Introoduction: Primary sclerosing cholangitis (PSC) is a rare disease, especially in Asian countries. PSC often develops during ulcerative colitis (UC). Little is known about the severity of PSC in patients with UC. Thus, this study aimed to investigate the impact of concomitant UC on the clinical course of patients with PSC using a nationwide database in Japan. Methods: We collected data on patients who were admitted for PSC using a nationwide database and divided eligible admissions according to concomitant UC (PSC-UC group vs. PSC-alone group). We conducted propensity score matching and compared the rates of liver transplantation, biliary drainage, and other clinical events between the two groups. We also conducted a multivariate analysis to identify the clinical factors that affect biliary drainage, cholangiocarcinoma, and liver transplantation. Results: We enrolled 672 patients after propensity score matching. The rate of liver transplantation in the PSC-UC group was lower than that in the PSC-alone group (2.2 vs. 5.4%, p = 0.002), whereas the rate of biliary drainage did not differ between the two groups (38.1 vs. 33.8%, p = 0.10). On multivariate analysis, concomitant UC was identified as a clinical factor that decreased the risk of liver transplantation (odds ratio = 0.40, 95% confidence interval: 0.23–0.68, p = 0.0007). Discussion: Concomitant UC in patients with PSC may decrease the risk of liver transplantation. The milder disease activity of PSC with UC is more likely compared to that of PSC without UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with repeated exacerbation and remission of unknown etiology and sometimes develops several extraintestinal manifestations (EIMs) [1, 2]. Primary sclerosing cholangitis (PSC) is a rare EIM of UC and is defined as a chronic cholestatic liver disease characterized by lesions in the intra- and/or extrahepatic bile duct [3]. There are no curative treatments for critical PSC, and several patients with end-stage PSC require liver transplantation [3].

As described above, PSC is a rare EIM of UC, with reports that PSC is diagnosed in 0.8–5.6% of patients with UC [3, 4]. In contrast, 50–80% of patients with PSC had UC in Northern Europe and the USA [5‒8], whereas the incidence of PSC in healthy controls was 2% in the UK [8]. These studies indicate that PSC and UC are expected to have a strong relationship and have the potential to affect each other’s clinical course. Several studies have reported that the clinical course of UC associated with PSC is better than that of UC alone [9‒14]. However, little is known about the impact of concomitant UC on the clinical course of PSC. The low incidence of PSC, even in the general population [6], especially in Eastern countries [15], makes analyses difficult because of the small number of samples in a single center. Moreover, the studies described above were mostly from Western countries. The influence of UC on PSC should be investigated in clinical practice.

The diagnosis procedure combination (DPC) database is a nationwide database of hospitalizations in Japan, which contains data from a large number of patients and is useful for analyzing rare diseases, including PSC. Therefore, the PSC-UC association may be better understood by performing an analysis of a large nationwide sample using DPC data. To date, clinical studies have been conducted using the DPC database [14, 16‒19]. This study aimed to investigate the impact of concomitant UC on the clinical course of patients with PSC, using a nationwide database in Japan.

DPC System

The DPC database, introduced in 2003, is a medical claims database of acute-care hospital admissions in Japan. The system was adopted by 1,764 hospitals in 2022 and covers approximately 85% of the acute care beds (approximately 480,000 beds) in Japan [20] . The DPC database contains patient demographics, medications, surgeries, procedures (including endoscopic and percutaneous biliary drainage), and condition at discharge [21‒24]. Disease diagnosis was categorized as “main diagnosis,” “main disease triggering admission,” “most resource-consuming diagnosis,” “second-most resource-consuming diagnosis,” “comorbidities at admission,” and “complications after admission.” Physicians input these patient diagnoses into the database according to the International Classification of Diseases, Tenth Revision (ICD-10). The diagnostic validity of UC using ICD-10 has been recognized [25, 26]. The DPC database cannot track the same patients if they are transferred to another hospital. Therefore, in this study, we extracted eligible admissions, instead of counting individuals.

Extraction of Eligible Admissions

This study included administrative claims data for all inpatients discharged from more than 1,000 participating hospitals, as well as for patients with PSC who were admitted to DPC-participating hospitals from April 2012 to March 2020. Eligible admissions due to PSC were identified as those with the phrase “primary sclerosing cholangitis disease (ICD-10 code: K830)” in one of the following categories in the DPC database: “main diagnosis,” “main disease triggering admission,” or “most resource-consuming diagnosis.” We then classified the eligible admissions into two groups: those with and without the phrase “ulcerative colitis” in their list of comorbidities at admission (Fig. 1).

Fig. 1.

Study flowchart. The eligible admissions were extracted from the database as per this flowchart.

Fig. 1.

Study flowchart. The eligible admissions were extracted from the database as per this flowchart.

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Data Collection

We collected the following data on patient and clinical characteristics, procedures, and conditions at discharge from the DPC database: age, sex, body mass index (BMI), smoking history (current or ex-smokers vs. nonsmokers), Charlson comorbidity index (CCI) [27], hospital type (academic hospital or not), duration of admission, in-hospital death, cancer (cholangiocarcinoma [CCA], colorectal cancer [CRC]) in any of the disease list, systemic steroid injection, biliary drainage (endoscopic stent insertion, endoscopic nasobiliary drainage, and percutaneous drainage), liver transplantation, and surgery for malignancy (hepatectomy, pancreaticoduodenectomy, hepatic hilar bile duct malignant tumor resection). CRC was identified using the phrase “colon cancer” or “rectal cancer” in the patient’s disease list. In addition, any disease name that contained the word “suspicious” was excluded.

Data Analysis

Eligible admissions were divided into two groups, with and without concomitant UC (PSC-UC group vs. PSC-alone group). We also classified the eligible admissions into two categories according to their age (elderly, aged ≥65 years; nonelderly, aged ≤64 years) based on the World Health Organization (WHO) classification [28]. We also classified the eligible admissions into three categories according to their BMI (underweight: <18.5 kg/m2, normal range: 18.5–24.9 kg/m2, and overweight: ≥25.0 kg/m2), based on the WHO classification [29]. The patients’ background (sex, average age, BMI, CCI, smoking status, hospital type, and median days of hospital stay), treatments (biliary drainage, surgery, and liver transplantation), comorbidities (CRC and CCA), and clinical events (in-hospital death) were compared between the two groups using χ2 tests. We also performed multivariate analysis using logistic regression to identify the clinical factors affecting drainage and transplantation procedures. Clinical factors, including age, sex, BMI, academic hospital, and smoking, were considered to affect disease severity. Systemic steroid injections have also been considered to affect the efficacy of biologics and surgery [1]. Therefore, these factors were selected as variables for the multivariable analysis.

We also performed a propensity score matching analysis to determine the effect of concomitant UC on the clinical activity of PSC. The following variables were used for propensity score matching: age, sex, BMI, smoking history, hospital type, and CCI. We calculated the C-statistics and standardized differences for each variable described earlier when we conducted propensity score matching. C-statistics are preferable if they are over 0.7. After matching, the two groups were comparable for all standardized differences <0.1. After propensity score matching, we compared the treatments, comorbidities, length of hospital stay, and clinical events between the two groups.

The threshold for statistical significance was set at p < 0.05. All analyses were performed using the JMP Pro14 software (SAS Institute, Tokyo, Japan).

Ethical Considerations

The study protocol was reviewed and approved by the Ethics Committee of the Tohoku University Graduate School of Medicine (2020-1-325). The requirement for informed consent was waived because of the anonymity of the data.

Patients’ Backgrounds

The background of eligible admissions is summarized in Table 1. We eventually included 6,226 eligible admissions, of which 924 were assigned to the PSC-UC group and the remaining 5,302 to the PSC-alone group. After propensity score matching, 672 pairs were selected, and there were no differences in background characteristics between the two groups. The C-statistic was 0.90, and the standardized difference for each variable was <0.1.

Table 1.

Comparison of the clinical characteristics of the study population between before and after propensity score matching

 Comparison of the clinical characteristics of the study population between before and after propensity score matching
 Comparison of the clinical characteristics of the study population between before and after propensity score matching

Comparison of Treatments, Comorbidities, and Clinical Events

The results of the comparison between the two groups are summarized in Table 2. Before propensity score matching, the rates of concomitant CCA and in-hospital death in the PSC-UC group were significantly lower than those in the PSC-alone group (2.3 vs. 4.4%, p = 0.0019; 1.7 vs. 3.9%, p = 0.0004). After propensity score matching, the liver transplantation rate in the PSC-UC group was significantly lower than that in the PSC-alone group (2.2 vs. 5.4%, p = 0.002).

Table 2.

Comparison of medical treatments, comorbidities, and clinical events in the study population

 Comparison of medical treatments, comorbidities, and clinical events in the study population
 Comparison of medical treatments, comorbidities, and clinical events in the study population

Multivariate Analysis for Biliary Drainage, CCA, and Liver Transplantation

The results of multivariate analysis of drainage are summarized in Table 3. Female sex was identified as a clinical factor that decreased the risk of biliary drainage (odds ratio [OR] = 0.80, 95% confidence interval [CI]: 0.71–0.88, p < 0.0001). Conversely, older age was identified as a clinical factor that increased the risk of biliary drainage (OR = 1.48, 95% CI: 1.33–1.66, p < 0.0001). Concomitant UC has not been identified as a clinical factor affecting the risk of biliary drainage.

Table 3.

Multivariate analysis of the association between clinical factors and three endpoints (biliary drainage, CCA, and liver transplantation)

 Multivariate analysis of the association between clinical factors and three endpoints (biliary drainage, CCA, and liver transplantation)
 Multivariate analysis of the association between clinical factors and three endpoints (biliary drainage, CCA, and liver transplantation)

Regarding CCA, only older age was identified as a clinical factor that increased the risk (OR = 2.45, 95% CI: 1.82–3.28, p < 0.0001). Other factors that affected the risk of CCA were not identified as clinical factors.

Multivariate analysis also showed the clinical factors that affected the risk of liver transplantation. Concomitant UC (OR = 0.40, 95% CI: 0.23–0.68, p = 0.0007) and elderly age (OR = 0.04, 95% CI: 0.01–0.13, p < 0.0001) were identified as clinical factors that decreased the risk of liver transplantation. Conversely, underweight (OR = 2.03, 95% CI: 1.40–2.97, p = 0.0003) and academic hospitals (OR = 15.2, 95% CI: 7.10–32.8, p < 0.0001) were identified as clinical factors that increased the risk of liver transplantation.

We investigated the impact of concomitant UC in patients with PSC by comparing treatment outcomes and clinical events using a DPC database. We also conducted multivariate analysis to identify the factors that affect the clinical course and activity of PSC. After propensity score matching, the rate of liver transplantation in the PSC-UC group was lower than that in the PSC-alone group. On multivariate analysis, our results also showed that concomitant UC was a clinical factor that decreased the risk of liver transplantation. However, our analysis did not show whether concomitant UC is related to the risk of biliary drainage and CCA.

After propensity score matching, the PSC-UC group demonstrated a lower rate of liver transplantation than the PSC-alone group. Multivariate analysis using the data before propensity score matching also revealed that concomitant UC decreased the OR for liver transplantation. To the best of our knowledge, this is the first study to demonstrate a lower risk of liver transplantation in patients with PSC-UC than in those with PSC alone. Although a retrospective single-center study reported a tendency for a lower rate of liver transplantation (including candidacy) in the PSC-UC group than in the PSC-alone group, there was no statistical difference between the two groups [30]. This may be because this study included a relatively small number of patients. In contrast, our study, which included a large number of cases, was able to identify the difference between the two groups. However, another study reported no association between concomitant UC and the rate of liver transplantation [13]. Several reports have described differences in the incidence and clinical course of UC and PSC between Western and Eastern countries [15, 31, 32]. Although our study included a large number of patients, its design was retrospective. Further prospective studies in Asian countries are warranted.

The DPC database does not include detailed clinical information such as endoscopic findings, laboratory data, computed tomography, and magnetic resonance imaging. Biliary drainage was selected as an indicator of PSC disease activity in this study. This study did not show a difference in the rate of biliary drainage between the two groups and demonstrated that concomitant UC was not associated with the risk of biliary drainage in multivariate analysis. These results indicate that the disease activity of PSC is not different, regardless of concomitant UC. We previously reported a study regarding the impact of concomitant PSC in patients with UC [14], whose relationship was opposite to that of this study. Our previous study indicated that UC patients with PSC might have lower UC disease activity than patients with UC alone. Conversely, the results of this study did not demonstrate such differences in disease activity between the PSC-UC and PSC-alone groups. The discrepancy between the results of biliary drainage and liver transplantation might be due to the low rate of liver transplantation in Japan. Liver transplantation is the only curative treatment for PSC. A multicenter survey reported that only 12% of patients undergo liver transplantation in Japan [33]. In Japan, the annual number of liver transplantation was only around 400 cases [34, 35]. The number of liver transplantation in other Asian countries including India and Korea were higher than that in Japan. Furthermore, the annual number of liver transplantation in the USA was about 8,000 cases in 2017 (source of information: http://www.transplant-observatory.org) (last accessed December 30, 2022). This small number of liver transplantation in Japan may lead to our results of low rate of liver transplantation. Palliative endoscopic or percutaneous biliary drainage should be performed instead of liver transplantation. As previously described, biliary drainage was selected as an indicator of PSC severity. Such palliative biliary drainage may not reflect the severity of PSC. We must conduct a prospective study to precisely evaluate the disease severity of PSC.

As PSC progresses, there is a risk of developing liver cirrhosis, CCA, and/or CRCs [36]. Our analysis did not demonstrate a difference in the rates of CCA and surgery, which are suspected to be related to CCA. Moreover, the rate of CRC did not differ between PSC-UC group and UC-alone group. Several studies from Asian countries have reported no difference in the rates of CRC between PSC-UC group and UC-alone group [30, 37]. On the contrary, a retrospective study from Japan reported that the rate of CCA in PSC-UC group was higher than that in UC-alone group [30]. The risk of malignancy in patients with PSC-UC is inconsistent. There may be geographical and genetic differences in the development of malignant tumors between Western and Eastern countries, as well as in the incidence of PSC.

This study has some limitations. First, the DPC database does not contain detailed patient information, including laboratory data and endoscopic and radiological findings, which are useful for evaluating the severity of PSC. Therefore, we indirectly evaluated the disease severity by investigating the rates of liver transplantation and biliary drainage. Second, the DPC database mainly includes data of in-hospital patients, not out-hospital patients, and cannot identify the same patients referred to another hospital. The number of admissions was counted. Moreover, our study design was cross-sectional owing to the nature of the DPC database. However, prospective or retrospective cohort studies are preferable for analyzing chronic diseases, such as PSC and IBD. Furthermore, selection bias is one of the limitations of this study. Our study design limited to inpatients who are expected to be more severe than outpatients. Another study using a database which was different from the DPC reported that 14.1% of patients with UC were hospitalized at onset [38]. We need to conduct a prospective cohort study or a retrospective study which includes outpatients’ data to eliminate selection bias. Third, we cannot deny the existence of confounding factors derived from the design of this study even though propensity score matching was performed. Fourth, the validity of PSC using ICD-10 is not completely confirmed [39]. However, another study described that the new PSC-specific ICD-10 code released in 2018 could deal with this issue [40]. Further investigations of validating for UC using ICD-10 code are warranted. Although this study has some limitations, the DPC database contains a large number of admissions, which enables us to analyze rare diseases and comorbidities.

In conclusion, concomitant UC in patients with PSC may decrease the risk of liver transplantation, although the risk of biliary drainage was not different regardless of the presence of concomitant UC. The milder disease activity of PSC with UC is more likely compared to that of PSC without UC. Further prospective studies are warranted to clarify the effect of concomitant UC on the clinical course of PSC.

We would like to thank Honyaku Center Inc. for English language editing.

The study protocol was reviewed and approved by the Ethics Committee of the Tohoku University Graduate School of Medicine (2020-1-325).The requirement for written informed consent was waived because of the anonymity of the data. This decision was approved by the Ethics Committee of the Tohoku University Graduate School of Medicine (2020-1-325).

The authors have no conflicts of interest to declare.

The current study was self-funded.

R.M., K.Y., K.T., Y.S., T.N., H.S., and Y. Kakuta contributed to the study conception and design. Material preparation, data collection, and analysis were performed by R.M., K.T., K. Fujimori, and K. Fushimi. The first draft of the manuscript was written by R.M. and revised critically by S.H., Y. Kunouchi, and A.M. All authors read and approved the final version of the manuscript.

Data cannot be shared with researchers who are not approved to access them by the Japanese Ministry of Health, Labour and Welfare. Further inquiries can be directed to the corresponding author.

1.
Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018 Mar;53(3):305–53.
2.
Garber A, Regueiro M. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, etiopathogenesis, and management. Curr Gastroenterol Rep. 2019 May 16;21(7):31.
3.
Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet. 2018 Jun 23;391(10139):2547–59.
4.
Fraga M, Fournier N, Safroneeva E, Pittet V, Godat S, Straumann A, et al. Primary sclerosing cholangitis in the swiss inflammatory bowel disease cohort study: prevalence, risk factors, and long-term follow-up. Eur J Gastroenterol Hepatol. 2017 Jan;29(1):91–7.
5.
Tischendorf JJW, Hecker H, Krüger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007 Jan;102(1):107–14.
6.
Da Cunha T, Vaziri H, Wu GY. Primary sclerosing cholangitis and inflammatory bowel disease: a review. J Clin Transl Hepatol. 2022 Jun 28;10(3):531–42.
7.
Bambha K, Kim WR, Talwalkar J, Torgerson H, Benson JT, Therneau TM, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003 Nov;125(5):1364–9.
8.
Liang H, Manne S, Shick J, Lissoos T, Dolin P. Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom. Medicine. 2017 Jun;96(24):e7116.
9.
Lundqvist K, Broomé U. Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis: a case control study. Dis Colon Rectum. 1997 Apr;40(4):451–6.
10.
Moayyeri A, Daryani NE, Bahrami H, Haghpanah B, Nayyer-Habibi A, Sadatsafavi M. Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis. J Gastroenterol Hepatol. 2005 Mar;20(3):366–70.
11.
Wang MH, Mousa OY, Friton JJ, Raffals LE, Leighton JA, Pasha SF, et al. Unique phenotypic characteristics and clinical course in patients with ulcerative colitis and primary sclerosing cholangitis: a multicenter US experience. Inflamm Bowel Dis. 2020;26(5):774–9.
12.
Sokol H, Cosnes J, Chazouilleres O, Beaugerie L, Tiret E, Poupon R, et al. Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis. World J Gastroenterol. 2008 Jun 14;14(22):3497–503.
13.
Aranake-Chrisinger J, Dassopoulos T, Yan Y, Nalbantoglu I. Primary sclerosing cholangitis associated colitis: characterization of clinical, histologic features, and their associations with liver transplantation. World J Gastroenterol. 2020 Jul 28;26(28):4126–39.
14.
Yano K, Moroi R, Shiga H, Tarasawa K, Shimoyama Y, Kuroha M, et al. Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: an investigation using a nationwide database in Japan. JGH Open. 2022 Jan;6(1):50–6.
15.
Tanaka A, Mertens JC. Ulcerative colitis with and without primary sclerosing cholangitis: two different diseases? Inflamm Intest Dis. 2016 Apr;1(1):9–14.
16.
Shiga H, Tarasawa K, Moroi R, Makuuchi M, Takahashi T, Shimoyama Y, et al. Long-term effectiveness of ustekinumab comparable to anti-tumor necrosis factor agents in patients with crohn’s disease. J Gastroenterol Hepatol. 2022 Sep 5;37(11):2105–12.
17.
Moroi R, Tarasawa K, Shimoyama Y, Kuroha M, Shiga H, Kakuta Y, et al. Effectiveness of colonic stent placement for obstructive colorectal cancers: an analysis of short-term results using a nationwide database in Japan. J Gastroenterol Hepatol. 2022 Jul;37(7):1316–25.
18.
Moroi R, Tarasawa K, Shiga H, Yano K, Shimoyama Y, Kuroha M, et al. Efficacy of urgent colonoscopy for colonic diverticular bleeding: a propensity score-matched analysis using a nationwide database in Japan. J Gastroenterol Hepatol. 2021 Jun;36(6):1598–604.
19.
Moroi R, Shiga H, Tarasawa K, Yano K, Shimoyama Y, Kuroha M, et al. The clinical practice of ulcerative colitis in elderly patients: an investigation using a nationwide database in Japan. JGH Open. 2021 Aug;5(8):842–8.
20.
Medical Division IB, Ministry of Health, Labor W. a. Outline of medical fee revision in 2022. (In Japanese) [cited 7/10/2022]. Available from: https://www.mhlw.go.jp/content/12400000/000920426.pdf..
21.
Yamana H, Moriwaki M, Horiguchi H, Kodan M, Fushimi K, Yasunaga H. Validity of diagnoses, procedures, and laboratory data in Japanese administrative data. J Epidemiol. 2017 Oct;27(10):476–82.
22.
Niikura R, Yasunaga H, Yamaji Y, Horiguchi H, Fushimi K, Yamada A, et al. Factors affecting in-hospital mortality in patients with lower gastrointestinal tract bleeding: a retrospective study using a national database in Japan. J Gastroenterol. 2015 May;50(5):533–40.
23.
Fujimoto S, Nakayama T. Effect of combination of pre- and postoperative pulmonary rehabilitation on onset of postoperative pneumonia: a retrospective cohort study based on data from the diagnosis procedure combination database in Japan. Int J Clin Oncol. 2019 Feb;24(2):211–21.
24.
Yamashita Y, Morimoto T, Yoshikawa Y, Yaku H, Sumita Y, Nakai M, et al. Temporal trends in the practice pattern for venous thromboembolism in Japan: insight from JROAD-DPC. J Am Heart Assoc. 2020 Jan 21;9(2):e014582.
25.
Takahashi S, Obara T, Kakuta Y, Shimoyama Y, Naito T, Moroi R, et al. Validity of diagnostic algorithms for inflammatory bowel disease in Japanese hospital claims data. Int J Environ Res Public Health. 2022 Jun 28;19(13):7933.
26.
Shigemi D, Morishima T, Yamana H, Yasunaga H, Miyashiro I. Validity of initial cancer diagnoses in the diagnosis procedure combination data in Japan. Cancer Epidemiol. 2021 Oct;74:102016.
27.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.
28.
World Health Organization. Men, ageing and health : achieving health across the life span. Geneva: World Health Organization; 2001.
29.
WHOCo Obesity, World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO consultation. Geneva: World Health Organization; 2000.
30.
Kumagai J, Taida T, Ogasawara S, Nakagawa T, Iino Y, Shingyoji A, et al. Clinical characteristics and outcomes of primary sclerosing cholangitis and ulcerative colitis in Japanese patients. PLoS One. 2018;13(12):e0209352.
31.
Ye BD, Yang SK, Boo SJ, Cho YK, Yang DH, Yoon SM, et al. Clinical characteristics of ulcerative colitis associated with primary sclerosing cholangitis in Korea. Inflamm Bowel Dis. 2011 Sep;17(9):1901–6.
32.
Song EM, Yang SK. Natural history of inflammatory bowel disease: a comparison between the East and the West. Intest Res. 2022;20(4):418–30.
33.
Tanaka A, Tazuma S, Nakazawa T, Isayama H, Tsuyuguchi T, Inui K, et al. No negative impact of serum IgG4 levels on clinical outcome in 435 patients with primary sclerosing cholangitis from Japan. J Hepatobiliary Pancreat Sci. 2017 Apr;24(4):217–25.
34.
Soyama A, Eguchi S, Egawa H. Liver transplantation in Japan. Liver Transpl. 2016 Oct;22(10):1401–7.
35.
Hibi T, Wei Chieh AK, Chi-Yan Chan A, Bhangui P. Current status of liver transplantation in Asia. Int J Surg. 2020 Oct;82s:4–8.
36.
Torres J, Pineton de Chambrun G, Itzkowitz S, Sachar DB, Colombel JF. Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease. Aliment Pharmacol Ther. 2011 Sep;34(5):497–508.
37.
Weng MT, Shih IL, Tung CC, Leong YL, Shieh MJ, Wang CY, et al. Association of young age and male sex with primary sclerosing cholangitis in Taiwanese patients with inflammatory bowel disease. Intest Res. 2022 Apr;20(2):224–30.
38.
Shimodaira Y, Watanabe K, Iijima K. Clinical course of ulcerative colitis associated with an age at diagnosis: a recent Japanese database survey. Tohoku J Exp Med. 2021 Sep;255(1):33–9.
39.
Molodecky NA, Myers RP, Barkema HW, Quan H, Kaplan GG. Validity of administrative data for the diagnosis of primary sclerosing cholangitis: a population-based study. Liver Int. 2011 May;31(5):712–20.
40.
Wang M, Auerbach A, Oreper SM, Hohmann SF, Lai JC, Rubin JB. Leveraging a new ICD-10 diagnosis code to characterize hospitalized patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2022 Sep 14.