Prediction and evaluation of high-risk patients with primary biliary cholangitis receiving ursodeoxycholic acid therapy: an early criterion

Abstract

Background and aims Current treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier. Methods Five hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32–79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion. Results A new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi’an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi’an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients’ capacity of Xi’an criterion was confirmed in both early and late-stage PBC. Conclusions Xi’an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi’an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Evaluation of potential hepatic recompensation criteria in patients with PBC and decompensated cirrhosis

“…In addition to the role of UDCA, we observed that the degree of liver dysfunction at index decompensation, as portrayed by the MELD‐Na score, was another important predictor of recompensation, which is in line with previous findings from studies conducted in ALD and viral liver disease 21,22,32,33 . Furthermore, elevated ALP and increased bilirubin at the time of decompensation were both associated with a significantly reduced likelihood of achieving recompensation, which is in line with previous studies that highlight the prognostic impact of ALP and bilirubin in PBC 5,11,37–39 . Lastly, we also observed an association between variceal bleeding as the index decompensation event and a higher likelihood of recompensation.…”

“…21,22,32,33 Furthermore, elevated ALP and increased bilirubin at the time of decompensation were both associated with a significantly reduced likelihood of achieving recompensation, which is in line with previous studies that highlight the prognostic impact of ALP and bilirubin in PBC. 5,11,[37][38][39] Lastly, we also observed an association between variceal bleeding as the index decompensation event and a higher likelihood of recompensation. Nevertheless, considering the differences in baseline characteristics within our cohort as well as the findings from previous studies, 40 this association may be due to a more preserved hepatic function and lower levels of systemic inflammation in patients with variceal bleeding when compared to patients with ascites or overt HE.…”

Effectiveness of Fenofibrate in Treatment-Naive Patients With Primary Biliary Cholangitis: A Randomized Clinical Trial

“…However, our study showed that the biochemical indicators of the patients changed drastically within 3 months of receiving treatment. It re-enforced retrospective analysis from our cohort, which indicated the treatment effect could be assessed in advance (33).…”

Hypericum perforatum L. and the Underlying Molecular Mechanisms for Its Choleretic, Cholagogue, and Regenerative Properties

“…However, more than 40% of the patients do not respond to UDCA and are considered to experience severe hepatic complications within 10 years [ 9 , 10 ]. Hence, a precise and helpful outcome of UDCA, as the first-line treatment, in the various stages of PBC, is considered doubtful, and the efficacy of second-line treatments has been investigated in trials [ 11 , 12 , 13 , 14 ]. UDCA seems not to be promising in unfavorable consequences of intrahepatic cholestasis of pregnancy [ 15 ].…”