Data from a Japanese cohort of patients with primary sclerosing cholangitis suggested ursodeoxycholic acid (UDCA) was significantly associated with reduced mortality or need for liver transplantation and was also likely to be associated with a reduction of biliary tract cancer.
Data from a Japanese cohort of patients with primary sclerosing cholangitis (PSC) presented at the Liver Meeting Digital Experience, held by the American Association for the Study of Liver Diseases, suggested ursodeoxycholic acid (UDCA) was significantly associated with reduced mortality or need for liver transplantation and was also likely to be associated with a reduction of biliary tract cancer.1
“Although a number of prospective clinical studies were conducted in the past to evaluate the efficacy of UDCA, results were conflicting mainly due to study design such as inappropriate definition of endpoints, limited number of patients and short follow-up,” co-author Toshihiko Arizumi, MD, assistant professor in the Department of Internal Medicine at Teikyo University School of Medicine, said in a press release.2 “As a result, it remains unclear whether UDCA treatment really improves liver transplantation-free survival of PSC patients, and currently there is no effective treatment for PSC. On the other hand, a prospective, randomized, placebo-controlled, well-designed/powered study of UDCA is extremely unlikely to be conducted in the future, since this is an inexpensive, off-patent, old drug, and pharmaceutical companies do not have an interest in such a large-scale study.”
“Therefore, we considered that this retrospective, well-characterized, cohort study would be the best option to demonstrate the clinical benefit of UDCA on long-term outcomes in patients with PSC,” Arizumi added. “We don’t think that UDCA is associated with an increased risk of development of biliary tract cancer. Rather, biliary tract cancer is one of the most troublesome, even fatal, comorbidities of PSC itself. It would be fantastic if UDCA reduces a risk of this cancer in patients with PSC.”
For this study, researchers used the PSC registry in Japan, which included a total of 435 patients with PSC. These patients were prospectively registered in nationwide surveys in 2012 and 2015.
Patients enrolled in had no missing data regarding sex, age at diagnosis, blood test results (including platelet counts, albumin, bilirubin, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase), fibrous indexes at diagnosis, the presence of any symptom at diagnosis, any history or presence of inflammatory bowel disease, past treatment with UDCA and/or bezafibrate, any development of biliary tract (bile duct or gallbladder) cancer, and their long-term outcomes, such as whether they were alive or dead or had undergone liver transplantation.
Of the 435 patients identified, 325 patients met these criteria and were enrolled, including 187 males and 138 females with a median age of 45.8 (IQR, 27.2-64.5). The median observational period was 5.1 (range, 2.3-7.4) years.
UDCA and bezafibrate treatment was given to 278 (86%) and 78 (24%) patients, respectively. During observation, 57 patients died, 24 patients underwent liver transplantation, and 26 patients developed biliary tract cancer, including 22 with bile duct cancer and 4 with gallbladder.
Moreover, multivariate analysis using the Cox proportional hazard model revealed that UDCA treatment was associated with an improvement of liver transplant‐free survival (adjusted HR, 0.467; 95% CI, 0.280‐0.778; P = .003) and a reduction in the development of biliary tract cancer (adjusted HR, 0.324; 95% CI, 0.135‐0.778; P = .012). Sensitivity analysis also suggested a similar significant association with UDCA treatment.
Even further, an inverse probability treatment weighting‐adjusted model indicated a significant association of UDCA with liver transplant‐free survival (adjusted HR, 0.429; 95% CI, 0.245‐0.753; P = .02), though not with biliary tract cancer (adjusted HR, 0.418; 95% CI, 0.158‐1.104; P = .10).
“We believe these findings definitely provide the most robust evidence to show clinical benefit of UDCA in PSC for the time being, and this will encourage more treatment with UDCA in patients with PSC,” concluded Arizumi. “Nevertheless, we don’t consider that this cohort has enough statistical power due to its medium sample size. A large-scale cohort with an international collaboration is required to produce more convincing evidences of UDCA in PSC.”
1. Arizumi T, Tazuma S, Nakazawa T, et al. THE ASSOCIATION OF UDCA TREATMENT WITH LONG‐TERM OUTCOME AND BILIARY TRACT CANCER IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS. Hepatology. doi: 10.1002/hep.31578
2. UDCA Treatment Lowers Biliary Tract Cancer, Need for Liver Transplantation in PSC Patients [news release]. Alexandria, Virginia. Published November 10, 2020. Accessed November 18, 2020. https://www.newswise.com/articles/udca-treatment-lowers-biliary-tract-cancer-need-for-liver-transplantation-in-psc-patients?sc=dwhr&xy=10019792