For decades, the morbidity and mortality from chronic liver disease has been rising. This is owed in part to late diagnosis, with almost three-quarters of patients presenting to hospitals with index admissions due to decompensated chronic liver disease. The natural history of most aetiologies of chronic liver disease means that there is a protracted process, during which there are windows of opportunity to reverse the disease process and prevent progression to advanced liver fibrosis and cirrhosis, which is responsible for much of the morbidity and mortality associated with liver disease. One window of opportunity is using abnormal liver function tests, which are commonly measured liver enzymes which can indicate inflammation or other pathologies within the liver. Around one fifth of abnormal liver function tests go underinvestigated, despite national and international guidelines for primary care physicians to utilise. Intelligent liver function testing (iLFT) is an automated pathway which provides diagnostic information to primary care in terms of aetiology of liver disease and fibrosis stage, along with recommendations on whether to refer to secondary care. This thesis explores the utility of this pathway. It describes how, in the two years following its launch, iLFT was increasingly used, to generate thousands of outcomes sent to primary care with instructions for patient care. It resulted in the diagnosis of cirrhosis in hundreds of patients, as well as diagnosing treatable diseases of the liver such as viral hepatitis and autoimmune liver diseases. It is well liked and utilised by primary care physicians. This thesis explores the diagnostic utility of one liver enzyme in particular, alanine aminostransferase, in advanced liver fibrosis and cirrhosis. Using statistical methods of sensitivity, specificity and area under the roc curve, it is shown that alanine aminotransferase is a poor diagnostic test for advanced fibrosis and cirrhosis, but when elevated, provides a window of opportunity for lifestyle intervention, as the vast majority of patients with cirrhosis have an elevated level in the five years prior to diagnosis. The diagnostic utility of abdominal ultrasound scanning in the diagnosis of advanced liver fibrosis and cirrhosis is also examined, concluding that in patients with isolated elevated levels of alanine aminotransferase and without elevated non-invasive fibrosis scores, ultrasound scanning does not confer additional diagnostic benefit, despite being part of major national and international guidelines. Finally, the prognostic value of the Enhanced Liver Fibrosis test in a community population without known liver disease is examined for the first time, showing that elevated scores are associated with time to mortality and time to admission to hospital with liver related events.
Iain Macpherson (Tue,) studied this question.