Published online Jan 7, 2027. doi: 10.3748/wjg.122855
Revised: June 13, 2026
Accepted: July 2, 2026
Published online: January 7, 2027
Processing time: 185 Days and 17.3 Hours
A substantial proportion of patients with ulcerative colitis experience clinical relapse despite achieving endoscopic improvement. While it is known that serum total cholesterol (TC) levels fluctuate with inflammatory activity, the clinical significance of longitudinal changes in serum TC after endoscopic improvement remains unclear.
To investigate longitudinal serum TC trajectories after endoscopic improvement and their association with subsequent clinical relapse.
This single-center retrospective cohort study at a tertiary hospital included 452 patients with ulcerative colitis who achieved endoscopic improvement (Mayo endoscopic subscore, 0-1) between 2018 and 2019. Patients were observed until clinical relapse or the last outpatient visit. Relapse was defined as worsening symptoms requiring systemic corticosteroids or step-up medical therapy. Serial serum TC levels were analyzed using generalized estimating equations, time-varying Cox models, and 1-year, 2-year, and 3-year landmark analyses.
During a median follow-up of 67.3 months, 199 patients (44%) experienced clinical relapse. Baseline serum TC levels at endoscopic improvement were similar between the groups; however, the longitudinal patterns differed significantly, showing a progressive increase in patients who later relapsed (time-by-group interaction, P = 0.002). In the time-varying Cox model, each 1 mmol/L increase in updated TC was associated with a higher hazard of clinical relapse (adjusted hazard ratio = 1.31; 95%CI: 1.03-1.66; P = 0.026). Supportive landmark analyses showed that higher maximal TC levels before each landmark were associated with subsequent clinical relapse.
Longitudinal serum TC patterns after endoscopic improvement are associated with the risk of subsequent clinical relapse and may provide complementary information regarding relapse risk.
Core Tip: Most studies link serum lipid levels, including total cholesterol (TC), to concurrent inflammatory activity, not to changes after endoscopic improvement. In this retrospective cohort of patients with ulcerative colitis, baseline serum TC did not distinguish outcomes, whereas exploratory trajectory analysis showed divergent serial TC patterns according to subsequent clinical relapse status. In the time-varying Cox model, each 1 mmol/L increase in updated TC was associated with a 1.31-fold higher hazard of clinical relapse. Supportive landmark analyses showed similar associations using maximal TC. Serial serum TC patterns may provide complementary information associated with relapse risk.
- Citation: Kim JY, Kim MJ, Kim M, Hong SN, Chang DK, Kim YH, Kim ER, Kim JE. Longitudinal serum total cholesterol patterns and subsequent clinical relapse in ulcerative colitis. World J Gastroenterol 2027; 33(1): 122855
- URL: https://www.wjgnet.com/1007-9327/full/v33/i1/122855.htm
- DOI: https://dx.doi.org/10.3748/wjg.122855
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course. Contemporary treatment strategies aim to achieve and sustain remission, with mucosal healing being recognized as a key therapeutic target. Nevertheless, a substantial proportion of patients experience disease relapse, despite clinical remission, endoscopic improvement, or both. Recurrent relapses increase the treatment burden and are associated with poorer quality of life, and longstanding UC is associated with colorectal neoplasia[1-4]. Accordingly, early identification of patients who are more likely to experience subsequent relapse during remission remains an important unmet need in the management of UC.
Established factors associated with UC relapse risk include endoscopic and histologic healing status, fecal calprotectin, and C-reactive protein (CRP). However, in routine clinical practice, assessment of mucosal healing through endoscopic and histologic evaluation requires invasive testing and is not feasible at every outpatient visit. Moreover, relapse may occur even after achieving endoscopic and histologic deep remission[5,6]. During routine follow-up after endoscopic improvement, we observed variability in serial serum total cholesterol (TC) levels that was not always readily attributable to medication exposure alone. These observations raised the possibility that longitudinal TC patterns may reflect disease-related changes not fully captured by conventional inflammatory markers such as fecal calprotectin and CRP.
Serum lipid levels, including TC, are traditionally regarded as metabolic indicators, and are frequently altered in IBD. Emerging evidence suggests that lipid metabolism is closely linked to systemic and intestinal inflammation, with cholesterol levels generally decreasing during active disease and increasing as inflammation resolves[7-10]. Nevertheless, existing studies on UC have largely relied on cross-sectional analyses, and the clinical significance of longitudinal changes in serum TC levels after endoscopic improvement remains unclear[7,8].
Therefore, this study aimed to evaluate longitudinal changes in serum TC levels after endoscopic improvement and assess their association with subsequent clinical relapse in patients with UC.
This single-center retrospective cohort study was conducted at Samsung Medical Center, a tertiary academic hospital in Seoul, Republic of Korea. We screened patients with a confirmed diagnosis of UC who underwent colonoscopy and demonstrated endoscopic improvement between January 2018 and December 2019. UC was previously diagnosed in all patients based on clinical presentation, endoscopic findings, and histologic confirmation. At our institution, clinically stable patients with UC undergoing routine outpatient follow-up are generally observed at 3-6 months intervals. At each visit, patient-reported symptoms were recorded in electronic medical records, and routine laboratory tests were performed. Since January 2018, two rectal biopsies have been routinely obtained during colonoscopy, regardless of endoscopic activity, according to institutional practice.
Data on serum TC levels and statin use were retrieved from the electronic medical records for the period from January 2018 to December 2024. According to institutional outpatient laboratory practice, serum TC measurements were obtained under fasting conditions, and TC was measured in the same central clinical laboratory throughout the study period using a standardized enzymatic method. As serum TC measurements were obtained retrospectively as part of routine clinical care, the frequency and timing of measurements varied among patients. Among the 491 patients with UC who demonstrated endoscopic improvement during the study period, patients were excluded if longitudinal TC assessment was insufficient to characterize longitudinal changes over time or if follow-up was inadequate. Exclusion criteria were: (1) No available TC laboratory data or only a single serum TC measurement during the observation period from January 2018 through December 2024 (n = 16); (2) Only a baseline TC measurement and one subsequent measurement obtained 6 or more months later, without any intervening measurement to assess interval change (n = 4); (3) Availability of only 1 of the 2 cholesterol measurements required to define change over a follow-up interval (n = 16); and (4) Laboratory follow-up less than 6 months (n = 3). After exclusion, 452 patients were included in the final analysis (Figure 1).
The following variables were collected at the time of endoscopy: (1) Age; (2) Age at diagnosis; (3) Sex; (4) Disease extent; (5) Disease duration; (6) Body mass index; (7) Medication; and (8) Laboratory findings including white blood cell count, hemoglobin level, platelet count, albumin level, erythrocyte sedimentation rate, and CRP level. The baseline serum TC was defined as the value closest to the index colonoscopy within a 6-month window, spanning 3 months before to 3 months after the colonoscopy at which endoscopic improvement was confirmed. Because high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol (LDL-C) level, and other lipid fractions were not consistently measured in this clinical cohort, the analysis was restricted to TC, the lipid parameter with the most complete longitudinal data during follow-up.
The endoscopic procedures were performed by gastroenterologists at our center. Three endoscopy specialists independently reviewed the endoscopic images and assigned Mayo endoscopic subscore (MES) values. The MES is an endoscopic component of the Mayo score that grades mucosal inflammation on a 4-point scale from 0 to 3 according to endoscopic findings[11]. Endoscopic improvement was defined as an MES score of 0 or 1.
Histological findings were reviewed by an experienced pathologist and recorded using Geboes score and Nancy histological index. Histological improvement was defined as a Geboes score less than 3.1 or a Nancy histological index grade of 0 or 1[12,13]. Clinical symptoms were assessed using patient-reported outcomes (PROs) recorded at the first outpatient visit after the index colonoscopy.
Clinical remission was defined using PRO-2, consisting of a rectal bleeding subscore of 0 and a stool frequency subscore of 0 or 1[14].
The primary outcome was time to clinical relapse. Exploratory longitudinal serum TC trajectories were compared between patients with subsequent clinical relapse and those without clinical relapse during follow-up. The secondary outcome was whether longitudinal changes in serum TC levels were associated with the risk of relapse.
Clinical relapse was defined as the worsening of UC-related symptoms such as diarrhea, increased stool frequency, or bloody stools, requiring the initiation of systemic corticosteroid therapy or step-up medical therapy.
Patients were observed at regular outpatient visits every 3-6 months. The follow-up period was defined as the time from index colonoscopy to the occurrence of clinical relapse or the last outpatient visit, whichever occurred first. Serum TC levels were not routinely measured at fixed protocol-defined time points during follow-up, but were obtained as part of routine care; therefore, the number of TC measurements and the intervals between measurements varied among patients. Serum TC values were analyzed longitudinally and summarized using the mean or maximal values within predefined follow-up intervals, depending on the analytical approach.
Baseline characteristics were summarized using descriptive statistics and are presented as medians with interquartile ranges for continuous variables and numbers with percentages for categorical variables.
To evaluate whether longitudinal serum TC trajectories differed between patients who subsequently experienced clinical relapse and those without clinical relapse during follow-up, repeated TC measurements were analyzed using generalized estimating equations (GEE) with an interaction term between relapse group and follow-up time. Because relapse grouping was determined based on future clinical outcomes, this analysis was intended primarily to describe longitudinal trajectory patterns rather than to establish predictive or causal associations.
Serum TC was analyzed as a time-varying covariate using Cox proportional hazards models with counting-process style data structures. Serum TC values were updated at each available laboratory measurement and assumed to remain unchanged until the next available measurement, clinical relapse, or censoring. The primary exposure in this model was updated serum TC as a continuous variable per 1 mmol/L increase. The model was adjusted for age, sex, baseline serum TC around the time of endoscopic improvement, infliximab use, statin use, and MES 0/1.
As supportive analyses, landmark analyses were performed at 1 year, 2 years, and 3 years after endoscopic im
The baseline characteristics of the patients with UC who achieved endoscopic improvement (MES 0-1) are presented in Table 1. A total of 452 patients with UC who achieved endoscopic improvement with MES 0 or 1 were included in the analysis; of these, 253 (56%) did not experience clinical relapse, while 199 (44%) experienced clinical relapse during the observation period. The median age at index endoscopy was 49 years, and 236 patients (52.2%) were male. The median duration of disease was 80.0 (33.5-149.0) months. A total of 205 patients (45.4%) had an MES score of 0, which was defined as complete endoscopic healing, whereas 247 (54.6%) had an MES score of 1. Histological improvement was observed in 316 patients (69.9%) using the Geboes score (< 3.1), and in 315 patients (69.7%) according to the Nancy index (< 2).
| Characteristics | All patients (n = 452) | Non-relapse | Relapse (n = 199) | HR (95%CI) | P value |
| Age (years) | 49 (37-58) | 49 (38-60) | 48 (37-56) | 0.994 (0.984-1.005) | 0.177 |
| Male | 236 (52.2) | 133 (52.6) | 103 (51.8) | 0.960 (0.727-1.268) | 0.773 |
| Age at diagnosis (years) | 39 (30-49) | 39 (30-49) | 38 (28-48) | 0.994 (0.984-1.005) | 0.283 |
| Disease duration (months) | 80.0 (33.5-149.0) | 78.0 (33.0-152.0) | 84.0 (34.0-144.0) | 0.999 (0.998-1.001) | 0.522 |
| Disease extent | |||||
| Proctitis | 182 (40.3) | 109 (43.1) | 73 (36.7) | Ref | 0.331 |
| Left-sided colitis | 130 (28.8) | 67 (26.5) | 63 (31.7) | 1.285 (0.874-1.890) | 0.2901 |
| Extensive colitis | 140 (31.0) | 77 (30.4) | 63 (31.7) | 1.176 (0.800-1.729) | 0.6931 |
| BMI (kg/m2) | 22.94 (20.94-25.08) | 23.11 (20.93-24.92) | 22.83 (20.96-25.28) | 1.009 (0.965-1.054) | 0.700 |
| Current medication | |||||
| 5-ASA, topical | 86 (19.0) | 51 (20.2) | 35 (17.6) | 0.935 (0.649-1.347) | 0.719 |
| 5-ASA, oral | 186 (41.2) | 92 (36.4) | 94 (47.2) | 1.363 (1.032-1.801) | 0.029 |
| 5-ASA, both | 156 (34.5) | 97 (38.3) | 59 (29.6) | 0.720 (0.531-0.976) | 0.034 |
| Steroid | 6 (1.3) | 2 (0.8) | 4 (2.0) | 2.312 (0.858-6.225) | 0.097 |
| Azathioprine | 28 (6.2) | 12 (4.7) | 16 (8.0) | 1.451 (0.870-2.419) | 0.154 |
| Biologic therapy | 36 (8.0) | 19 (7.5) | 17 (8.5) | 1.088 (0.662-1.789) | 0.740 |
| Statin use history | 57 (12.6) | 31 (12.3) | 26 (13.1) | 1.023 (0.677-1.545) | 0.915 |
| Laboratory findings | |||||
| WBC (/μL) | 6130 (5155-7320) | 6080 (5130-7280) | 6160 (5230-7450) | 1.003 (0.996-1.011)2 | 0.409 |
| Hemoglobin (g/dL) | 14.1 (13.0-15.2) | 14.0 (13.1-15.2) | 14.1 (13.0-15.0) | 1.001 (0.999-1.002) | 0.315 |
| Platelet count (× 103/μL) | 247.0 (214.0-291.5) | 242 (204.0-277.0) | 263.0 (225.0-302.0) | 1.005 (1.003-1.007) | < 0.001 |
| ESR (mm/hour) | 11.0 (5.0-20.0) | 11.0 (5.0-20.0) | 12.0 (7.0-20.0) | 1.009 (1.000-1.019) | 0.060 |
| Albumin (g/dL) | 4.6 (4.4-4.8) | 4.6 (4.4-4.8) | 4.6 (4.4-4.8) | 0.847 (0.623-1.152) | 0.290 |
| CRP (mg/dL) | 0.05 (0.03-0.11) | 0.04 (0.03-0.11) | 0.05 (0.03-0.11) | 1.513 (0.949-2.412) | 0.082 |
| Baseline TC (mmol/L) | 4.64 (4.09-5.20) | 4.60 (4.06-5.15) | 4.71 (4.14-5.20) | 1.123 (0.962-1.361) | 0.163 |
| PRO-2 | |||||
| PRO-2 remission | 306 (67.7) | 179 (70.8) | 127 (63.8) | Ref | |
| No PRO-2 remission | 146 (32.3) | 74 (29.2) | 72 (36.2) | 1.337 (1.001-1.786) | 0.049 |
| Endoscopic finding | |||||
| MES 0 | 205 (45.4) | 133 (52.6) | 72 (36.2) | Ref | |
| MES 1 | 247 (54.6) | 120 (47.4) | 127 (63.8) | 1.684 (1.261–2.249) | < 0.001 |
| Histologic finding | |||||
| Geboes score < 3.1 | 316 (69.9) | 191 (75.5) | 125 (62.8) | Ref | |
| Geboes score ≥ 3.1 | 136 (30.1) | 62 (24.5) | 74 (37.2) | 1.687 (1.265-2.249) | < 0.001 |
| Nancy index < 2 | 315 (69.7) | 190 (75.1) | 125 (62.8) | Ref | |
| Nancy index ≥ 2 | 137 (30.3) | 63 (24.9) | 74 (37.2) | 1.659 (1.244-2.212) | < 0.001 |
During a median follow-up of 67.3 months, 199 patients (44%) experienced clinical relapse. The median time to clinical relapse was not reached during follow-up. Baseline TC level was not significantly associated with subsequent clinical relapse (HR = 1.12; 95%CI: 0.96-1.36; P = 0.163). Patients who were not in PRO-2 remission at baseline had a significantly higher risk of relapse compared with those in PRO-2 remission (HR = 1.34; 95%CI: 1.00-1.79; P = 0.049).
Endoscopic and histological disease activity was strongly associated with relapse risk. Patients with MES 1 had a higher hazard of relapse compared with those with MES 0 (HR = 1.68; 95%CI: 1.26-2.25; P < 0.001). Similarly, active histologic inflammation was associated with an increased risk of relapse, as defined by both the Geboes score (≥ 3.1 vs < 3.1: HR = 1.69; 95%CI: 1.27-2.25; P < 0.001) and the Nancy index ( ≥ 2 vs < 2: HR = 1.66; 95%CI: 1.24-2.21; P < 0.001).
Figure 2 illustrates the mean serum TC trajectories according to subsequent clinical relapse status. At baseline, around the time of endoscopic improvement (time 0), mean TC levels were similar between patients without clinical relapse and those with subsequent clinical relapse (4.58 mmol/L and 4.56 mmol/L, respectively). Over time, TC levels increased more prominently among patients who later experienced clinical relapse, whereas they remained relatively stable among those without clinical relapse. In the exploratory GEE analysis, the time-by-group interaction was significant (P = 0.002).
Because serum TC was measured as part of routine clinical care rather than at protocol-defined intervals, we compared the annual testing frequency between groups to assess potential differential surveillance. The number of serum TC measurements per patient-year did not differ significantly between the non-relapse and relapse groups (2.47 ± 1.54 vs 2.58 ± 1.73; median, 2 in both groups; GEE P = 0.383, Supplementary Table 1).
To address potential bias related to grouping by future relapse status, we analyzed serum TC as a time-varying covariate. In the time-varying Cox model, each 1 mmol/L increase in updated serum TC was independently associated with a higher hazard of clinical relapse (adjusted HR = 1.31; 95%CI: 1.03-1.66; P = 0.026) after adjustment for age, sex, baseline serum TC, infliximab use, statin use, and MES 0/1.
In supportive landmark analyses among patients who remained relapse-free at each predefined landmark, higher maximal TC levels during the pre-landmark period were associated with subsequent clinical relapse beyond the landmark (Table 2).
| Landmark time | Cutoff group | Patients | Univariable analysis | Multivariable analysis | |||
| Non-relapse | Relapse | HR (95%CI) | P value | Adjusted HR (95%CI) | P value | ||
| 1-year | < 4.53 mmol/L | 82 | 29 | Ref | Ref | ||
| ≥ 4.53 mmol/L | 166 | 121 | 1.73 (1.15-2.60) | 0.008 | 1.85 (1.11-3.07) | 0.018 | |
| 2-year | < 4.53 mmol/L | 58 | 14 | Ref | Ref | ||
| ≥ 4.53 mmol/L | 181 | 90 | 1.88 (1.07-3.30) | 0.028 | 2.05 (1.05-4.01) | 0.036 | |
| 3-year | < 5.56 mmol/L | 148 | 28 | Ref | Ref | ||
| ≥ 5.56 mmol/L | 87 | 32 | 1.92 (1.16-3.18) | 0.012 | 2.16 (1.11-4.22) | 0.024 | |
At the 1-year landmark (n = 398), patients with a maximal TC level of 4.53 mmol/L or higher during the first year after endoscopic improvement had a significantly higher hazard of subsequent clinical relapse compared with those with levels less than 4.53 mmol/L (univariable HR = 1.73; 95%CI: 1.15-2.60; P = 0.008). This association remained significant after adjustment for age, sex, baseline serum TC, infliximab use, statin use, and MES 0/1 (adjusted HR = 1.85; 95%CI: 1.11-3.07; P = 0.018).
At the 2-year landmark (n = 343), a maximal TC level of 4.53 mmol/L or higher between endoscopic improvement and the 2-year landmark was again associated with a higher hazard of subsequent clinical relapse (adjusted HR = 2.05; 95%CI: 1.05-4.01; P = 0.036).
A higher cutoff value was identified at the 3-year landmark (n = 295). Patients with a maximal TC level of 5.56 mmol/L or higher before the 3-year landmark had a significantly higher hazard of clinical relapse beyond the landmark compared with those below this threshold (adjusted HR = 2.16; 95%CI: 1.11-4.22; P = 0.024).
The stratified landmark analyses based on statin exposure are shown in Supplementary Table 2. In the statin never-use group, point estimates were generally in the same direction across landmark time points, although statistical significance was not retained at the 2-year landmark. Among statin ever-users, however, the sample size and number of relapse events were limited, resulting in wide confidence intervals and reduced statistical precision; nevertheless, point estimates were generally in the same direction as those observed in the overall population.
Consistently, Kaplan-Meier analyses demonstrated lower relapse-free survival among patients with higher maximal TC levels at each landmark time point (Figure 3).
Supportive continuous landmark sensitivity analyses using maximal and mean TC levels are provided in Supplementary Table 3. Because landmark-derived cutoff values were data-driven and internally derived within this cohort, they should be interpreted as exploratory rather than definitive clinical thresholds.
In this study of patients with UC who achieved endoscopic improvement, serial serum TC patterns during follow-up differed according to subsequent clinical relapse status despite similar baseline serum TC levels. Higher serum TC values observed after endoscopic improvement were associated with subsequent clinical relapse.
These findings may appear partly inconsistent with previous cross-sectional studies reporting that serum TC and other lipid fractions are lower in patients with active UC than in those in remission and may increase after remission or inflammation resolution[7,8,15-17]. However, most previous studies compared lipid levels according to disease activity measured at the same time point, whereas the present study focused on patients who had already achieved endoscopic improvement and evaluated whether changes in TC during follow-up were associated with later relapse. Therefore, our findings should not be interpreted as indicating that higher TC levels directly cause relapse. Rather, TC dynamics may reflect residual inflammation, treatment exposure, dietary or body weight changes, or broader metabolic instability before clinically overt relapse.
UC relapse risk is associated with established inflammatory markers, including endoscopic healing status, histologic activity, fecal calprotectin, and CRP[18-22]. The longitudinal TC pattern observed in this study should not be regarded as a substitute for these established markers. Instead, our findings suggest that serum TC, a laboratory parameter repeatedly measured in routine care, may provide complementary information associated with relapse risk. However, because TC measurements were not obtained at protocol-defined time points and the landmark cutoffs were derived using a data-driven approach, prospective validation is required before clinical application.
The association between lipid metabolism and intestinal inflammation has been suggested in previous literature[7,17,23,24]. Several explanations are possible for the association between TC dynamics and subsequent UC relapse observed in this study. An increase in TC levels may partly reflect inflammatory recovery as active inflammation resolves. Serum TC levels may also be influenced by treatment-related metabolic changes, including exposure to systemic corticosteroids, Janus kinase inhibitors, and potentially infliximab[17,24]; however, no patients in this cohort received Janus kinase inhibitors during the period in which TC data were retrieved. Therefore, an increase in serum TC after endoscopic improvement may not simply indicate resolved inflammation, but may reflect broader disease-related metabolic instability involving inflammatory recovery, therapeutic exposure, and metabolic change.
Furthermore, previous studies suggest that cholesterol dysregulation may be connected to intestinal immune regulation and barrier function[25-27], providing a biological context for interpreting the association between longitudinal TC patterns and subsequent relapse risk observed in the present study. Observational studies reporting that statin use is associated with a less severe IBD course[28], together with studies describing the anti-inflammatory effects of statins[29-31], further support the potential interconnection between lipid metabolism and intestinal inflammation. Therefore, our findings may be interpreted as hypothesis-generating observations suggesting that serial TC patterns may reflect inflammatory, treatment-related, and metabolic changes in the disease course of UC.
This study has several strengths. First, it analyzed repeated TC measurements during long-term follow-up after endoscopic improvement in a relatively large and well-characterized cohort of patients with UC. Second, cohort entry was defined using an endoscopic criterion of MES 0-1, which helped reduce disease activity-related heterogeneity compared with previous studies of lipid metabolism in UC that used heterogeneous or poorly defined remission criteria or classified disease status as active or inactive without explicit endoscopic assessment[7,16,24]. Third, we used a structured and complementary longitudinal analytical framework, including exploratory trajectory-based GEE analysis, time-varying Cox model of updated continuous TC exposure, and supportive landmark analyses, to evaluate serial TC dynamics and subsequent clinical relapse. Finally, unlike previous studies that focused mainly on single-time-point or cross-sectional lipid measurements[16,32], this study evaluated repeated TC measurements during follow-up.
However, this study has several limitations, many of which are related to its retrospective, single-center cohort study design. First, selection bias and limited generalizability should be considered. Second, because serum TC was measured during routine clinical care rather than at protocol-defined intervals, this may have introduced measurement frequency bias. Although the annual frequency of TC testing was similar between patients with and without clinical relapse (Supplementary Table 1), residual surveillance bias cannot be excluded. To reduce reliance on maximal TC values, we added a time-varying Cox analysis using updated continuous TC values. Third, diet, body weight changes, medication exposure, and other metabolic factors could not be fully controlled; therefore, the landmark-specific TC cutoffs should be interpreted as data-driven exploratory thresholds requiring external validation. Fourth, because high-density lipoprotein cholesterol, LDL-C, and other lipid fractions were not sufficiently or repeatedly measured, only TC was analyzed. Future prospective studies utilizing standardized LDL-C profiling are warranted, and lipid-modifying or lipid-altering medications should be considered as time-varying exposures. Fifth, because the definition of clinical relapse was based on symptoms and treatment escalation, it may be influenced by physician decision-making. In this retrospective study, objective inflammatory assessments at the time of relapse were not obtained in all patients according to a protocolized schedule. Given that CRP and fecal calprotectin normalization are included among STRIDE-II intermediate treatment targets[14], future prospective studies should incorporate standardized objective assessments, including CRP and fecal calprotectin, to better characterize relapse events. Finally, the precision of the estimates at later landmarks was limited due to reductions in sample size and the number of events.
This study demonstrated that after achieving endoscopic improvement, serial serum TC levels differed between patients with UC who experienced clinical relapse and those who did not. In the time-varying Cox analysis, higher updated TC was associated with a higher hazard of clinical relapse, and supportive landmark analyses showed similar associations using maximal TC levels. In conclusion, longitudinal serum TC patterns after endoscopic improvement were associated with the risk of subsequent clinical relapse in patients with UC. These findings should be interpreted as hypothesis-generating and require validation in prospective studies with standardized follow-up and comprehensive lipid profiling.
| 1. | Colman RJ, Rubin DT. Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review. Intest Res. 2016;14:202-210. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 41] [Cited by in RCA: 63] [Article Influence: 6.3] [Reference Citation Analysis (0)] |
| 2. | Casellas F, Arenas JI, Baudet JS, Fábregas S, García N, Gelabert J, Medina C, Ochotorena I, Papo M, Rodrigo L, Malagelada JR. Impairment of health-related quality of life in patients with inflammatory bowel disease: a Spanish multicenter study. Inflamm Bowel Dis. 2005;11:488-496. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 194] [Cited by in RCA: 194] [Article Influence: 9.2] [Reference Citation Analysis (0)] |
| 3. | Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clin Gastroenterol Hepatol. 2018;16:343-356.e3. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 411] [Cited by in RCA: 380] [Article Influence: 47.5] [Reference Citation Analysis (2)] |
| 4. | Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526-535. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 2395] [Cited by in RCA: 2141] [Article Influence: 85.6] [Reference Citation Analysis (14)] |
| 5. | Liverani E, Scaioli E, Digby RJ, Bellanova M, Belluzzi A. How to predict clinical relapse in inflammatory bowel disease patients. World J Gastroenterol. 2016;22:1017-1033. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in CrossRef: 82] [Cited by in RCA: 117] [Article Influence: 11.7] [Reference Citation Analysis (4)] |
| 6. | Zeina T, Gandhi S, Mittal A, Levy AN, Weinstock J, Singh S, Jangi S. Predictors and Etiologies of Clinical Relapse Among Patients With Ulcerative Colitis in Deep Remission. J Clin Gastroenterol. 2024;58:195-199. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2] [Cited by in RCA: 7] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
| 7. | Chen H, Li W, Hu J, Xu F, Lu Y, Zhu L, Shen H. Association of serum lipids with inflammatory bowel disease: a systematic review and meta-analysis. Front Med (Lausanne). 2023;10:1198988. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 29] [Cited by in RCA: 32] [Article Influence: 10.7] [Reference Citation Analysis (0)] |
| 8. | Zhu L, Tian L, Li S, Huo L. Blood Lipid Levels and Their Value as Markers of Disease Activity in Severe Ulcerative Colitis. Int J Gen Med. 2025;18:671-680. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 3] [Reference Citation Analysis (0)] |
| 9. | Sleutjes JAM, Roeters van Lennep JE, van der Woude CJ, de Vries AC. Lipid Changes After Induction Therapy in Patients with Inflammatory Bowel Disease: Effect of Different Drug Classes and Inflammation. Inflamm Bowel Dis. 2023;29:531-538. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 20] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
| 10. | Hyun HK, Cheon JH. Metabolic Disorders and Inflammatory Bowel Diseases. Gut Liver. 2025;19:307-317. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 15] [Cited by in RCA: 20] [Article Influence: 20.0] [Reference Citation Analysis (0)] |
| 11. | Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625-1629. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2583] [Cited by in RCA: 2391] [Article Influence: 61.3] [Reference Citation Analysis (15)] |
| 12. | Cushing KC, Tan W, Alpers DH, Deshpande V, Ananthakrishnan AN. Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission. Aliment Pharmacol Ther. 2020;51:347-355. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 67] [Cited by in RCA: 64] [Article Influence: 10.7] [Reference Citation Analysis (4)] |
| 13. | Mosli MH, Feagan BG, Zou G, Sandborn WJ, D'Haens G, Khanna R, Shackelton LM, Walker CW, Nelson S, Vandervoort MK, Frisbie V, Samaan MA, Jairath V, Driman DK, Geboes K, Valasek MA, Pai RK, Lauwers GY, Riddell R, Stitt LW, Levesque BG. Development and validation of a histological index for UC. Gut. 2017;66:50-58. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 309] [Cited by in RCA: 292] [Article Influence: 32.4] [Reference Citation Analysis (5)] |
| 14. | Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160:1570-1583. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2368] [Cited by in RCA: 2364] [Article Influence: 472.8] [Reference Citation Analysis (23)] |
| 15. | Wang D, Zhao XJ, Cui XF, Li LZ, Zhang HJ. [Correlation of serum lipid profile and disease activity in patients with inflammatory bowel disease]. Zhonghua Nei Ke Za Zhi. 2021;60:834-836. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 4] [Reference Citation Analysis (0)] |
| 16. | Liu Z, Tang H, Liang H, Bai X, Zhang H, Yang H, Wang H, Wang L, Qian J. Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China. Nutrients. 2022;14:3040. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 18] [Article Influence: 4.5] [Reference Citation Analysis (0)] |
| 17. | Agouridis AP, Elisaf M, Milionis HJ. An overview of lipid abnormalities in patients with inflammatory bowel disease. Ann Gastroenterol. 2011;24:181-187. [PubMed] |
| 18. | Mao R, Xiao YL, Gao X, Chen BL, He Y, Yang L, Hu PJ, Chen MH. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis. 2012;18:1894-1899. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 240] [Cited by in RCA: 236] [Article Influence: 16.9] [Reference Citation Analysis (3)] |
| 19. | Christensen B, Hanauer SB, Erlich J, Kassim O, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes. Clin Gastroenterol Hepatol. 2017;15:1557-1564.e1. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 181] [Cited by in RCA: 176] [Article Influence: 19.6] [Reference Citation Analysis (7)] |
| 20. | Park S, Abdi T, Gentry M, Laine L. Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis. Am J Gastroenterol. 2016;111:1692-1701. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 202] [Cited by in RCA: 176] [Article Influence: 17.6] [Reference Citation Analysis (3)] |
| 21. | Singh A, Bhardwaj A, Sharma R, Kahlon BK, Dhaliwal AS, Singh D, Kaur S, Jain D, Bansal N, Mahajan R, Kaur K, Singh A, Narang V, Kaur H, Midha V, Sood A. Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis. Intest Res. 2025;23:144-156. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 8] [Article Influence: 8.0] [Reference Citation Analysis (0)] |
| 22. | Viscido A, Valvano M, Stefanelli G, Capannolo A, Castellini C, Onori E, Ciccone A, Vernia F, Latella G. Systematic review and meta-analysis: the advantage of endoscopic Mayo score 0 over 1 in patients with ulcerative colitis. BMC Gastroenterol. 2022;22:92. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 41] [Cited by in RCA: 37] [Article Influence: 9.3] [Reference Citation Analysis (2)] |
| 23. | Bigeh A, Sanchez A, Maestas C, Gulati M. Inflammatory bowel disease and the risk for cardiovascular disease: Does all inflammation lead to heart disease? Trends Cardiovasc Med. 2020;30:463-469. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 94] [Cited by in RCA: 77] [Article Influence: 12.8] [Reference Citation Analysis (0)] |
| 24. | Sleutjes JAM, Roeters van Lennep JE, Boersma E, Menchen LA, Laudes M, Farkas K, Molnár T, Kennedy NA, Pierik MJ, van der Woude CJ, de Vries AC. Systematic review with meta-analysis: effect of inflammatory bowel disease therapy on lipid levels. Aliment Pharmacol Ther. 2021;54:999-1012. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 2] [Cited by in RCA: 15] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
| 25. | Yang Q, Li Y, Wang X, Ding Q, Tao Y, Li P, Lian X, Chen Y, Zhao L. A high cholesterol diet aggravates experimental colitis through SREBP2-modulated endocytosis and degradation of occludin and Zo-1 proteins. FEBS J. 2025;292:1052-1069. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 8] [Cited by in RCA: 9] [Article Influence: 9.0] [Reference Citation Analysis (0)] |
| 26. | Astorga J, Gasaly N, Dubois-Camacho K, De la Fuente M, Landskron G, Faber KN, Urra FA, Hermoso MA. The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD. Front Immunol. 2022;13:1028953. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 38] [Cited by in RCA: 33] [Article Influence: 8.3] [Reference Citation Analysis (1)] |
| 27. | Bashiri K, Mattar MC, Meighani A, Mason AL. Peroxisome proliferator-activated receptors in inflammatory bowel disease: linking immunometabolism, lipid signaling, and therapeutic potential. Intest Res. 2026;24:11-26. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 5] [Reference Citation Analysis (0)] |
| 28. | Khalili H, Forss A, Söderling J, Bröms G, Eriksson C, Sun J, Ludvigsson JF, Olén O. Statin Use is Associated with a Less Severe Disease Course In Inflammatory Bowel Disease: A Nationwide Cohort Study 2006-2020. Inflamm Bowel Dis. 2025;31:2787-2797. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 4] [Cited by in RCA: 13] [Article Influence: 13.0] [Reference Citation Analysis (0)] |
| 29. | Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14:37-44. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 454] [Cited by in RCA: 459] [Article Influence: 25.5] [Reference Citation Analysis (0)] |
| 30. | Côté-Daigneault J, Mehandru S, Ungaro R, Atreja A, Colombel JF. Potential Immunomodulatory Effects of Statins in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016;22:724-732. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 31] [Cited by in RCA: 48] [Article Influence: 4.8] [Reference Citation Analysis (0)] |
| 31. | Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet. 1996;348:1079-1082. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 498] [Cited by in RCA: 472] [Article Influence: 15.7] [Reference Citation Analysis (0)] |
| 32. | Pang X, Yang H, Li M, Suarez-Farinas M, Tian S. To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis. eGastroenterology. 2024;2:e100034. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 5] [Reference Citation Analysis (0)] |