How to Estimate the Probability of Tolerance Long-Term in Liver Transplant Recipients.

BACKGROUND: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. PATIENTS AND METHODS: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. RESULTS: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). CONCLUSION: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.

Clinical and Histological Long-Term Follow-Up of De Novo HBV-Infection after Liver Transplantation.

Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7-5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123-9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.

Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection.

Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (p = 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear.

Minimization of Immunosuppressive Therapy Is Associated with Improved Survival of Liver Transplant Patients with Recurrent Hepatocellular Carcinoma.

INTRODUCTION: Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown. METHODS: All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed. RESULTS: Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0-203.0), with the majority presenting early after transplantation (63.0%, <2 years). Median survival after rHCC diagnosis was 10.6 months (0.3-228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (n = 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months). CONCLUSION: Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.