UDCA for primary sclerosing cholangitis may lower biliary tract cancer risk

Patients with primary sclerosing cholangitis (PSC) who are treated with ursodeoxycholic acid (UDCA) may have a lower risk of liver transplantation, all-cause death, or biliary tract cancer, according to a study from Japan.

Using the Japanese PSC registry which comprises 435 patients with PSC, investigators of this observational study identified and enrolled the 325 patients who met study criteria* (median age 45.8 years, 57.5 percent male). Eighty-six and 24 percent of patients were treated with UDCA and bezafibrate, respectively, with 202 and two patients, respectively, receiving these drugs as monotherapy, and 76 as combination therapy. Forty-five patients did not receive treatment.

The median observation period was 5.1 years, during which time there were 57 deaths. Twenty-four patients underwent liver transplantation. Biliary tract cancer occurred in 26 patients, which were primarily of the bile duct (n=22), while the remaining four patients developed gallbladder cancer.

Treatment with UDCA was associated with a reduced risk of all-cause death or need for liver transplantation compared with non-receipt of UDCA (adjusted hazard ratio [adjHR], 0.467, 95 percent confidence interval [CI], 0.280–0.778; p=0.003). [AASLD 2020, abstract 100]

Women treated with UDCA had a reduced risk of all-cause death or liver transplantation (adjHR, 0.57; p=0.018), while older age (adjHR, 2.04; p<0.001), presence of symptoms (adjHR, 2.13; p=0.003), albumin <3.5 g/dL (adjHR, 3.80; p<0.001), and AST >30 U/L (adjHR, 2.52; p=0.033) were associated with an increased risk.

A model adjusted for inverse probability treatment weighting (IPTW) showed that the improvement in liver transplantation-free survival with UDCA treatment remained significant (adjHR, 0.429, 95 percent CI, 0.245–0.753; p=0.02). The primary analysis results also remained significant in the sensitivity analysis comparing patients who received UDCA monotherapy vs untreated patients (n=247; adjHR, 0.55; p=0.032).

UDCA treatment was also tied to a reduced risk of biliary tract cancer (adjHR, 0.324, 95 percent CI, 0.135–0.778; p=0.012). The significance was lost in the IPTW model (adjHR, 0.42; p=0.10), though the findings remained significant in the sensitivity analysis (adjHR, 0.39; p=0.043).

Increasing age was associated with an increased risk of biliary tract cancer (adjHR, 2.70; p<0.001), while the risk was reduced in women (adjHR, 0.34; p=0.029).

Due to the lack of alternative medical treatment options for PSC, UDCA is frequently used as a first-line treatment for most patients with PSC in Japan, noted study author Dr Toshihiko Arizumi from the Teikyo University School of Medicine, Tokyo, Japan, who presented the findings on behalf of the Japan PSC Study Group at the AASLD 2020 Liver Meeting.

This is despite it remaining unclear if UDCA confers long-term benefits in the treatment of PSC, he said.

“In this Japanese PSC cohort, UDCA treatment was significantly associated with an improvement in liver transplantation-free survival,” said Arizumi.

UDCA was also likely to be associated with a reduction in biliary tract cancer, though this result was not consistently significant, he continued, pointing out that the small sample size was at least partly to blame.