Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease

BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.

Autofluorescence imaging endoscopy for identifi cation and assessment of inflammatory ulcerative colitis

AIM:To validate the clinical relevance of autofluores-cence imaging(AFI)endoscopy for the assessment of inflammatory ulcerative colitis(UC).METHODS:A total of 572 endoscopic images were se-lected from 42 UC patients:286 taken with white light imaging(WLI)and 286 with AFI from the same sites.WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore(MES),and for seven characteristic endoscopic features.Likewise,AFI photographs were scored according to relative abundance of red,green and blue color com-ponents within each image based on an RGB additive color model.WLI and AFI endoscopic scores from the same sites were compared.Histological evaluation of biopsies was according to the Riley Index.RESULTS:Relative to red(r=0.52,P<0.01)or blue(r=0.56,P<0.01)color component,the green color component of AFI(r=-0.62,P<0.01)corresponded more closely with mucosal inflammation sites.There were signif icant differences in green color components between MES-0(0.396±0.043)and MES-1(0.340± 0.035)(P<0.01),and between MES-1 and ≥ MES-2(0.318±0.037)(P<0.01).The WLI scores for "vascu-lar patterns"(r=-0.65,P<0.01),"edema"(r=-0.62,P<0.01),histology scores for "polymorphonuclear cells in the lamina propria"(r=-0.51,P<0.01)and "crypt architectural irregularities"(r=-0.51,P<0.01)showed correlation with the green color component of AFI.There were significant differences in green color components between limited(0.399± 0.042)and extensive(0.375±0.044)(P=0.014)polymorpho-nuclear cell inf iltration within MES-0.As the severity of the mucosal inflammation increased,the green color component of AFI decreased.The AFI green color com-ponent was well correlated with the characteristic en-doscopic and histological inflammatory features of UC.CONCLUSION:AFI has application in detecting inflammatory lesions,including microscopic activity in the co-lonic mucosa of UC patients,based on the green color component of images.

Antioxidant therapy for chronic hepatitis C after failure of interferon:Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM： To investigate the correlation between hepatitis B virus surface antigen （HBsAg）, hepatitis C virus （HCV） expression in hepatocellular carcinoma （HCC）, the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein （AFP） level. METHODS： The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immunohistochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index （HAIl score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups： patients positive for HBsAg （HBsAg group）, patients positive for HCV （HCV group）, patients negative for both HCV and HBsAg （NBNC group） and patients positive for both HBsAg and HCV （BC group）. RESULTS： The BC group had significantly higher HAI scores than the other three groups. （BC 〉 HCV 〉 HBsAg 〉 NBNC）. HBV and HCV virus infection was positively correlated with HAI （rs = 0.39, P = 0.00011. The positive rate of AFP （85.7%） and the value of AFP （541.2 ng/mL） in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate （53.3%） of AFP and the value of AFP （ 53.3 ng/mL） in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP（rs = 0.38, P = 0.0001）. CONCLUSION： The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The-serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman＇s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.