Reply: Living donor liver transplantation for people with PSC

We appreciate the interest in and discussion by Heinemann and colleagues of our recent AASLD Practice Guidance on primary sclerosing cholangitis (PSC) and cholangiocarcinoma.1 Indeed, we believe that living donor liver transplantation (LDLT) remains a promising option for PSC patients who might not otherwise have access to deceased donor liver transplantation (LT). Heinemann et al.2 queried the European Liver Transplant Registry (ELTR) and found that survival in adults and children with PSC was significantly lower after LDLT compared with deceased donor LT. They also found that LDLT recipients were at increased risk of biliary complications and recurrent PSC. These findings are intriguing and important; however, the analysis was not performed on an intention-to-treat basis and, therefore, does not account for the waitlist dropout of PSC patients awaiting deceased donor LT. In addition, the LT programs represented in the ELTR are low LDLT volume programs and LDLT volume has been associated with outcomes, including recipients undergoing LDLT for autoimmune hepatitis or cholestatic liver disease at high LDLT volume centers who had a significantly lower risk of graft failure than those transplanted at low LDLT volume centers.3 Furthermore, data from the Adult to Adult Living Donor Liver Transplantation (A2ALL) Cohort demonstrated a similar risk of recurrent PSC for recipients of either LDLT or deceased donor LT, with excellent overall survival despite recurrence.4 Finally, one of the authors (Gonzalo Sapisochin) has observed that at their high LDLT volume transplant center outcomes for PSC patients who have a potential living donor are better compared with those without a living donor option on an intention-to-treat basis (Gonzalo Sapisochin). Unlike other liver disease etiologies such as hepatitis C–associated or alcohol-associated liver disease, PSC patients tend to maintain hepatocellular synthetics function until very late stages of the disease. As a result, patients with PSC tend to have comparatively low Model for End-stage Liver Disease scores, dependent primarily on bilirubin elevation associated with recurrent cholangitis and jaundice. In this context, biological Model for End-stage Liver Disease of PSC patients may not accurately reflect the candidate’s risk of death on the waitlist. Although stratified by disease type, a recent study from Jackson et al.5 demonstrated that LDLT offers a substantial survival benefit to patients with end-stage liver disease even at Model for End-stage Liver Disease–Sodium scores as low as 11 compared with those who remained on the waitlist. This provides even more evidence to encourage LDLT for patients with PSC, especially in low Model for End-stage Liver Disease patients. There is no treatment to alter PSC’s natural history; so, disease progression is anticipated. Moreover, while the timing of overall disease progression varies, PSC patients may experience many severe symptoms, such as fatigue and pruritus, that significantly impact health-related quality of life. All studies of LT in PSC are limited by small sample sizes, wide variability in patient characteristics, and differing definitions of recurrent PSC. Differences in outcomes after LT across studies may also be skewed by referral and selection biases, variable access to LDLT, and clinical experience. We agree that more studies are needed to determine rates of recurrent PSC in patients receiving LDLT and the factors impacting recurrence rates and outcomes.