Assessment and diagnosis of HCV
Screening for HCV provides a gateway to prevention and treatment services.
In Europe, hepatitis C virus (HCV) infection remains significantly under-diagnosed and under-treated.
Of the estimated 3.2 million patients in the EU with chronic HCV, nearly two-thirds are unaware of their status and need to be identified before treatment can be considered.1
Community-based management will be necessary to reduce the burden of HCV in the Europe. It is therefore important that a range of healthcare providers, particularly those in community care, have the necessary skills to diagnose patients living with HCV and either manage them with specialist support as needed, or refer them for specialist care. It is also important for community care providers to recognise that:
The majority of patients with HCV do not have severe liver injury and can be managed safely and effectively in the community.2,3
The introduction of direct-acting antiviral (DAA) regimens is a major advance for HCV therapy.4 Their high efficacy, short duration and excellent tolerability mean that most patients will now be suitable for treatment, and that most patients who start treatment will be cured.5,6
Furthermore, community-based management of HCV provides an ideal avenue to:7
Provide counselling about the disease process and potential complications.
Discuss transmission, risk behaviours, prevention strategies and vaccination where applicable.
Review general issues of nutrition, psychosocial support and lifestyle.
Present individuals with specific treatment options and potential side effects.
The purpose of this section is to provide a practical overview of the approach to testing for HCV infection within the community setting, the details of specific HCV tests, and the interpretation of test results.
Screening for HCV
Efforts to eliminate HCV have been hampered by the fact that a substantial proportion of patients living with the disease are unaware of their status.1,8,9 Therefore, opportunistic testing of at-risk individuals should be undertaken in community settings to identify infected patients and engage them in care.
For patients with HCV, access to healthcare services in familiar environments with their trusted, long-term doctors removes an important barrier to treatment and will improve the cascade of care.3,5
All individuals with a risk factor for HCV infection should be tested (Table 1) and when possible, screening strategies should be based on local epidemiology and conducted within the framework of national plans.9
Table 1: Populations at to consider for HCV screening5,6,9,10
Informed consent and pre-test discussion
It is important that information and support be provided as part of the testing process, with the goal of minimising the personal and social impacts of HCV infection. The nature of the information should take into consideration the patient’s cultural beliefs and practices, health literacy, behaviour and language.
Issues to address during the pre-test consultation include:11,12
The reason for testing, information about the testing process, how the results will be provided, and the time period involved.
Information about what happens to the test results (i.e., the notification process).
Assessment of the patient’s preparedness to be tested.
Information about what a negative or positive result means, including basic printed information about HCV.
Information about confidentiality and privacy.
Assessment of support mechanisms while waiting for the test result and/or if the result is positive.
In all cases, it is important that informed consent be gained prior to testing.
Screening tests for HCV
When assessing someone with possible HCV infection:5,11
HCV serology (HCV antibody) and liver function tests (LFTs) should be performed. A positive serology test indicates exposure to HCV but does not prove active infection.
The HCV serology result can be confirmed by a polymerase chain reaction (PCR) assay for HCV RNA, which documents viraemia and thus active infection. HCV RNA tests can either be qualitative (i.e., the result is either positive or negative) or quantitative (i.e., the results provide viral load values).
A positive HCV serology test and an elevated alanine aminotransferase (ALT) level, particularly in the setting of risk factors for transmission, is highly suggestive of active HCV infection.
Table 2: HCV infection – initial testing11
|HCV Ab||If positive, shows evidence of previous exposure to HCV virus. Remains positive following successful treatment.|
|HCV PCR test||If positive shows active infection (i.e., viraemia).|
|ALT||If elevated in the context of positive HCV Ab, generally indicates some level of HCV virus and a likely active HCV infection.|
For patients who are seronegative but have ongoing risk factors for HCV transmission, annual HCV serological testing is recommended.5
Approximately 25% of patients with acute HCV infection spontaneously clear the virus without treatment, generally within 3 to 6 months.
These patients continue to be HCV antibody-positive but do not have detectable HCV RNA in plasma.
A patient can be considered to have cleared the HCV infection if they have two negative PCR tests, carried out at least 3 months apart.
Annual HCV RNA testing is recommended only in the setting of ongoing risk factors for HCV transmission. These patients do not require repeated serological testing, as most patients will have detectable HCV antibodies for life, regardless of antiviral treatment.
Approximately 75% of patients infected with HCV progress to chronic HCV infection.
Chronic HCV infection is defined by a positive HCV PCR test ≥ 6 months after initial infection.
All patients with chronic HCV should be considered for treatment, except those with limited life expectancy (e.g., < 12 months) due to non-liver related or non-HCV-related comorbidities.
Treatment may still be challenging for some clinicians. In such cases, support from an experienced colleague, nurse, pharmacist or specialist should be sought. It is important that all patients with HCV infection are linked to a clinician who is prepared to provide comprehensive management.
Figure 1. Interpreting tests for HCV15
The post-test discussion provides an opportunity to discuss health issues, referrals and prevention strategies. It is important that the test result be given in person, in a confidential manner that is appropriate to gender, level of literacy, cultural beliefs, and ongoing risk. Support mechanisms and individual requirements can be reassessed at this time and referral given to a support agency if necessary.12
Table 3 provides guidance on issues to consider when conveying a positive or negative test result.
Table 3. Points to discuss when conveying a HCV test result10,12
|Negative test result||Positive test result|
Pre-treatment assessment of patients with chronic HCV
It is important that all patients considered for treatment undergo a pre-treatment assessment. Treatment history, HCV virology and the degree of liver disease can influence the choice of treatment and duration of the regimen. Key elements of the pre-treatment assessment are briefly discussed below and summarised in Table 4.
HCV genotype testing can assist with treatment-related decision-making and need not be delayed until specialist review.2
With pan-genotypic HCV drug regimens, it is possible to treat patients without identifying their HCV genotype and subtype. However, Guidelines continue to recommend HCV genotyping as it can provide clinically relevant information.5,9 For example:
- Some DAAs are genotype-specific and the HCV genotype should be determined before such regimens are prescribed.
- In patients with a high risk of reinfection, a genotype switch can help to differentiate reinfection from relapse.
Initial evaluation includes a comprehensive medical history. Aspects that deserve close attention include prior treatment for HCV infection: the type of treatment, regimen duration, adherence, and response can influence the choice of future therapy.5
It is not always possible to determine the exact duration of infection. It is important not to assume that the date of first positive HCV serology test is the date of infection. Given the asymptomatic nature of the disease, many patients will not have been aware of their infection and so not been tested for some time following exposure. A rule of thumb is to determine the year of the first injection and assume infection two to three years subsequent to that.11
It is important to screen for factors associated with an elevated risk of cirrhosis. Clinical risk factors for cirrhosis include:5,9
- Male sex
- Older age at infection
- Heavy alcohol intake (e.g., >4 standard drinks/day)
- The duration of infection (e.g., >20 years)
- Coinfection with HIV or HBV
- Obesity and type 2 diabetes
A physical examination can uncover evidence of more advanced liver disease. Several clinical signs warrant further investigation:11
- palmar erythema
- spider naevi
- scleral icterus
Evaluate for cirrhosis
Non-invasive assessment of fibrosis is essential before starting therapy for HCV as the results can change after treatment and patients at risk of long-term complications such as hepatocellular carcinoma (HCC) can be missed.2,5,9
Non-invasive tests for fibrosis based on validated serum-based markers can be used in younger patients with a short duration of infection or patients without a history of excessive alcohol intake or metabolic risk factors.2 Examples of non-invasive tests include: 2,5,6,9,14
- The aminotransferase/platelet ratio index, or APRI score.
- Fibrosis-4 (FIB-4)
These tests are based on calculations from routine blood tests and the below online calculator can assist clinicians. In general, a low score excludes cirrhosis. Patients with a high score (e.g., an APRI score ≥1) have an increased likelihood of cirrhosis and should be assessed further.2,6,9,14
Figure 2. APRI and FIB-4 formulas14
APRI = [(AST (IU/L)/AST_ULN (IU/L))×100]/platelet count (109/L)
FIB-4 = [(age years) x AST (IU/L)/platelet count (109)/L x [ALT (IU/L)1/2]
This FIB-4 calculator helps to assess liver fibrosis/cirrhosis.
Entering the values into the boxes will produce a final FIB-4 score.
No data or values are stored in this calculator
Transient elastography, or Fibroscan® measures liver stiffness. It is the most common method used for diagnosing cirrhosis and can be used in patients requiring more accurate assessment of liver fibrosis. These are fixed or portable machines and testing can generally be arranged through the local health district or other providers. As with serum markers, a low score is accurate for excluding cirrhosis, but a median liver stiffness value of at least 12.5 kPa is associated with a significantly higher chance of cirrhosis. These patients require specialist review and long-term surveillance for HCC and other liver-related complications.2,5,9
Figure 3. Fibroscan scoring card16
Laboratory testing includes assessment of renal function, blood glucose, other blood-borne infections such as HIV and HBV, LFTs and full blood count. LFTs can provide information about the extent of liver inflammation and assess synthetic function:5,11
- Reduced albumin and raised bilirubin are important markers of advanced liver disease.
- A reduced albumin, particularly if combined with low platelet count suggests underlying cirrhosis.
Other indicators of cirrhosis include:
- Elevated bilirubin (although if isolated may indicate Gilbert’s syndrome)
- Prolonged prothrombin time (PT)
- An aspartate aminotransferase (AST)/ALT ratio of >1.0
- An AST/platelet ratio of >1.5.
Patients coinfected with HCV and HIV or HBV (HBsAg positive) are at increased risk of disease progression. They should be closely monitored and treatment considered.5,11
Risk of drug-drug interactions
It is important to consider existing medications and the potential for drug-drug interactions with DAAs. For example, carbamazepine and phenytoin are contraindicated with all regimens, due to the risk of reduced DAA plasma concentrations. Other commonly prescribed medicines that may lead to drug-drug interactions include proton pump inhibitors, statins, antidepressants, anti-psychotics, cardiovascular drugs, immunosuppressants, recreational/illicit drugs, and antiretrovirals (ARVs) for HIV.14
The Summary of Product Characteristics (SmPC) should be reviewed to ensure safety when prescribing antiviral regimens. The University of Liverpool’s Hepatitis Drug Interactions website (www.hep-druginteractions.org ) is an additional resource with information that is updated regularly.17
Context and links to HCV pre-treatment assessment, diagnosis, HCV treatment and ongoing care.
Community based management
Community-based management is essential to reduce HCV in the United Kingdom and European Union.
- European Union HCV Collaborators. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. Lancet Gastroenterol Hepatol 2017;2:325–336.
- Strasser S. Managing hepatitis C in general practice. Aust Prescr 2017;40:64-9.
- Khoo A and Tse E. A practical overview of the treatment of chronic hepatitis C virus infection. AFP 2016;45:718-20.
- Sievert W, et al. Enhanced antiviral treatment efficacy and uptake in preventing the rising burden of hepatitis C-related liver disease and costs in Australia. J Gastroenterol Hepatol 2014;29(Suppl 1):1-9.
- Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement (September 2018). Melbourne: Gastroenterological Society of Australia, 2018.
- American Association for the Study of Liver Diseases (AASLD). HCV Guidance: recommendations for testing, managing, and treating hepatitis C. Sept 21, 2017. Available at: www.hcvguidelines.org (accessed November 2018).
- Australian Society for HIV Medicine (ASHM). HIV, viral hepatitis and STIs: a guide for primary care. 2008;122.
- Public health England. Hepatitis C in the UK: 2018 report. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/732469/HCV_IN_THE_UK_2018_UK.pdf (accessed November 2018).
- European Association for the Study of the Liver (EASL). EASL recommendations on treatment of hepatitis C 2018. J Hepatol 2018;69:461-511.
- British Association for Sexual Health and HIV (BASHH). National guidelines for the management for viral hepatitides. 2017 interim update. Available at: https://www.bashh.org/guidelines (accessed November 2018).
- Wodak A. An overview of hepatitis C clinical management in opiate pharmacotherapy settings. Available at: ashm.org.au/publications. (accessed November 2018).
- National HCV Testing Policy Expert Reference Committee. National HCV Testing Policy 2017. Available at: http://testingportal.ashm.org.au (accessed November 2018).
- Biddle ML, et al. Nurse-led clinic: effective and efficient delivery of assessment and review of patients with hepatitis B and C. Intern Med J 2014;44:581-585.
- World Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. July 2018. Available at: https://www.who.int/hepatitis/publications/hepatitis-c-guidelines-2018/en/ (accessed November 2018).
- Wheeler E. Hepatitis C: your crucial role as a primary health care nurse. 2016. Available at: ashm.org.au/resources (accessed November 2018).
- Liverscan Australia. Available at: http://liverscanaustralia.com.au/liverscan/fibroscan-fibroscore/ (accessed November 2018).
- The University of Liverpool, Hepatitis Drug Interactions website. Available at: hep-druginteractions.org (accessed November 2018).
LID/IHQ/18-12//1048b Date of preparation: January 2019