Predicting Mucosal Proliferation in Ulcerative Colitis by Assessing Mucosal Vascular Pattern Under Narrow Band Imaging Colonoscopy

Background: Proliferative abnormalities are believed to represent an early phase of colorectal carcinogenesis. Narrow band imaging (NBI) colonoscopy allows visual assessment of the mucosal vascular pattern (MVP) without dyeing. The aim of this study was to investigate the predictive value of MVP for mucosal proliferation in ulcerative colitis (UC).Methods: A total of 119 colorectal lesions were analyzed from 42 patients with UC who underwent NBI colonoscopy. Both the MVP and the Mayo endoscopic score (MES) were assessed. The mucosal inflammation was histologically graded using a colitis score. The proliferation marker Ki-67 was assessed by immunohistochemical staining.Results: The results showed that MVP correlated well with the MES (r = 0.796, P < .001). There was moderate correlation between the distribution of Ki-67 staining and MVP (r = 0.492, P < .001), and the Ki-67 labeling index increased with the orderly patterns of MVP (P < .001). An expansion of Ki-67 staining upward from the crypt base may be caused by active inflammation.Conclusion: MVP based on NBI colonoscopy can predict mucosal proliferation which is associated with inflammation in patients with UC.     

Fecal calprotectin as a noninvasive test to predict deep remission in patients with ulcerative colitis

Mucosal healing (MH) has become a major target in the management of ulcerative colitis (UC). Because repeat endoscopy is expensive and invasive, we aimed to evaluate fecal calprotectin (FC) as an alternative marker to predict MH in UC.Eighty patients with UC in clinical remission were consecutively included in a prospective observational study. FC was measured using a quantitative enzyme-linked immunosorbent assay. The colonic mucosa was assessed for endoscopic and histological measures of inflammatory status. Endoscopic and histological remission were defined according to the Mayo endoscopic subscore (MES) and Geboes score (GS), respectively. Deep remission was defined as a combination of the MES and GS. FC performance and cutoff values for identifying MH and deep remission were determined using contingency tables and receiver operator characteristic (ROC) and area under the curve (AUC) analysis.The median FC concentration in patients who met the criteria for deep remission (MES ≤1 and GS < 3.1) was 65.5 μg/g, while that in patients with disease activity was 389.6 μg/g (P = .025). A FC cutoff value of 100 μg/g, determined by the ROC analysis, resulted in sensitivity and specificity of 91.7% and 57.1%, respectively, for histological remission, and 82.4% and 60.9%, respectively, for deep mucosal remission. Positive correlations were detected between FC concentrations with the histologic (CC: 0.435; P < .001) and the combined endoscopic and histologic (CC: 0.413; P < .001) scores.FC can be used confidently as a noninvasive biomarker to predict deep remission in patients with UC in clinical remission when concentrations are below 100 μg/g.     

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results,mucosal healing,and risk of relapse

AIM: To assess the risk of relapse in ulcerative colitis(UC) patients in clinical remission using mucosal status and fecal immunochemical test(FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores(MESs) and FIT results.RESULTS: Patients with an MES of 0(n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3(n = 100, 52%)(HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result(fecal hemoglobin concentrations ≤ 100 ng/m L) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score(HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse(HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing(MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.     

Clinical significance of expression of tissue factor and tissue factor pathway inhibitor in ulcerative colitis

AIM: To investigate the clinical significance of expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in ulcerative colitis (UC).METHODS: Thirty UC specimens taken by colonoscopy from patients with active UC treated at the Department of Pathology, Central Hospital Affiliated to Shenyang Medical College from February 2010 to January 2012 were included in an experimental group, and 30 normal colon tissue samples taken by colonoscopy from non-UC patients were included in a control group. Expression of TF and TFPI in UC and normal colon tissue samples was detected by immunohistochemistry.RESULTS: The positive rate of TF in UC was significantly higher than that in normal colon tissue (63% vs 33%, χ² = 5.41, P < 0.05). The positive rate of TFPI in UC was also significantly higher than that in normal colon tissue (43% vs 17%, χ² = 5.08, P < 0.05).CONCLUSION: Positive rates of TF and TFPI expression in UC are significantly higher than those in normal colon tissue. TF and TFPI may play an important role in the pathogenesis of UC.     

Correlation of Intestinal Mucosal Healing and Tight Junction Protein Expression in Ulcerative Colitis Patients

Background

The aim of this study was to investigate the relationship between intestinal mucosal healing and tight junction (TJ) protein expression in patients with ulcerative colitis (UC).

Prognostic values of procalcitonin and platelet in the patient with urosepsis

Background:The patient suffering from urinary sepsis is often accompanied by elevated serum procalcitonin (PCT) levels and a decline in the average platelet count (PLT), which could result in a poor prognosis. This study aimed to evaluate the value of PCT and PLT in determining the severity of urinary sepsis.Methods:A total of 120 urosepsis patients enrolled were divided into a survival group and a death group, respectively, according to their status within 14 days after admission. Changes in PCT and PLT levels between the 2 groups were compared at different time points. A receiver operating characteristic (ROC) curve was eventually obtained to predict the prognostic value of PCT and PLT.Results:The PCT levels in the survival group declined gradually after admission, and the PLT decreased at first but increased rapidly in subsequence. The PCT level in the death group, however, declined in a flat-slope trend or was hardly noticeable together with the number of PLT reduced significantly. In particular, it is on the 3rd day that PCT tended to positively correlate with acute physiological and chronic health score II (APACHE II) score (r = 0.730, P < .05), but negatively with PLT (r = 0.472, P < .05). The APACHE II score and PLT (r = 0.612, P < .05) were also negatively correlated with each other. As indicated by the ROC curve, the PCT level on the 3rd day after admission was of great value for the clinical mortality prognosis, and the area under the curve was 0.858. Moreover, PLT also has a high predictive value for prognosis. Area under the curve is 0.951. When the PLT was more than 51 × 10⁹ /L, the sensitivity was up to 90%, and the specificity was 90%.Conclusion:PLT and PCT levels are closely related to the APACHE II score, which could indicate the severity of urosepsis in patients. The contribution of this study was to confirm that dynamic monitoring of the changes in PCT and PLT helps determine the prognosis of urosepsis patients.     

Prognostic significance of preoperative platelet count in patients with gallbladder cancer

AIM:To investigate the prognostic value of preoperative platelet count(PLT) in patients with primary gallbladder cancer(GBC).METHODS:The clinical data of 223 GBC patients after surgery was retrospectively reviewed.A receiver operating characteristic(ROC) curve was plotted to verify the optimum cutoff point for PLT.Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis.RESULTS:The ROC curve showed that the optimum cutoff point for PLT was 178 × 109/L,and the entire cohort was stratified into group A with PLT 178 × 109/L and group B with PLT ≤ 178 × 109/L.Group A had a better survival than group B(P 0.001).There was an obvious difference between the two groups in terms of the differentiation degree,advanced tumor stage,lymph node metastasis(P 0.001) and pathological type(P 0.05).The univariate analysis demonstrated that tumor location,differentiation degree,TNM stage,Nevin stage,lymph node metastasis and PLT were associated with overall survival(P 0.001).In the multivariate analysis,PLT(P = 0.032),lymph node metastasis(P = 0.007),tumor location(P 0.001) and TNM stage(P = 0.005) were independent prognostic factors.CONCLUSION:PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.     

Physician global assessments or blood tests do not predict mucosal disease activity in ulcerative colitis

BACKGROUND:

Mucosal healing has been proposed as the therapeutic end point in the treatment of patients with ulcerative colitis (UC).

OBJECTIVE:

To investigate the relationship between physician global assessment (PGA) and laboratory blood tests (complete blood count, ferritin, C-reactive protein, albumin) and endoscopic findings in UC to determine whether they could be adequate surrogates for endoscopy.

METHODS:

A retrospective chart review of patients known to have UC from July 2008 to November 2012 was performed at the Health Sciences Centre, Winnipeg, Manitoba. Patients included individuals with UC who underwent colonoscopy within one month of clinic assessment. Blood tests were standard at the time of colonoscopy. Patients presenting through the emergency department, those with colonoscopies performed outside the authors’ institution, or whose colonoscopies and clinical assessments were undertaken more than one month apart were excluded. The PGA was used to determine disease activity in patients before colonoscopy. The Ulcerative Colitis Endoscopic Index of Severity, a validated scoring system to rate endoscopic disease severity in ulcerative colitis, was adapted.

RESULTS:

A total of 154 patients (mean [± SD] age 44±15.7 years) with UC were identified including 82 (53%) men. Mean hemoglobin level was 139 g/L, mean platelet level was 296×10⁹/L, mean ferritin level was 102 μg/L, mean C-reactive protein level was 10 mg/L and mean albumin level was 40 g/L. Using endoscopy as the ‘gold standard’ for assessing UC activity (moderate-severe), abnormalities in laboratory parameters and PGA were both highly specific but not sensitive for identifying individuals with at least moderately active endoscopic disease. The PGA had higher positive and negative predictive values than the laboratory parameters.

CONCLUSION:

Neither blood tests nor PGA could replace endoscopy for assessing mucosal healing. When patients experienced active symptoms and abnormal serum markers, they were highly likely to have abnormal endoscopy. However, inactive symptoms or normal laboratory values did not preclude having active endoscopic disease.     

Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT

Despite the overall benefit from allogeneic hematopoietic stem cell transplantation observed in patients with poor cytogenetic risk acute myeloid leukemia in first complete remission, the precise effect of this procedure for different poor-risk subtypes has not been fully analyzed. This retrospective analysis was performed to investigate whether allogeneic hematopoietic stem cell transplantation performed in first complete remission in patients with monosomal karyotype can overcome the adverse prognosis associated with these patients. Of the 4635 patients included in the study, 189 (4%) harbored a monosomal karyotype. The presence of a monosomal karyotype was associated with a worse outcome, with an inferior leukemia-free survival and overall survival (5-year leukemia-free survival and overall survival: 24±3% and 26±3% vs. 53±1% and 57±1% in monosomal-karyotype and non-monosomal-karyotype, respectively; P<0.0001) and higher relapse risk after transplantation (cumulative incidence of relapse at 5 years: 56±4% in monosomal-karyotype vs. 28±1% in non-monosomal-karyotype; P<0.0001). The adverse negative impact of monosomal karyotype cytogenetics was confirmed in the entire cohort in a multivariate analysis [Hazard Ratio (HR): 1.88, 95% Confidence Interval (CI):1.29–2.73, P=0.001 for relapse incidence; HR:1.71, 95%CI:1.27–2.32, P<0.0001 for leukemia-free survival; HR:1.81, 95%CI:1.32–2.48, P=0.0002 for overall survival], and was independent of the presence of other poor-risk cytogenetic subtypes. In summary, monosomal karyotype arises as a strong negative prognostic feature in acute myeloid leukemia also in patients who undergo allogeneic hematopoietic stem cell transplantation in first complete remission, stressing the need to develop additional pre- and post-transplantation strategies aimed at improving overall results. Nonetheless, allogeneic hematopoietic stem cell transplantation in early phase is currently the best therapy for this very poor-risk acute myeloid leukemia subtype.     

Fecal calprotectin is more accurate than fecal immunochemical test for predicting mucosal healing in quiescent ulcerative colitis: a prospective multicenter study

Abstract

Objective: Non-invasive stool tests, including the fecal immunochemical test (FIT) and fecal calprotectin (FC), are reliable biomarkers for mucosal healing (MH) in ulcerative colitis (UC). However, which fecal test is superior for predicting MH in inactive UC patients requires evaluation. We aimed to compare the accuracy of FIT and FC results for predicting MH in quiescent UC patients.

Methods: This prospective, multicenter study was conducted at three tertiary hospitals. UC patients in clinical remission for at least three?months underwent colonoscopy and MH was evaluated using the Mayo endoscopic sub-score (MES). The receiver operating characteristic (ROC) curve and cutoff value with the best accuracy for predicting MH were assessed.

Results: Among 127 patients, 65 (51.2%) showed MH (MES = 0). The area under the curve (AUC) for predicting MH (MES = 0) was significantly higher for FC than for FIT (AUC 0.858 (95% confidence interval (CI) 0.784–0.913) vs. 0.707 (95% CI 0.620–0.784), p?<?.001); there was no difference when MH included MES = 1 (MES ≤ 1) (AUC 0.820 (95% CI 0.742–0.883) vs. 0.813 (95% CI 0.734–0.877), p?=?.891). When the cutoff value was 70?μg/g for FC and 10?ng/mL for FIT, the sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3, respectively, for FC and 92.3, 50, 65.9, and 86.1, respectively, for FIT.

Conclusion: FC is more accurate than FIT for predicting MH in quiescent UC patients. The superiority of FC might be related to the distinctive performance of FC in differentiating inflammatory levels, particularly in low-grade mucosal activity.     

Platelet count combined with right liver volume and spleen volume measured by magnetic resonance imaging for identifying cirrhosis and esophageal varices

AIM: To determine whether the combination of platelet count(PLT) with spleen volume parameters and right liver volume(RV) measured by magnetic resonance imaging(MRI) could predict the Child-Pugh class of liver cirrhosis and esophageal varices(EV).METHODS: Two hundred and five cirrhotic patients with hepatitis B and 40 healthy volunteers underwent abdominal triphasic-enhancement MRI and laboratory examination of PLT in 109/L. Cirrhotic patients underwent endoscopy for detecting EV. Spleen maximal width(W), thickness(T) and length(L) in mm together with spleen volume(SV) and RV in mm3 were measured by MRI, and spleen volume index(SI) in mm3 was obtained by W × T × L. SV/PLT, SI/PLT and RV × PLT/SV(RVPS) were calculated and statistically analyzed to assess cirrhosis and EV.RESULTS: SV/PLT(r = 0.676) and SI/PLT(r = 0.707) increased, and PLT(r =-0.626) and RVPS(r =-0.802) decreased with the progress of Child-Pugh class(P 0.001 for all). All parameters could determine the presence of cirrhosis, distinguish between each class of Child-Pugh class, and identify the presence of EV [the areas under the curve(AUCs) = 0.661-0.973]. A m o n g p a ra m e t e r s, R V P S c o u l d b e s t d e t e r m i n e presence and each class of cirrhosis with AUCs of 0.973 and 0.740-0.853, respectively; and SV/PLT could best identify EV with an AUC of 0.782.CONCLUSION: The combination of PLT with SV and RV could predict Child-Pugh class of liver cirrhosis and identify the presence of esophageal varices.     

Fecal calprotectin correlated with endoscopic remission for Asian inflammatory bowel disease patients

AIM: To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients.METHODS: Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn’s disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring.RESULTS: A total of 88 IBD patients [36 patients with Crohn’s disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P < 0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS < 6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 μg/g as the cut-off. When using 191 μg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS < 3) with 88% sensitivity and 75% specificity (AUC: 0.87).CONCLUSION: fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.     

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the pat...     

Factors Associated with Significant Platelet Count Improvement in Thrombocytopenic Chronic Hepatitis C Patients Receiving Direct-Acting Antivirals

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 10³/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 10³/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99–1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06–1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58–0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98–0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71–0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.     

Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation

Background: The aim of the study was to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in clinical, endoscopic, and histologic remission and in relation to both the depth of remission and inflammation markers. Methods: Patients with ulcerative colitis (UC) and with Crohn’s disease (CD) in clinical remission for at least 6 months were enrolled in the study. All of the patients underwent colonoscopy, and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. Patients were evaluated according to Rome III criteria for IBS. Fecal calprotectin level and blood samples for C-reactive protein (CRP), sedimentation rate, and fibrinogen levels were studied.Results: IBS frequency was 20.9% in UC cases and 28.9% in CD cases in clinical remission. Rates with and without endoscopic remission in UC (20.5% vs. 22.2%, P = .727) and CD (25% vs. 33.3%, P = .837, respectively) were not different. Similarly, rates with and without histopathologic remission in UC (15.7% vs. 26.6%, P = .723), and CD (21.4% vs. 33.3%, P = .999) were not statistically different. Also, it was not related to inflammation markers.Conclusion: IBS frequency among IBD patients with remission was in a substantial rate; these rates kept up with the process of deep remission and even complete mucosal healing and were irrelevant to inflammation.     

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC).METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex^® Kit. Additional clinical and laboratory data were collected from the medical records.RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0.05).CONCLUSION: The multiplex PCR assay that was used to analyze the stool samples in this study may serve as a non-invasive approach that can be used to exclude the possibility of CMV infection in patients with active UC who are treated with immunosuppressive therapy.     

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With İnflammatory Bowel Disease: A Multicenter Study

Background: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously.Methods: Children with IBD (334 ulcerative colitis (UC), 224 Crohn’s disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined.Results: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/heterozygous) in patients with UC (P < .05).There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007).Conclusion: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.     

Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

AIM: To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.METHODS: We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals. Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis. A new fibrosis index [globulin/platelet (GP) model] was developed, including globulin (GLOB) and platelet count (PLT). GP model = GLOB (g/mL) × 100/PLT (× 10⁹/L). We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.RESULTS: Thirteen clinical biochemical and hematological variables [sex, age, PLT, alanine aminotransferase, aspartate aminotransferase (AST), albumin, GLOB, total bilirubin (T.bil), direct bilirubin (D.bil), glutamyltransferase, alkaline phosphatase, HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1, F2-F3 and F4). Bivariate Spearman’s rank correlation analysis showed that six variables, including age, PLT, T.bil, D.bil, GLOB and PT, were correlated with the three fibrosis stages (FS). Correlation coefficients were 0.23, -0.412, 0.208, 0.220, 0.314 and 0.212; and P value was 0.014, < 0.001, 0.026, 0.018, 0.001 and 0.024, respectively. Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT: F = 11.772, P < 0.001; GLOB: F = 6.612, P = 0.002). Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R² = 0.237). By Spearman’s rank correlation analysis, GP model was significantly correlated with the three FS (r = 0.466, P < 0.001). The median values in F0-F1, F2-F3 and F4 were 1.461, 1.720 and 2.634. Compared with the six available models (fibrosis index, AST-platelet ratio, FIB-4, fibrosis-cirrhosis index and age-AST model and age-PLT ratio), GP model showed a highest correlation coefficient. The sensitivity and positive predictive value at a cutoff value < 1.68 for predicting minimal fibrosis F0-F1 were 72.4% and 71.2%, respectively. The specificity and negative predictive value at a cutoff value < 2.53 for the prediction of cirrhosis were 84.5% and 96.7%. The area under the curve (AUC) of GP model for predicting minimal fibrosis and cirrhosis was 0.762 [95% confidence interval (CI): 0.676-0.848] and 0.781 (95% CI: 0.638-0.924). Although the differences were not statistically significant between GP model and the other models (P all > 0.05), the AUC of GP model was the largest among the seven models.CONCLUSION: By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.     

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy

BACKGROUNDInfliximab trough level (ITL) severely affects therapeutic outcomes of Crohn’s disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIMTo explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODSCD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn’s disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn’s disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTSAt week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).CONCLUSIONCombination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.