Audit of medical (non-targeted) liver biopsy specimen quality, pathology reporting and effect on patient management

Aims: To evaluate our medical liver pathology practice and its influence on patient management, using audit templates published by the UK Royal College of Pathologists (RCPath). Methods: We audited medical liver biopsies reported in our centre in 2019 using RCPath proformas. Data were collected from pathology reports and corresponding electronic patient record. Results: 60 cases were selected for audit from 135 eligible biopsies reported in 2019. 58/60 cases were core biopsies and 2/60 were laparoscopic wedge biopsies. 53/57 (93%) core biopsies with available data met RCPath adequacy criteria (length >15 mm and/or ≥6 portal tracts). Most reports (57/60; 95%) were judged to have helped patient management. 25/60 (42%) biopsy reports helped to clarify the clinical diagnosis and 48/60 (80%) led to altered management. Conclusions: We demonstrate the utility of the RCPath audit templates, highlighting the clinical value of medical liver biopsies in the diagnostic work-up and management of patients with liver disease

SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide and a growing healthcare burden. The pathobiology of NAFLD is complex, disease progression is variable and unpredictable, and there are no qualified prognostic biomarkers or licensed pharmacotherapies that can improve clinical outcomes; it represents an unmet precision medicine challenge. We established a retrospective multicentre national cohort of 940 patients, across the complete NAFLD spectrum, integrating quantitative digital pathology, hepatic RNA-sequencing and 5.67 million days of longitudinal electronic health record follow-up into a secure, searchable, open resource (SteatoSITE) to inform rational biomarker and drug development and facilitate personalised medicine approaches for NAFLD. A complementary web-based gene browser was also developed. Here, our initial analysis uncovers disease stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with disease progression in NAFLD. Additionally, we construct novel transcriptional risk prediction tools for the development of future hepatic decompensation events

An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. We established a retrospective national cohort of 940 histologically defined patients (55.4% men, 44.6% women; median body mass index 31.3; 32% with type 2 diabetes) covering the complete MASLD severity spectrum, and created a secure, searchable, open resource (SteatoSITE). In 668 cases and 39 controls, we generated hepatic bulk RNA sequencing data and performed differential gene expression and pathway analysis, including exploration of gender-specific differences. A web-based gene browser was also developed. We integrated histopathological assessments, transcriptomic data and 5.67 million days of time-stamped longitudinal electronic health record data to define disease-stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with adverse outcomes in MASLD. We constructed a 15-gene transcriptional risk score to predict future hepatic decompensation events (area under the receiver operating characteristic curve 0.86, 0.81 and 0.83 for 1-, 3- and 5-year risk, respectively). Additionally, thyroid hormone receptor beta regulon activity was identified as a critical suppressor of disease progression. SteatoSITE supports rational biomarker and drug development and facilitates precision medicine approaches for patients with MASLD