Once a diagnosis of chronic HCV infection has been established, further investigation should be directed toward assessing for the presence or absence of cirrhosis. Although all people with chronic HCV infection are eligible for treatment, regardless of liver fibrosis stage, the presence of cirrhosis can influence treatment duration and regimen (see Treatment for chronic hepatitis C), and a person’s cirrhosis status must be provided at the time of seeking PBS authority to write a prescription for DAA medicines. The presence of cirrhosis also identifies people who require lifelong surveillance for HCC and portal hypertension.
Clinical risk factors for cirrhosis include male sex, older age at infection, prolonged duration of HCV infection (> 20 years) and comorbidities, including excessive alcohol consumption, diabetes, obesity, the metabolic syndrome and coinfection with HBV or HIV. Clues to the presence of advanced liver disease include peripheral stigmata of chronic liver disease (eg, leukonychia, spider naevi) and markers of portal hypertension, including splenomegaly and thrombocytopaenia. Low albumin levels, raised bilirubin levels and a raised international normalised ratio (INR) are markers of reduced liver functional reserve and decompensated liver disease.
Formal evaluation for cirrhosis with a non-invasive test is recommended for all individuals with chronic HCV infection. Evaluation of liver fibrosis stage should be performed before commencing treatment. None of the non-invasive tests have been validated for diagnosing cirrhosis after SVR, and there is a risk of false negative results when performed after treatment. However, the inability to organise liver fibrosis assessment beforehand should not preclude starting DAA therapy, especially in marginalised individuals who may become lost to follow-up. People should be given the opportunity to have a cirrhosis assessment performed, but curing hepatitis C should be prioritised to reduce the risk of liver-related morbidity and mortality.
Transient elastography (e.g. using FibroScan®; EchoSens, Paris) measures liver stiffness and is the most common method used for diagnosing cirrhosis. It has been extensively evaluated and validated in people with chronic HCV infection  and outperforms serum biomarkers for detecting cirrhosis.  FibroScan® is available in most metropolitan centres. A liver stiffness measurement (LSM) of > 12.5 kPa using FibroScan® is a reasonable threshold for identifying people with cirrhosis for treatment decision making. [42,43] Alternative elastography methods for measuring liver stiffness include shear wave elastography and acoustic radiation force impulse (ARFI) technology. These techniques can be offered as an add-on to liver ultrasound using many machines but have been less well validated for the assessment of fibrosis stage in the setting of chronic HCV infection, and the cut-offs for identification of cirrhosis are different.
Serum biomarkers for liver fibrosis have also been developed, such as the APRI (aspartate aminotransferase [AST] to platelet ratio index), Fibrosis-4 (FIB-4), Hepascore, Enhanced Liver Fibrosis (ELF) test and FibroTest. The APRI is a simple biochemical marker that can be calculated from routine blood test results. The FIB-4 is similar to the APRI but also incorporates age into the algorithm. Hepascore and the ELF test are alternative serum fibrosis markers that are available in Australia but not currently MBS-reimbursed. FibroTest is not yet available in Australia. Serum biomarkers may be used to exclude the presence of cirrhosis in settings where other tools, such as transient elastography, are not accessible in a timely fashion. Supplementary Table 1 presents further information and key clinical thresholds for excluding the presence of cirrhosis in people using the serum biomarkers for liver fibrosis that are available in Australia.
It is important to remember that none of the methods for non-invasive assessment of liver fibrosis are perfectly accurate, and the results must be interpreted in the context of the pre-test probability based on other clinical information. For example, a 50-year-old obese man with a 30-year duration of HCV infection, a past history of heavy alcohol consumption, spider naevi evident on examination and a platelet count of 90 x 109/L is very likely to have cirrhosis, even if the LSM is 9.0 kPa using FibroScan®. If there is concern about the accuracy of the liver fibrosis assessment, referral for further assessment for the presence of cirrhosis by a specialist with experience in assessing liver disease severity and managing patients with advanced liver disease is recommended. There is no routine role for liver biopsy. Liver biopsy is generally reserved for people in whom there is uncertainty about the underlying cause of liver disease, or where there is uncertainty about the liver fibrosis stage. Liver histology is not required for accessing antiviral therapy.