National audit day 2024 - meeting report

15th November 2024, Royal College of Pathologists

Report by Hannah Fearon and Nicola Barlow, LabMed Regional Audit leads.

The National Audit Day 2024, held on 15th November at the Royal College of Pathologists, provided an excellent platform for clinical scientists, medical staff, and laboratory professionals to share insights into recent audits and review current practices in laboratory medicine. The meeting was a key opportunity to explore audits in the areas of diabetes, haemochromatosis, and Wilson disease, as well as to discuss emerging trends and future audits.  Dr Wassif, National Audit Lead, opened the day by welcoming over 110 delegates to the day which was being held for the first time in a hybrid format.

 

Audit Highlights

National Audit on Diabetes Mellitus
Funmi Akinlade, Barking, Havering and Redbridge University Hospitals NHS Trust

The national audit on diabetes mellitus aimed to assess laboratory practices, diagnostic methods, and consistency in the diagnosis and monitoring of diabetes across the UK. The audit found significant variation in the use of methods for HbA1c testing, with most laboratories using ion-exchange HPLC (56%) and capillary electrophoresis (24%). A key finding was that 73% of laboratories could not differentiate between samples for diagnosis and monitoring.

Key recommendations from the audit included:

• HbA1c should not be used for diagnosing diabetes in children.
• Laboratories should inform users when HbA1c is unsuitable for diagnosis.
• A review of diagnostic criteria for gestational diabetes mellitus (GDM) in the UK population is needed.
• GTTs for GDM should be differentiated from non-antenatal GTTs.

Diabetes: Current and Future Management
Phil Newland-Jones, Southampton General Hospital

Phil Newland-Jones presented on the evolution of diabetes management, with a focus on Type 1 and Type 2 diabetes. The discussion covered the growing overlap between Type 1 and Type 2 diabetes, especially in adults over 30 years old. New therapies such as Teplizumab (a monoclonal antibody for Type 1 diabetes) and GLP-1 receptor agonists were highlighted as potential game-changers for disease management.The talk emphasized the importance of continuous glucose monitors (CGM) and hybrid closed-loop systems, which have shown promising results in improving HbA1c and reducing complications such as retinopathy.A new trend in Type 2 diabetes management is a focus on cardiovascular risk reduction, with medications like SGLT2 inhibitors showing both glucose-lowering and cardiovascular benefits.

C-Peptide Testing in Diabetes
Mark Strachan, Western General Hospital, Edinburgh

Mark Strachan’s presentation focused on the utility of C-peptide testing in distinguishing between Type 1 and Type 2 diabetes. C-peptide levels help identify insulin deficiency and misclassification, particularly in patients who may be misdiagnosed as Type 1 diabetes when they actually have Type 2 or monogenic diabetes.

Key findings included:

• C-peptide >900 pmol/L is indicative of Type 2 diabetes.
• C-peptide <200 pmol/L typically suggests insulin deficiency, common in Type 1 diabetes.
• Misclassification of diabetes types can occur based on clinical features and antibody testing, highlighting the importance of genetic testing and C-peptide measurement for accurate diagnosis.

 

Hybrid Closed Loop Systems
Alistair Lumb, Oxford, UK

Alistair Lumb discussed the advancements in hybrid closed-loop systems for managing Type 1 diabetes. These systems use continuous glucose monitoring (CGM) to adjust insulin delivery in real time, offering better control over blood glucose levels and reducing the risk of severe hypoglycemia and hyperglycemia. The future of diabetes management lies in fully automated, multi-hormone closed-loop systems that could also deliver glucagon to raise blood glucose when necessary.  NICE has already approved hybrid closed-loop systems for managing blood glucose levels in Type 1 diabetes, and early trials indicate that these systems improve HbA1c and time spent in the target glucose range, ultimately reducing the risk of complications.

Clinical Audit of Primary Care ACR Requesting at Airedale Hospital
Thomas Bancroft, 3rd Year STP, Airedale NHSFT Hospital

This audit aimed to evaluate whether the assessment and management of chronic kidney disease (CKD) at Airedale NHS Foundation Trust met the standards set by NICE guidelines (NG203). The audit found significant gaps in the adherence to guidelines, with only 79% of patients with eGFR <90 receiving appropriate ACR testing. Furthermore, a substantial number of patients with elevated ACR levels were not referred to secondary care as required.

Recommendations:

• Improved education for primary care practitioners on the use of ACR testing.
• A region-wide approach to standardizing ACR testing and commenting.
• A follow-up re-audit to assess improvements.

Audit of Immunoglobulin Monitoring and Hypogammaglobulinemia After B-Cell Targeted Therapy
Mohammed Yousuf Karim, Sidra Medicine, Doha

Mohammed Yousuf Karim presented the findings of an audit assessing immunoglobulin (Ig) monitoring in patients receiving B-cell targeted therapies (BCTT) for autoimmune diseases and hematological malignancies. The audit found that while 89.1% of patients had baseline Ig testing, only 79.3% had follow up testing despite 34% exhibiting hypogammaglobulinemia after follow-up testing.

Key recommendations:

• Standardize immunoglobulin monitoring protocols across specialties.
• Raise awareness among clinicians regarding the importance of Ig monitoring, especially in patients undergoing BCTT.
• Consider clinical immunology review for patients with persistent low immunity or recurrent infections.

Wilson Disease national audit
Nicola Barlow, Black Country Pathology Services and Chris Harrington, Berkshire and Surrey Pathology Services

The liver-themed afternoon session commenced with a summary of the findings from the national audit on Wilson Disease, co-presented by clinical scientists, Dr Nicola Barlow and Dr Chris Harrington, from the Birmingham and Guildford SAS Trace Element Laboratories respectively. Wilson Disease is a rare disorder of copper metabolism, which is often difficult to diagnose, requiring effective multidisciplinary working to obtain the best possible outcomes for patients. To complicate matters further, there are three different sets of guidance (BASL, EASL and AASLD) that are used in the UK. The audit considered laboratory and clinical aspects of diagnosis and monitoring of Wilson Disease and attracted 52 responses, with representation from both non-specialist hospitals and specialist Wilson Disease centres. Perhaps unsurprisingly for such a niche area, most centres did not have any specific clinical protocols for Wilson Disease. Furthermore, the data revealed substantial variation in practice, in some cases reflecting the lack of agreement between the guidance, e.g., whether the D-penicillamine challenge test may be used and around diagnostic threshold values, or in other cases, not in keeping with any of the guidance, including restricting screening tests based on age, use of the D-penicillamine challenge test in adults, over-requesting of serum copper and the very wide range of diagnosis-related thresholds in use, particularly for caeruloplasmin and 24-hour urine copper excretion. 

Clinical aspects, assessment of and management of Wilson Disease
Aftab Ala, Royal Surrey NHS Foundation Trust

Complimenting the national audit, Professor Aftab Ala, a Hepatologist and clinical Wilson Disease expert from Kings College, London, gave a thought-provoking summary of the clinical challenges of Wilson Disease through a series of case presentations. The audience learned about the variable clinical presentation of Wilson Disease ranging from a decline in academic performance at school to asymptomatic persistently raised transaminases to fulminant liver failure. This variability hinders clinical recognition of the disease leading to delayed treatment initiation. Professor Ala emphasised that Wilson Disease may at times mimic other more common liver diseases, for example, autoimmune hepatitis or fatty liver disease, or of course, co-exist with these diseases. A case of Wilson Disease presenting in two siblings in their seventies re-enforced the message that Wilson Disease may present at any age. The challenges of diagnosing Wilson Disease, with no single test alone being sufficient to diagnose the disease, was highlighted as a reason for which multidisciplinary working is vital. Professor Ala then showcased some of the newer treatment approaches that are in development, although robust multi-centred trials are still required before they will replace the currently available treatments. Finally, for the clinical biochemists amongst us, a tell-tale sign that fulminant liver failure is caused by Wilson Disease is an alkaline phosphatase to bilirubin ratio of less than two, important to look out for considering that early recognition of Wilson Disease as the cause, is key to survival. 

National audit on iron overload and HFE mutation
Dimitris Grammatopoulos, Warwick Medical School

The second national audit of the afternoon on iron overload and HFE mutation analysis was presented by Professor Dimitris Grammatopoulus from the University of Warwick. Hereditary haemochromatosis is a genetic condition that is likely to be underdiagnosed in patients at risk due to non-specific early symptoms but which may also be misdiagnosed in patients with the genetic predisposition but no evidence of iron overload, owing to incomplete penetrance of the C282Y mutation. The audit aimed to capture current practice in the assessment of iron overload (serum ferritin and transferrin saturation) and the use of targeted analysis of specific mutations of the HFE gene (C282Y and H63D). Again, an excellent response rate was reported (n = 64), comprising laboratories from across the UK. The first striking finding was the inconsistency in reference ranges for serum ferritin across different laboratories and this was largely unrelated to the immunoassay platform being used. Joint protocols between laboratories and clinical teams were generally lacking and communication of a new significant hyperferritinaemia was rarely undertaken. Furthermore, many laboratories did not have a ferritin cut-off concentration above which hereditary haemochromatosis would be suspected in a symptomatic patient or any recommendation for follow up of a raised transferrin saturation with a fasting sample. A lack of clear responsibility for serum ferritin between Biochemistry and Haematology was highlighted as a potential barrier to improving pathways. 

 

Hyperferritinaemia and haemochromatosis - the clinical perspective
Jeremy Shearman, South Warwickshire University NHS Foundation Trust

Consultant Gastroenterologist and Hepatologist, Dr Jeremy Shearman, from South Warwickshire University NHS Foundation Trust, then delivered a clinical perspective on hyperferritinaemia and haemochromatosis. The presentation started with a rather entertaining metaphor, to help us remember some key aspects of iron metabolism, "iron is like the uninvited house party guest", which, amongst other things, “will never leave of its own accord.” Dr Shearman then went on to remind us that whilst a low ferritin is a reliable indicator of iron deficiency, a high ferritin only might reflect iron overload. Furthermore, C282Y homozygosity identifies the “at risk” population for hereditary haemochromatosis, which constitutes approximately 0.6% of the UK population, but only 56.4% of males and 40.5% of females who are C282Y homozygotes will actually go on to develop iron overload by the age of 80. Many of us will be familiar with the liver manifestations of hereditary haemochromatosis, but it was interesting to learn that joint problems are also common in this condition, as well as there being increasing evidence of adverse effects on the central nervous system. We also heard that measurement of liver iron concentration by MRI was an important yet underutilised tool for detecting tissue iron overload for the purpose of risk stratification. In those patients with raised serum ferritin who do not have hereditary haemochromatosis or another genetic iron overload condition, a diagnosis of metabolic hyperferritinaemia should be considered. This is a relatively common condition in which raised serum ferritin is associated with metabolic dysfunction and fatty liver. Patients with metabolic hyperferritinaemia have varying degrees of iron accumulation, which may be quantified using MRI. Addressing all disease risk factors, e.g., alcohol intake, fatty liver, obesity etc, is crucial to mitigate an increased risk of cardiovascular and liver disease. 

 

Metabolic dysfunction-associated steatotic liver disease
Kevin Fernando, North Berwick Health Centre

A lively final talk, "NAFLD to MASLD, what's in a name", delivered by Dr Kevin Fernando, a GP with a specialist interest in diabetes and cardiovascular, renal and metabolic disease, neatly tied together the themes of the day. We learned that the recent change in nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated steatotic liver disease (MASLD) not only aims to improve patient identification and reduce stigma but also emphasises that MASLD is the liver’s manifestation of metabolic syndrome and is heavily influenced by lifestyle factors. Early detection and successful management of patients with MALSD, to slow or stop progression of the liver disease and reduce mortality from cardiovascular complications, is an important national health issue considering that it is the most common liver disorder in Western countries, affecting more than 30% of adults in the UK and 90% of those living with obesity or type 2 diabetes. Screening for this condition with liver fibrosis markers should be considered in those with type 2 diabetes, abdominal obesity or additional metabolic risk factors and abnormal liver function tests. Interventions to improve metabolic liver disease include weight loss, a mediterranean diet, exercise and abstinence from alcohol and furthermore, statins are beneficial in many patients as long as serum transaminases do not exceed three times the upper limit of normal. Finally, Dr Fernando presented some of the emerging pharmacological treatments for MASLD, which linking in with earlier talks of the day, included incretins (e.g., GLP 1 receptor agonists), however, they are not yet licensed for this indication. 

 

Feedback and closing remarks
W Wassif, National Audit Lead

In his closing remarks Dr Wassif thanked all the speakers for their excellent educational content, extended thanks to the delegates for their participation, and commended the LabMed office for their excellent organisational efforts. Feedback from attendees was outstanding and overwhelmingly positive, with many highlighting the educational value and the engaging nature of the discussions.  We look forward to seeing everyone at future meetings and continuing our shared efforts to improve laboratory practices and patient outcomes.