[1, 2] This process relies not only on proliferative cascades, in which hepatocytes switch from a quiescent to a proliferative phenotype,[1, 2] but also on metabolic pathways that help maintain cellular homeostasis after liver injury.[3] Growth factors are particularly important for this process, and insulin specifically regulates both metabolism and proliferation in the liver.[4, 5] However, insulin’s effects on liver regeneration are less well understood than those of other growth factors, such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF).[6, 7] Insulin acts through the insulin receptor (IR), a heterotetrameric receptor tyrosine

kinase (RTK) composed of two extracellular alpha subunits, which have ligand-binding activity, and two transmembrane beta subunits that possess tyrosine kinase activity.[8] Once insulin binds to the IR, protein Y-27632 tyrosine kinase is activated, resulting in phosphorylation of the tyrosine residues within the beta subunit. This, in turn, leads to the recruitment of several adaptor proteins, including src-homology 2 domain (SH2)-containing proteins such as phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PLC).[9] PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2), resulting

in the formation of diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol-1,4,5-trisphosphate (InsP3), which promotes Ca2+ release from intracellular stores upon binding to the InsP3 receptor (InsP3R).[10] Several RTKs, including the IR and the receptors for EGF, HGF, and fibroblast growth factor (FGF), have been found learn more in the nucleus.[11-15] Evidence suggests that the IR, like

the HGF receptor, c-met,[14] translocates to the nucleus upon ligand medchemexpress stimulation to selectively hydrolyze nuclear PIP2 and locally generate InsP3-dependent Ca2+ signals there.[11] Additionally, nucleoplasmic, rather than cytosolic, Ca2+ is important for cellular proliferation and is necessary in particular for progression through early prophase.[16] However, metabolic effects of insulin result from cytosolic, rather than intranuclear, events, typified by activation of protein kinase B/Akt (PKB).[17] Therefore, we examined whether the cytosolic and nuclear effects of IR are mediated separately and whether the subpopulation of IRs reaching the nucleus upon insulin stimulation locally induces InsP3-dependent Ca2+ signals to regulate the proliferative effects of insulin. The liver cancer cell line, SkHep-1, was obtained from the American Type Culture Collection (Manassas, VA). Cells were cultured at 37°C in 5% CO2 in Dulbecco’s modified Eagle’s medium (Gibco, Grand Island, NY), supplemented with 10% fetal bovine serum (FBS), 1 mM of sodium pyruvate, 50 units/mL of penicillin, and 50 g/mL of streptomycin (Gibco, Grand Island, NY).

[1, 2] This process relies not only on proliferative cascades, in which hepatocytes switch from a quiescent to a proliferative phenotype,[1, 2] but also on metabolic pathways that help maintain cellular homeostasis after liver injury.[3] Growth factors are particularly important for this process, and insulin specifically regulates both metabolism and proliferation in the liver.[4, 5] However, insulin’s effects on liver regeneration are less well understood than those of other growth factors, such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF).[6, 7] Insulin acts through the insulin receptor (IR), a heterotetrameric receptor tyrosine

kinase (RTK) composed of two extracellular alpha subunits, which have ligand-binding activity, and two transmembrane beta subunits that possess tyrosine kinase activity.[8] Once insulin binds to the IR, protein selleck screening library tyrosine kinase is activated, resulting in phosphorylation of the tyrosine residues within the beta subunit. This, in turn, leads to the recruitment of several adaptor proteins, including src-homology 2 domain (SH2)-containing proteins such as phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PLC).[9] PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2), resulting

in the formation of diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol-1,4,5-trisphosphate (InsP3), which promotes Ca2+ release from intracellular stores upon binding to the InsP3 receptor (InsP3R).[10] Several RTKs, including the IR and the receptors for EGF, HGF, and fibroblast growth factor (FGF), have been found beta-catenin phosphorylation in the nucleus.[11-15] Evidence suggests that the IR, like

the HGF receptor, c-met,[14] translocates to the nucleus upon ligand 上海皓元医药股份有限公司 stimulation to selectively hydrolyze nuclear PIP2 and locally generate InsP3-dependent Ca2+ signals there.[11] Additionally, nucleoplasmic, rather than cytosolic, Ca2+ is important for cellular proliferation and is necessary in particular for progression through early prophase.[16] However, metabolic effects of insulin result from cytosolic, rather than intranuclear, events, typified by activation of protein kinase B/Akt (PKB).[17] Therefore, we examined whether the cytosolic and nuclear effects of IR are mediated separately and whether the subpopulation of IRs reaching the nucleus upon insulin stimulation locally induces InsP3-dependent Ca2+ signals to regulate the proliferative effects of insulin. The liver cancer cell line, SkHep-1, was obtained from the American Type Culture Collection (Manassas, VA). Cells were cultured at 37°C in 5% CO2 in Dulbecco’s modified Eagle’s medium (Gibco, Grand Island, NY), supplemented with 10% fetal bovine serum (FBS), 1 mM of sodium pyruvate, 50 units/mL of penicillin, and 50 g/mL of streptomycin (Gibco, Grand Island, NY).

In addition, our finding that the hiPSC-derived hepatocytes are competent to respond to hepatoselective pharmaceuticals implies that patient-specific iPSC-derived hepatocytes will facilitate the identification of drugs that can treat inborn errors of liver metabolism. We thank Paula North for analyses of teratomas, Tom Wagner for technical support, and Brian Link for advice with confocal analyses. Additional Supporting Information may be found in the online version of this selleck compound article. “
“One of the serious sequelae of chronic hepatitis B virus (HBV) infection is hepatocellular carcinoma (HCC). Among all the proteins encoded by the HBV genome, hepatitis B virus X protein (HBx)

is highly associated with the development of HCC. Although Notch1 signaling has been found to exert a tumor-suppressive function during HCC development, the mechanism of interaction between HBx expression and Notch1 signaling needs to be explored. In this study, we report that HBx expression in hepatic and hepatoma cells resulted in decreased endogenous protein levels of Notch1 intracellular domain (ICN1) and messenger RNA levels of its downstream target genes. These effects Daporinad nmr were due to a reduction of Notch1 cleavage by HBx through the suppression

of presenilin1 (Psen1) transcription rather than inhibition of Notch1 transcription or its ligands’ expression. medchemexpress Through transient HBx expression, decreased ICN1 resulted in enhanced cell proliferation, induced G1-S cell cycle progression, and blunted cellular senescence in vitro. Furthermore, the effect of blunted senescence-like growth arrest by stable HBx expression through suppression of ICN1 was shown in a nude mouse xenograft transplantation model. The correlation of inhibited Psen1-dependent Notch1 signaling and blunted senescence-like growth arrest was also observed in HBV-associated HCC patient tumor samples. Conclusion: Our results reveal a novel function of HBx in blunting

senescence-like growth arrest by decreasing Notch1 signaling, which could be a putative molecular mechanism mediating HBV-associated hepatocarcinogenesis. (HEPATOLOGY 2010;) Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related death in humans, with nearly 600,000 deaths annually worldwide.1, 2 Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor for the development of HCC, especially in southeastern Asia and sub-Saharan Africa.3-5 Several processes are involved in the development of HBV-associated hepatocellular carcinoma, including integration of HBV genes into host cell genome, sustained cycles of necrosis-inflammation-regeneration, activation of oncogenic pathways, and inactivation of tumor-suppressive pathways by various viral proteins.

In addition, our finding that the hiPSC-derived hepatocytes are competent to respond to hepatoselective pharmaceuticals implies that patient-specific iPSC-derived hepatocytes will facilitate the identification of drugs that can treat inborn errors of liver metabolism. We thank Paula North for analyses of teratomas, Tom Wagner for technical support, and Brian Link for advice with confocal analyses. Additional Supporting Information may be found in the online version of this Selleckchem Caspase inhibitor article. “
“One of the serious sequelae of chronic hepatitis B virus (HBV) infection is hepatocellular carcinoma (HCC). Among all the proteins encoded by the HBV genome, hepatitis B virus X protein (HBx)

is highly associated with the development of HCC. Although Notch1 signaling has been found to exert a tumor-suppressive function during HCC development, the mechanism of interaction between HBx expression and Notch1 signaling needs to be explored. In this study, we report that HBx expression in hepatic and hepatoma cells resulted in decreased endogenous protein levels of Notch1 intracellular domain (ICN1) and messenger RNA levels of its downstream target genes. These effects Wee1 inhibitor were due to a reduction of Notch1 cleavage by HBx through the suppression

of presenilin1 (Psen1) transcription rather than inhibition of Notch1 transcription or its ligands’ expression. MCE Through transient HBx expression, decreased ICN1 resulted in enhanced cell proliferation, induced G1-S cell cycle progression, and blunted cellular senescence in vitro. Furthermore, the effect of blunted senescence-like growth arrest by stable HBx expression through suppression of ICN1 was shown in a nude mouse xenograft transplantation model. The correlation of inhibited Psen1-dependent Notch1 signaling and blunted senescence-like growth arrest was also observed in HBV-associated HCC patient tumor samples. Conclusion: Our results reveal a novel function of HBx in blunting

senescence-like growth arrest by decreasing Notch1 signaling, which could be a putative molecular mechanism mediating HBV-associated hepatocarcinogenesis. (HEPATOLOGY 2010;) Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related death in humans, with nearly 600,000 deaths annually worldwide.1, 2 Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor for the development of HCC, especially in southeastern Asia and sub-Saharan Africa.3-5 Several processes are involved in the development of HBV-associated hepatocellular carcinoma, including integration of HBV genes into host cell genome, sustained cycles of necrosis-inflammation-regeneration, activation of oncogenic pathways, and inactivation of tumor-suppressive pathways by various viral proteins.

Physicians taking care of patients with advanced HCC after a VB episode should individualize therapies according to clinical practice, common sense, and patient needs. Some may judge that the survival benefit in these BCLC C and D patients who received secondary prophylaxis is not clinically relevant Atezolizumab manufacturer (average, 3 months) and that more-interventional therapies (banding ligation) should be avoided, taking into account the possible adverse effects. Nevertheless, this survival benefit is similar to the survival benefit offered with sorafenib treatment in BCLC C patients,

which also has side effects, which may affect quality of life. The present study, showing a global survival effect of prophylaxis patients with advanced HCC, provides further evidence to indicate prophylaxis in this subgroup of patients as long as their clinical condition

allows them to do so. There are several setbacks to the study. Some patients with very advanced HCC and UGI bleeding were not included in the study because no endoscopy was performed. This could lead to some bias in the results, because it is probable that these patients who were not included would be the ones who would be most likely to die. However, the decision to exclude these patients from the study was based on several MAPK Inhibitor high throughput screening reasons. First, although suspected, the cause of the bleeding was not proven because endoscopy was not performed. It is well established that approximately one third of UGI bleeding

episodes MCE in patients with cirrhosis are the result of other causes, rather than esophageal varices.[40, 41] Second, most likely, the patients who would not receive endoscopy would probably be the sickest ones and therefore with the most dismal outcome. Therefore, inclusion of these patients in the analysis might further enhance the differences in the outcomes of VB in patients with and without HCC. Furthermore, and although it seems that patients with HCC without secondary prophylaxis were more sick than the ones who received secondary prophylaxis, which may have influenced the physician’s opinion, it could be that there are other factors that influenced this decision that are not included in the analysis. Unfortunately, the study design does not allow analysis of the effect of sorafenib treatment on variceal bleeding. It has been established, both in animal and human studies, that sorafenib has a portal hypotensive effect, perhaps through an inhibition of angiogenesis.[42, 43] Therefore, there could be an effect of the administration of this drug on the outcomes. In the present study, sorafenib was administered exclusively to patients with advanced HCC; therefore, it is logical to speculate that lack of sorafenib could further worsen the outcome of these patients, who already have a dismal prognosis. Another limitation of the study is the uneven distribution of the etiologies among patients with and without HCC.

Key Word(s): 1. water; 2. dehydration; Presenting Author: TAO

YU Additional Authors: RUI LIU, MAO LI, XIAN LI, OU QIANG, WEI HUANG, CHENG-WEI TANG Corresponding Author: RUI LIU Affiliations: West China Hospital, Sichuan University Objective: To investigate focal fatty infiltration of the pancreas in high-fat diet induced obesity rats and the effect of octreotide intervention on it Methods: SD rats were designed into the control group (n = 14) and the high-fat diet group (n = 36). Obese rats from the high-fat diet group were further divided into an obese group selleck chemical (n = 14) and an octreotide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide for 8 days. Body weight, fasting insulin (FINS), and fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels, and pancreatic TG content were determined. Homeostatic model assessment (HOMA) value was calculated. Pathological changes of pancreas were examined with light microscopy. Results: Body weight, Lee’s index, FPG, TG, TC, FINS levels and HOMA value were significantly higher and HDL-C level was significantly lower in the obese rats than those in the controls (p < 0.05). Pancreatic TG contents in the obese group were significantly increased compared

with those in the control group, and obvious pancreatic interlobular fatty infiltration was observed in the obese group. After octreotide treatment, body weight, Lee’s index, HOMA value, as well as above other plasma

parameters MK0683 in the obese rats showed decreased (p < 0.05). In the octreotide-treated group pancreatic TG content was significantly decreased compared with that in the non-treated obese group (p < 0.05) and pancreatic interlobular fatty infiltration MCE公司 was alleviated. Conclusion: Octreotide might improve pancreatic fatty infiltration, insulin resistance and lipid disorder in the high-fat diet induced obesity rats, and alleviate pancreatic injury. Key Word(s): 1. octreotide; 2. obesity; 3. high-fat diet; 4. fatty infiltration; Presenting Author: PENG QIU-PING Additional Authors: FENG QING-QING Corresponding Author: PENG QIU-PING Affiliations: Nanchang University Objective: Primary colon malignant lymphoma is relatively rare. In order to improve the diagnosis and treatment level of primary colon malignant lymphoma, the clinical presentations, diagnosis, treatment and prognostic factors of primary colon malignant lymphoma were investigated in our study. Methods: the clinical data of patients with primary colon malignant lymphoma admitted by our hospitals from January 1990 to December 2008 were analyzed retrospectively, and the prognostic factors were evaluated. Results: 37 patients were observed in this study, the male 23 cases, female 14 cases, at the age of 22 to 75, average 46.2.

Key Word(s): 1. water; 2. dehydration; Presenting Author: TAO

YU Additional Authors: RUI LIU, MAO LI, XIAN LI, OU QIANG, WEI HUANG, CHENG-WEI TANG Corresponding Author: RUI LIU Affiliations: West China Hospital, Sichuan University Objective: To investigate focal fatty infiltration of the pancreas in high-fat diet induced obesity rats and the effect of octreotide intervention on it Methods: SD rats were designed into the control group (n = 14) and the high-fat diet group (n = 36). Obese rats from the high-fat diet group were further divided into an obese group http://www.selleckchem.com/products/bgj398-nvp-bgj398.html (n = 14) and an octreotide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide for 8 days. Body weight, fasting insulin (FINS), and fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels, and pancreatic TG content were determined. Homeostatic model assessment (HOMA) value was calculated. Pathological changes of pancreas were examined with light microscopy. Results: Body weight, Lee’s index, FPG, TG, TC, FINS levels and HOMA value were significantly higher and HDL-C level was significantly lower in the obese rats than those in the controls (p < 0.05). Pancreatic TG contents in the obese group were significantly increased compared

with those in the control group, and obvious pancreatic interlobular fatty infiltration was observed in the obese group. After octreotide treatment, body weight, Lee’s index, HOMA value, as well as above other plasma

parameters www.selleckchem.com/products/Rapamycin.html in the obese rats showed decreased (p < 0.05). In the octreotide-treated group pancreatic TG content was significantly decreased compared with that in the non-treated obese group (p < 0.05) and pancreatic interlobular fatty infiltration MCE公司 was alleviated. Conclusion: Octreotide might improve pancreatic fatty infiltration, insulin resistance and lipid disorder in the high-fat diet induced obesity rats, and alleviate pancreatic injury. Key Word(s): 1. octreotide; 2. obesity; 3. high-fat diet; 4. fatty infiltration; Presenting Author: PENG QIU-PING Additional Authors: FENG QING-QING Corresponding Author: PENG QIU-PING Affiliations: Nanchang University Objective: Primary colon malignant lymphoma is relatively rare. In order to improve the diagnosis and treatment level of primary colon malignant lymphoma, the clinical presentations, diagnosis, treatment and prognostic factors of primary colon malignant lymphoma were investigated in our study. Methods: the clinical data of patients with primary colon malignant lymphoma admitted by our hospitals from January 1990 to December 2008 were analyzed retrospectively, and the prognostic factors were evaluated. Results: 37 patients were observed in this study, the male 23 cases, female 14 cases, at the age of 22 to 75, average 46.2.

Infants with perinatal subtype of BA have higher tissue levels of PROM1 expression than those with embryonic subtype. Conclusion: Expansion of collagen-producing PROM1pos cells within regions of

periportal fibrosis is associated with activated FGF and TGFβ pathways in both experimental and human BA. PROM1pos cells may therefore play an important role in the biliary MAPK inhibitor fibrosis of BA. (Hepatology 2014;60:941–953) “
“This chapter contains sections titled: Epidemiology Histopathology Etiology and pathophysiology Clinical features and diagnosis One or two diseases? Treatment of microscopic colitis References “
“The reported prevalence of cancer associated with a primary choledochal cyst ranges from 2.5%[1]to 26%.[2] Total cyst excision is the standard procedure to prevent malignant changes. An essential part of this surgery is the termination of the find more reflux of pancreatic juice into the bile duct through the anomalous pancreaticobiliary duct union, so as to avoid activation of pancreatic enzymes involved in the pathogenesis of bile duct carcinoma. Theoretically, biliary malignancy should not develop after excision of the choledochal cyst because the presumed cause was abrogated by separation-operation. However, although the incidence of biliary malignancy after excision of choledochal cyst was 0.6% in Korean multicenter

study[3] and 0.7% in a Japanese nationwide study,[4] far lower than that associated with unresected choledochal cysts, it is still higher (about 200 times) than the incidence of biliary cancer in the general population in Japan. The main issues about the biliary malignancy after cyst excision are the perspective it might give on risk factors for oncogenesis, the relevance of cyst excision as a standard treatment and risk factors. In this issue of the Journal of Gastroenterology and Hepatology, Ohashi et al.[5] provided cumulative incidence data on subsequent biliary malignancy increase

more than 15 years after choledochal cyst excision, describe unfavorable outcomes, and provide a comprehensive review of biliary malignancy after cyst excision. However, several questions mentioned remained unanswered. The authors searched only the English literature. Because choledochal cyst is a relatively rare disease in the West and medchemexpress more than half of the reported cases have occurred in Japan, we searched both English and Japanese language literature. Between 1970 and 2011, 58 cases were identified, and among them, data of site of malignancy can be available in 54 cases[3, 6-47] (Table 1). According to Todani’s classification, 24 of 41 patients (59%) were classified into type IVa, and 17 (42%) were into type I. The most common site of involvement in 54 cases was the hepatic duct, at or near the choledocho-enteric anastomosis (43%) followed by the intrahepatic duct (41%) and distal choledochus (17%).

The therapeutical effect is very good not only for induction of remission of the intestinal inflammation, but also for a long-term maintenance treatment. For some patients, however, BT is associated with the occurrence of sometimes serious side effects. Their pathogenesis is not known yet and in some cases these serious side effects are the cause of the termination of the treatment. Methods: In the period 2007–2012, 136 patients with IBD TNF-α were treated at the Department of Internal Medicine II of the University Hospital in Olomouc. In this set of patients, the occurrence of serious side effects of TNF-α was observed

within the dispensarization. The difference in the occurrence of side events was compared with the control set of 114 patients with IBD, who underwent only conventional therapy (aminosalicylates, corticosteroids, immunosuppressants). SCH772984 The observed side effects included skin, articulary, Selleck GSK2126458 ocular, infectious, metabolic and hematopoietic disorders. The data were statistically processed

using standard descriptive methods for continuous data. Results: The serious side effects were documented in 12 (8.8%) patients with TNF-α therapy; the most common complications were skin complications (54.3%). In the set of patients under the conventional therapy, the side effects of the treatment have been reported in 8 (7.0%) patients, mostly involving hematopoietic disorders (61.2%). The observed difference of occurrence of serious side effects was not statistically significant (p = 0.11). Conclusion: In the last decade, the introduction of BT has caused a significant change in the routine clinical treatment of IBD. It turns out that this treatment is relatively safe, the incidence of serious side effects is not higher than when using conventional drug therapy.

It is necessary to indicate the TNF-α treatment properly, the patient must be carefully examined before the initiation of the treatment and intensively monitored during the course of the treatment. Key Word(s): 1. biological therapy; 2. conventional therapy; 3. ulcerative colitis; 4. Crohn’s disease; Presenting MCE公司 Author: XIAOMIN LV Additional Authors: XIAOLAN ZHANG Corresponding Author: XIAOLAN ZHANG Affiliations: The Second Hospital of Hebei Medical University; The Second Hospital of Hebei Medical University Objective: Ulcerative colitis is a chronic non-specific easy-to-relapse inflammatory rectum and colon diseases, which main cause remains unknown. Recent years, researchers find TNF ligand-related molecule-1A (TL1A) is a new member of tumor necrosis factor superfamily (TNFSF), which can bind DcR3 to induce some inflammation, also may provide a new biological therapeutic target with IBD. Methods: Patient were grouped as follows: 1.

The therapeutical effect is very good not only for induction of remission of the intestinal inflammation, but also for a long-term maintenance treatment. For some patients, however, BT is associated with the occurrence of sometimes serious side effects. Their pathogenesis is not known yet and in some cases these serious side effects are the cause of the termination of the treatment. Methods: In the period 2007–2012, 136 patients with IBD TNF-α were treated at the Department of Internal Medicine II of the University Hospital in Olomouc. In this set of patients, the occurrence of serious side effects of TNF-α was observed

within the dispensarization. The difference in the occurrence of side events was compared with the control set of 114 patients with IBD, who underwent only conventional therapy (aminosalicylates, corticosteroids, immunosuppressants). Linsitinib The observed side effects included skin, articulary, CH5424802 mw ocular, infectious, metabolic and hematopoietic disorders. The data were statistically processed

using standard descriptive methods for continuous data. Results: The serious side effects were documented in 12 (8.8%) patients with TNF-α therapy; the most common complications were skin complications (54.3%). In the set of patients under the conventional therapy, the side effects of the treatment have been reported in 8 (7.0%) patients, mostly involving hematopoietic disorders (61.2%). The observed difference of occurrence of serious side effects was not statistically significant (p = 0.11). Conclusion: In the last decade, the introduction of BT has caused a significant change in the routine clinical treatment of IBD. It turns out that this treatment is relatively safe, the incidence of serious side effects is not higher than when using conventional drug therapy.

It is necessary to indicate the TNF-α treatment properly, the patient must be carefully examined before the initiation of the treatment and intensively monitored during the course of the treatment. Key Word(s): 1. biological therapy; 2. conventional therapy; 3. ulcerative colitis; 4. Crohn’s disease; Presenting 上海皓元 Author: XIAOMIN LV Additional Authors: XIAOLAN ZHANG Corresponding Author: XIAOLAN ZHANG Affiliations: The Second Hospital of Hebei Medical University; The Second Hospital of Hebei Medical University Objective: Ulcerative colitis is a chronic non-specific easy-to-relapse inflammatory rectum and colon diseases, which main cause remains unknown. Recent years, researchers find TNF ligand-related molecule-1A (TL1A) is a new member of tumor necrosis factor superfamily (TNFSF), which can bind DcR3 to induce some inflammation, also may provide a new biological therapeutic target with IBD. Methods: Patient were grouped as follows: 1.