Evaluation of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis

Abstract

This article relates to the discussion of a recent study published by Wohl et al. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease that affects the intra- and extrahepatic bile ducts and is strongly associated with ulcerative colitis (UC). Endoscopic evaluation of UC is feasible and reliable in routine clinical practice, and the Mayo endoscopic subscore (MES) is one of the most commonly used endoscopic evaluation measures for UC. Patients with PSC-UC are at higher risk of developing cancer and biliary tract cancer. Endoscopic scoring alone appears unreliable, and histopathological evaluation is essential to accurately assess and make effective therapeutic decisions for PSC-UC. Therefore, we aimed to discuss the accuracy of MES in patients with UC and PSC-UC and to explore the consistency between MES and the Nancy histological index.

Key Words: Primary sclerosing cholangitis; Ulcerative colitis; Diagnosis; Mayo endoscopic subscore; Nancy histological index

Core Tip: Patients with ulcerative colitis and primary sclerosing cholangitis have a high risk of colonic neoplasia and are more likely to have pancolitis, backwash ileitis, and rectal sparing. Both endoscopic and histological inflammation evaluation are important for the diagnosis and treatment of ulcerative colitis with concomitant primary sclerosing cholangitis. Therefore, this study aimed to explore the consistency between endoscopic and histological evaluation.

TO THE EDITOR

We were interested in the prospective study conducted by Wohl et al[1]. This study indicates that the Mayo endoscopic subscore (MES) insufficiently identifies microscopic inflammation in ulcerative colitis with concomitant primary sclerosing cholangitis (PSC-UC), and that histological evaluation should become a routine diagnostic and grading system for both PSC-UC and primary sclerosing cholangitis (PSC). PSC is a chronic immune-mediated cholestatic liver disease, and its main clinical manifestations are closely related to inflammatory bowel disease (IBD), particularly ulcerative colitis (UC)[2]. Patients with PSC-UC have a higher risk of colorectal cancer, biliary tract cancer, and a higher risk of death than patients with IBD and the general population[3]. One study found more healthcare use, medication use, and adverse clinical events of surgery in patients with PSC-UC than in patients with UC-alone, and medications, including immunomodulators and biologics, were prescribed significantly more often in the PSC-UC group[4]. Therefore, the accurate diagnosis and assessment of the severity of PSC-UC are crucial.

We often use endoscopic assessment of mucosal disease activity to determine eligibility and response to therapy in UC clinical trials. MES, one of the most commonly used endoscopic measures, is a four-point scoring system in which patients with normal, inactive, mild, moderate, or severe disease have scores of zero, one, two, or three, respectively[5]. Although increasing importance has been placed on the use of MES as an outcome measure, its validity and reliability require further consideration. Histological remission is an appropriate endpoint for clinical trials on UC. The Nancy histological index (NHI) is an easy-to-use histological assessment index with high interobserver reliability for the assessment of histological disease activity in patients with UC in a real-world setting[6]. PSC-UC is characterized by milder but more extensive intestinal inflammation, rectal sparing, and backwash ileitis[7]. It is novel and interesting to explore the concordance between MES and NHI for assessing the severity of PSC-UC and will provide guidance for clinical practice.

WE WOULD LIKE TO DRAW ATTENTION TO SEVERAL ASPECTS CONCERNING THIS STUDY

The authors conducted a single-center prospective longitudinal study incorporating 59 Caucasian adult patients, which could have led to less objective results. This study had a small sample size, which may have increased the risk of bias and affected the validity and reliability of the results. The limited sample size may be related to the low prevalence of PSC-UC, which is elaborated upon in the discussion. Second, UC, as the other primary endpoint of interest in the article, should also be given the appropriate diagnostic criteria. The inclusion and exclusion criteria of patients with UC for the study should have been more detailed, as the prevalence of UC is much higher than that of PSC-UC.

Wohl et al[1] describe the hematologic parameters in the section “Laboratory and Biochemical Parameters”; however, this information is not included in the manuscript, suggesting that the section could be removed. Additionally, the authors mention “fecal calprotectin” but fail to clarify its relationship with PSC or UC. It would be better to incorporate relevant references and provide further explanation of the role of fecal calprotectin in relation to PSC and UC. Heterogeneity exists in the assessment of white-light endoscopic images of UC and PSC-UC by different endoscopists. Therefore, this study should describe the qualifications and number of endoscopists involved in the study and standardize the MES methods in detail.

Moreover, the number of UC patients using biological treatment was significantly higher than that of patients with PSC-UC, whereas all PSC-UC patients were treated with ursodeoxycholic acid, and it is worth considering whether this affects the concordance between MES and NHI. The authors demonstrated a lack of correlation between MES and NHI in patients with PSC-UC and indicated that MES insufficiently identified ongoing microscopic inflammation in these patients, underscoring the importance of histological scoring in clinical practice. This finding is interesting and has implications for clinical applications. A previous study including 23 PSC-UC patients and 120 UC patients found that PSC-UC patients in clinical remission had increased subclinical endoscopic disease activity and histologic activity in the right colon compared to UC patients without PSC, and PSC-UC patients had a more severe grade of histologic than endoscopic inflammation in the proximal colon[8]. Both studies highlighted the inconsistency between endoscopic disease activity assessment and histological assessment in patients with PSC-UC. However, further exploration is required to determine whether MES underestimates or overestimates the degree of inflammation in PSC-UC. Another study on children found that patients with PSC-IBD in clinical remission had a significantly higher risk of active endoscopic and histologic scores than children with colitis without PSC using MES and UC endoscopic index of severity scores; however, a correlation analysis of endoscopic and histological scores was not performed[9]. The importance of MES in clinical practice cannot be ignored, and more studies with larger sample sizes are needed to further explore the correlation between MES and NHI.

CONCLUSION

We concur with the authors’ viewpoint, emphasizing the significance of inspecting all colonic segments (ileum, cecum, rectum, sigmoid, descending, transverse, and ascending colon) using both colonoscopy and histopathology to obtain a comprehensive understanding of the disease presentation in patients with PSC-UC. This facilitates the detection of favorable sites for PSC-UC and is in line with the guideline-recommended multi-point biopsy. This study found that MES has limited validity in scoring the severity of PSC-UC, variously underestimating or overestimating the severity of inflammation, but the validity and reliability of other endoscopic scoring methods, such as the Baron score, UC endoscopic index of severity scores, and UC colonoscopic index of severity deserve further exploration. As the authors expect, we look forward to the application of artificial intelligence in the endoscopic diagnosis and assessment of PSC-UC. Lastly, we acknowledge and thank the authors for their efforts and contributions and suggest further multicenter studies with larger sample sizes.