g., after pinealectomy and exposure to dark to stimulate melatonin release from the pineal gland) in the regulation of biliary functions are ongoing. Having demonstrated that AANAT is expressed by cholangiocytes and that AANAT expression is up-regulated by BDL and melatonin administration, we proposed to demonstrate that reduction of biliary AANAT expression (by Vivo-Morpholino) increases cholangiocyte proliferation and IBDM as well as the expression of SR, CFTR, and Cl−/HCO AE2 in cholangiocytes. After BDL, the increase of biliary proliferation and IBDM is followed

by the extension of the peribiliary plexus and the increase of surrounding connective tissue, which is organized HCS assay around bile ducts and vessels.10 In our model, we only observed a slight Trametinib ic50 difference in collagen tissue content in BDL rats treated with mismatch Morpholino versus BDL rats treated with AANAT Vivo-Morpholino. This low increase of connective tissue cannot determine a clear hepatic fibrosis in our model of short time of BDL. Further studies are needed to evaluate the long-term effects of BDL on the modulation of melatonin synthesis on liver fibrosis. Also, the novel concept that AANAT regulates SRCFTRCl−/HCO AE2 expression is supported by our previous study16 showing that in vivo administration of melatonin to BDL rats decreases secretin-induced choleresis. To determine that the effects of down-regulation of AANAT

on biliary growth depend on direct effects on bile ducts, cholangiocytes see more were treated in vitro with melatonin that decreased the biliary proliferation and expression of SR, CFTR, and Cl−/HCO AE2. We overexpressed AANAT in cholangiocytes and demonstrated a decrease

in biliary proliferation and secretin-stimulated cAMP levels and Cl− efflux. In vitro, overexpression of AANAT in cholangiocytes leading to decreased biliary proliferation and secretin receptor-dependent ductal secretion (in the absence of intestinal secretin supply) was likely the result of the fact that cholangiocytes express SR and express the message for secretin and secrete secretin,7, 39, 40 which (similar to what is observed in vivo) is an important autocrine factor sustaining biliary proliferation. We propose that the modulation of biliary melatonin secretion (by chronic administration of melatonin or changes in AANAT expression; Fig. 6) may be a valuable therapeutic approach for regulating the balance between biliary growth/apoptosis. In support of this view, we have shown that in the first stage of primary biliary cirrhosis, there is an increase of cholangiocyte proliferation that resulted in a positive balance between growth and apoptosis.41 By contrast, the end stage is characterized by the collapse of the proliferative capacity of cholangiocytes, resulting in the reduction (high apoptosis rate) of the number of bile ducts (vanishing bile duct syndrome).

In this study, we demonstrated the photochemical changes before and after colony formation. In the laboratory, light curves showed that colonies were more responsive to high light than single cells. The values of the maximal slope of electron transport rate (ETR)—light curve (α), relative maximal electron transport rate (rETRmax), and onset of light saturation (Ik) of colonies were significantly higher than those of single cells (P < 0.05), indicating that colonies

have higher photosynthetic capability than single cells, especially in high light, where values of rETRmax and Ik of colonies were 2.32 and 2.41 times those of single cells. Moreover, the dark-light experiments showed that colonial cells can more effectively resist darkness damage. In addition, pigments of colonial cells were higher than those of PDGFR inhibitor single cells (P < 0.05). The higher pigment contents probably contribute to higher photosynthetic capability. In the field, the inhibition rate of Fv/Fm in single cells increased significantly

faster than that of colonies selleck screening library as light increased (P < 0.05), but nonphotochemical quenching (NPQ) value of colonies was higher (32.4%) than that of single cells at noon, which indicated colonial cells can more effectively resist high-light inhibition than single cells (P < 0.05). Polysaccharides of colonies were significantly Progesterone higher compared to those in unicellular cells (P < 0.05) based on their contents and ultrastructural characteristics. This finding implies that colonies could not effectively decrease photoinhibition by negative buoyancy regulation. In fact, NPQ may be an important mechanism for avoiding photodamage. All of these phenomena can help explain the ecological success of colonial M. aeruginosa in eutrophic water. "
“The attachment of the psammophytic alga Caulerpa mexicana Sond. ex Kütz., a coenocytic green alga, to crushed CaCO3

particles was examined utilizing the scanning electron microscope and fluorescently tagged antivitronectin antibodies. Plants attached to the substrate through morphologically variable tubular rhizoidal extensions that grew from the stolon. In this study, we describe two means of attachment: (i) the rhizoid attachment to limestone gravel by thigmoconstriction, where tubular extensions of the rhizoid wrapped tightly around the substrate and changed morphology to fit tightly into crevices in the limestone, and (ii) through adhesion pads that formed in contact with the limestone granules. Flattened rhizoidal pads were observed to secrete a fibrillar material that contained vitronectin-like proteins identified through immunolocialization and that facilitated binding of the rhizoid to the substrate. “
“The diazotrophic cyanobacteria Trichodesmium spp. contribute approximately half of the known marine dinitrogen (N2) fixation.

Five microliters of the reaction was treated with DpnI for 1 hour at 37°C prior to transformation. All constructs were verified by sequencing. Cells were cotransfected with 2 μg DNMT1-WT or DNMT1-MUT construct and 2 μg pRL-TK Renilla luciferase expression construct followed by a precursor miRNA at 100 nM final concentration selleck products using TransIT-LT1 and TransIT-TKO reagents (Mirus, Madison, WI) for DNA vectors and precursor miRNA, respectively. Luciferase assays were performed after 48 hours using the Dual Glo Assay system (Promega, Madison, WI) and a multiwell plate luminometer (Veritas, Turner Biosystems, Sunnyvale, CA). Cells grown in 100-mm culture dishes were washed twice with ice-cold phosphate-buffered

saline and then lysed by incubation for 20 minutes in 1 mL of ice-cold cell lysis buffer (Cell Signaling Inc., Beverly, MA). For analysis of xenograft tumor tissue, the tissue was homogenized, and lysates were obtained. The protein concentration in the lysates was measured using a Bradford protein assay kit (Bio-Rad, Hercules, CA). Equivalent amounts of protein were mixed with 4× sodium dodecyl sulfate–polyacrylamide gel electrophoresis sample buffer, electrophoresed in a 4% to 12% linear gradient Tris-HCl–ready gel (Bio-Rad), Alectinib in vitro and transferred to nitrocellulose membranes. The membranes were blocked

with 5% nonfat dry milk in Tris-buffered saline (pH 7.4) containing 0.05% Tween 20 and were incubated with primary antibodies and IRDye700 and IRDye800-labeled secondary antibodies (Rockland, Gilbertsville, PA). The protein of interest was visualized and quantitated using the LI-COR Odyssey Infrared Imaging System (LI-COR Fossariinae Bioscience, Lincoln, NE). Eight-week-old male athymic nu/nu mice were obtained from Charles River Laboratories (Wilmington,

MA) and fed food and water ad libitum. The mice were maintained in accordance with the Institutional Animal Care and Use Committee procedures and guidelines. They were housed three or four per cage, and fluorescent light was controlled to provide alternate light and dark cycles of 12 hours each. Mz-IL-6 or Mz-1 control cells (5 × 106 cells) were suspended in 0.25 mL of extracellular matrix gel, and the mixture was injected subcutaneously into the right and left flanks. Xenograft growth was monitored by serial measurements. For analysis of protein expression in vivo, the xenografts were excised once visible tumors had formed, and tissue was homogenized. An aliquot of the lysates was used for protein expression studies. Pre-miR miRNA precursors of pre-miR-148a, pre-miR-152, pre-miR-301 and control pre-miR-precursor were purchased from Ambion (Austin, TX). Antibodies against DNMT-1 and p16INK4a were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA), Rassf1A was obtained from Abcam (Cambridge, MA), and α-tubulin was obtained from Sigma (St. Louis, MO).

Conclusion: Galectin-3 expression and inflammasome activation are induced in PBC patients and in dnTGFβRII mice. DCA induces inflammasome activation in KC resulting in the release of proinflammatory mediators, in a galectin 3-dependent manner. Galectin-3 hence could be a potential therapeutic target in PBC. Disclosures: Natalie Torok – Consulting: Genentech/Roche The following people have nothing to disclose: Jijing Tian, Tzu-I Chao, Yu Sasaki, Fu-Tong Liu, M. Eric Gershwin, Joy Jiang Obeticholic acid (OCA, 6-ethyl chenodeoxycholic acid) is a highly potent, selective FXR agonist. In Ph2 PBC studies, 10-50mg OCA (±UDCA) produced significant biochemical

improvement in cholestasis and inflammatory markers. The Global PBC Study Group (GPBCSG) confirms patients with alkaline phosphatase (ALP) > 1.67x ULN or bilirubin >ULN have a greatly increased risk of liver transplant or death [HR (95% CI): 2.83 (2.4-3.4); p =1×10−34]. This was an international, double-blind, Bortezomib supplier placebo-controlled (PBO) trial. PBC patients ±UDCA (if taking UDCA, on a stable dose) with ALP≥1.67x ULN or bilirubin <2x ULN were

randomized to PBO, OCA 5 or 10mg for 12mo. Patients randomized to 5mg were titrated to 10mg after 6mo, if necessary; pre-study UDCA continued. The primary endpoint was attaining the GPBCSG ALP/Bilirubin goal and ALP reduction ≥15%. Markers of inflammation (CRP) and apoptosis (CK18) were also evaluated selleck screening library at 6 and 12mo. All groups were well-matched. Mean age: 55.8yrs, female: 91%, Caucasian: 94%. The median

UDCA dose was 15.4 mg/kg; 7% were UDCA-intolerant. Overall, 91% of patients completed the study. The primary endpoint was achieved: OCA was superior to PBO, a highly statistically significantly greater proportion of OCA treated patients achieved the ALP/Bili response goal (see table). After 6mo, ALP significantly improved (p<0.0001) with OCA dose: PBO, −6.8% (±3.5), 5mg, −27.4% (±3.4), 10mg, −36.5% (±3.5). Pruritus, generally mild to moderate, was the most common and dose related adverse event (AE). The incidence of AEs other than pruritus was no worse with OCA (PBO, 90%, 5/10mg OCA, 89%, 10mg OCA, 86%). An 82-yr old patient with pre-existing congestive heart failure taking OCA died due to worsening of the condition. Overall, serious adverse events (SAEs) occurred in 22 (10%) Abiraterone concentration of patients and, although there were more SAEs in the OCA groups, none were considered drug-related and there were no apparent patterns. Modest mean reductions in HDL (16%,5/10mg OCA, 26%,10mg OCA) were observed with OCA. OCA produced highly statistically, clinically meaningful improvements in biochemical criteria that are strongly correlated with clinical benefit. Pruritus was the principal AE, but had a lower incidence in the titration group compared to 10 mg. Starting patients on 5mg OCA and titration to 10mg based on the clinical response appears to be an appropriate dosing strategy.

5 mg/dL at day 3, compared with only five of the 22 patients (23%) in whom serum creatinine did not decrease 0.5 mg/dL or increased at day 3 compared with baseline (P = 0.001). Similar figures were observed when the cutoff value of change in serum creatinine used was 1 mg/dL instead of 0.5 mg/dL (80% and 36%, respectively; P = 0.016). The value of the reduction in serum creatinine at day 3 as predictor of response to therapy was confirmed in a multivariate analysis (odds ratio, 6.5; P = 0.047). Thirty-five patients (90%) developed a total of 43 major complications of cirrhosis during

treatment: 31 cases of hepatic encephalopathy, nine cases of bacterial infection, and three cases of gastrointestinal bleeding. There was no significant difference BMS-354825 supplier between the frequency of bacterial infections between nonresponders and responders (33% versus 11% , respectively; P = 0.10). The development of bacterial infections during treatment with terlipressin and albumin was slightly more frequent (yet not significantly different) in patients with a baseline leukocyte count above the median value of 7,900/mm3 than in those with a leukocyte count below the median value (32% versus 15% , respectively; P = 0.27). Patients with a baseline leukocyte count above the median value developed pneumonia (n = 3), sepsis (n = 2), and spontaneous

bacterial peritonitis (n = 1) after a mean of 5 days (range, 2–13 days), whereas patients with Cyclic nucleotide phosphodiesterase a baseline leukocyte count below the median value developed urinary tract infections (n = 2) Selleck LY2606368 and pneumonia (n = 1) after a mean of 5 days (range, 2–8 days). It should be noted that none of these patients had proven bacterial infection at the time of initiation of therapy with terlipressin and albumin. Eleven patients (28%) developed

side effects likely related to treatment with terlipressin and albumin. Five patients developed signs of circulatory overload, which improved after temporary suppression of albumin together with administration of furosemide and did not require discontinuation of terlipressin. Two patients developed abdominal signs suggestive of intestinal ischemia (one of which was associated with circulatory overload), which subsided after discontinuation of treatment. Two patients developed transient arrhythmia (bradycardia and ventricular extrasystolia, respectively) that did not require permanent treatment discontinuation. One patient developed myocardial infarction and signs suggestive of intestinal ischemia (associated with circulatory overload). One patient developed signs of tongue ischemia. In the two latter patients, symptoms disappeared after treatment withdrawal. Three months after the start of therapy, 28 (72%) patients had died, four (10%) had undergone transplantation, five (13%) were alive, and two (5%) were lost to follow-up.

This month Dr Michael Charlton has offered his turn at the microphone

to Dr. Donald Jensen and Dr Andrew Aronsohn from the University of Chicago, in order that they can address a pressing issue that will emerge in tandem with the likely approval by the U.S. Food and Drug Administration of boceprevir and/or telaprevir. DAA, direct-acting antiviral; HCV, hepatitis C virus. More than 120 million people are infected with hepatitis C worldwide.1 Hepatitis C virus (HCV) is a leading cause of liver-related mortality and is the most common indication for liver transplantation in the United States.2 Since the introduction of pegylated this website interferon and ribavirin nearly 10 years ago, response rates have been relatively stagnant, with less than half of treated patients achieving a sustained virological response.2 Data from the first direct-acting antiviral (DAA) agent, BILN 2061, was initially presented at the American Association for the Study of Liver Diseases annual meeting in 2002, which sparked enthusiasm over improving therapeutic efficacy.3

Nearly a decade later, we find ourselves on the brink of a new era of HCV therapy. Telaprevir Trametinib and boceprevir will likely receive U.S. Food and Drug Administration approval by mid-2011, and based on phase 2 and 3 data, will significantly improve rates of sustained virological response in patients infected with HCV genotype 1 when compared to current standard-of-care therapy.4-7 This improved efficacy has been well-publicized for years, and anticipation of DAA availability

has already become part of the HCV treatment algorithm. Greater understanding of the natural history of HCV and identification of risk factors for progression to advanced liver disease has allowed many physicians to recommend deferral of standard-of-care therapy in favor of waiting for DAA availability Etoposide research buy for patients who are at low risk to progress to significant liver disease in the near future. This was demonstrated in a large VA-based study of 4084 patients evaluated for HCV therapy with interferon and ribavirin.8 Of the eligible patients who declined therapy, 50.3% stated they had deferred treatment in anticipation of more effective medications.8 Treatment-naive patients who have deferred standard-of-care therapy, in addition to patients who have failed previous regimens of HCV treatment, will likely create a surge of requests to initiate therapy in mid-2011. The influx of patients requesting HCV therapy will present a significant problem. HCV therapy is becoming increasingly complex, and the addition of DAAs will only add to the time needed to effectively educate and appropriately monitor patients while they are receiving treatment. This may be partially offset by response-guided therapy that shortens treatment duration.

The aim of this study was to assess the prevalence of NAFLD in older Australians and their self-awareness of this problem. Methods: We recently completed a comprehensive health survey of residents, over the age of 65, living on the Central Coast. We recruited 831 community-based participants who completed a questionnaire assessing their medical history, including 5-Fluoracil datasheet all types of liver diseases, metabolic risk factors, medications and alcohol

intake. These subjects had their BMI, body anthropometry and biochemistry analysed. Fatty liver index (FLI)2 is a validated non-invasive method of estimating the likelihood of NAFLD in individuals. FLIs were calculated and subjects classified into three categories, FLI < 30 (No NAFLD), 30 ≤ FLI < 60 (Borderline) and FLI ≥ 60 (NAFLD). Local Human Research Ethics Committee approval was given and informed consent obtained. Results: For analysis, subjects with other liver diseases and alcohol intake > 20 g/day

were excluded, leaving 510 individuals. Only one of the participants with FLI≥ 60 and one with a borderline value self-reported NAFLD. Results are given as means ±SD.   Fatty Liver Index p value <30 ≥60 n (%) 135 (26.5) 226 (44.3)   Age (yrs) 78.7 ± 7.5 77.1 ± 6.5 ns Sex (F/M) 100/35 111/115  < 0.0001 BMI (kg/m2) 23.4 ± 2.5 32.0 ± 4.1  < 0.0001 Waist circumference (cm) 83.4 ± 7.6 108.3 ± 9.8  < 0.0001 ALT (U/L) 20.3 ± 9.4 23.8 ± 11.2 0.011 γ-glutamyltransferase (U/L) 23.9 ± 11.3 44.5 ± 43.0 <0.0001 Triglycerides SCH727965 datasheet (mg/dL) 84.3 ± 31.3 149.7 ± 66.3 <0.0001 Type 2 DM (%) 7 (5.3) 51 (22.7) <0.0001 Insulin (mIU/L) 4.8 ± 3.1 10.9 ± 6.9 <0.0001 Alcohol intake (g/day) 4.6 ± 6.1 5.4 ± 6.2 ns Conclusions: This is the first report of the prevalence of NAFLD in an elderly

Australian population (44.3%) and this value is higher than clonidine the previous estimates used. Older Australians appear to be unaware of this condition and its impact on their health. 1 GESA/ALA. The economic cost and health burden of liver disease in Australia. Deloitte Access Economics, February 2013 2 Koehler E et al. External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-based Study. Clin Gastroenterol Hepatol. 2013 doi:10.1016/j.cgh.2012.12.031 E ZHAO,1 L HORSFALL,2 BJ RUFFIN,3 KJ FAGAN,1,2 KM IRVINE,1 EE POWELL1,2 1Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Princess Alexandra Hospital; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital; Brisbane, 3The University of Queensland, School of Nursing. Introduction: Ascites is the most common complication of cirrhosis, a chronic disease state that leads to recurrent hospital admissions and huge health-care costs. In other common chronic diseases such as congestive heart failure and chronic obstructive pulmonary disease, risk factors for early readmission have been identified.

1997). Finally, there is no indication of infection or related pathologies from surgical biopsy wounds (Weller et al. 1997). Bruce-Allen and Geraci (1985) described

the wound healing process in captive bottlenose dolphins following incisions through the epidermis and into the dermis. Their study demonstrated that cuts are histologically repaired by 7 Lorlatinib order d, but are still visible on dolphins as white linear marks. High rates of cell proliferation enable cetaceans to rapidly heal from wounds they obtain in their natural habitat. For example, bottlenose dolphins with large, open wounds, probably inflicted by sharks, heal substantially within the first month and can be completely healed within 6–7 mo (Corkeron et al. 1987, Lockyer and Morris 1990). The successful healing of these larger traumas in the wild is perhaps one of the strongest arguments to suggest

that the majority of biopsy wounds will heal rapidly and that biopsy sampling will most likely not impact survival (International Whaling Commission 1991). Aguilar and Borrell (1994a) also concluded that the small wound produced by a standard biopsy dart (0.25 cm diameter) should not lead to significant physical trauma in sampled animals. To date, no studies have investigated the stress response in cetaceans targeted by remote biopsy sampling methods. In comparison, a small number of researchers have investigated physiological and behavioral responses in dolphins to assess selleck products stress associated with encirclement by nets and handling, which are required during manual biopsy procedures. St. Aubin et al. (1996) found that bottlenose dolphins had elevated stress hormones (aldosterone and cortisol) following capture and handling, check details while most dolphins in a similar study by Ortiz and Worthy (2000) did not exhibit elevated stress hormone levels. Authors of both studies concluded that the increases in hormone levels were indicative of a mild stress response

only. Another study found that bottlenose dolphin blood cells increase gene expression related to metabolism and stress, which also indicates that dolphins undergo a stress response during capture-release health assessments (Mancia et al. 2008). Finally, Esch and colleagues (2009) showed that signature whistle parameters, which may be potential indicators of stress, changed in bottlenose dolphins during brief capture-release events. However, none of the studies examined the long-term impacts of these short-lived stress responses or how physiological responses change with repeated captures of the same individual. These, as well as examining the stress response in remotely biopsied cetaceans, are important areas of future research, as the cumulative impacts of repeated capture and/or biopsy sampling (by both manual and remote methods) may be substantial.

The Paris criteria were recognized as the best validated and easiest to use.7, 11 Using published criteria, we sought selleck compound to determine whether a biochemical response as early as 3 to 6 months instead of 1 year would similarly identify patients with poor long-term outcome; if true, it could facilitate a more rapid selection of patients suitable

for new therapeutic approaches. In the present study, we analyzed prospectively collected data of 187 patients with a mean follow-up period of 5.9 years. First, we found that serum bilirubin, ALP, GGT, AST, ALT, and IgM levels most prominently decreased within the first 3 months of UDCA therapy. These laboratory parameters continued to decrease gradually, with the maximum response seen at either 6 months or 1 year. Second, we found that the Paris, Barcelona, Toronto, and Ehime definition applied at 3, 6, and 12 months all significantly Selleckchem Stem Cell Compound Library discriminated the patients

in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Finally, we found that biochemical response at the sixth month can more accurately identify patients with good or poor prognosis compared with that at 1 year. The long-term evolution of laboratory liver parameters beyond 1 year UDCA therapy has been documented, suggesting that biochemical response to UDCA can be maintained for up to 15 years.3, 16 In contrast, laboratory parameters within the first year were seldom reported in a large cohort of patients. Our cohort consisted of 187 patients who were followed at 3-month

intervals. Laboratory investigations were performed and data were collected prospectively. All of the laboratory parameters studied showed a prominent improvement in the first 3 months and then stayed relatively stable for the following months within the first C1GALT1 year of UDCA treatment (Fig. 1). This led us to hypothesize that an early biochemical response as short as 3 to 6 months may be used in place of that after 1 year of UDCA therapy. We then evaluated the prognostic impact of multiple criteria in our patients. By all definitions except the Rotterdam criteria, biochemical response at 3, 6, and 12 months significantly discriminated our patients in terms of long-term outcome (Table 3 and Fig. 3). Our results tend to agree with those of the study recently published by the Paris group.14 The Paris group’s study included 165 patients with early PBC, and no significant association was found between the long-term outcomes and the Rotterdam definition. Since the Rotterdam criteria have been demonstrated to be more potent prognostic indicators of long-term outcome in late rather than early stages of PBC,8 they may not be applicable in a cohort of patients that contains high proportions of early PBC.

The Paris criteria were recognized as the best validated and easiest to use.7, 11 Using published criteria, we sought Rapamycin to determine whether a biochemical response as early as 3 to 6 months instead of 1 year would similarly identify patients with poor long-term outcome; if true, it could facilitate a more rapid selection of patients suitable

for new therapeutic approaches. In the present study, we analyzed prospectively collected data of 187 patients with a mean follow-up period of 5.9 years. First, we found that serum bilirubin, ALP, GGT, AST, ALT, and IgM levels most prominently decreased within the first 3 months of UDCA therapy. These laboratory parameters continued to decrease gradually, with the maximum response seen at either 6 months or 1 year. Second, we found that the Paris, Barcelona, Toronto, and Ehime definition applied at 3, 6, and 12 months all significantly buy BGJ398 discriminated the patients

in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Finally, we found that biochemical response at the sixth month can more accurately identify patients with good or poor prognosis compared with that at 1 year. The long-term evolution of laboratory liver parameters beyond 1 year UDCA therapy has been documented, suggesting that biochemical response to UDCA can be maintained for up to 15 years.3, 16 In contrast, laboratory parameters within the first year were seldom reported in a large cohort of patients. Our cohort consisted of 187 patients who were followed at 3-month

intervals. Laboratory investigations were performed and data were collected prospectively. All of the laboratory parameters studied showed a prominent improvement in the first 3 months and then stayed relatively stable for the following months within the first ADAM7 year of UDCA treatment (Fig. 1). This led us to hypothesize that an early biochemical response as short as 3 to 6 months may be used in place of that after 1 year of UDCA therapy. We then evaluated the prognostic impact of multiple criteria in our patients. By all definitions except the Rotterdam criteria, biochemical response at 3, 6, and 12 months significantly discriminated our patients in terms of long-term outcome (Table 3 and Fig. 3). Our results tend to agree with those of the study recently published by the Paris group.14 The Paris group’s study included 165 patients with early PBC, and no significant association was found between the long-term outcomes and the Rotterdam definition. Since the Rotterdam criteria have been demonstrated to be more potent prognostic indicators of long-term outcome in late rather than early stages of PBC,8 they may not be applicable in a cohort of patients that contains high proportions of early PBC.