Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference

Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort

Background & Aims: Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort. Methods: We retrospectively studied PSC patients attending two tertiary referral hospitals over 20 years. Diagnosis of PSC was made according to international guidelines by positive cholangiography and/or liver biopsy (for small duct PSC) with supporting clinical and laboratory evidence. Results: Of 208 PSC patients (61% male) were studied (2271patient-years follow-up). The median age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40 years vs 42 years, P =.35). All 33 deaths occurred in PSC-IBD patients while there were no deaths in PSC-only patients (21% vs 0%, P <.01). However, there were no significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P =.45) and transplant-free survival between PSC-only and PSC-IBD patients (P =.43). On multivariate Cox regression, only elevated international normalized ratio (INR) was associated with a greater risk of death or liver transplant (HR 2.0, 95% CI 1.1-3.6, P =.02). Development of gastrointestinal malignancy was higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P <.01). Conclusion: Australian PSC patients have similar characteristics compared to European and North American cohorts. IBD is a significant predictor of gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall transplant-free survival remained similar in PSC-IBD and PSC-only groups. An elevated INR was an independent predictor of death or liver transplantation

Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index

Background and Aim: Donor liver steatosis can impact on liver allograft outcomes. The aim of the present study was to comprehensively report on the impact of type and grade of donor steatosis, as well as donor and recipient factors, including the reported Donor Risk Index (DRI), on liver allograft outcomes. Methods: Areview of unit data for all adult liver transplant procedures from 2001 to 2007, as well as donor offers. Donor liver biopsies were regraded for steatosis by an experienced histopathologist. Results: Steatosis was detected in 184/255 (72%) of biopsies, of which 114 (62%) had microvesicular steatosis (MiS; 68 mild, 22 moderate, 24 severe) and 70 (38%) macrovesicular steatosis (MaS; 59 mild, 7 moderate, 4 severe). The majority (66/70, 94%) of biopsies with MaS also contained MiS. Allograft steatosis was associated with increasing donor body mass index (P = 0.000), plus donor male sex (P <0.05). Primary non function (P = 0.002), early renal failure (P = 0.040), and requirement for retransplantation (P = 0.012) were associated only with severe MaS. Early biliary complications were associated with moderate MaS (P = 0.039). Only severe MaS was significantly associated with inferior allograft survival at 3 months (relative risk = 12.09 [8.75-19.05], P = 0.000) and 1 year (P = 0.000). Conclusions: MiS is a common finding and frequently coexists with MaS on liver allograft biopsy, while isolated MaS is uncommon. Only the presence of moderate to severe MaS is associated with inferior early allograft outcomes. The impact of severe MaS on allograft survival appears greater than other donor factors, including the calculated DRI

Circulating fibroblast activation protein activity and antigen levels correlate strongly when measured in liver disease and coronary heart disease

textabstractBackground and aim: Circulating fibroblast activation protein (cFAP) is a constitutively active enzyme expressed by activated fibroblasts that has both dipeptidyl peptidase and endopeptidase activities. We aimed to assess the correlation between cFAP activity and antigen levels and to compare variations in levels. Methods: In plasma of 465 control individuals, 368 patients with coronary heart disease (CHD) and 102 hepatitis C virus (HCV) infected patients with severe liver disease before and after liver transplant, cFAP activity levels were measured with a newly developed cFAP activity assay. In the same samples, cFAP antigen levels were measured using a commercially available cFAP ELISA. Correlation analyses between activity and antigen levels were performed by calculating Pearson's correlation coefficient (ρ). Additionally, normal ranges, determinants and differences between cohorts and between anticoagulants were investigated. Results: cFAP activity and antigen levels significantly correlated in controls (ρ: 0.660, p<0.001) and in CHD patients (ρ: 0.709, p<0.001). cFAP activity and antigen levels in the HCV cohort were significantly lower in the samples taken after liver transplantation (p<0.001) and normalized toward levels of healthy individuals. Furthermore, cFAP activity and antigen levels were higher in men and significantly associated with body mass index. Also, cFAP activity and antigen levels were higher in EDTA plasma as compared to the levels in citrated plasma from the same healthy individuals. Conclusions: For analyzing cFAP levels, either activity levels or antigen levels can be measured to investigate differences between individuals. However, it is of importance that blood samples are collected in the same anticoagulant

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

Screening Emergency Admissions at Risk of Chronic Hepatitis C (SEARCH) to diagnose or 're-diagnose' infections is effective in Australia

The World Health Organization has set ambitious viral hepatitis elimination targets; however, difficulties in identifying and engaging patients remain. The emergency visit is an opportunity for enhanced linkage to care (LTC). We assessed the effectiveness of an automated Emergency Department (ED) screening service in identifying patients with hepatitis C (HCV) and achieving LTC. A retrospective evaluation was undertaken, analysing the first 5000 patients screened through an automatic Australian service termed ‘Screening Emergency Admissions at Risk of Chronic Hepatitis’ (SEARCH). Screening was performed for those recommended in the Australian national testing policy, specifically overseas born (OB) and Aboriginal or Torres Strait Islanders (ATSI). Healthcare worker education, patient information materials and opt-out informed consent were used to test sera already collected for biochemistry assays. 5000 of 5801 (86.2%) consecutive eligible patients were screened (OB: 4778, ATSI: 222) from 14 093 ED presentations. HCV antibody was positive in 181 patients (3.6%); 51 (1.0%) were HCV RNA positive. Of 51 HCV RNA–positive patients, 12 were new diagnoses, 32 were ‘re-diagnoses’ (aware but lost to follow-up [LTFU]), and 7 were previously known but treatment contraindicated. LTC was successful in 38 viraemic patients (7 deceased, 4 LTFU, 1 treatment ineligible and 1 declined). Of RNA-negative patients, 75 were previously treated and 49 had presumed spontaneous clearance. Opt-out consent was acceptable to all patients and staff involved. ED screening can lead to additional diagnosing and ‘re-diagnosing’ of HCV, with high rates of LTC. Opt-out consent and automation removed major obstacles to testing