Adequate assessment of liver disease severity should be performed in all people with HCV before prescribing DAA treatment. The patient’s cirrhosis status is a requirement when seeking PBS authority, and adequate assessment of liver disease severity helps determine clinical decisions surrounding: treatment priority; factors that may adversely affect treatment efficacy, and therefore the choice of DAA therapy and its duration course; and whether ongoing HCC surveillance post treatment is required.

Concurrent HBV or HIV is found in a higher prevalence in people with HCV compared to the general population, and both should also be tested for. Testing should be performed before initiation of HCV treatment, but confirmation of results should not delay commencement of treatment. If HBV and HIV testing is not performed prior to starting treatment, it should be performed within 4 weeks of starting DAA therapy. Vaccination against hepatitis A (HAV) and HBV (if seronegative) is recommended in all patients with HCV^15,18.

Non-invasive testing consisting of a combination of serum biomarkers and transient elastography (e.g., FibroScan®; EchoSens, Paris) improves the accuracy of establishing liver staging of fibrosis, thus avoiding the need for a liver biopsy, and is now the recommended practice according to the international consensus statements^15,18,19. It is important to stress that non-invasive assessment of liver fibrosis is not completely accurate, and interpretation of results should be corroborated with the clinical context. FibroScan® is readily available in the tertiary care setting, and its accuracy in diagnosing cirrhosis has been extensively validated in clinical studies in people with chronic HCV^20,21. Shearwave elastography is now emerging as a diagnostic alternative to FibroScan®, with its benefits being that it can be performed at the same time as an ultrasound. However, shearwave elastography has not yet been extensively evaluated, and its validity tested, in the setting of HCV. Therefore, there should be caution in interpreting these results within this population cohort. Factors that may adversely affect the liver stiffness measurement (LSM) include obesity, elevated ALT levels, and post-prandial eating. These should be taken into consideration prior to testing¹⁸.

A new nomenclature of advanced chronic liver disease (ACLD) which does not require a liver biopsy has now been denoted to identify the population group who are likely representing severe fibrosis and cirrhosis based on LSM and platelet count. Patients with ACLD but without a prior decompensation event are denoted the term compensated (c) ACLD. A LSM by transient elastography of <10 kPa excludes ACLD, while values between 10 and 15 kPa are suggestive, and ≥15 kPa effectively rules in ACLD¹⁰. Transient elastography can further rule in clinically significant portal hypertension (CSPH). Presence of CSPH can be presumed in the presence of: LSM >25 kPa; LSM between 20 and 25 kPa plus a platelet count <150 ×10⁹/L; or a LSM between 15 and 20 kPa plus a platelet count <110 ×10⁹/L. CSPH is considered effectively excluded when LSM is <15 kPa plus platelet count >150 ×10⁹/L²³. In the setting of CSPH, commencement of a non-selective beta blocker such as carvedilol is recommended for both primary prophylaxis against variceal haemorrhage and preventing decompensation events^22-24. Caution should be exercised with the use of non-invasive tools to assess fibrosis stage post therapy, as this is considered less reliable in this clinical setting¹⁸.

There are numerous well-established fibrosis serum biomarkers that have been developed and are readily accessible, simple, and considered reliable. These include the aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 (FIB-4). The ease of use with these serum biomarker tools is that they can be calculated from routine blood tests. Both the APRI and FIB-4 calculation are similar, except FIB-4 considers patient age in addition.

Although the advancement of non-invasive testing means a liver biopsy is no longer recommended as routine screening, the need for liver histology is still reserved in situations of diagnostic uncertainty or incongruent non-invasive testing results leading to an indeterminant staging of fibrosis^15,18.

In all people with cirrhosis (METAVIR score F4) or advanced (bridging) fibrosis (METAVIR score F3), they should be evaluated for hepatic decompensation, as this may impact treatment choice. They should also undergo liver ultrasound to exclude extrahepatic complications of cirrhosis and have routine screening for HCC. Ongoing surveillance for HCC with ultrasound every 6 months should be continued in people with F3 and F4 fibrosis, even after achieving post-treatment SVR, as the risk of HCC is only reduced and not abolished¹⁸.