Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria

AIM:To investigate the relationship between Helicobacter pylori(H.pylori) seropositivity and the presence of microalbuminuria.METHODS:Between December 2003 and February 2010,asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H.pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio(UACR) were included.All study subjects completed a structured questionnaire,anthropometric measurements and laboratory tests.Anti-H.pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit.A random single-void urine sample,collected using a clean-catch technique,was obtained to determine the UACR.The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg.The presence of diabetes mellitus(DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication.Multiple logistic regression analysis was performed to identify the risk factors.The dependent variable was microalbuminuria,and the independent variables were the other study variables.RESULTS:A total of 2716 subjects(male,71.8%;mean age,54.9 years) were included.Among them,224 subjects(8.2%) had microalbuminuria and 324 subjects(11.9%) had been diagnosed with DM.Subjects with microalbuminuria had a significantly higher H.pylori seropositivity rate than subjects without microalbuminuria(60.7% vs 52.8%,P = 0.024).Multivariate analysis after adjustment for age,body mass index(BMI),waist circumference,and glucose and triglyceride levels showed that H.pylori seropositivity was significantly associated with microalbuminuria [odds ratio(OR),1.40,95% CI,1.05-1.89,P = 0.024].After the data were stratified into cohorts by glucose levels(≤ 100 mg/dL,100 mg/dL < glucose < 126 mg/dL,and ≥ 126 mg/dL or history of DM),H.pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age,BMI and serum creatinine level(OR,2.21,95% CI,1.20-4.08,P = 0.011).In addition,the subjects were divided into five groups.Those without microalbuminuria(an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values,and subjects with microalbuminuria comprised their own group.Notably,H.pylori seropositivity gradually increased with an increase in UACR(P = 0.001) and was highest in subjects with microalbuminuria(OR,2.41,95% CI,1.14-5.11).This suggests that H.pylori seropositivity is positively associated with microalbuminuria in diabetic subjects.CONCLUSION:H.pylori seropositivity was independently associated with microalbuminuria,and the prevalence of H.pylori seropositivity was associated with the severity of UACR in diabetic subjects.

Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population

AIM: To investigate the relationship between gallstone disease and nonalcoholic fatty liver disease(NAFLD) in a large Asian population. METHODS: A cross-sectional study including 17612 subjects recruited from general health check-ups at the Seoul National University Hospital, Healthcare System Gangnam Center between January 2010 and December 2010 was conducted. NAFLD and gallstone disease were diagnosed based on typical ultrasonographic findings. Subjects who were positive for hepatitis B or C, or who had a history of heavy alcohol consumption(> 30 g/d for men and > 20 g/d for women) or another type of hepatitis were excluded. Gallstone disease was defined as either the presence of gallstones or previous cholecystectomy, and these two entities(gallstones and cholecystectomy) were analyzed separately. Clinical parameters including body mass index, waist circumference, hypertension, diabetes, smoking status, and regular physical activity were reviewed. Laboratory parameters, including serum levels of gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, total cholesterol, triglycerides, and high-density lipoprotein, were also reviewed.RESULTS: The mean age of the subjects was 48.5± 11.3 years, and 49.3% were male. Approximately 30.3% and 6.1% of the subjects had NAFLD and gallstone disease, respectively. The prevalence of gallstone disease(8.3% vs 5.1%, P < 0.001), including both the presence of gallstones(5.5% vs 3.4%, P < 0.001) and a history of cholecystectomy(2.8% vs 1.7%, P < 0.001), was significantly increased in the NAFLD group. In the same manner, the prevalence of NAFLD increased with the presence of gallstone disease(41.3% vs 29.6%, P < 0.001). Multivariate regression analysis showed that cholecystectomy was associated with NAFLD(OR = 1.35, 95%CI: 1.03-1.77, P = 0.028). However, gallstones were not associated with NAFLD(OR = 1.15, 95%CI: 0.95-1.39, P = 0.153). The independent association between cholecystectomy and NAFLD was still significant after additional adjustment for insulin resistance(OR = 1.45, 95%CI: 1.01-2.08, P = 0.045). CONCLUSION: This study shows that cholecystectomy, but not gallstones, is independently associated with NAFLD after adjustment for metabolic risk factors. These data suggest that cholecystectomy may be an independent risk factor for NAFLD.

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P < 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.

Clinicopathologic and molecular features associated with patient age in gastric cancer

AIM: To compare characteristics and prognosis of gastric cancer based on age.METHODS: A retrospective study was conducted on clinical and molecular data from patients(n =1658) with confirmed cases of gastric cancer in Seoul National University Bundang Hospital(Seoul, South Korea) from 2003 to 2010 after exclusion of patients diagnosed with lymphoma, gastrointestinal stromal tumor, and metastatic cancer in the stomach. DNA was isolated from tumor and adjacent normal tissue,and a set of five markers was amplified by polymerase chain reaction to assess microsatellite instability(MSI). MSI was categorized as high, low, or stable if ≥ 2, 1, or 0 markers, respectively, had changed.Immunohistochemistry was performed on tissue sections to detect levels of expression of p53, human epidermal growth factor receptor(HER)-2, and epidermal growth factor receptor. Statistical analysis of clinical and molecular data was performed to assess prognosis based on the stratification of patients by age(≤ 45 and> 45 years).RESULTS: Among the 1658 gastric cancer patients, the number of patients with an age ≤ 45 years was 202(12.2%; 38.9 ± 0.4 years) and the number of patients> 45 years was 1456(87.8%; 64.1 ± 0.3 years).Analyses revealed that females were predominant inthe younger group(P < 0.001). Gastric cancers in the younger patients exhibited more aggressive features and were at a more advanced stage than those in older patients. Precancerous lesions, such as atrophic gastritis and intestinal metaplasia, were observed less frequently in the older than in the younger group(P < 0.001). Molecular characteristics, including overexpression of p53(P < 0.001), overexpression of HER-2(P = 0.006), and MSI(P = 0.006), were less frequent in gastric cancer of younger patients. Cancer related mortality was higher in younger patients(P= 0.048), but this difference was not significant after adjusting for the stage of cancer.CONCLUSION: Gastric cancer is distinguishable between younger and older patients based on both clinicopathologic and molecular features, but stage is the most important predictor of prognosis.

Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: A nationwide, population-based study

BACKGROUND There is a growing evidence regarding an increased risk of inflammatory bowel disease(IBD)among patients with airway diseases.AIM To investigate the influence of chronic obstructive pulmonary disease(COPD)on the risk of IBD.METHODS A nationwide,population-based study was conducted using data from the National Health Insurance Service database.A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified.The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria.The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models.The cumulative incidences of IBD were compared between the groups.RESULTS The COPD group had higher incidences of IBD compared to non-COPD controls(incidence rate,9.98 vs 7.18 per 100000 person-years,P<0.001).The risk of IBD in the COPD group was increased by 1.38(adjusted hazard ratio(HR);95%CI:1.25-1.52).The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group(12.39 vs 9.77 per 100000 person-year,P<0.001).The severity of COPD was associated with an increased risk of IBD(adjusted HR 1.70 in severe COPD,95%CI:1.27-2.21 and adjusted HR 1.35 in mild COPD,95%CI:1.22-1.49)CONCLUSION The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.

How to improve patient satisfaction during midazolam sedation for gastrointestinal endoscopy?

To determine the procedure-related factors that affect sedation satisfaction and to make a suggestion to improve it.METHODSWe prospectively enrolled a total of 456 patients who underwent outpatient endoscopy procedures with midazolam sedation between March 2014 and August 2014. All patients completed both pre- and post-endoscopy questionnaires about sedation expectations and satisfaction.RESULTSThe study cohort included 167 (36.6%) patients who underwent esophagogastroduodenoscopy (EGD), 167 (36.6%) who underwent colonoscopy, and 122 (26.8%) who underwent a combined procedure (EGD and colonoscopy). Over 80% of all patients were satisfied with sedation using midazolam. In univariate and multivariate analyses, total procedure time in the EGD group, younger age (≤ 50 years), and longer colonoscopy withdrawal time in the colonoscopy group were related to decreased satisfaction with sedation. However, in active monitoring and intervention group, there was no decrease in grade of satisfaction despite longer procedure time due to more procedures during colonoscopy. Younger age (≤ 50 years), longer inter-procedure time gap, and colonoscopy withdrawal time were related to decreased satisfaction in the combined EGD and colonoscopy group.CONCLUSIONMidazolam is still a safe and effective sedative for gastrointestinal endoscopy. Satisfaction with sedation depends on several factors including age (≤ 50 years) and procedure time duration. To improve patient satisfaction with sedation, active monitoring of sedation status by the endoscopist should be considered for patients who require long procedure time.

Association of visceral obesity and early colorectal neoplasia

AIM:To examine whether visceral adipose tissue(VAT)serves as a risk factor for colorectal adenoma-early colorectal cancer(CRC)sequence.METHODS:A retrospective case-control study was conducted with 153 patients with stageⅠCRC,age/sex-matched 554 patients with colorectal adenoma and557 normal controls.All subjects underwent various laboratory tests,abdominal fat computed tomography(CT),and colonoscopy.VAT was defined as an intraabdominal adipose tissue area measured by CT scan.Adipose tissue area was measured at the level of the umbilicus from CT scan.We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.RESULTS:The body mass index(BMI),total cholesterol,fasting glucose and VAT areas were significantly different among normal,adenoma and CRC groups.The VAT area was 120.6±49.0 cm2in normal controls,130.6±58.4 cm2in adenoma group and 117.6±51.6cm2in CRC group(P=0.002).In univariate analysis,increased BMI was a risk factor for CRC compared to control(P=0.025).However,VAT area was not a risk factor for CRC compared to control.In multivariate analysis that adjusted for smoking,alcohol consumption and subcutaneous adipose tissue area,VAT area was inversely related to CRC,compared to the adenoma(OR=0.53,95%CI:0.31-0.92,highest quartile vs lowest quartile).CONCLUSION:Our study shows that visceral obesity is not a risk factor for early CRC.Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.

Complications after ileal pouch-anal anastomosis in Korean patients with ulcerative colitis

AIM: To investigate the outcomes of treatments for complications after ileal pouch-anal anastomosis (IPAA) in Korean patients with ulcerative colitis.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.

Repeatedly elevatedγ-glutamyltransferase levels are associated with an increased incidence of digestive cancers:A population-based cohort study

BACKGROUND The association between elevatedγ-glutamyltransferase(GGT)at a certain point and incident cancer has been suggested;however,no study has evaluated the association between repeatedly elevated GGT and cancer incidence.AIM To investigate the effects of repeatedly elevated GGT on the incidence of digestive cancers.METHODS Participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations were enrolled.GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements(0-4 points).Multivariable Cox proportional hazard regression models were applied.RESULTS In total,3559109 participants were included;among them,43574 digestive cancers developed during a median of 6.8 years of follow-up.The incidence of total digestive cancers increased in a dose-response manner in men[adjusted hazard ratio(aHR)compared with those with 0 GGT points=1.28 and 95%confidence interval(CI)=1.24-1.33 in those with 1 point;aHR=1.40 and 95%CI=1.35-1.46 in those with 2 points;aHR=1.52 and 95%CI=1.46-1.58 in those with 3 points;aHR=1.88 and 95%CI=1.83-1.94 in those with 4 points;P for trend<0.001].This trend was more prominent in men than in women and those with healthy habits(no smoking,no alcohol consumption,and a low body mass index)than in those with unhealthy habits.CONCLUSION Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner,particularly in men and those with healthy habits.Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.

Is a split-dose regimen of 2 L polyethylene glycol plus ascorbic acid tolerable for colonoscopy in an early morning visit to a comprehensive medical check-up?

To evaluate the effectiveness and tolerability of a split-dose 2 L polyethylene glycol (PEG)/ascorbic acid (AA) regimen for healthy examinees who visited for comprehensive medical check-up in the early morning.METHODSFrom February 2015 to March 2015, examinees of average risk who were scheduled for a colonoscopy in the morning were retrospectively enrolled.RESULTSThe 189 examinees were divided into split-dose and non-split-dose groups. The adequacy of bowel preparation for the split-dose group vs the non-split-dose group was 96.8% vs 85.2%, respectively, P < 0.001, and the compliance of the last meal restriction was 74.6% vs 58.2%, respectively, P < 0.001. The sleep disturbance (P < 0.001) was more prevalent in the split-dose group, however the willingness to repeat the same preparation method (P = 0.243) was not different in both groups. The split-dose regimen was the most important factor influencing adequate bowel preparation in multivariate analysis (HR = 10.89, 95%CI: 6.53-18.17, P < 0.001).CONCLUSIONA split-dose regimen of 2 L PEG/AA for an early morning colonoscopy was more effective and showed better compliance for diet restriction without any difference in satisfaction and discomfort. Introducing a split-dose regimen of 2 L PEG/AA to morning colonoscopy examinees is effective and tolerable in a comprehensive medical check-up setting.

Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy

BACKGROUND Midazolam is commonly used for sedation during gastrointestinal procedures.However,some patients experience paradoxical reactions characterized by excessive movement or excitement.AIM To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper endoscopy.METHODS We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital,Healthcare System Gangnam Center,from July 2013 to December 2018.Among them,361 patients with a history of paradoxical reaction during sedative upper endoscopy were enrolled.The characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic regression.RESULTS Paradoxical reactions occurred in 0.86%(1054/122152)of endoscopies,and in 1.51%(888/58553)of patients.Among the 361 subjects with previous paradoxical reactions in sedative endoscopies,111(30.7%)experienced further paradoxical reactions.Univariable analysis revealed that the total midazolam dose used was higher in the recurrent group(6.74±2.58 mg)than in the non-recurrent group(5.49±2.04 mg;P<0.0001).Patients were administered a lower dose of midazolam than previous doses:1 mg less in the recurrent group and 2 mg less in the non-recurrent group.Multivariable analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction(odds ratio:1.213,95%CI:1.099-1.338,P=0.0001).CONCLUSION The rate of recurrence of paradoxical reactions is significantly associated with midazolam dosage.The dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.

Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease.

DNA Microarray Analysis of Gene Expression in Eutopic Endometrium from Patients with Endometriosis

Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients with and without endometriosis. Five patients with proven advanced-stage endometriosis and 5 controls underwent endometrial biopsy in the late secretory phase. Analysis of eutopic endometrial gene expression was performed using Affymetrix gene arrays and differentially expressed genes were assigned to gene ontology groups based on overrepresented analysis using Database for Annotation, Visualization, and Integrated Discovery software. Four hundred sixty two genes were identified as up-regulated such as matrix metalloproteinase 10, cytochrome P450 family 24 subfamily A polypeptide 1, matrix metalloproteinase 3, chemokine (C-C motif) ligand 20, Rho family GTPase 1, interleukin 1-beta, and insulin-like growth factor binding protein 1. Six hundred forty three genes were down-regulated in all endometriotic samples. A lot of genes related with metabolic process, cellular ketone metabolic process and ncRNA metabolic processing were included. Expression patterns of selected five genes were validated by quantitative real time PCR. The results of this analysis support that the eutopic endometrium from patients with advanced-stage endometriosis has distinct gene expression profile from eutopic endometrium of control without endometriosis.

Gender-and Age-Group Specific Association of Persistent Organic Pollutants(POPs)Exposure with Diabetes Mellitus:Korean National Environmental Health Survey(KoNEHS)2015−2017

Exposure to persistent organic pollutants(POPs)has been reported as a potential risk factor for diabetes in adults.However,effect modifications by sex and age,especially among Asian populations,have seldom been investigated.In the present study,we assessed associations of major POPs exposure including organochlorine pesticides(OCPs),polychlorinated biphenyls(PCBs),and polybrominated diphenyl ethers(PBDEs),with diabetes in Korean adults(n=1,295),a subset of the Korean National Environmental Health Survey(KoNEHS)Cycle 3(2015−2017).In the adult population,serum levels of dichlorodiphenyltrichloroethanes(DDTs)and PCB167 showed an increased odds ratio(OR)for diabetes.When stratified by gender,associations became stronger and more consistent in women:In women,serum levels of OCPs including p,p′-DDT,p,p′-dichlorodiphenyldichloroethylene(p,p′-DDE),andΣOCPs and mono-ortho PCBs,such as PCB118 and PCB157,were significantly associated with diabetes.In the male participants,however,no significant positive associations were detected.When stratified by a cutoff age of 50 years,most studied POPs except PBDEs,i.e.,p,p′-DDT,p,p′-DDE,PCB118,PCB157,PCB167,PCB138,and PCB153,showed significant associations with diabetes,in the older adults.In the younger group,however,no measured POPs showed a significant positive association.Effects of endogenous sex hormones or interaction of POPs on aryl hydrocarbon receptors may partly explain the observed differences by gender and age,although further experimental confirmations should follow.Our findings show that POPs exposure at the current levels is associated with diabetes among general Korean adults,and such associations could be modified by gender and age.

Predicted pro-inflammatory hs-CRP score and non-alcoholic fatty liver disease

Background:Non-alcoholic fatty liver disease(NAFLD)is a major contributor to liver diseases globally,yet there are limited studies investigating the impact of diet and lifestyle factors on its development.This study aimed to examine the association between the prevalence of NAFLD and predicted pro-inflammatory high-sensitivity C-reactive protein(hs-CRP)score.Methods:We included 1,076 Korean adults who underwent a medical examination at the Seoul National University Hospital Gangnam Healthcare Center in Korea between May and December 2011 and updated in 2021.The predicted pro-inflammatory hs-CRP score was derived from pro-inflammatory demographic,lifestyle,dietary,and anthropometric factors,and NAFLD was diagnosed using liver ultrasound.Multivariable-adjusted odds ratios(ORs)and 95%confidence intervals(CIs)of NAFLD odds according to predicted pro-inflammatory hs-CRP score were estimated using logistic regression at a two-sided P<0.05.Results:Among the 1,076 participants,320 had NAFLD.The multivariable-adjusted ORs and 95%CIs for NAFLD by tertiles of predicted pro-inflammatory hs-CRP score were 1.00,3.30(2.06,5.30),18.25(10.47,31.81;P<0.0001)in men and women combined,1.00,1.77(1.10,2.84),and 3.26(2.02,5.28;P<0.0001)among men only,and 1.00,3.03(1.39,6.62),and 16.71(7.05,39.63;P<0.0001)among women only.Conclusions:Predicted pro-inflammatory hs-CRP score was associated with higher odds of NAFLD.Adopting dietary and lifestyle changes related to lower inflammation might be a valuable strategy for preventing NAFLD.

Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients withmetabolic dysfunction-associated fatty liver disease:a population-based cohort study with 9.7 million Korean subjects

Introduction:Although an association between metabolic dysfunctionassociated fatty liver disease(MAFLD)and cardiovascular disease or overall mortality has been reported,it is unclearwhether there is an association between MAFLD and cancer incidence or mortality.We aimed to investigate the differential risk of all-and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease.Methods:Using the Korean National Health Insurance Service database,we stratified the participants into three groups:(1)single-etiology MAFLD(SMAFLD)or MAFLD of pure metabolic origin;(2)mixed-etiology MAFLD(M-MAFLD)or MAFLD with additional etiological factor(s)(i.e.,concomitant liver diseases and/or heavy alcohol consumption);and(3)non-MAFLD.Hepatic steatosis and fibrosiswere defined using the fatty liver index and the BARDscore,respectively.Cox proportional hazards regression was performed to estimate the risk of cancer events.Results:Among the 9,718,182 participants,the prevalence of S-MAFLD and M-MAFLD was 29.2%and 6.7%,respectively.During the median 8.3 years of follow-up,510,330(5.3%)individuals were newly diagnosed with cancer,and 122,774(1.3%)cancer-related deaths occurred among the entire cohort.Compared with the non-MAFLD group,the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group(incidence,adjusted hazard ratio[aHR]=1.03;95%confidence interval[CI]:1.02−1.04;mortality,aHR=1.06;95%CI:1.04−1.08)and highest among patients with M-MAFLD group(incidence,aHR=1.31;95%CI:1.29−1.32;mortality,aHR=1.45;95%CI:1.42−1.48,respectively).The M-MAFLD with fibrosis group(BARD score≥2)showed the highest relative risk of all-cancer incidence(aHR=1.38,95%CI=1.36–1.39),followed by the M-MAFLD without fibrosis group(aHR=1.09,95%CI=1.06–1.11).Similar trends were observed for cancer-related mortality.Conclusions:MAFLD classification,by applying additional etiologies other than pure metabolic origin,can be used to identify a subgroup of patients with poor cancer-related outcomes.