Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e17. Learning Objective: Upon completion of this CME activity, successful learners will be able to identify the factors associated with recurrence of primary biliary cholangitis after liver transplantation and define its effect on graft and patient survival. 785 pts received Liver Transplant (LT) due to Primary Biliary Cholangitis (PBC) Global PBC Group 240 pts developed Recurrence of PBC Gastroenterology 2019;156:96-107 CLINICAL LIVER transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years). RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P ¼ .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin !100 mmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P ¼ .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P ¼ .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P ¼ .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P ¼ .02). CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.

Use of Nakanuma staging and cytokeratin 7 staining for diagnosing recurrent primary biliary cholangitis after living‐donor liver transplantation

“…The rate of rPBC after liver transplantation is reportedly as high as 37% at 10 years . Despite the high incidence, rPBC has not been shown to affect graft/patient survival until recently . In a non‐transplant setting, asymptomatic PBC patients are known to have a shorter life expectancy than the general population, and early initiation of UDCA administration reduces the risk of liver‐related failure .…”

“…Although approximately 30% of liver transplant recipients are diagnosed with recurrent PBC (rPBC), recurrence of PBC has been thought not to affect graft or patient survival . Recently, a multicenter cohort study showed that recurrence of PBC was associated with impaired survival . It is therefore important to assess disease recurrence after liver transplantation, and also to prevent recurrence or progression of PBC.…”

Review article: pathophysiology and management of primary biliary cholangitis

“…Given at 13‐15 mg/kg/d, ursodeoxycholic acid (UDCA) is the first‐line therapy used in PBC treatment for all disease stages, 35 with improvements in serum hepatic biochemistry, delayed histological progression, delayed development of esophageal varices, and improved transplant‐free survival 60,61 …”

Recurrence of Primary Biliary Cholangitis After Liver Transplantation: Is Tacrolimus Really Worse Than Other Drugs?

“…We read with great interest the study of Montano-Loza et al 1 regarding outcomes after liver transplantation for primary biliary cholangitis (PBC) and factors associated with its recurrence. We first want to congratulate the authors for their work reporting the largest multicenter cohort published, allowing the identification of risk factors of PBC recurrence like young age at liver transplantation, the presence of biochemical markers of cholestasis after transplantation, and the use of tacrolimus.…”

“…Reply. We thank Rayar et al and Moro et al, for their interest in our recent publication 1 and for highlighting some challenging issues regarding primary biliary cholangitis (PBC) recurrence after liver transplantation (LT).…”