Incidence, epidemiology and outcomes of acute allograft rejection following liver transplantation in Australia.

BACKGROUND: Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology and outcomes of acute rejection have not been well-described in Australia. METHODS: We retrospectively studied consecutive adults who underwent deceased-donor LT at a single centre between 2010-2020. Donor and recipient data at time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed and only a graft's first instance of biopsy-proven acute rejection was analysed. RESULTS: During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p=0.11). The median time to first episode of rejection was 71 days post-LT: 2.2% hyperacute, 50.4% early (≤90 d) and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI 0.97-1.00, p=0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI 1.27-5.09, p<0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI 0.08-0.58, p<0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI 2.21-4.42, p<0.001) and patient survival (aHR 3.42, 95% CI 2.35-4.98, p<0.001). CONCLUSION: In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.

Epidemiology, characteristics, and outcomes of patients with acute-on-chronic liver failure in Australia.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is distinct from acute decompensation (AD) of cirrhosis in its clinical presentation, pathophysiology, and prognosis. There are limited published Australian ACLF data. METHODS: We performed a single-center retrospective cohort study of all adults with cirrhosis admitted with a decompensating event to a liver transplantation (LT) centre between 2015 and 2020. ACLF was defined using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) definition while those who did not meet the definition were classified as AD. The primary outcome of interest was 90-day LT-free survival. RESULTS: A total of 615 patients had 1039 admissions for a decompensating event. On their index admission, 34% (209/615) of patients were classified as ACLF. Median admission model for end-stage liver disease (MELD) and MELD-Na scores were higher in ACLF patients compared with AD (21 vs 17 and 25 vs 20 respectively, both P < 0.001). Both the presence and severity of ACLF (grade ≥ 2) significantly predicted worse LT-free survival compared with patients with AD. The EASL-CLIF ACLF score (CLIF-C ACLF), MELD and MELD-Na scores performed similarly in predicting 90-day mortality. Patients with index ACLF had a higher risk of 28-day mortality (28.1% vs 5.1%, P < 0.001) and shorter times to readmission compared with those with AD. CONCLUSION: ACLF complicates over a third of hospital admissions for cirrhosis with decompensating events and is associated with a high short-term mortality. The presence and grade of ACLF predicts 90-day mortality and should be identified as those at greatest risk of poor outcome without intervention such as LT.

Impact of Intensive Care Unit Discharge Delay on Liver Transplantation Outcomes.

Background: For general intensive care unit (ICU) patients, ICU discharge delay (ICUDD) has been associated with an increased hospital length of stay (LOS) and the acquisition of multi-resistant organism (MRO) infections. The impact of ICUDD on liver transplant (LT) recipients is unknown. Methods: We retrospectively studied consecutive adult LT between 2011 and 2019. ICUDD was defined as >8 h between a patient being cleared for discharge to ward and the patient leaving the ICU. Results: 550 patients received LT and the majority (68.5%) experienced ICUDD. The median time between clearance for ward and the patient leaving the ICU was 25.6 h. No donor or recipient variables were associated with ICUDD. Patients cleared for discharge early in the week (Sunday-Tuesday) and those discharged outside routine work hours were more likely to experience ICUDD (p = 0.001 and p < 0.001, respectively). The median hospital LOS was identical (18 days, p = 0.96) and there were no differences in other patient outcomes. Patients who became colonized with MRO in the ICU spent a longer time there compared to those who remained MRO-free (9 vs. 6 days, p < 0.001); however, this was not due to ICUDD. Conclusion: ICUDD post-LT is common and does not prolong hospital LOS. ICUDD is not associated with adverse patient outcomes or MRO colonization.

Differential Impact of Extended Criteria Donors After Brain Death or Circulatory Death in Adult Liver Transplantation.

Using grafts from extended criteria donors (ECDs) and donation after circulatory death (DCD) donors is a strategy to address organ shortage in liver transplantation (LT). We studied the characteristics and outcomes of ECD and DCD grafts. We retrospectively studied consecutive adults who underwent deceased donor LT between 2006 and 2019. ECD was defined using modified Eurotransplant criteria. Our primary outcomes were graft and patient survival. A total of 798 grafts were used for LT, of which 93.1% were donation after brain death (DBD; 59.9% were also ECD) and 6.9% were DCD grafts (49.1% were also ECD). Among DBD graft recipients, donors having >33% liver steatosis or 3 ECD criteria resulted in poorer graft survival. Otherwise ECD graft recipients had similar graft and patient survival compared with non-ECD graft recipients. DCD graft recipients also had similar patient survival compared with DBD recipients. However, DCD grafts from an ECD appeared to have worse outcomes. DCD graft recipients experienced higher rates of early allograft dysfunction (50.9% versus 24.7%; P < 0.001) and ischemic biliopathy (16.4% versus 1.5%; P < 0.001) compared with DBD graft recipients. Use of DBD grafts from ECDs did not impact outcomes unless there was significant donor steatosis or 3 Eurotransplant criteria were met. DCD graft recipients have similar patient survival compared with DBD graft recipients as long as the donor was not an ECD. We recommend that DBD donors with 3 or more ECD features or >33% steatosis and DCD donors with any ECD features be used with caution in adult LT.

Impact of Having a Planned Additional Operation at Time of Liver Transplant on Graft and Patient Outcomes.

Advances in liver transplantation (LT) have allowed for expanded indications and increased surgical complexity. In select cases, additional surgery may be performed at time of LT rather than prior to LT due to the significant risks associated with advanced liver disease. We retrospectively studied the characteristics and outcomes of patients who underwent an additional planned abdominal or cardiac operation at time of LT between 2011-2019. An additional operation (LT+) was defined as a planned operation performed under the same anesthetic as the LT but not directly related to the LT. In total, 547 patients were included in the study, of which 20 underwent LT+ (4%). Additional operations included 10 gastrointestinal, 5 splenic, 3 cardiac, and 2 other abdominal operations. Baseline characteristics between LT and LT+ groups were similar. The median total operating time was significantly longer in LT+ compared to LT only (451 vs. 355 min, p = 0.002). Graft and patient survival, intraoperative blood loss, transfusion of blood products, length of hospital stay, and post-operative complications were not significantly different between groups. In carefully selected patients undergoing LT, certain additional operations performed at the same time appear to be safe with equivalent short-term outcomes and liver graft survival as those undergoing LT alone.

Visuospatial dysfunction in Alzheimer's disease and behavioural variant frontotemporal dementia.

OBJECTIVES: Approximately 30% of Alzheimer's disease (AD) patients are misdiagnosed due to overlapping and evolving clinical features. In particular, the distinction of AD from behavioural variant frontotemporal dementia (bvFTD) can be challenging. Measures of visuospatial ability, which rely on parietal lobe function, show promise as markers of AD as the parietal lobe is preferentially affected early in the disease course. We hypothesise that traditional measures of visuospatial function may help distinguish AD from bvFTD. MATERIALS & METHODS: The Addenbrooke's Cognitive Examination (ACE) visuospatial subtask, Rey-Osterrieth Complex Figure (RCF) task, and subtests of the visual object and space perception battery (VOSP) were used to examine visuospatial abilities in 55 AD patients, 51 bvFTD patients, and 54 healthy Controls. A subgroup analysis was performed in patients with Pittsburgh Compound B positron emission tomography (PiB-PET) data. RESULTS: Relative to Controls, AD and bvFTD patients were impaired on almost all visuospatial tasks. Significantly worse performance was observed in AD relative to bvFTD patients on drawing tasks (ACE pentagons/loops copy, cube copy, and all RCF scores) and tasks of spatial orientation (VOSP cube analysis), when controlling for disease severity. CONCLUSIONS: Visuospatial measures demonstrate limited ability to distinguish between AD and bvFTD unless disease severity is taken into consideration. Controlling for disease severity reveals a disproportionate visuospatial impairment in AD compared to bvFTD. Development of targeted measures of visuospatial function is required to improve differential diagnosis of these syndromes.

Can visuospatial measures improve the diagnosis of Alzheimer's disease?

INTRODUCTION: Overlapping and evolving symptoms lead to ambiguity in the diagnosis of dementia. Visuospatial function relies on parietal lobe function, which may be affected in the early stages of Alzheimer's disease (AD). This review evaluates visuospatial dysfunction in patients with AD, frontotemporal dementia, dementia with Lewy bodies, and vascular dementia to determine the diagnostic and prognostic potential of visuospatial tasks in AD. METHODS: A systematic search of studies (1960-2016) investigating visuospatial dysfunction in dementia was conducted. RESULTS: Tests measuring construction, specifically Block Design and Clock Drawing Test, and visual memory, specifically Rey-Osterrieth Complex Figure recall and topographical tasks, show the greatest diagnostic potential in dementia. The Benton visual retention, Doors and People, and topographical memory tests show potential as prognostic markers. DISCUSSION: Tests of visuospatial function demonstrate significant diagnostic and prognostic potential in dementia. Further studies with larger samples of pathologically confirmed cases are required to verify clinical utility.