Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis.

Background & Aims: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Methods: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. Conclusions: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Impact and implications: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. Clinical trial registration: UME-ID-10042.

Safe for Mother, Baby, and Graft? Pregnancy After Liver Transplant: A Single-Center Experience.

BACKGROUND: Although fertility is reduced in patients with liver cirrhosis, recovery of menstrual cycle is acquired after liver transplantation (LT) in most patients, and pregnancy in LT recipients is not unusual. The aim of this study was to evaluate the outcomes of pregnancies in LT recipients in our center. METHODS: Data of 24 pregnancies in 14 LT recipients were collected and statistically analyzed. Demographic and clinical data were documented in each trimester of pregnancy and thereafter. The analysis was conducted in accordance with the 1975 Declaration of Helsinki and was approved by the ethics committee of the University Hospital Essen. RESULTS: Median patient age was 21.5 years (range, 2-32 years) at LT and 31 years (range, 19-41 years) at conception. Median time between LT and conception was 126 months (range, 38-332 months), and median gestation time of completed pregnancies was 38 weeks (range, 29-40 weeks). Seven pregnancies terminated in abortions (29%). Of all deliveries, 6 resulted in preterm births (35%) with median gestation time of 34.5 weeks (range, 29-37 weeks). Gestational diabetes mellitus was the most common maternal complication, occurring in 4 patients (17%). One patient suffered from preeclampsia (4%). Pregnancy-induced hypertension or acute cellular rejection was not reported in our cohort. None of the children had serious complications. CONCLUSIONS: Our data show favorable outcome for pregnancy in LT recipients for mother and offspring. However, these patients are still at risk, particularly regarding high rates of preterm delivery, and preconception counseling and multidisciplinary monitoring are crucial to manage possible complications.

Real-World Administration of Once-Daily MeltDose® Prolonged-Release Tacrolimus (LCPT) Allows for Dose Reduction of Tacrolimus and Stabilizes Graft Function Following Liver Transplantation.

The calcineurin inhibitor tacrolimus is included in most immunosuppressive protocols after liver transplantation. This retrospective, observational 24-month study investigated the tolerability of once-daily MeltDose® prolonged-release tacrolimus (LCPT) after switching from twice-daily immediate-release tacrolimus (IR-Tac) in a real-world cohort of 150 patients with previous liver transplantation. No graft rejection or new safety signals were observed. Only 7.3% of patients discontinued LCPT due to side effects. In the overall patient population, median liver transaminases, total cholesterol, triglycerides, glucose, and HbA1c remained constant after switching to LCPT. Total cholesterol significantly decreased (p ≤ 0.002) in patients with initially elevated levels (>200 mg/dL). A total of 71.8% of 96 patients maintained a glomerular filtration rate >60 mL/min/1.73 m2 throughout the study, while 44.7% of patients were classified as fast metabolizers and 55.3% as slow metabolizers. Median daily tacrolimus dose could be reduced by 50% in fast metabolizers and by 30% in slow metabolizers, while trough levels were maintained in the target range (4-6 ng/mL). In conclusion, our observational study confirmed previous evidence of good overall tolerability and a favorable outcome for the patients after switching from IR-Tac to LCPT after liver transplantation.