative Hauraki Gulf, and the Coastal and Oceanic populations, although no significant differentiation was detected between the Coastal and Oceanic groups. Φst values did not indicate any significant differentiation (Table 2). The AMOVA analysis indicated 98% of the overall variation due to variance within populations (Vc = 0.49, FST 0.0168, P = 0.00098). In contrast, pairwise comparisons of FST values based on microsatellites showed a small but significant differentiation between Oceanic and Coastal populations, a result supported by Jost’s DEST values (Table 2). However, the result obtained with AMOVA, which gave us an overall estimate of FST, was not significant (FST = 0.00953, P = 0.81916). When testing for sex-biased dispersal, there was no significant difference (P > 0.05) for FIS, FST, HE, and HO between males and females. However, this test is known to have relatively low power, particularly when small sample sizes are used (see Goudet et al. 2002).

Liver tissues were fixed in 10% neutral-buffered formalin, processed, and then embedded in paraffin for light microscopy. Sections were stained with hematoxylin

and eosin (H&E) for histological examination. Quantitative morphometric selleck compound analysis of hepatocellular necrosis was performed in a blinded fashion with histologic sections at low power (×10) using image analysis software (Adobe Systems, San Jose, CA). Necrotic area was expressed as percentage of total area examined. Liver content of TNF-α, macrophage inflammatory protein-2 (MIP-2), and keratinocyte chemokine (KC) was assessed by ELISA (R&D Systems). Liver samples were weighed and immediately placed in 10 volumes (wt/vol) of a protease inhibitor cocktail containing 10 nmol/L ethylenediaminetetraacetic acid (EDTA), 2

mmol/L phenylmethylsulfonyl fluoride, 0.1 mg/mL soybean trypsin inhibitor, 1.0 mg/mL bovine serum albumin, and 0.002% sodium azide in isotonic PBS, pH 7.0. Tissues were disrupted with a tissue homogenizer and lysates were incubated at 4°C for 2 hours. Samples were clarified by two rounds of centrifugation at 12,500g for 10 minutes at 4°C. Liver myeloperoxidase (MPO) content was assessed by methods described elsewhere.22 Briefly, liver tissue (100 mg) was homogenized in 2 mL of buffer A (3.4 mmol/L KH2HPO4, 16 mmol/L Na2HPO4, pH 7.4). After being centrifuged buy Compound Library for 20 minutes at 10,000g, the pellet was resuspended in 10 volumes of buffer B (43.2 mmol/L KH2HPO4, 6.5 mmol/L Na2HPO4, 10 mmol/L EDTA, 0.5% hexadecyltrimethylammonium, pH 6.0) and sonicated for 10 seconds. After being heated for 2 hours at 60°C, the supernatant was reacted with 3,3′,3,5′-tetramethylbenzidine and the optical density MCE was read at 655

nm. Hepatocytes were isolated from male wildtype mice by nonrecirculating collagenase perfusion through the portal vein. Livers were perfused in situ with 45 mL Gibco Liver Perfusion Media (Invitrogen, Carlsbad, CA) followed by 45 mL of Gibco Liver Digestion Media (Invitrogen). The liver was excised, minced, and strained through a steel mesh. The dispersed hepatocytes were collected by centrifugation at 50g for 2 minutes at 4°C and washed twice with Williams media (Invitrogen). Hepatocytes were isolated by way of Percoll separation and washed twice with Williams media. The final pellet was resuspended with Williams media. Hepatocytes were counted and viability was checked by Trypan blue exclusion. Kupffer cells were contained in the supernatants from the above wash. Cells were pelleted by centrifugation at 500g for 9 minutes, resuspended in sterile Ca2+- and Mg2+-free Hank’s buffered salt solution (HBSS) (pH 7.4), and subjected to fractionation by elutriation. Centrifugal elutriation was performed using a Beckman Coulter J20-XPI centrifuge with a JE 5.0 elutriator rotor at a constant speed of 3,200 rpm with stepwise increases in perfusion rates. Kupffer cells were collected at the 44 mL/min fraction.

DNA oxidation was quantified by immunohistochemical analysis of 8-OHdG. The staining of 8-OHdG was classified as strong (2+), moderate (1+), or weak (-). HCC-free survival after biopsy was analyzed retrospectively using Kaplan-Meier method. Methylation of 10 TSGs

(HIC-1, GSTP1, CHIR-99021 order SOCS1, RASSF1, CDKN2A, APC, RUNX3, PRDM2, CASP8, CACNA1G) was determined by MethyLight. Significant factors contributing to increased number of methylated TSGs was determined by multivariate analysis using age, gender, fibrosis stage, amount of 8-OHdG and iron deposit as covariables. (2) HepG2 cells were treated with H2O2 and chromatin immunoprecipitation (ChIP) was performed before and after treatment using antibodies against trimethyl-H3K4, acethylated-H4K1 6 for active chromatin,

trimethyl-H3K27 for repressed chromatin, 8-OHdG for damaged DNA elements, pan-histone H3 for positive ChIP control, and rabbit IgG for negative ChIP control. Quantitative PCR (qPCR) was performed for promoters of 25 different TSGs, which reportedly showed methylation in human Histone Acetyltransferase inhibitor cancer using EpiScope® Promoter qPCR Array (TaKaRa). Alterations in chromatin status on damaged DNA (DNA element with 8-OHdG) was also determined. Results: Increased 8-OHdG content was significantly associated with shorter time to HCC emergence in CHC patients (p=0.0026, log-rank test). Multivariate analysis revealed that high levels of 8-OHdG was the only variable that significantly associated with increased number of methylated TSGs (p<0.0001), and showed dose-related effect between amount of 8-OHdG and number of methylated TSGs (RR=3.53, CI=5.97∼2.15 for 2+ v.s. -; RR=2.01, CI=3.42∼1.18 for 2+ v.s 1+; RR=1.76, CI=2.83∼1.11 for 1+ v.s. -). ChIP-qPCR revealed that DNA elements carrying 8-OHdG after H2O2 treatment showed alteration of active chromatin (trimethyl-H3K4 and acethylated-H4K1 6 dominant) to repressive chromatin status (trimethyl-H3K27 dominant). Conclusion: We conclude that oxidative stress induces alteration of chromatin status, which lead to abnormal methylation of TSGs, and contribute to hepa-tocarcinogenesis

MCE公司 in CHC patients. Disclosures: The following people have nothing to disclose: Naoshi Nishida, Masatoshi Kudo, Tadaaki Arizumi, Masahiro Takita, Satoshi Kitai, Norihisa Yada, Tatsuo Inoue, Satoru Hagiwara, Yasunori Minami, Toshiharu Sakurai, Kazuomi Ueshima, Takeshi Nagasaka, Ajay Goel Background: Hepatocellular carcinoma (HCC) is a worldwide health issue; however, it remains poorly understood. Previously, we found that the introduction of HBV X protein (HBx) and an oncogenic allele of Ras induced the tumorigenic transformation of immortalized human fibroblasts. However, it remains unclear if these observations apply to human hepatocytes. Moreover, recent evidence suggests that HCC contains a subset of cells with stem cell features.

Treatment with MARS was associated with a decrease in serum bilirubin, with a reduction of serum creatinine to less than 1.5 mg/dL, and with a marked improvement of hepatic encephalopathy (decrease of HE from grade II-IV to grade 0-I) in a high proportion of patients. These features occurred more frequently in patients treated by MARS plus standard medical therapy than in those only receiving standard medical

treatment alone (percent decrease in serum bilirubin: 26.4% versus 8.9%; P < 0.001; improvement of hepatic encephalopathy: OR: 0.37; 95% CI 0.12-1.09; P = 0.07; reversal of HRS OR: 0.40; 95% CI 0.15-1.07; P = 0.07). It is important Ku-0059436 research buy to point out that the more frequent decrease of serum creatinine below the 1.5 mg/dL threshold observed in patients treated with MARS occurred despite that patients in the control group received treatment with terlipressin plus albumin and a significant number of them also received artificial renal support. There was a clear relationship between the dose of MARS and its effects in the support of organ function since these were evident within the first 4 days of treatment, a period in which patients received one MARS session per day, but not during the subsequent weeks in which, according to the study protocol, a maximum of one session every 2 days was administered. Despite the beneficial effects of the use

of MARS in organ support, no improvement in short-term or mid-term transplant-free survival was observed. The 28- and 90-day probabilities GS-1101 order of survival were similar in patients treated with MARS plus standard medical therapy 上海皓元 and in those

receiving standard medical therapy alone. This lack of a survival improvement was also observed in three different predetermined subgroups (patients with hepatic encephalopathy, HRS, or progressive hyperbilirubinemia). Finally, a logistic model adjusted to potential confounding variables not completely balanced at baseline showed a slight reduction in 28-day transplant-free mortality in the MARS arm, but the difference was nonsignificant. Similar results have recently been reported in another large randomized controlled trial using the fractionated plasma separation and absorption device.26 The lack of improvement in survival with MARS despite observed improvement of HE and amelioration of renal function is a paradoxical finding that represents a major point of our study. One potential explanation is that the beneficial effects of MARS could have been counterbalanced by complications associated with the procedure. Another possibility is that although renal and/or cerebral function improved in many patients in the MARS arm, the difference between the effects obtained with MARS plus standard medical therapy versus those with standard medical therapy alone was not high enough to influence survival. Our results suggest that this possibility is the most likely explanation.

Thus, each tissue block (NT and T) was represented by three independent spots in the TMA. IHC experiments were performed using an automated Discovery XT immunostaining device (Ventana Medical System, Tucson, AZ). TMA sections (4 μm thick) were evaluated for the expression of collagen 4, laminin, osteopontin, TGFβ2, and KIAA0101 (Supporting Table 1). Antigens were retrieved from deparaffinized and rehydrated Crizotinib mouse tissues by incubating the slides for 48 minutes at 95°C in CC1 Tris-based buffer (pH 8.0) (laminin, collagen 4, and KIAA0101) or in Ultra CC2 citrate buffer

(pH 6.0) (osteopontin and TGFβ2) (Ventana Medical System). Detection was performed using a streptavidin-biotin-peroxidase kit (OmniMap, Biotin-free DAB Detection Systems, Ventana Medical System). TMA slides were analyzed by two experienced pathologists (B.T., F.L.G.) in a blinded manner. Staining intensity in the stroma was scored as follows: negative (0), RG7420 cell line mild (1), moderate (2), or strong (3). Given that each stromal sample was represented in triplicate, the sum of the three values was performed to obtain a score of with a range of 0 to 9. This score was finally categorized into four groups to optimize the statistical analysis and to take into account extreme values: 0 (score 0-1), 1 (score 2-3), 2 (score 4-7), and 3 (score 8-9). Differences in protein expression (NT fibrous tissue versus T stroma) were evaluated by chi-squared testing. Relationships

between protein expression and clinical parameters were evaluated using the chi-squared or Fisher’s exact probability test for categorical variables and using the analysis of variance for numerical variables. The correlation of the scoring performed by the two pathologists was estimated by a weighted kappa coefficient; disagreements were weighted according to their squared distance from a perfect agreement in the correlation matrix. The Kaplan-Meier method was used to estimate the overall (OS) MCE and disease-free survival (DFS), and group differences were analyzed with the log-rank test. A trend analysis was also performed. Univariate

and multivariate Cox regression models for the hazards of OS and DFS mortality were used to evaluate the effect of protein expression. Correlation between the different variables was also evaluated in order to identify putative interaction and confounding factors. The most suited Cox model was selected using a stepwise regression, selecting variables based on the Akaike Information Criterion (AIC). P < 0.05 was considered statistically significant. Statistical analysis was performed with R (v. 2.15.1). Relevant biomarkers for ICC prognosis were investigated by the unsupervised gene expression analysis of the stroma in mass-forming type ICC. To increase the robustness of the study, an initial cohort of clinically well-annotated cases of patients with ICC (n = 87) was used to build a testing set and a validating set as described.

Thus, each tissue block (NT and T) was represented by three independent spots in the TMA. IHC experiments were performed using an automated Discovery XT immunostaining device (Ventana Medical System, Tucson, AZ). TMA sections (4 μm thick) were evaluated for the expression of collagen 4, laminin, osteopontin, TGFβ2, and KIAA0101 (Supporting Table 1). Antigens were retrieved from deparaffinized and rehydrated PLX4032 tissues by incubating the slides for 48 minutes at 95°C in CC1 Tris-based buffer (pH 8.0) (laminin, collagen 4, and KIAA0101) or in Ultra CC2 citrate buffer

(pH 6.0) (osteopontin and TGFβ2) (Ventana Medical System). Detection was performed using a streptavidin-biotin-peroxidase kit (OmniMap, Biotin-free DAB Detection Systems, Ventana Medical System). TMA slides were analyzed by two experienced pathologists (B.T., F.L.G.) in a blinded manner. Staining intensity in the stroma was scored as follows: negative (0), selleck kinase inhibitor mild (1), moderate (2), or strong (3). Given that each stromal sample was represented in triplicate, the sum of the three values was performed to obtain a score of with a range of 0 to 9. This score was finally categorized into four groups to optimize the statistical analysis and to take into account extreme values: 0 (score 0-1), 1 (score 2-3), 2 (score 4-7), and 3 (score 8-9). Differences in protein expression (NT fibrous tissue versus T stroma) were evaluated by chi-squared testing. Relationships

between protein expression and clinical parameters were evaluated using the chi-squared or Fisher’s exact probability test for categorical variables and using the analysis of variance for numerical variables. The correlation of the scoring performed by the two pathologists was estimated by a weighted kappa coefficient; disagreements were weighted according to their squared distance from a perfect agreement in the correlation matrix. The Kaplan-Meier method was used to estimate the overall (OS) 上海皓元 and disease-free survival (DFS), and group differences were analyzed with the log-rank test. A trend analysis was also performed. Univariate

and multivariate Cox regression models for the hazards of OS and DFS mortality were used to evaluate the effect of protein expression. Correlation between the different variables was also evaluated in order to identify putative interaction and confounding factors. The most suited Cox model was selected using a stepwise regression, selecting variables based on the Akaike Information Criterion (AIC). P < 0.05 was considered statistically significant. Statistical analysis was performed with R (v. 2.15.1). Relevant biomarkers for ICC prognosis were investigated by the unsupervised gene expression analysis of the stroma in mass-forming type ICC. To increase the robustness of the study, an initial cohort of clinically well-annotated cases of patients with ICC (n = 87) was used to build a testing set and a validating set as described.

(Hepatology 2014;60:1494–1507) “
“Although the inflammation-associated cytokine interleukin-6 (IL-6) has been implicated in cholangiocarcinoma this website growth, the relationship between IL-6 and oncogenic changes is unknown.

IL-6 can increase expression of DNA methyltransferase-1 (DNMT-1) and epigenetically regulate the expression of several genes, including microRNAs (miRNAs). DNMT-1 up-regulation occurs in hepatobiliary cancers and is associated with a poor prognosis. To understand the potential regulation of DNMT-1 by IL-6–dependent miRNAs, we examined the expression of a group of miRNAs which have sequence complementarity to the 3′-untranslated region of DNMT-1, namely miR-148a, miR-152, and miR-301. The expression of these miRNAs was decreased in cholangiocarcinoma cells. Moreover, the expression of all three miRNAs was decreased Selleckchem PLX4032 in IL-6–overexpressing malignant cholangiocytes in vitro and in tumor cell xenografts. There was a concomitant decrease in expression of the methylation-sensitive tumor suppressor genes Rassf1a and p16INK4a.

Using luciferase reporter constructs, DNMT-1 was verified as a target for miR-148a and miR-152. Precursors to miR-148a and miR-152 decreased DNMT-1 protein expression, increased Rassf1a and p16INK4a expression, and reduced cell proliferation. Conclusion: These data indicate that IL-6 can regulate the activity of DNMT-1 and expression of methylation-dependent tumor suppressor genes by modulation MCE公司 of miR-148a and miR-152, and provide a link between this inflammation-associated cytokine and oncogenesis in cholangiocarcinoma. (HEPATOLOGY 2010.) Cholangiocarcinomas are primary malignancies of the biliary tract epithelia that are typically associated with chronic inflammation.1 The inflammation-associated cytokine interleukin-6 (IL-6) has been identified as contributing to the abnormal growth and survival of malignant cholangiocytes through an autocrine–paracrine mechanism.2–4 However, the precise role of IL-6 in cholangiocarcinogenesis has

not been fully characterized. Recent studies provide evidence for the involvement of epigenetic modifications of critical genes in mediating the effects of IL-6. IL-6 can increase overall methylation activity with the suppression of key regulatory onco-suppressor genes.5 We and others have shown that IL-6 can increase DNA methyltransferase-1 (DNMT-1), the most abundant methyltransferase in mammalian cells that play a key role in the maintenance of DNA methylation.5, 6 Although DNMT-1 is considerably more active on hemimethylated DNA as compared with unmethylated substrate in vitro, it is also active in de novo methylation, similar to other DNMTs.7 Enforced expression of IL-6 in cholangiocarcinoma increases the expression of DNMT-1 and increases overall methylation activity.6, 8, 9 The modulation of methyltransferases provides an attractive mechanism through which IL-6 can restore and maintain methylation of critical genes.

(Hepatology 2014;60:1494–1507) “
“Although the inflammation-associated cytokine interleukin-6 (IL-6) has been implicated in cholangiocarcinoma Olaparib chemical structure growth, the relationship between IL-6 and oncogenic changes is unknown.

IL-6 can increase expression of DNA methyltransferase-1 (DNMT-1) and epigenetically regulate the expression of several genes, including microRNAs (miRNAs). DNMT-1 up-regulation occurs in hepatobiliary cancers and is associated with a poor prognosis. To understand the potential regulation of DNMT-1 by IL-6–dependent miRNAs, we examined the expression of a group of miRNAs which have sequence complementarity to the 3′-untranslated region of DNMT-1, namely miR-148a, miR-152, and miR-301. The expression of these miRNAs was decreased in cholangiocarcinoma cells. Moreover, the expression of all three miRNAs was decreased click here in IL-6–overexpressing malignant cholangiocytes in vitro and in tumor cell xenografts. There was a concomitant decrease in expression of the methylation-sensitive tumor suppressor genes Rassf1a and p16INK4a.

Using luciferase reporter constructs, DNMT-1 was verified as a target for miR-148a and miR-152. Precursors to miR-148a and miR-152 decreased DNMT-1 protein expression, increased Rassf1a and p16INK4a expression, and reduced cell proliferation. Conclusion: These data indicate that IL-6 can regulate the activity of DNMT-1 and expression of methylation-dependent tumor suppressor genes by modulation 上海皓元医药股份有限公司 of miR-148a and miR-152, and provide a link between this inflammation-associated cytokine and oncogenesis in cholangiocarcinoma. (HEPATOLOGY 2010.) Cholangiocarcinomas are primary malignancies of the biliary tract epithelia that are typically associated with chronic inflammation.1 The inflammation-associated cytokine interleukin-6 (IL-6) has been identified as contributing to the abnormal growth and survival of malignant cholangiocytes through an autocrine–paracrine mechanism.2–4 However, the precise role of IL-6 in cholangiocarcinogenesis has

not been fully characterized. Recent studies provide evidence for the involvement of epigenetic modifications of critical genes in mediating the effects of IL-6. IL-6 can increase overall methylation activity with the suppression of key regulatory onco-suppressor genes.5 We and others have shown that IL-6 can increase DNA methyltransferase-1 (DNMT-1), the most abundant methyltransferase in mammalian cells that play a key role in the maintenance of DNA methylation.5, 6 Although DNMT-1 is considerably more active on hemimethylated DNA as compared with unmethylated substrate in vitro, it is also active in de novo methylation, similar to other DNMTs.7 Enforced expression of IL-6 in cholangiocarcinoma increases the expression of DNMT-1 and increases overall methylation activity.6, 8, 9 The modulation of methyltransferases provides an attractive mechanism through which IL-6 can restore and maintain methylation of critical genes.

75, corrected P-value = 0.015). Haplotype analysis revealed that TGGTA protected females from SGSD development (odds ratio = 0.75, corrected P-value = 0.02). Based on our findings, IL18 rs5744247C>G polymorphism could be a potential genetic marker to predict SGSD susceptibility in Han

Chinese women. “
“In Taiwan, a screening system using an infant stool color card to promote the early diagnosis of biliary atresia (BA) was established in 2002. This study aimed to investigate the 5-year outcome of BA before and after using the screening program. BA patients were divided into three cohorts according to their birth dates. The patients in cohort A (n = 89) were born before the stool card screening program (1990-2000); those in cohort B (n = 28) were screened by the stool card regional screening program (2002-2003); and those in cohort C (n = 74) were screened by the stool card universal HKI-272 screening program (2004-2005). The relative odds ratios were computed using logistic regression to compare the different factors affecting survival time.

The rate of age at Kasai operation <60 days was 49.4% and 65.7% in cohorts A and B+C, respectively (P = 0.02). The jaundice-free (total serum bilirubin <2.0 mg/dL) rate 3 months after surgery was AZD6244 in vivo 34.8% and 60.8% in cohorts A and B+C, respectively (P < 0.001). The 3-year jaundice-free survival rate with native liver was 31.5% in cohort A and 56.9% in cohort B+C (P < 0.001), whereas the 3-year overall survival rates were 64.0% and 89.2%, respectively (P < 0.001). The 5-year jaundice-free survival rate with native liver was 27.3% in cohort A and 64.3% in cohort B (P < 0.001), and the 5-year overall survival rates were 55.7% and 89.3%, respectively (P < 0.001). Conclusion: The stool color card screening program for BA allows for earlier Kasai operation, which increases the jaundice-free rate at 3 months postsurgery. With higher surgical success rates, the 3- and 5-year outcome of BA patients in Taiwan improves remarkably. 上海皓元 (HEPATOLOGY 2011.) Biliary atresia (BA) is an inflammatory, progressive fibro-sclerosing cholangiopathy of infancy that variably affects

both the extrahepatic and intrahepatic bile ducts,1, 2 resulting in the destruction and obstruction of the biliary tract.2-4 If untreated, BA progresses to cirrhosis with portal hypertension and liver failure leading to death within 2 to 3 years. Since the Kasai operation was first used for BA in 1959, there have been encouraging results in treating this disease such that it has become the first-line treatment. The Kasai operation can restore bile flow through a reconstructed hepatic portoenterostomy to a jejunal loop. Once the cholestasis progresses and/or complications of liver cirrhosis occur, liver transplantation remains the salvage way for BA. Although ongoing cholestasis, which further aggravates liver cirrhosis, is present in most BA children,5 a successful Kasai operation may still delay or even decrease the need for liver transplantation.