Abstract
Objectives: To evaluate the features and frequency of hepatobiliary diseases in individuals with Inflammatory bowel disease (IBD).
Methods: This retrospective study included all IBD patients at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The primary focus was on the prevalence of hepatobiliary diseases, such as primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH), and others. The secondary focus was identifying predictors of these hepatobiliary manifestations in IBD patients. Associations were analyzed using simple and multiple logistic regression analyses.
Results: Among a total of 885 patients with IBD patients, 4.3% presented with hepatobiliary manifestations. Of these cases, 31.6% were linked to Crohn’s disease (CD). While 65.8% were associated with ulcerative colitis (UC). Primary sclerosing cholangitis (PSC) was most prevalent, especially in females. PSC was linked to specific IBD sites 39.3% of UC patients have the left-sided disease and 10.7% of patients with ileocolonic CD had PSC. The absence of comorbidities was associated with lower odds of developing PSC, while UC diagnosis, adalimumab use, and infliximab use were associated with higher odds of developing PSC.
Conclusion: A small percentage of IBD patients experience hepatobiliary complications, with PSC being the most prevalent. The study emphasizes the importance of closely monitoring IBD patients, especially those undergoing anti-TNF therapy.
Inflammatory bowel disease (IBD is a long-term inflammatory disorder of the gastrointestinal tract with an unpredictable course. It includes two primary forms: Crohn’s disease (CD) and ulcerative colitis (UC).1 Recent reports indicate a rising incidence of IBD in the Arab world, with UC affecting approximately 2.33 per 100,000 individuals annually and CD affecting 1.46 per 100,000 individuals annually in the region.2 Inflammatory bowel disease has multiple complications that lead to an increased disease burden on the affected patient. The complications are not limited to the gastrointestinal tract; IBD can lead to extra-intestinal manifestations (EIMs), occurring in approximately 30% of patients. These may include hepatobiliary complications such as PSC, autoimmune hepatitis, cholelithiasis, portal venous thrombosis, hepatic abscesses, and hepatic amyloidosis.3
Research suggests that liver dysfunction can affect up to half of all IBD patients, with non-alcoholic fatty liver disease (NAFLD) being the most prevalent hepatobiliary disease, followed by PSC.4,5 Non-alcoholic fatty liver disease, characterized by fat accumulation in liver cells, is influenced by factors like obesity, insulin resistance, and metabolic syndrome, with a prevalence rate among IBD patients ranging from 30% to 40%.6,7 Primary sclerosing cholangitis, on the other hand, is a chronic cholestatic liver condition affecting 2–7% of IBD cases, potentially leading to severe complications such as cholangiocarcinoma and colon cancer.4,8,9 Studies have shown a relation between IBD and PSC, with over half of IBD patients experiencing hepatobiliary diseases.10,11 PSC in IBD is regarded as an extraintestinal manifestation, and it can even precede the development of gastrointestinal symptoms.12 Moreover, PSC linked to IBD is thought to have a complex etiopathogenesis that includes immune-mediated mechanisms, genetic susceptibility, persistent portal bacteriemia, and altered gut microbiota.13 A 2019 case-control study in Brazil emphasized recognizing and managing such patients to prevent severe complications like colon and biliary tree malignancies.8
Despite substantial international research on the hepatobiliary manifestations of IBD, there is a significant lack of data specific to Saudi Arabia.5,10,14–19 Consequently, the prevalence, patterns, and types of these complications remain poorly understood and inadequately characterized. Therefore, this research aims to assess the prevalence and characteristics of hepatobiliary manifestations and identify their predictors in individuals with IBD in Saudi Arabia.
Methods
This retrospective study was carried out at King Abdulaziz University Hospital (KAUH), a specialized tertiary care facility in Jeddah, Saudi Arabia. It included all patients with IBD following up at the hospital from 2018 to 2023. This study obtain the ethical approval from the Institutional Review Board of KAUH approved this study.
All IBD patients who were 13 or older and following up at KAUH were included. Patients with incomplete data on the hospital records system were excluded from the analysis. Patient data was accessed through the inflammatory bowel disease information system (IBDIS) registry at KAUH. A predefined checklist on Google Forms was utilized for data collection. The first section gathered demographic information such as age, gender, weight, and height. The second section focused on past medical history, including any coexisting conditions, details about the type of IBD, time of diagnosis, presenting symptoms, severity level, medications, and surgical interventions. The third section provided specifics about the presentation and type of hepatobiliary diseases reported for each patient. The hepatobiliary disease was defined and assessed based on established clinical guidelines and diagnostic criteria for each specific condition. Definitions of hepatobiliary diseases, including PSC, cholelithiasis, NAFLD, portal vein thrombosis, viral hepatitis, autoimmune hepatitis, pancreatitis, and hepatic cysts, among others, were thoroughly identified. Diagnostic modalities utilized for hepatobiliary assessment included magnetic resonance cholangiopancreatography (MRCP), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), fibroscan, and endoscopic retrograde cholangiopancreatography (ERCP), among others. These modalities were chosen based on their efficacy in diagnosing hepatobiliary diseases and were applied according to the clinical presentation and individual patient circumstances. Missing data may have occurred due to various factors, including incomplete medical records, insufficient documentation, or patients referred to KAUH with pre-existing diagnoses from other healthcare facilities.
Additionally, the fourth segment included inquiries related to laboratory blood analysis, including liver function tests (LFT), viral markers, and serological markers. Lastly, the fifth part covered radiographic findings and procedures performed.
Statistical analysis
The data were input using Microsoft Excel 2019, and statistical analysis was performed with IBM SPSS Statistics for Windows, version 21 (IBM Corp., Armonk, N.Y., USA). Descriptive statistics for categorical variables were presented as frequencies. Continuous variables with a normal distribution were summarized using means and standard deviations. For inferential statistics, the Chi-square test was used to analyze categorical variables and identify potential risk factors. An independent T-test was employed to examine relationships for normally distributed variables, while the Mann-Whitney U test was applied to non-parametric data. Thirty-eight (4.3%) patients experienced hepatobiliary manifestations of IBD. The most prevalent hepatobiliary disease was PSC (n=28, 73%), followed by cholelithiasis (n=6, 15.8%). Two of the PSC patients had other hepatobiliary diseases in combination with PSC; one of them had cholelithiasis, and the other had NAFLD (Table 2). Patients with UC accounted for 65.8% of patients with hepatobiliary diseases, compared to 31.6% with CD (p=0.009) (Table 1). Of the 28 patients with PSC, 60.7% (n=17) were female, and 7.8% had UC. In CD, the majority had the ileocolonic disease (10.7%, n = 3), and 39.3% (n=11) of UC patients had the left-sided disease (Table 3). Individual characteristics of patients with PSC are summarized in Appendix 1.
- Baseline demographic of patients with IBD and hepatobiliary manifestations.
- Prevalence of hepatobiliary diseases in cohort study (N=38).
- Characteristics of primary sclerosing cholangitis-associated in the study cohort.
According to multiple logistic regression analysis, individuals classified as medically free exhibited significantly lower odds of having PSC than their counterparts (p<0.001). Conversely, patients with UC had substantially higher odds of PSC than those with CD (p<0.001). The absence of perianal disease was associated with markedly lower odds of PSC (p<0.001) analyses. The type of IBD also showed significant associations, with UC presenting a substantially increased risk of PSC compared to CD in both simple (OR = 4.81, 95% CI: 2.04–13.22, p=0.001) and multiple (OR = 15.61, 95% CI: 4.33–76.82, p< 0.001) logistic regression analyses. Age at diagnosis exhibited a univariate association with PSC (OR = 1.03, 95% CI: 1.00–1.05, p=0.046), but this association became non-significant in the multiple logistic regression analysis (OR=1.01, 95% CI: 0.97–1.04, p=0.748). The absence of perianal disease emerged as a robust protective factor against PSC in both simple (OR = 0.01, 95% CI: 0.00–0.04, p<0.001) and multiple (OR = 0.01, 95% CI: 0.00–0.04, p<0.001) analyses. Additionally, Adalimumab and Infliximab showed significant associations with increased odds of PSC in both simple and multiple analyses (Table 4).
- Present multivariable logistic regression (PSC) in odds ratio (OR) form.
Discussion
This study included 38 patients with IBD who had associated hepatobiliary disease, representing approximately 4.3% of the overall included patients. This is emphasized by a study published in August 2021, which showed that only 2.16% of the general patients had PSC as an EIM of IBD. Hence, the relation of PSC with IBD is widely recognized.10 A cohort study of IBD patients found that PSC was present in approximately 5-7% of cases, with a higher prevalence in ulcerative colitis compared to Crohn’s disease.20 Hepatobiliary manifestations are associated with systemic diseases in over 50% of affected individuals, reflecting their clinical significance. Furthermore, the presence of one EIM in IBD significantly increases the risk of developing additional EIMs, as supported by a recent European cohort study.21 Our study finds a significant association between IBD and hepatobiliary diseases. Moreover, we showed that the prevalence of hepatobiliary manifestations was significantly more frequent in patients with UC, with a prevalence of 6.7% compared with 2.44% in patients with CD. This emphasized by a result from a study published in 2020 showed that the extra intestinal manifestation was prominent in almost half of the total study participants with ulcerative being the primary inflammatory disease rather than CD.22 A similar result was reported in a study conducted in Saudi Arabia, which found that patients with ulcerative colitis were more likely to have EIMs compared to those with Crohn’s diseases.23
We found that PSC was the most prevalent type of hepatobiliary condition, with a prevalence of 3.2% of the total sample and 73.6% of cases diagnosed with hepatobiliary conditions. This aligns with previously published literature identifying PSC as the most prevalent hepatobiliary condition linked to IBD. A study conducted in Saudi Arabia at 2023 PSC showed the most frequent EIMs by 46.2%.23 In 2022 Saudi cohort study published The percentage of PSC among was 4.1%and it was more common among UC patients.24
Studies have demonstrated that approximately 70–80% of patients with primary sclerosing cholangitis (PSC) are diagnosed with ulcerative colitis (UC), while Crohn’s disease (CD), particularly colonic or ileocolonic involvement, accounts for 1.3–14% of cases. This highlights a stronger association of PSC with UC compared to CD.25,26 Moreover, recent analyses confirm that UC remains the predominant IBD phenotype in PSC-IBD cases globally, which is similar to our results, which showed that 21 patients (60.7%) were UC patients compared with 5 patients in the CD group (17.8%).27
The second most common hepatobiliary disease diagnosed in IBD patients was cholelithiasis, with a rate of 15.8%. Cholelithiasis demonstrates a significantly higher prevalence among patients with inflammatory bowel disease (IBD), affecting approximately 13-34% of this population, compared to the general population. Patients with Crohn’s disease (CD) exhibit a two-fold increased risk of gallstone formation. This heightened risk is primarily attributed to bile salt malabsorption, particularly in cases involving ileal disease, which diminishes the bile acid pool and results in gallbladder bile supersaturation. These pathophysiological changes collectively contribute to the increased likelihood of gallstone development.17,28
Despite its valuable contribution to understanding hepatobiliary diseases in individuals with IBD, several limitations of this study should be acknowledged. The limited sample size affects the generalizability of the results, leading to an underpowered regression model. and its retrospective design brings inherent biases like selection and referral bias. Data from a single center might not fully represent the broader community. Additionally, incomplete data could affect the accuracy of the results. Future studies should aim for larger, more diverse samples and address data completeness systematically for more reliable results.
In conclusion, this retrospective study of Saudi IBD patients found that only a small proportion had hepatobiliary pathology, with PSC being the most prevalent, followed by cholelithiasis. A significant association was seen between the site of IBD and PSC, and treatment with anti-TNF agents was associated with PSC.
Acknowledgment
We would like to thank PaperTrue for the English language editing.
- Description of hepatobiliary pathology in individuals with inflammatory bowel disease.
Footnotes
Disclosure. Authors have no conflict of interests, and the work was not supported or funded by any drug company.
- Received September 1, 2024.
- Accepted December 11, 2024.
- Copyright: © Saudi Medical Journal
This is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work.
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