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대한소화기학회> Gut and Liver> Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease

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Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease

Eunha Chang , Jae Seung Chang , In Deok Kong , Soon Koo Baik , Moon Young Kim , Kyu-sang Park
  • : 대한소화기학회
  • : Gut and Liver 16권2호
  • : 연속간행물
  • : 2022년 03월
  • : 171-189(19pages)
Gut and Liver

DOI


목차

INTRODUCTION
CURRENT DIAGNOSTIC APPROACHES
FAT BIOMARKERS
MITOCHONDRIAL STRESS BIOMARKERS
INFLAMMATION BIOMARKER
PERSPECTIVES ON DIAGNOSTIC STRATEGIES FOR NAFLD
CONFLICTS OF INTEREST
ACKNOWLEDGEMENTS
ORCID
REFERENCES

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Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/ prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD. (Gut Liver 2022;16:171-189)

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간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • :
  • : 격월
  • : 1976-2283
  • : 2005-1212
  • : 학술지
  • : 연속간행물
  • : 2007-2022
  • : 1486


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6Management of Helicobacter pylori Infection: A Comparison between Korea and the United States

저자 : Sung Eun Kim , Joo Ha Hwang

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 4호 발행 연도 : 2022 페이지 : pp. 503-514 (12 pages)

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Helicobacter pylori has been well known to cause gastritis, peptic ulcers, mucosa-associated lymphoid tissue, and gastric cancer. The importance of H. pylori eradication has been emphasized; however, the management of H. pylori infection is difficult in clinical practice. In both Eastern and Western countries, there has been a constant interest in confirming individuals who should be tested and treated for H. pylori infection and developing methods to diagnose H. pylori infection. Many studies have been implemented to successfully eradicate H. pylori, and various combinations of eradication regimens for H. pylori infection have been suggested worldwide. Based on the findings of previous studies, a few countries have published their own guidelines that are appropriate for their country; however, these country-specific guidelines may differ depending on the circumstances in each country. Evidence-based guidelines and clinical practice updates for the treatment of H. pylori infection have been published in Korea and the United States in 2021. This review will summarize the similarities and differences in the management of H. pylori infection in Korea and the United States, focusing on indications, diagnosis, and treatments based on recent guidelines and recommendations in both countries. (Gut Liver 2022;16:503-514)

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7Therapeutic Drug Monitoring of Biologics for Patients with Inflammatory Bowel Diseases: How, When, and for Whom?

저자 : Jia-feng Wu

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During the past decade, we have entered an era of biologics for the treatment of Crohn's disease and ulcerative colitis. The therapeutic goal of inflammatory bowel disease (IBD) management has evolved from symptom control and clinical remission to mucosal healing or even deep remission. Histological remission for ulcerative colitis and transmural healing of Crohn's disease are potential future goals. With the adoption of the treat-to-target concept, and given the need for tight control of IBD activity, therapeutic drug monitoring (TDM) is an important element of precision medicine. TDM involves the measurement of serum biologics and anti-drug antibodies levels, to confirm whether the right drug with the right dosage was prescribed to reach the right serum levels. TDM may help clinicians adjust biologics based on objective biomarkers instead of using empirical dosage escalation or making symptom-based therapeutic adjustments. Wellestablished reactive TDM algorithms have been proposed, and emerging evidence supports the clinical application of a proactive TDM strategy to enhance the duration of effective biologics and improve clinical outcomes. Recently, the proactive TDM strategy was shown to avoid the secondary loss of response to biologics, and improve long-term clinical outcomes in IBD patients. This review summarizes data from trials, and practice guidelines, on the clinical application of proactive and reactive TDM strategies for the daily care of biologic-treated IBD patients. (Gut Liver 2022;16:515-524)

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8Endoscopic Reintervention for Recurrence of Malignant Biliary Obstruction: Developing the Best Strategy

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발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 4호 발행 연도 : 2022 페이지 : pp. 525-534 (10 pages)

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Drainage therapy for malignant biliary obstruction (MBO) includes trans-papillary endoscopic retrograde biliary drainage (ERBD), percutaneous transhepatic biliary drainage (PTBD), and transgastrointestinal endoscopic ultrasound-guided biliary drainage (EUS-BD). With the development of chemotherapy, many MBO cases end up needing endoscopic reintervention (E-RI) for recurrent biliary obstruction. To achieve a successful E-RI, it is necessary to understand the various findings regarding E-RI in MBO cases reported to date. Therefore, in this review, we focus on E-RI for ERBD of distal MBO, ERBD of hilar MBO, and EUS-BD. To plan an appropriate E-RI strategy for biliary stent occlusion for MBO, the following must be considered on a case-by-case basis: the urgency of the drainage, the cause of the occlusion, the original route of drainage (PTBD/ERBD/EUS-BD), the initial stent used (plastic stent or self-expandable metallic stent), and in the case of self-expandable metallic stents, the type used (fully covered or uncovered). Regardless of the original method of stent placement, if the inflammation caused by obstructive cholangitis is severe and/or the patient is in shock, PTBD should be considered as the first choice. Finally, it is important to keep in mind that in many cases, performing E-RI will be difficult. (Gut Liver 2022;16:525-534)

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9Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial

저자 : Yoon Jin Choi , Yong Chan Lee , Jung Mogg Kim , Jin Il Kim , Jeong Seop Moon , Yun Jeong Lim , Gwang Ho Baik , Byoung Kwan Son , Hang Lak Lee , Kyoung Oh Kim , Nayoung Kim , Kwang Hyun Ko , Hye-kyung Jung

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 4호 발행 연도 : 2022 페이지 : pp. 535-546 (12 pages)

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Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.
Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.
Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.
Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223). (Gut Liver 2022;16:535-546)

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10Long-term Outcomes of Additional Endoscopic Treatments for Patients with Positive Lateral Margins after Endoscopic Submucosal Dissection for Early Gastric Cancer

저자 : Tae-se Kim , Byung-hoon Min , Yang Won Min , Hyuk Lee , Poong-lyul Rhee , Jae J. Kim , Jun Haeng Lee

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 4호 발행 연도 : 2022 페이지 : pp. 547-554 (8 pages)

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Background/Aims: It is uncertain whether additional endoscopic treatment may be chosen over surgery in patients with positive lateral margins (pLMs) as the only non-curative factor after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to compare the long-term outcomes of additional endoscopic treatments in such patients with those of surgery and elucidate the clinicopathological factors that could influence the treatment selection.
Methods: A total of 99 patients with 101 EGC lesions undergoing additional treatment after noncurative ESD with pLMs as the only non-curative factor were analyzed. Among them, 25 (27 lesions) underwent ESD, 29 (29 lesions) underwent argon plasma coagulation (APC), and 45 (45 lesions) underwent surgery. Clinicopathological characteristics and long-term outcomes were compared.
Results: Residual tumor was found in 73.6% of cases. The presence of multiple pLMs was associated with higher risk of residual tumor (p=0.046). During a median follow-up of 58.9 months, recurrent or residual lesions after additional ESD and APC were found in 4% (1/25) and 6.8% (2/29) of patients, respectively. However, all were completely cured with surgery or repeated ESD. There were no extragastric recurrences after additional endoscopic treatment. Lymph node metastasis was identified after additional surgery in one (2.2%) patient with an EGC showing histological heterogeneity.
Conclusions: Given the favorable long-term outcomes, additional ESD or APC may be an acceptable choice for patients with pLMs as the only non-curative factor after ESD for EGC. However, clincopathological characteristics such as multiple pLMs and histological heterogeneity should be considered in the treatment selection. (Gut Liver 2022;16:547-554)

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4Chemopreventive Effect of Metformin on Gastric Cancer Development

저자 : Ka Shing Cheung , Kit Lam Chung , Wai K. Leung

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 147-156 (10 pages)

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Although Helicobacter pylori infection is the most important causative factor for gastric cancer (GC), H. pylori eradication alone does not completely eliminate the GC risk. In addition to H. pylori eradication, other risk factors for GC should be identified and targeted. Diabetes mellitus (DM) confers a 20% increased risk of GC, which could be mediated via several biological mechanisms including the stimulation of cell proliferation via hyperinsulinemia and increased insulin-growth factor production, the promotion of angiogenesis, and DNA damage. With a current global prevalence of 9.3% and a predicted rise to 10.2% by 2030, DM could contribute substantially to the burden of GC cases worldwide. Emerging evidence showed that metformin possesses chemopreventive effects via both direct (e.g., adenosine monophosphate-activated protein kinase activation and subsequent inhibition of the mammalian target of rapamycin pathway) and indirect (e.g., modulation of the interaction between tumor cells and their microenvironment and gut microbiota) pathways. A recent meta-analysis of observational studies showed that metformin use was associated with 24% lower GC risk. However, many available observational studies related to metformin effects suffered from biases including the failure to adjust for the H. pylori infection status and serial glycemic control and time-related biases. Future prospective studies addressing these pitfalls are needed. (Gut Liver 2022;16:147-156)

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5Long-term Disease Course of Crohn's Disease: Changes in Disease Location, Phenotype, Activities, and Predictive Factors

저자 : Choong Wui Cho , Myung-won You , Chi Hyuk Oh , Chang Kyun Lee , Sung Kyoung Moon

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 157-170 (14 pages)

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Crohn's disease (CD) is a chronic destructive inflammatory bowel disease that affects young people and is associated with significant morbidity. The clinical spectrum and disease course of CD are heterogeneous and often difficult to predict based on the initial presentation. In this article, changes in the disease location, behavior, clinical course during long-term follow-up, and predictive factors are reviewed. Generally, four different patterns of clinical course are discussed: remission, stable disease, chronic relapsing disease, and chronic refractory disease. Understanding the long-term disease course of CD is mandatory to reveal the underlying pathophysiology of the disease and to move toward a more optimistic disease course, such as remission or stability, and less adverse outcomes or devastating sequelae. (Gut Liver 2022;16:157-170)

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6Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease

저자 : Eunha Chang , Jae Seung Chang , In Deok Kong , Soon Koo Baik , Moon Young Kim , Kyu-sang Park

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 171-189 (19 pages)

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Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/ prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD. (Gut Liver 2022;16:171-189)

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7Optimal Management of Gastric Outlet Obstruction in Unresectable Malignancies

저자 : Stephanie Lok Hang Cheung , Anthony Yuen Bun Teoh

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 190-197 (8 pages)

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The aim of this article is to review the different treatment options for malignant gastric outlet obstruction (GOO) and compare their safety and efficacy. We describe the history and evolution of gastrojejunostomy (GJ), endoscopic stenting and endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) and analyze the current evidence regarding these three methods available in the literature, comparing their applicability, safety, complications and cost when used for the treatment of malignant GOO. We conclude that given the benefits of endoscopic techniques and the ability to place a stent away from the tumor, EUS-GE is a promising technique that may yield an efficacy similar to that of surgical GJ and duodenal stenting, with lower reintervention rates and fewer adverse events. (Gut Liver 2022;16:190-197)

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8Effect of Antithrombotic Therapy on Bleeding after Argon Plasma Coagulation for Gastric Neoplasms

저자 : Seol So , Jin Hee Noh , Ji Yong Ahn , Hee Kyong Na , Kee Wook Jung , Jeong Hoon Lee , Do Hoon Kim , Kee Don Choi , Ho June Song , Gin Hyug Lee , Hwoon-yong Jung

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 198-206 (9 pages)

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Background/Aims: Postprocedural bleeding is known to be relatively low after argon plasma coagulation (APC) for gastric neoplasms; however, there are few studies proving the effect of antithrombotic agents. This study aimed to analyze the incidence of delayed bleeding (DB) based on antithrombotic agents administered and to identify the risk factors for DB in APC for gastric tumors.
Methods: A total of 785 patients with 824 lesions underwent APC for single gastric neoplasm between January 2011 and January 2018. After exclusion, 719 and 102 lesions were classified as belonging to the non-antithrombotics (non-AT) and AT groups, respectively. The clinical outcomes were compared between the two groups, and we determined the risk factors for DB in gastric APC.
Results: Of the total 821 cases, DB occurred in 20 cases (2.4%): 17 cases in the non-AT group and three cases in the AT group (2.4% vs 2.9%, p=0.728). Multivariate analysis of the risk factors for DB confirmed the following significant, independent risk factors: male sex (odds ratio, 7.66; 95% confidence interval, 1.02 to 57.69; p=0.048) and chronic kidney disease (odds ratio, 4.51; 95% confidence interval, 1.57 to 13.02; p=0.005). Thromboembolic events and perforation were not observed in all patients regardless of whether they took AT agents.
Conclusions: AT therapy is acceptably safe in gastric APC because it does not significantly increase the incidence of DB. However, patients with chronic kidney disease or male sex need to receive careful follow-up on the incidence of post-APC bleeding. (Gut Liver 2022;16:198-206)

KCI등재

9Primary Gastrointestinal Follicular Lymphomas: A Prospective Study of 31 Patients with Long-term Follow-up Registered in the French Gastrointestinal Lymphoma Study Group (GELD) of the French Federation of Digestive Oncology (FFCD)

저자 : Tamara Matysiak-budnik , Philippe Jamet , Nicolas Chapelle , Bettina Fabiani , Paul Coppo , Agnès Ruskoné-fourmestraux

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 207-215 (9 pages)

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Background/Aims: Primary gastrointestinal follicular lymphomas (PGFL) are very rare. Our aim was to analyze the clinical features, management, and long-term outcomes in a prospective series of patients diagnosed with PGFL.
Methods: All adult patients with PGFL, consecutively enrolled into the multicenter French study between 1990 and 2017, were evaluated and followed up prospectively after undergoing a complete work-up. Clinical, pathological and endoscopic features, as well as treatment outcomes, were analyzed.
Results: Thirty-one patients (16 men, median age 62 years, range 33 to 79 years) with PGFL were included. The median follow-up was 92 months (range, 6 to 218 months). In the majority of patients (n=14), lymphoma was incidentally diagnosed during endoscopy. Otherwise, the most frequent circumstances of diagnosis were abdominal pain (n=7) and dyspepsia (n=5). The duodenum was the most common site of involvement (n=19) and multifocal localizations were seen in seven patients (22%). The most frequent first line strategy was surveillance applied in 22 patients (71%), of whom nine reached spontaneous, complete remission and 11 had stable disease. Seven patients (23%) received chemotherapy as first line treatment, and two underwent resection. Of seven patients who received chemotherapy, four achieved complete remission. In three patients, transformation into a high-grade lymphoma occurred.
Conclusions: The diagnosis of PGFL is frequently fortuitous. The most common localization is in the duodenum. The disease has an indolent course and a good prognosis, however, rare cases of transformation into aggressive high-grade lymphoma may occur. An appropriate characterization and follow-up of these lymphomas is mandatory for their optimal management. (Gut Liver 2022;16:207-215)

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10Changes in the Long-term Prognosis of Crohn's Disease between 1986 and 2015: The Population-Based Songpa-Kangdong Inflammatory Bowel Disease Cohort Study

저자 : Byong Duk Ye , Sung Noh Hong , Seung In Seo , Ye-jee Kim , Jae Myung Cha , Kyoung Hoon Rhee , Hyuk Yoon , Young-ho Kim , Kyung Ho Kim , Sun Yong Park , Seung Kyu Jeong , Ji Hyun Lee , Hyunju Park , Joo

발행기관 : 대한소화기학회 간행물 : Gut and Liver 16권 2호 발행 연도 : 2022 페이지 : pp. 216-227 (12 pages)

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Background/Aims: The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the long-term prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. (Gut Liver 2022;16:216-227)

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