Liver transplantation in adults with liver disease due to common variable immunodeficiency leads to early recurrent disease and poor outcome

Abstract

Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency characterized by antibody deficiency, recurrent bacterial infections, and autoimmunity. Advanced chronic liver disease occurs in a subset of patients with CVID and manifests with various histological features, such as nodular regenerative hyperplasia, inflammation, fibrosis, and cholangiopathy. We present a case series characterizing the outcomes in adult patients transplanted for primary CVID-related liver disease. We discuss the unique transplantation challenges faced in this primary immunodeficiency group including susceptibility to infections and early disease recurrence. There is a statistically significant decrease in 3-year and 5-year survival after liver transplantation in those with CVID-related liver disease (55% at 3 and 5 years) compared with all-comers (89% at 3 years, 81% at 5 years), prompting a need for discussion of suitability of transplantation in this group of patients as well as methods for reducing posttransplantation risk such as scrupulous search for infectious agents and reduction of immunosuppression. Liver Transplantation 24 171-181 2018 AASLD.

Liver Transplantation in Adults With Liver Disease Due to Common Variable Immunodeficiency Leads to Early Recurrent Disease and Poor Outcome

“…Subsequent biopsies were overshadowed by cholangiopathy. This is in line with the early manifestation of NRH in CVID-related liver disease described by Azzu et al (1)…”

“…We read with interest the description from Azzu et al (1) of 4 cases of liver transplantation for nodular regenerative hyperplasia secondary to common variable immunodeficiency (CVID)-related liver disease. The authors describe overall poor outcomes with liver disease recurrence and infectious complications.…”

Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders

“…Noteworthy, histological examination showed NRH changes and cholestasis in all three patients undergoing post-transplant biopsy, as already previously described in non-immunodeficiency subjects (144). After a revision of literature data, including 18 patients, the authors found that CVID patients undergoing LT had a higher mortality compared to LT in general population, with only 55% subjects alive after 3-5 years of post-transplant follow-up (138). Moreover, CVID patients undergoing LT due to CVID-related liver disease (namely NRH) exhibited a worse 5-year survival compared to CVID patients who received LT for any cause (mainly chronic viral hepatitis) (138).…”

“…On the other hand, the theoretical increase of infectious and neoplastic risk related to the long-term concomitant immunosuppressive therapy has historically determined a reluctance to perform LT in CVID patients. In the last decade, a growing number of reports described the outcome of LT performed in adult and pediatric CVID patients with viral hepatitis or NRH (137)(138)(139)(140)(141)(142)(143).…”

“…This different outcome is likely to be related to the changes in immunosuppressive drug regimens from the 1990s to 2009-2013, which consist in the decrease of the glucocorticoid doses. More recently, Azzu et al described four CVID patients undergoing LT for end-stage liver failure, in whom histological examination revealed NRH-like changes (138). In three subjects out of four, post-transplant course was complicated by multiple infectious complications (including Pneumocystis jiroveci pneumonia, toxoplasmosis, neuro-aspergillosis, and CMV proctitis), early recurrent disease, and in one patient, death due to malignancy within 3 years of transplantation.…”