Outcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis.

OBJECTIVE: To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986-2017; to determine the factors that influence survival. DESIGN: Retrospective cohort analysis (registry data). SETTING, PARTICIPANTS: Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986-2017, in all four paediatric and six adult liver transplantation centres in the two countries. MAIN OUTCOME MEASURES: Graft and patient survival at one, 5, 10 and 15 years. RESULTS: 142 liver retransplantations were undertaken in children (59 during 1986-2000, 83 during 2001-2017). Kaplan-Meier survival analysis indicated that survival was significantly greater during 2001-2017 than 1986-2000 (P < 0.001). During 2001-2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03-1.4 years) during 1986-2000, and 1.8 years (IQR, 0.1-6.8 years) during 2001-2017 (P = 0.002). The proportion of graft failures that involved split grafts was larger during 2001-2017 (35 of 83, 42%) than 1986-2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. CONCLUSION: Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

Combination therapy is not associated with improved rates of clinical or endoscopic remission in patients with inflammatory bowel disease treated with ustekinumab or vedolizumab: a retrospective study.

Background: Management of inflammatory bowel disease (IBD) involves biological agents, often in combination with thiopurines or methotrexate. The aim of our study was to compare clinical and endoscopic outcomes in IBD patients treated with vedolizumab or ustekinumab, as monotherapy or in combination with thiopurines or methotrexate. Methods: We conducted a retrospective cohort study of all patients aged ≥18 years with a diagnosis of ulcerative colitis or Crohn's disease, commenced on vedolizumab or ustekinumab between October 2015 and March 2022. Primary outcome was clinical remission or response calculated by partial Mayo score (remission: <3; response: improvement >1) for ulcerative colitis or Harvey-Bradshaw index (<5, >2 respectively) for Crohn's disease over 1 year. Secondary endpoints were treatment failure, relapse, endoscopic remission at 1 year. Statistical analysis was done using 2-sample Student's t and chi-square tests. Results: A total of 159 IBD patients were included in the study, 85 (53%) on vedolizumab and 74 (47%) on ustekinumab. For those on vedolizumab, 61 (72%) patients had ulcerative colitis, and 24 (28%) has Crohn's disease. All patients on ustekinumab had Crohn's disease. Mean disease duration in was 9.4 and 13.5 years respectively. There was no difference in clinical response or remission for vedolizumab or ustekinumab monotherapy compared to combination therapy at 1 year. There was also no difference in treatment failure, relapse or endoscopic remission. Conclusion: Combining vedolizumab or ustekinumab with an immunomodulator is not superior to monotherapy in terms of clinical response or endoscopic remission up to 1 year in IBD.

Safety and efficacy of transitioning inflammatory bowel disease patients from intravenous to subcutaneous infliximab: a single-center real-world experience.

Background: A new subcutaneous (SC) formulation exists for infliximab (CT-P13 SC). The aim of this study was to assess the durability of clinical and endoscopic responses after a switch from intravenous (IV) to SC infliximab. Methods: Patients were transitioned on maintenance infliximab, including those with dose-optimized therapy. The primary outcome was clinical, biochemical and overall remission at 6 months, as defined by a Harvey-Bradshaw Index <5 for Crohn's disease or a partial Mayo score <3 for ulcerative colitis, C-reactive protein less than 10 mg/L, and fecal calprotectin less than 100 µg/g. Results: Forty patients were switched from IV to SC infliximab. Twenty-seven (68%) had a diagnosis of Crohn's disease and 13 (33%) had ulcerative colitis. Twenty-three (58%) were on 5 mg/kg of IV infliximab every 8 weeks and 15 (38%) 5 mg/kg every 6 weeks. There were 2 patients (4%) on 10 mg/kg every 6 weeks. At the time of their switch, 37 (93%) patients were in clinical remission, 25 (76%) were in biochemical remission, and 25 (76%) were in both biochemical and clinical remission. At 6 months the proportion of patients in clinical remission decreased from 93% to 82%, with an overall relapse rate of 11%. Treatment persistence at 6 months was 77.5%. Conclusion: Switching patients from IV infliximab to 120 mg fortnightly SC injections is a safe and effective option for the treatment of inflammatory bowel disease, including for those patients on dose-escalated infliximab or with active disease at the time of switch.

Excellent Contemporary Graft Survival for Adult Liver Retransplantation: An Australian and New Zealand Registry Analysis From 1986 to 2017.

BACKGROUND: Liver retransplantation is technically challenging, and historical outcomes are significantly worse than for first transplantations. This study aimed to assess graft and patient survival in all Australian and New Zealand liver transplantation units. METHODS: A retrospective cohort analysis was performed using data from the Australia and New Zealand Liver Transplant Registry. Graft and patient survival were analyzed according to era. Cox regression was used to determine recipient, donor, or intraoperative variables associated with outcomes. RESULTS: Between 1986 and 2017, Australia and New Zealand performed 4514 adult liver transplants, 302 (6.7%) of which were retransplantations (278 with 2, 22 with 3, 2 with 4). The main causes of graft failure were hepatic artery or portal vein thrombosis (29%), disease recurrence (21%), and graft nonfunction (15%). Patients retransplanted after 2000 had a graft survival of 85% at 1 year, 75% at 5 years, and 64% at 10 years. Patient survival was 89%, 81%, and 74%, respectively. This was higher than retransplantations before 2000 (P < 0.001). Univariate analysis found that increased recipient age (P = 0.001), recipient weight (P = 0.019), and donor age (P = 0.011) were associated with decreased graft survival prior to 2000; however, only increased patient weight was significant after 2000 (P = 0.041). Multivariate analysis found only increased recipient weight (P = 0.042) and donor age (P = 0.025) was significant prior to 2000. There was no difference in survival for second and third retransplants or comparing time to retransplant. CONCLUSIONS: Australia and New Zealand have excellent survival following liver retransplantation. These contemporary results should be utilized for transplant waitlist methods.

Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome.

AIM: To establish if serial Hepascore tests (referred to as delta Hepascore) in those with chronic hepatitis C (CHC) correlate with the increase and/or decrease in risk of liver related complications. METHODS: Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28 (8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis and subsequent clinical outcomes in chronic liver disease. RESULTS: Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation (P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint (P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year (P = 0.03). CONCLUSION: In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.