1UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK.
AbstractChronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care.
In summary, a battery of non-invasive markers is available for the determination of fibrosis and monitoring the progression and regression of fibrosis in chronic HBV patients. The selection of the tests depends on individual patient factors, as well as the cost, accuracy, reliability and availability of these tests. With the constant evolution of non-invasive tests for fibrosis, which demonstrate excellent diagnostic performance for cirrhosis, as well as prognostic prediction of liver-related outcomes, the role of liver biopsy is becoming less prominent. Specifically for chronic HBV infection, treatment decisions sometimes depend on the presence of necroinflammation rather than fibrosis, therefore in such cases liver histology is still irreplaceable. The challenge now is to decide on how best to apply validated non-invasive tests in HBV management. It is likely that a combination approach (i.e., blood and imaging test at screening) will give the highest diagnostic accuracy, obviate the need for the greatest number of liver biopsies, and inform the clinician and patient regarding prognosis and the need for therapy. Furthermore, a consensus on the use of non-invasive markers to replace liver biopsy as trial endpoints would greatly enhance HBV clinical research trials, ultimately benefiting the patient.