According to a report from Deloitte Access Economics, commissioned by the Gastroenterological Society of Australia and the Australian Liver Association, over 6 million Australians are, or have been, affected by liver disease, including non-alcoholic fatty liver disease (NAFLD). More than 7000 Australians die each year from chronic liver diseases, cirrhosis and liver cancer, and liver disease is among the top ten leading causes of premature death in Australia. Cirrhosis is the advanced stage of a range of chronic liver diseases, such as chronic hepatitis B and C, NAFLD and alcohol-related liver disease.
NAFLD affects approximately 30% of the general population, more than half of patients with type 2 diabetes and over two-thirds of people with obesity. Although most people remain asymptomatic with simple fatty liver only, a small proportion (5–10%) will develop non-alcoholic steatohepatitis (NASH), with or without significant fibrosis. Of those patients who develop NASH, around 11% progress to cirrhosis over a 15-year period, but the rate of fibrosis progression is very variable.
NAFLD progresses silently, which means most people aren’t aware that they have liver disease. By the time liver symptoms develop, liver damage is often advanced and many patients are diagnosed for the first time when they present with cirrhosis or serious complications of progressive liver fibrosis. The most important predictor of mortality in NAFLD is the extent of liver fibrosis. The early identification of people with NAFLD and advanced liver disease is therefore vital.
With NAFLD being the most common liver disorder seen in primary care, GPs are ideally positioned to identify patients at risk of significant disease. While standard liver function tests and ultrasonography are shown to have little prognostic value in identifying patients at risk of progressive fibrosis, many GPs largely rely on these tests to assess a patient’s prognosis.
Many clinicians underestimate the prevalence of NAFLD in the community and under-recognise the clinical spectrum of the disease and how it is assessed. In a recent study, we evaluated GPs’ current approaches to diagnosis, management and referral of NAFLD and showed that over 85% of GPs do not stratify patients according to risk of advanced fibrosis. Seventy-one per cent said they were unlikely to refer a patient with NAFLD for liver specialist assessment unless routine liver function tests were abnormal, and 51% considered the prevalence of NAFLD in the general population to be 10% or less.
GPs are likely to encounter more than 300 cases of NAFLD for every 1000 patients consulted. Underappreciation of the prevalence of NAFLD is likely to contribute to many affected patients with advanced fibrosis remaining undiagnosed. While not all patients with NAFLD need to be referred to specialist liver clinics, patients at high risk of advanced fibrosis do. The initial assessment of liver fibrosis should occur in primary care. If significant fibrosis cannot be ruled out, patients should be referred to a liver clinic for specialist assessment.
A key difficulty lies in the accurate diagnosis of progressive liver fibrosis without the use of invasive tools (eg, liver biopsy). Non-invasive tools for the assessment of fibrosis are recommended by clinical practice guidelines for initial fibrosis assessment. Some tools (FibroScan and ELF [Enhanced Liver Fibrosis] test) are not widely available in the community and there is no Medicare rebate available, but non-invasive biomarker algorithms such as NAFLD Fibrosis Score (NFS) (available here) and Fibrosis 4 test (FIB-4) (available here) can be readily used in primary care because they are calculated from routine blood tests and clinical risk factors for fibrosis, such as age and diabetes.
NFS and FIB-4 have a high negative predictive value and are used to rule out significant fibrosis. Adults aged > 35 years with NAFLD with a low FIB-4 score (< 1.3 for those aged < 65 years or < 2.0 for those ≥ 65 years) or low NFS (< −1.45 for those aged < 65 years or < 0.12 for those ≥ 65 years) are at low risk of advanced fibrosis and can be managed in primary care. Patients with indeterminate FIB-4 (1.3–2.67) or NFS scores (−1.45 to 0.67) should undergo further testing with a second-line test (FibroScan or ELF test). For patients with elevated FIB-4 (> 2.67) or NFS scores (> 0.67), or with evidence of cirrhosis on imaging or biochemical abnormalities consistent with cirrhosis (eg, low platelet count, low serum albumin level, reversal of the aspartate transaminase/alanine transaminase ratio) specialist referral should be considered.
With the increasing prevalence of NAFLD, educational strategies aimed at empowering clinicians to confidently assess and manage NAFLD and to identify and refer patients at high risk of advanced fibrosis for specialist assessment are imperative. We need clear guidelines and patient referral pathways that are aligned with fibrosis tests available in the Australian community setting. NAFLD is the outcome of a multifactorial process that is shared with type 2 diabetes, metabolic syndrome and cardiovascular disease. Therefore, we should not think of these conditions within independent disease silos. Active collaboration between GPs and specialists, as well as dialogue between different specialist groups may create opportunities to discuss the assessment of liver health during routine diabetic or cardiovascular review.
Associate Professor Patricia Valery is the head of the Cancer and Chronic Disease research group at QIMR Berghofer Medical Research Institute. Her research focus includes the epidemiology and management of chronic liver disease and liver cancer.
Professor Elizabeth Powell is a Hepatologist and Senior Staff Specialist, in the Department of Gastroenterology and Hepatology, Princess Alexandra Hospital. She is also Professor at the School of Medicine at the University of Queensland and Director of the network Centre for Liver Disease Research in this University.