Introduction

Crohn's disease (CD) and ulcerative colitis (UC) are chronic and progressive inflammatory bowel diseases (IBD). It is estimated that up to 30-50% of patients with IBD develop intestinal fibrosis leading to complications such as strictures. Liver fibrosis occurs up to 16.7% of patients with IBD. However, the impact of liver fibrosis on the response to therapy in patients with IBD is unknown.

Aims & Methods

Our aim was to investigate the association between liver fibrosis before starting an advanced therapy and response to treatment in IBD.We conducted a retrospective analysis of data that were prospectively gathered from consecutive patients with a confirmed diagnosis of UC or CD, spanning from November 2021 to December 2023. All patients who started an advanced therapy and had transaminase concentrations, body mass index (BMI), history of diabetes, and platelet counts available were eligible. Several scores of liver fibrosis were measured including AST/ALT ratio (AAR), AAR platelet ratio index (AARPRI), AST to platelet ratio index (APRI), body mass index AST/ALT ratio and diabetes mellitus score (BARD), fibrosis index based on four factors (FIB -4), and modified FIB-4 (m-FIB4). All available clinical (partial Mayo score for UC and Harvey-Bradshaw index for CD), biochemical (fecal calprotectin, FC), and endoscopic (endoscopic Mayo score for UC and simple endoscopic score for Crohn's Disease (SES-CD) and Rutgeert’s score for CD) data at 6 months were collected. A logistic regression multivariate analysis was performed to identify any correlation between scores of liver fibrosis at baseline and response to advanced therapies. Analyses were subjected to correction using the false discovery rate (FDR) method.

Results

In total, 122 patients were included in the analysis (73 UC (59.8%), 65 female (53.3%), median age of 42.8 years). Approximatively half of the patients were biologic naïve (60, 49.2%), while among biologic-experienced subjects 23/62 (37.1%) had been treated with more than one advanced therapy. Patients were treated with ustekinumab (46, 37.8%), infliximab (33, 27.0%), vedolizumab (16, 13.1%), adalimumab (15, 12.3%), upadacitinib (6, 4.9%), tofacitinib (4, 3.3%), golimumab (1, 0.8%), filgotinib (1, 0.8%). A small proportion of patients (16/122, 13.1%, 2 CD and 14 UC) discontinued treatment at 6 months. Clinical remission at 6 months was achieved in approximately half of CD (23/49, 46.9%) and UC patients (39/73, 53.4%). Similarly, half of CD patients (25/49, 51.0%) and one third of UC patients (22/73, 30.1%) had FC normalization (<150µg/g). A quarter of CD patients (4/16, 25.0%) and UC patients (9/28, 32.1%) achieved endoscopic remission at 6 months. Two UC patients (2.7%) were hospitalized. Five patients (4.1%) underwent surgery (2 UC-related and 3 CD-related). No cases of neoplasia or death occurred. In the multivariate analysis, mFIB-4 at baseline was a predictor of clinical activity at 6 months in CD (FDR=0.08), while AARPRI and AAR at baseline predicted clinical activity at 6 months in UC (FDR=0.08 and FDR=0.06, respectively).

Conclusion

Patients with IBD and concomitant liver fibrosis have a lower rate of clinical remission after 6 months of advanced therapy. Scores of liver fibrosis could predict the response to therapy. Further prospective studies are warranted to implement their use in clinical practice.

Introduction

Bowel urgency (BU) is a common symptom in patients with inflammatory bowel disease (IBD). More than 80% of patients with ulcerative colitis (UC) and more than 60% of patients with Crohn’s disease (CD) experience BU during their life. Although BU negatively impacts the quality of life and psychosocial status, currently it is an overlooked symptom. Furthermore, there is little evidence of the effectiveness of available advanced therapies on BU.

Aims & Methods

We aimed to evaluate the impact of different advanced therapies for IBD in improving BU. This was a retrospective cohort study conducted at two third-level centers (IRCCS San Raffaele hospital and university of Naples Federico II) between April 2023 and April 2024. All consecutive patients with confirmed diagnosis of CD or UC who started an advanced therapy (any biological drug or small molecule) with available data regarding BU at baseline (before starting an advanced therapy) and after induction therapy were eligible. BU was assessed using the numeric rating scale urgency score (NRS-us), a validated tool for quantifying BU in IBD. BU was defined as ≥3 in NRS-us. All available clinical (partial Mayo score for UC and Harvey-Bradshaw Index (HBI) for CD), biochemical (fecal calprotectin (FC) and C-reactive protein (CRP)), endoscopic (Mayo endoscopic score or SES-CD score) and intestinal ultrasound data were collected before and after the induction of an advanced therapy. Patients with history of bowel surgery or radiotherapy were excluded. The primary endpoint was BU improvement, defined as an NRS-us ≤3 or a score reduction of at least 2 points. A logistic regression multivariate analysis was performed to identify any correlation between socio-demographic factors, disease features, and treatment at baseline and changes in NRS-us. Analyses were subjected to correction using the false discovery rate (FDR) method.

Results

In total, 159 patients were included (89 male (56%) with a median age of 36 years and a median BMI of 22,1, 104 (65,4%) UC) (Table 1). Patients were treated with infliximab (24,5%), adalimumab (24,5%), ustekinumab (22,6%), vedolizumab (13,2%), upadacitinib (9,4%), tofacitinib (3,1%), filgotinib (1,3%), golimumab (0,6%) risankizumab (0,6%). A small proportion of patients underwent concomitant steroid (8,8%) or immunosuppressant therapy (12,6%). At baseline the median NRS-us was 7. Approximately half of the patients (81, 50,9%) experienced BU improvement after induction with a mean reduction of NRS-us of 2,3 ± 2,9. In the multivariate analysis, improvement in BU was associated with clinical remission (FDR=0.009 for CD and FDR=0.01 for UC), normalization of fecal calprotectin (FDR=0.001) and CRP (FDR=0.008), and normalization of bowel wall thickness to IUS (FDR=0.0006). No statistically significant difference in obtaining an improvement in BU was identified between the different drugs investigated.

Conclusion

The available advanced therapies improve bowel urgency after the induction phase. Improvement in BU is associated with clinical, biochemical, and ultrasound remission.

Introduction

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract. The introduction of targeted therapies has significantly improved patient outcomes, although a substantial proportion of patients still do not respond adequately. Genetic factors, including single nucleotide polymorphisms (SNPs), may influence therapeutic efficacy.

Aims & Methods

This study investigated the potential correlation between four SNPs in four cytokine genes and the response to targeted molecular therapies.
This prospective cohort study enrolled 197 patients with IBD (144 with Crohn’s disease CD and 55 with ulcerative colitis UC) receiving molecularly targeted therapies. The following SNPs were analyzed: TGF-β -cod10 T/C (rs1982073), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IL-10 -1082 G/A (rs1800896). These SNPs were assessed in relation to baseline patient characteristics. Therapeutic response to molecularly targeted therapies (adalimumab, infliximab, ustekinumab, vedolizumab and tofacitinib) was evaluated in two cohorts: 134 patients in the per-protocol analysis (who maintained the drug for 12 months) and 155 patients in the intention-to-treat analysis. Response was also assessed in the cohort receiving anti-TNF agents (infliximab and adalimumab), including 73 patients in the per-protocol cohort and 87 in the intention-to-treat cohort. After 12 months, response was defined as biochemical remission (absence of steroid therapy, CRP <5 mg/L, and fecal calprotectin <250 µg/g).

Results

The TNF-α -308 mutated allele was more frequently associated with CD than UC (the GA polymorphism was present in 33% of patients with CD and in 21% of patients with UC, while the AA polymorphism was present only in patients with CD, at 4.3%; p = 0.020). The wild-type IL-6 -174 SNP was associated with an older age at diagnosis, with a median age of 30y (22-41) vs 25y (19-36) (p = 0.049) and showed a partial association with a lower history of surgical interventions (p = 0.076). In the cohort of patients who had calprotectin and CRP values at T12, only the mutated IL-10 -1082 SNP was significantly associated with response in the per-protocol cohort (73.4% of patients who did not respond to therapy had the wild-type genotype; p = 0.041) [OR = 2.14 (95% CI 1.03–4.44)] and showed a trend toward significance in the intention-to-treat cohort (p = 0.053). Regarding anti-TNF therapy response, the mutated IL-10 -1082 SNP was associated with better therapeutic outcomes in the per-protocol cohort (84.8% of patients who did not respond to therapy had the wild-type genotype; p = 0.034) [OR = 3.36 (95% CI 1.07–10.58)], but not in the intention-to-treat cohort (p = 0.103). Additionally, a statistically significant correlation was found between TNF-α -308 SNP genotypes (wild-type, heterozygous mutated, and homozygous mutated) and response to anti-TNF therapy in the per-protocol cohort (p = 0.040) [OR = 2.82 (95% CI 1.01–7.85)].

Conclusion

Although four cytokine SNPs were analyzed, the most significant associations were observed with the IL-6 polymorphism, where the mutation was linked to a more aggressive disease course, and the IL-10 cytokine SNP, where the CC+GC genotypes appeared to be associated with a better response to target therapies.

Introduction

Non-alcoholic fatty liver disease (NAFLD) prevalence is elevated in patients with inflammatory bowel disease (IBD) in Western nations. Both intestinal inflammation and metabolic factors contribute to IBD-associated NAFLD. However, the burden of NAFLD in non-Western populations remains unclear.

Aims & Methods

This study aimed to evaluate the prevalence of NAFLD and liver fibrosis in a cohort of Tunisian IBD patients.

Results

Conclusion

This study demonstrates a 28.57% prevalence of NAFLD in Tunisian IBD patients. Higher BMI and older age at IBD diagnosis were associated with NAFLD. Hepatic fibrosis occurred predominantly in Crohn's disease patients. Further longitudinal studies are warranted to elucidate the impact of IBD on hepatic complications.

Introduction

There is a well-known association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). It is estimated that approximately 2% of IBD patients have PSC. However, there is little data regarding the impact of PSC on the prognosis of patients with IBD.

Aims & Methods

We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare outcomes of patients with IBD and those with both IBD and concomitant PSC between 2003 and 2023. All patients with a confirmed diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis with or without PSC were eligible. One-to-one propensity score matching was employed to balance demographic parameters, comorbid conditions, and IBD medications between cohort 1 (IBD) and cohort 2 (IBD and concomitant PSC). The primary endpoint was a composite endpoint including risk of mortality, hospitalization, and surgery. Secondary endpoints were the risk of mortality, IBD-related surgery, and IBD-related hospitalization. Risks were expressed as Hazard Ratio (HR) with a 95% confidence interval (CI).

Results

A total of 409,104 IBD patients were analyzed, including cohort 1 (405,923) and cohort 2 (3,181). After propensity score matching, 3007 patients from each group were included (mean age 48.1 ± 19.4 years, female 40%, UC 75%, CD 24,8%). Cohort 2 patients had an higher risk of experiencing the composite endpoint compared to cohort 1 group (HR 1.326, CI 1.232-1.428). Similarly, a higher risk of experiencing hospitalization and mortality was identified in subjects with IBD and concomitant PSC (HR 1.326, CI 1.224-1.436 and HR 1.697, CI 1.467-1.963 respectively). No difference was detected in terms of surgery between the two groups (HR 1.181, CI 0.970-1.438). Another analysis was performed to compare the outcomes of patients with CD or UC with or without concomitant PSC. Both CD and UC patients with concomitant PSC had an higher risk of achieving the composite endpoint (HR 1.186, CI 1.026-1.372 and HR 1.293, CI 1.189-1.408, respectively). An increased risk of mortality and hospitalization was found both in patients with CD (HR 2.164, CI 1.587-2.952, and 1.207, CI 1.031-1.412, respectively) and UC (HR 1.875, CI 1.578-2.228 and HR 1.279, CI 1.168-1.401, respectively) and concomitant PSC. In patients with CD or UC and concomitant PSC no increased risk of surgery was found (HR 0.954, CI 0.641-1.421 and HR 1.102, CI 0.886-1.369, respectively).

Conclusion

In the largest case series of patients with IBD and PSC, concomitant PSC increased risk of mortality and IBD-related hospitalization.

Introduction

Inflammatory Bowel Disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition affecting the gastrointestinal tract. Although primarily associated with intestinal symptoms, IBD has also been linked to various extraintestinal complications, including liver fibrosis (LF). Additionally, metabolic-associated steatotic liver disease (MASLD), a common liver condition driven by metabolic risk factors such as obesity and insulin resistance, could intersect with IBD, given its systemic nature.
While both LF and MASLD are prevalent among the general population, their incidence and associated risk factors in IBD patients remain underexplored. Understanding these liver-related complications is crucial for developing effective screening and management strategies for patients with IBD.

Aims & Methods

We aimed to assess the prevalence of LF and MASLD in IBD patients compared to matched controls. In this cross-sectional, case-control study, we enrolled consecutive IBD patients from an IBD referral center and matched controls from the general population based on age, sex, type 2 diabetes (T2D) status, and body mass index (BMI) in a 1:1 ratio. Liver fibrosis and MASLD were confirmed through shear-wave elastography (SWE) measurements of stiffness and attenuation coefficient. Potential risk factors were analyzed using multivariate logistic regression.

Results

We included 378 participants, comprising 200 IBD patients (106 with CD and 94 with UC) and 178 controls. There were no statistically significant differences regarding distribution by gender, age, T2D status and BMI. The prevalence of LF (SWE ≥ 6.78 kPa) and advanced LF (SWE ≥ 9.15 kPa) was 42.5% and 16.0%, respectively, in IBD patients (48.1% in CD vs. 36.2% in UC; p=0.088) and 28.1% and 9.0%, respectively, in the control group (p<0.05). For UC, history of complicated disease (OR 7.5, CI95% 1.2-46.2 p<0.05) and multiple hospitalizations due to acute disease (OR 5.6, CI95% 1.3-24.8; p<0.05) were significant risk factors. As for CD, previous hospitalizations (OR 9.7, CI95% 1.4-65.8; p<0.05) and heavy smoking habits (OR 4.9, CI95% 2.0-12.4; p<0.001) were the main risk factors. Extraintestinal manifestations, higher fecal calprotectin level at the time of liver stiffness measurement and latest endoscopic activity were not associated with presence of LF. MASLD was not significantly different between IBD and control group (42.0% vs. 51.7%, respectively; p>0.05). Higher BMI, higher waist circumference, higher abdominal wall thickness and metabolic syndrome were significant risk factors for MASLD (p<0.001).

Conclusion

Our case-control study demonstrates that patients with IBD have a higher prevalence of liver fibrosis compared to matched controls, with significant risk factors including a history of complicated disease, multiple hospitalizations, and heavy smoking habits. Conversely, the prevalence of MASLD does not significantly differ between IBD patients and controls, suggesting that metabolic factors might play a more substantial role in MASLD risk. Given these findings, it is critical for clinicians to implement routine liver fibrosis surveillance in IBD patients, especially in those with identified risk factors. Proactive management strategies aimed at reducing risk factors, such as smoking cessation and minimizing hospitalizations through effective disease management, could mitigate liver fibrosis risk in this population. These insights emphasize the need for integrated care approaches that address both IBD-related complications and associated liver health.