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Original Articles
Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn’s disease during biological remission
Naohiro Nakamura, Yusuke Honzawa, Yuka Ito, Yasuki Sano, Naoto Yagi, Sanshiro Kobayashi, Mamiko Aoi, Takashi Tomiyama, Tomomitsu Tahara, Norimasa Fukata, Toshiro Fukui, Makoto Naganuma
Received March 15, 2024  Accepted June 11, 2024  Published online August 19, 2024  
DOI: https://doi.org/10.5217/ir.2024.00042    [Epub ahead of print]
AbstractAbstract PDFPubReaderePub
Background/Aims
Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn’s disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD.
Methods
This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD.
Results
Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=–0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification.
Conclusions
LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.
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IBD
Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis
Ryo Karashima, Shintaro Sagami, Yoko Yamana, Masa Maeda, Aya Hojo, Yusuke Miyatani, Masaru Nakano, Takahisa Matsuda, Toshifumi Hibi, Taku Kobayashi
Intest Res 2024;22(4):473-483.   Published online June 5, 2024
DOI: https://doi.org/10.5217/ir.2023.00135
AbstractAbstract PDFPubReaderePub
Background/Aims
Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated.
Methods
Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed.
Results
A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8.
Conclusions
LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.

Citations

Citations to this article as recorded by  
  • The diagnostic accuracy of plasma and serum calprotectin is inferior to C-reactive protein in patients with suspected Crohn’s disease
    M. H. Rasmussen, J. B. Brodersen, C. L. Brasen, J. S. Madsen, T. Knudsen, J. Kjeldsen, M. D. Jensen
    Scandinavian Journal of Gastroenterology.2025; : 1.     CrossRef
  • Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis
    Yuki Aoyama, Sakiko Hiraoka, Eriko Yasutomi, Toshihiro Inokuchi, Takehiro Tanaka, Kensuke Takei, Shoko Igawa, Keiko Takeuchi, Masahiro Takahara, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Jun Kato, Hiroyuki Okada, Motoyuki Otsuka
    Scientific Reports.2025;[Epub]     CrossRef
  • 2,024 View
  • 202 Download
  • 1 Web of Science
  • 2 Crossref
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Review
Colorectal neoplasia
Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration
Chang Kyo Oh, Young-Seok Cho
Intest Res 2024;22(2):131-151.   Published online February 1, 2024
DOI: https://doi.org/10.5217/ir.2023.00115
AbstractAbstract PDFPubReaderePub
Colorectal cancer (CRC) ranks third in cancer incidence and stands as the second leading cause of cancer-related deaths globally. CRC tumorigenesis results from a cumulative set of genetic and epigenetic alterations, disrupting cancer-regulatory processes like cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Key epigenetic modifications observed in cancers encompass abnormal DNA methylation, atypical histone modifications, and irregularities in noncoding RNAs, such as microRNAs and long noncoding RNAs. The advancement in genomic technologies has positioned these genetic and epigenetic shifts as potential clinical biomarkers for CRC patients. This review concisely covers the fundamental principles of CRC-associated epigenetic changes, and examines in detail their emerging role as biomarkers for early detection, prognosis, and treatment response prediction.

Citations

Citations to this article as recorded by  
  • The role of suppressor of cytokine signaling 3 in inflammatory bowel disease and its associated colorectal cancer
    Pengfei Zhang, Bing Pei, Chengxue Yi, Francis Atim Akanyibah, Fei Mao
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(2): 167578.     CrossRef
  • miR-3065-5p and miR-26a-5p as Clinical Biomarkers in Colorectal Cancer: A Translational Study
    Berenice Carbajal-López, Antonio Daniel Martínez-Gutierrez, Eduardo O. Madrigal-Santillán, Germán Calderillo-Ruiz, José Antonio Morales-González, Jossimar Coronel-Hernández, Joey Lockhart, Oliver Millan-Catalan, Monica G. Mendoza-Rodriguez, Leonardo S. Li
    Cancers.2024; 16(21): 3649.     CrossRef
  • Influence of Lifestyles on Polyp Burden and Cancer Development in Hereditary Colorectal Cancer Syndromes
    Hye Kyung Hyun, Ji Soo Park, Jihye Park, Soo Jung Park, Jae Jun Park, Jae Hee Cheon, Tae Il Kim
    Journal of Gastroenterology and Hepatology.2024;[Epub]     CrossRef
  • 4,539 View
  • 207 Download
  • 3 Web of Science
  • 3 Crossref
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Original Articles
IBD
Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn’s disease activity confirmed by balloon-assisted enteroscopy
Ami Kawamoto, Kento Takenaka, Shuji Hibiya, Yoshio Kitazume, Hiromichi Shimizu, Toshimitsu Fujii, Eiko Saito, Kazuo Ohtsuka, Ryuichi Okamoto
Intest Res 2024;22(1):65-74.   Published online November 9, 2023
DOI: https://doi.org/10.5217/ir.2023.00092
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Background/Aims
Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.
Methods
One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.
Results
Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.
Conclusions
The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.

Citations

Citations to this article as recorded by  
  • Leucine-rich alpha-2 glycoprotein in combination with C-reactive protein for predicting endoscopic activity in Crohn’s disease: a single-centre, cross-sectional study
    Yoshiaki Takada, Hiroki Kiyohara, Yohei Mikami, Masataka Taguri, Ryoya Sakakibara, Yasuhiro Aoki, Kosaku Nanki, Takaaki Kawaguchi, Yusuke Yoshimatsu, Shinya Sugimoto, Tomohisa Sujino, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Motohiko Kato, Yasushi
    Annals of Medicine.2025;[Epub]     CrossRef
  • Which biomarkers best reflect the degree of inflammation in Crohn’s disease?
    Jihye Park
    Intestinal Research.2024; 22(1): 1.     CrossRef
  • Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn’s disease small bowel lesion in capsule endoscopy
    Teppei Omori, Miki Koroku, Shun Murasugi, Ayumi Ito, Maria Yonezawa, Shinichi Nakamura, Katsutoshi Tokushige
    Intestinal Research.2024; 22(4): 464.     CrossRef
  • Selection of anti-cytokine biologics by pretreatment levels of serum leucine-rich alpha-2 glycoprotein in patients with inflammatory bowel disease
    Takahiro Amano, Takeo Yoshihara, Shinichiro Shinzaki, Yuko Sakakibara, Takuya Yamada, Naoto Osugi, Satoshi Hiyama, Yoko Murayama, Koji Nagaike, Hideharu Ogiyama, Toshio Yamaguchi, Yuki Arimoto, Ichizo Kobayashi, Shoichiro Kawai, Satoshi Egawa, Takashi Kiz
    Scientific Reports.2024;[Epub]     CrossRef
  • 3,762 View
  • 305 Download
  • 4 Web of Science
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IBD
Ischemia-modified albumin: a novel blood marker of endoscopic mucosal healing in inflammatory bowel disease
Seung Bum Lee, Hyun-Ki Kim, Sang Hyuk Park, Ji-Hun Lim, Sang Hyoung Park
Intest Res 2024;22(1):75-81.   Published online November 1, 2023
DOI: https://doi.org/10.5217/ir.2023.00065
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Background/Aims
The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity.
Methods
A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn’s disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings.
Results
Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed.
Conclusions
IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.

Citations

Citations to this article as recorded by  
  • A novel serum biomarker of endoscopic mucosal healing in inflammatory bowel disease
    Hyoun Woo Kang
    Intestinal Research.2024; 22(1): 3.     CrossRef
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  • 247 Download
  • 1 Crossref
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Microbiota
Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease
Seung Yong Shin, Young Kim, Won-Seok Kim, Jung Min Moon, Kang-Moon Lee, Sung-Ae Jung, Hyesook Park, Eun Young Huh, Byung Chang Kim, Soo Chan Lee, Chang Hwan Choi, on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases
Intest Res 2023;21(1):148-160.   Published online June 14, 2022
DOI: https://doi.org/10.5217/ir.2021.00168
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Background/Aims
The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD.
Methods
Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline.
Results
The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD.
Conclusions
The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

Citations

Citations to this article as recorded by  
  • Gut bacteriome in inflammatory bowel disease: An update on recent advances
    Aditya Bajaj, Manasvini Markandey, Saurabh Kedia, Vineet Ahuja
    Indian Journal of Gastroenterology.2024; 43(1): 103.     CrossRef
  • An Update on the Role and Potential Molecules in Relation to Ruminococcus gnavus in Inflammatory Bowel Disease, Obesity and Diabetes Mellitus
    Jinni Hong, Tingting Fu, Weizhen Liu, Yu Du, Junmin Bu, Guojian Wei, Miao Yu, Yanshan Lin, Cunyun Min, Datao Lin
    Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 1235.     CrossRef
  • Research advancements and perspectives of inflammatory bowel disease: A comprehensive review
    Junyi Bai, Ying Wang, Fuhao Li, Yueyao Wu, Jun Chen, Meng Li, Xi Wang, Bin Lv
    Science Progress.2024;[Epub]     CrossRef
  • Integrated Analysis of Microbiome and Metabolome Reveals Disease-Specific Profiles in Inflammatory Bowel Diseases and Intestinal Behçet’s Disease
    Yehyun Park, Jae Bum Ahn, Da Hye Kim, I Seul Park, Mijeong Son, Ji Hyung Kim, Hyun Woo Ma, Seung Won Kim, Jae Hee Cheon
    International Journal of Molecular Sciences.2024; 25(12): 6697.     CrossRef
  • Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets
    Han Na Oh, Seung Yong Shin, Jong-Hwa Kim, Jihye Baek, Hyo Jong Kim, Kang-Moon Lee, Soo Jung Park, Seok-Young Kim, Hyung-Kyoon Choi, Wonyong Kim, Woo Jun Sul, Chang Hwan Choi
    Gut Pathogens.2024;[Epub]     CrossRef
  • Potential of Gut Microbe-Derived Extracellular Vesicles to Differentiate Inflammatory Bowel Disease Patients from Healthy Controls
    Min Heo, Young Soo Park, Hyuk Yoon, Nam-Eun Kim, Kangjin Kim, Cheol Min Shin, Nayoung Kim, Dong Ho Lee
    Gut and Liver.2023; 17(1): 108.     CrossRef
  • Ruminococcus gnavus: friend or foe for human health
    Emmanuelle H Crost, Erika Coletto, Andrew Bell, Nathalie Juge
    FEMS Microbiology Reviews.2023;[Epub]     CrossRef
  • The Relationship Between Rosacea and Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
    Yu Kyung Jun, Da-Ae Yu, Yoo Min Han, Soo Ran Lee, Seong-Joon Koh, Hyunsun Park
    Dermatology and Therapy.2023; 13(7): 1465.     CrossRef
  • Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea
    Oh Chan Kwon, See Young Lee, Jaeyoung Chun, Kyungdo Han, Yuna Kim, Ryul Kim, Min-Chan Park, Jie-Hyun Kim, Young Hoon Youn, Hyojin Park
    Frontiers in Medicine.2023;[Epub]     CrossRef
  • Comments on Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
    Kwang Woo Kim
    Gut and Liver.2023; 17(6): 954.     CrossRef
  • Evaluation of Bacterial and Fungal Biomarkers for Differentiation and Prognosis of Patients with Inflammatory Bowel Disease
    Hyuk Yoon, Sunghyouk Park, Yu Kyung Jun, Yonghoon Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee
    Microorganisms.2023; 11(12): 2882.     CrossRef
  • A Machine Learning-Based Diagnostic Model for Crohn’s Disease and Ulcerative Colitis Utilizing Fecal Microbiome Analysis
    Hyeonwoo Kim, Ji Eun Na, Sangsoo Kim, Tae-Oh Kim, Soo-Kyung Park, Chil-Woo Lee, Kyeong Ok Kim, Geom-Seog Seo, Min Suk Kim, Jae Myung Cha, Ja Seol Koo, Dong-Il Park
    Microorganisms.2023; 12(1): 36.     CrossRef
  • 5,220 View
  • 480 Download
  • 12 Web of Science
  • 12 Crossref
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