Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning.

Non-invasive alloimmune risk stratification of long-term liver transplant recipients.

Background & Aims: Management of long-term immunosuppression following liver transplantation (LT) remains empirical. Surveillance liver biopsies in combination with transcriptional profiling could overcome this challenge by identifying recipients with active alloimmune-mediated liver damage despite normal liver tests, but this approach lacks applicability. Our aim was to investigate the utility of non-invasive tools for the stratification of stable long-term survivors of LT, according to their immunological risk and need for immunosuppression.

A retrospective analysis of post-transplant lymphoproliferative disorder following liver transplantation.

Objective: To evaluate response rates and survival in adults developing post-transplant lymphoproliferative disorder (PTLD) following liver transplantation.

Methods: Patients were identified retrospectively and data collected through local liver and haematology electronic databases and pharmacy records.

Results: Forty-five patients were identified.

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

Background: Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.

Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease.

Background & Aims: Models of non-alcohol-related fatty liver disease (NAFLD) reveal features of accelerated ageing, such as impaired regeneration, and an increased risk of hepatocellular carcinoma. The relation between accelerated ageing, disease progression and clinical outcome has not been previously investigated and is the subject of the current study.

Methods: Liver sections from 70 patients with NAFLD (105 biopsies) and 60 controls were studied for telomere length, nuclear area, DNA damage and cell cycle phase markers, using quantitative fluorescent in situ hybridization and immunohistochemistry.

Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver.

Unlabelled: Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in "normal" liver tissue, but these studies were compromised by small sample size, limited age range, tissue derived from individuals with an increased risk of senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes.

Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis.

Unlabelled: Patients with primary biliary cirrhosis (PBC) frequently experience significant fatigue thought to result from as-yet-unidentified central nervous system (CNS)-mediated processes. Pilot studies have suggested that autonomic dysfunction is a frequent occurrence in PBC and may contribute to the pathogenesis of this fatigue. The degree to which autonomic dysfunction affects the PBC population as a whole, and its interrelationship with other symptoms experienced by PBC patients remains unstudied.