Published papers

The gut-liver axis is of clinical importance as a potential therapeutic target in a wide range of liver diseases; however, the mechanisms underlying interactions between microbial products and immune responses in the liver remain unknown. In this study, we demonstrated that IL-10-producing macrophages contribute to immune tolerance in the inflamed liver under intestinal barrier disruption in a murine tandem model of dextran sulfate sodium (DSS) colitis and concanavalin A (Con A) hepatitis. Intestinal barrier disruption protected mice from subsequent liver injury, and the severity of colitis directly affected susceptibility to such injury. The protective effect of DSS-Con A was canceled in gut-sterilized mice, suggesting that gut microbiota play a substantial role in this process. Altered gut microbiota and their metabolites, along with a disrupted intestinal barrier, directly gave rise to immunological permissiveness in the inflamed liver. We identified 1-methylnicotinamide (1-MNA) as a candidate metabolite capable of suppressing liver injury with the potential to induce IL-10-producing macrophages. Consistently, expression of nicotinamide N-methyltransferase, which converts nicotinamide to 1-MNA, was upregulated in the liver of DSS-Con A mice, and this effect was abrogated by gut sterilization. Collectively, our results provide a mechanistic insight into the regulation of immunological balance in the liver via the gut-liver axis.

Copyright © 2019 World Gastroenterology Organisation. All rights reserved. Background and Aims: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). Methods: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥ 6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. Results: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥ 6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. Conclusions: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

© 2018 S. Karger AG, Basel. Background/Aims: Although colonic diverticular bleeding (CDB) often ceases spontaneously, re-bleeding occurs in about 30%. Bleeding diverticulum can be treated directly by endoscopic hemostasis; however, it is difficult to perform colonoscopy in all cases with limited medical resource and certain risks. The aim of this study was to clarify who should undergo colonoscopy as well as appropriate methods of initial management in CDB patients. Methods: A total of 285 patients who were diagnosed as CDB and underwent colonoscopy from March 2004 to October 2015 were retrospectively analyzed. First, the association between re-bleeding and various factors including patients' background and initial management were analyzed. Second, the examination conditions that influenced bleeding point identification were analyzed. Results: Of 285 patients, 187 were men and 98 were women. Median age was 75 years, and the median observation period was 17.5 months. Re-bleeding was observed in 79 patients (28%). A history of CDB (OR 2.1, p = 0.0090) and chronic kidney disease (CKD; OR 2.3, p = 0.035) were risk factors, and bleeding point identification (OR 0.20, p = 0.0037) was a preventive factor for re-bleeding. Bleeding point identification significantly reduced approximately 80% of re-bleeding. Furthermore, extravasation on CT (OR 3.7, p = 0.031) and urgent colonoscopy (OR 5.3, p < 0.001) were predictors for identification of bleeding point. Compared to bleeding point identification of 11% in all patients who underwent colonoscopy, identification rate in those who had extravasation on CT and underwent urgent colonoscopy was as high as 70%. Conclusions: Contrast-enhanced CT upon arrival is suggested, and patients with extravasation on CT would be good candidates for urgent colonoscopy, as well as patients who have a history of CDB and CKD.

© 2017 Elsevier Inc. Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression signatures for specific subtypes, their functional differences remain elusive. Here, we established a pancreatic tumor organoid library encompassing 39 patient-derived PDACs and identified 3 functional subtypes based on their stem cell niche factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in the absence of Wnt and R-spondin. Transcriptome analysis of PDAC organoids revealed gene-expression signatures that associated Wnt niche subtypes with GATA6-dependent gene expression subtypes, which were functionally supported by genetic perturbation of GATA6. Furthermore, CRISPR-Cas9-based genome editing of PDAC driver genes (KRAS, CDKN2A, SMAD4, and TP53) demonstrated non-genetic acquisition of Wnt niche independence during pancreas tumorigenesis. Collectively, our results reveal functional heterogeneity of Wnt niche independency in PDAC that is non-genetically formed through tumor progression. Sato and colleagues established a library of patient-derived pancreas cancer organoids and identified heterogeneous patterns of dependency on Wnt ligands among pancreas cancers. Biological and genetic analyses highlighted GATA6 as a mediator of the Wnt niche requirement, which links pancreatic tumor progression to independence from the stem cell niche.

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Objective Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. Methods This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. Results Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). Conclusions The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

© 2018 International Institute of Anticancer Research.All right reserved. Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.

© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: A missense variant of the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene (R139C) predisposes Asian patients with inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study evaluates the long-term effect of NUDT15 R139C heterozygosity on hematological parameters during thiopurine administration. Methods: We enrolled 83 Japanese IBD patients who were on anti-tumor necrosis factor-α agents and had used thiopurine. NUDT15 R139C was genotyped by polymerase chain reaction. We retrospectively reviewed patient clinical charts to collect data on white blood cell (WBC) count, mean corpuscular volume (MCV), hemoglobin, and platelet count during the 24 months following thiopurine initiation. Results: The included patients had either Crohn's disease (54; 65.1%) or ulcerative colitis (29; 34.9%). Genotyping of NUDT15 R139C identified 62 patients (74.7%) of genotype C/C and 21 (25.3%) of genotype C/T. The median dose of thiopurine was lower in the C/T group than in the C/C group after starting thiopurine. At 6 months, the mean WBC count of the C/T group became significantly lower than that of the C/C group (P = 0.008) and remained lower through the 24 months. The C/T group developed grade 2–4 leukopenia by 6 months, which persisted through 12–24 months. The mean MCV in the C/T group became higher than that of the C/C group after 3 months. Conclusions: NUDT15 R139C heterozygosity affected the WBC count and MCV for 24 months after thiopurine administration. Our results indicate that careful monitoring of leukopenia and dose adjustment are necessary throughout treatment in IBD patients heterozygous for the NUDT15 R139C.

The number of patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) is increasing. We describe a case of MTX-LPD of the stomach. After treatment with methotrexate for rheumatoid arthritis, the patient developed left cervical lymphadenopathy and an ulcerative lesion in the stomach, which was presumed to be a mucosa-associated lymphoid tissue (MALT) lymphoma. However, we suspected MTX-LPD, based on the clinical course and the positivity of in situ hybridization for the detection of the Epstein-Barr encoding region. After the cessation of MTX, the left cervical lymphadenopathy and the gastric lesion disappeared. This is first report of gastric MTX-LPD that was presumed to be MALT lymphoma.

© 2019 John Wiley & Sons, Ltd. Rationale, aims, and objectives: The aim of this observational study is to identify factors by which some pancreatic cystic lesions (PCLs) were undetectable at transabdominal ultrasonography (TAUS), using magnetic resonance imaging (MRI) as reference standard. Methods: The database for 781 consecutive subjects who underwent a health checkup including fat computed tomography and upper abdominal MRI as option was searched. The presence of fatty liver and fatty pancreas was diagnosed by TAUS, and atrophic pancreas was determined by reevaluating the image of the pancreas in the chest computed tomography for screening. Subjects with PCL detected and those undetected at TAUS were statistically compared in clinical characteristics. Results: The prevalence of PCL detected at MRI was 17.8% in the general population. Multivariate logistic regression analysis showed that fatty liver, body mass index, and the size of PCL were significantly associated with the factors influencing the visualization of PCL at TAUS (odds ratio [OR]: 0.337, 95% confidence interval [CI]: 0.154-0.734, P = 0.006; OR: 0.852, 95% CI: 0.737-0.985, P = 0.030; OR:1.120, 95% CI: 1.045-1.200, P =.001). Thirty-six PCLs (64.3%) in a total of 56 PCLs were undermeasured by TAUS. Additionally, nine (56%) out of 16 PCLs (≥ 15 mm) were undermeasured by 5 mm or more by TAUS, although a significantly higher detection rate was observed for PCLs (≥ 15 mm) in comparison with that for PCLs (< 15 mm) (80% vs 33.6%, P =.000). Conclusions: It should be noted that coexisting fatty liver may lower the detection of PCL, and its size may be underestimated by TAUS.

© Author(s) (or their employer(s)) 2019. Background and aims There is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO 2 insufflation. Methods Non-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO 2 (EtCO 2 ) was continuously monitored during the procedure under CO 2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO 2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system. Results Eleven patients were enrolled. Measurement of EtCO 2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s). Conclusion This study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO 2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO 2 insufflation.

© 2019 Japan Gastroenterological Endoscopy Society There are no reports on detailed endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) except for relatively small case series. Herein, we conducted a prospective observational study to investigate the relationship between endoscopic findings and histopathological diagnosis of SNADET. A total of 163 SNADET diagnosed using magnified endoscopic examination with image-enhanced endoscopy (IEE-ME) were prospectively registered in this study. We investigated location, size, macroscopic type, color, and IEE-ME findings including surface structure (closed- or open-loop) and presence of white opaque substance (WOS) in SNADET. We analyzed association between these findings and histopathological diagnosis of SNADET based on the Vienna classification (VCL) using logistic regression analysis. In univariate analysis, lesion size, superficial structure, and WOS deposition showed statistical significance, and the oral side of the lesion location showed statistical tendency for association with VCL C4/5. In multivariate analysis, lesion size (odds ratio [OR], 2.92; 95% CI, 1.94–4.39; P < 0.05) and negative WOS (OR, 5.59; 95% CI, 1.72–18.1; P < 0.05) were significantly associated with VCL C4/5 lesions. Superficial structures with a closed-loop pattern on the surface showed statistical tendency for predicting VCL C4/5 lesions (OR, 2.15; 95% CI, 0.86–5.37; P = 0.10). Based on these findings, we concluded that negative WOS by IEE-ME and lesion size were independent predictors of VCL C4/5 SNADET. These factors may help us to understand of pathophysiology of SNADET and to select appropriate therapeutic strategies.

© 2019 Japan Gastroenterological Endoscopy Society Objective: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. Methods: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. Results: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). Conclusions: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. Registry and the registration number: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

© 2019, Japanese Society of Gastroenterology. Background: We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness. Methods: In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5–2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8. Results: The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8. Conclusions: In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.

© 2019 Japan Gastroenterological Endoscopy Society Despite the rarity of colorectal poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig), they are more frequent in patients with ulcerative colitis (UC). However, little is known about these components of early colitis-associated cancer due to the difficulty of detection at an early stage. Here, we reviewed colitis-associated high-grade dysplasia/cancer with Por/Sig components within the submucosa among 103 lesions of 79 UC patients who presented between 1997 and 2017. In total, one Sig in situ, three intramucosal and two submucosal carcinomas (8.7%) were identified among 69 lesions within the submucosa. Depressed appearance, loss of crypt architecture and amorphous surface pattern suggested the presence of Por/Sig, rather than submucosal infiltration. All lesions were located in the rectosigmoid colon and included high-grade dysplasia. While the surrounding noncancerous mucosa expressed E-cadherin and MUC5AC, the expression of E-cadherin was reduced and the expression of MUC5AC was negative in all of the carcinomas except for the Sig in situ. The gastric type metaplasia associated with altered MUC5AC profiles may be a sign of the stepwise accumulation of molecular alterations, including TP53 defects and a reduced expression level of E-cadherin.

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Although much less common than localized zoster, initial presentation of varicella-zoster virus (VZV) as visceral infection can occur especially after allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of post-transplant visceral VZV infection presenting as fatal acute liver failure. It developed 4 years after allogeneic HSCT when a long-term prophylactic anti-VZV agent administration was discontinued. VZV should be listed as a causative pathogen of acute liver failure even years after allogeneic HSCT. Indication for, and duration of anti-VZV prophylaxis should be further investigated.

© 2019 American Society for Gastrointestinal Endoscopy Background and Aims: Endoscopic submucosal dissection (ESD) is being performed more frequently as a local treatment for superficial duodenal epithelial tumors (SDETs). However, ESD for SDETs is technically difficult because of specific anatomic features that increase the risk of perforation and often require surgery. This study was performed to evaluate the management of ESD-related perforation in patients with SDETs. Methods: Patients who underwent ESD for SDETs from July 2010 to December 2018 were studied. We collected data on complete closure, insertion of endoscopic nasobiliary and pancreatic duct drainage (ENBPD) tubes, and additional interventions. We also evaluated clinical outcomes, including the fasting period, hospital stay, and maximum serum C-reactive protein level. Results: ESD was completed in 264 patients with SDETs. Perforation was observed in 36 patients, including 4 patients with delayed perforation. Among 32 patients with intraoperative perforation, complete closure was achieved in 13 patients. Compared with patients without complete closure, the fasting period and hospital stay were significantly shorter and the maximum serum C-reactive protein level was significantly lower in patients with complete closure, which were equivalent to those in patients without perforation. In patients without complete closure for mucosal defect, no additional interventions were required when an ENBPD tube was inserted, whereas 2 patients without ENBPD tube insertion underwent additional interventions such as percutaneous drainage and a surgical operation. Conclusions: Perforation associated with ESD for SDETs required complex conservative management with complete closure or insertion of an ENBPD tube.

© 2019 Naganuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. Methods This is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled. Results Among 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9–43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51–1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04–5.45). Conclusion This is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.

Sporadic reports have described cancer cases in which multiple driver mutations (MMs) occur in the same oncogene1,2. However, the overall landscape and relevance of MMs remain elusive. Here we carried out a pan-cancer analysis of 60,954 cancer samples, and identified 14 pan-cancer and 6 cancer-type-specific oncogenes in which MMs occur more frequently than expected: 9% of samples with at least one mutation in these genes harboured MMs. In various oncogenes, MMs are preferentially present in cis and show markedly different mutational patterns compared with single mutations in terms of type (missense mutations versus in-frame indels), position and amino-acid substitution, suggesting a cis-acting effect on mutational selection. MMs show an overrepresentation of functionally weak, infrequent mutations, which confer enhanced oncogenicity in combination. Cells with MMs in the PIK3CA and NOTCH1 genes exhibit stronger dependencies on the mutated genes themselves, enhanced downstream signalling activation and/or greater sensitivity to inhibitory drugs than those with single mutations. Together oncogenic MMs are a relatively common driver event, providing the underlying mechanism for clonal selection of suboptimal mutations that are individually rare but collectively account for a substantial proportion of oncogenic mutations.

Late-onset acute liver failure due to Wilson’s disease (WD-ALF) is rare. A 44-year-old female patient presenting acute hepatic decompensation with extreme coagulopathy was transferred to our hospital for evaluation for liver transplantation (LT). Alveolar hemorrhage and Coombs-negative acute hemolysis occurred during workup. Mechanical ventilation, plasmapheresis, and hemodiafiltration with zinc and chelation were started immediately before placing the patient on the waitlist for deceased donor LT (DDLT), with a tentative diagnosis of WD-ALF using the Leipzig score and quick diagnostic criteria suggested by the Acute Liver Failure Study Group Registry. The peak MELD score was 40, and the revised version of King’s score for WD was 13. Serum free copper levels and the patient’s overall general condition were stabilized with artificial support systems, although triphasic wave on electroencephalogram and liver atrophy were noted. She successfully underwent emergent DDLT approximately 2 weeks after suffering from acute hemolysis and survived. The genetic tests confirmed mutations at 2 loci in the ATP7B gene and, therefore, the diagnosis of WD. This is the first and oldest patient reported in Japan to present late-onset WD-ALF that was successfully treated with emergent DDLT.

Background: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.