Hepatitis C: The silent virus

Ms Theresa Lowry-Lehnen provides an overview of the detection and treatment of hepatitis C

Hepatitis C, caused by the hepatitis C virus (HCV), is an infectious disease that primarily affects the liver. Although vaccines exist for hepatitis A and hepatitis B, there is currently no vaccine available to prevent hepatitis C. The development of a vaccine has proven challenging because HCV has six different genotypes and mutates easily, making it difficult to create a vaccine. It is also possible for a person to be infected with more than one genotype.

Hepatitis C is spread primarily by blood-borne contact associated with intravenous drug use, poorly sterilised medical equipment, needle-stick injuries and blood transfusions. In developed countries like Ireland, injecting drug use (IDU) is the major risk factor. Globally, more than 130 million people have hepatitis C, 80 million with chronic infection, and approximately 700,000 people worldwide die each year from related liver diseases. HCV infection has been a notifiable disease in Ireland since 2004. About 700-to-800 new cases are recorded every year. It is estimated that over 30,000 people in Ireland are currently living with hepatitis C, with over half of these cases undiagnosed. Between 2004 and 2016, 14,107 cases in Ireland were notified. In recent years there has been a decrease in notified cases, however, the number of new cases appears to be stabilising rather than declining.

Notification data includes only diagnosed cases. Where risk factor data is available in Ireland, IDU is the most common risk factor reported, at 80 per cent; possible sexual exposure, 5 per cent; receipt of blood or blood products, 4 per cent; vertical transmission, 2 per cent; and tattooing or body piercing, 1 per cent. In 7 per cent of notified cases, no risk factor was identified (HPSC, 2015).

Hepatitis C can be acute or chronic and the onset of the disease is one-to-six months after initial exposure. Often referred to as the ‘silent virus’, it commonly has no or very few symptoms, both in the acute and early chronic stages. The acute stage of infection often tends to go unnoticed. Acute hepatitis C usually lasts from two-to-eight weeks, while chronic hepatitis C can last for decades. Carriers of the virus may have few or no symptoms but they can infect others. If symptoms do develop in the acute stage, which is rare, they can include nausea, loss of appetite, aching muscles and mild fever. Later, jaundice may develop and the urine may darken.

Between 15 and 45 per cent of people infected with hepatitis C recover spontaneously with no ill effects, while the remaining 55-to-85 per cent of those infected develop chronic HCV infection. Chronic infection can cause liver inflammation, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), liver failure and death. Chronic liver disease develops over many years and signs and symptoms may not be evident for decades until serious liver damage has occurred. Progression to chronic liver disease is associated with excessive alcohol intake, co-infection with HIV or hepatitis B, superinfection with hepatitis A, and older age at infection. Recommendations for managing hepatitis C infection include cutting out alcohol, drugs and smoking, having a healthy diet, exercising regularly, avoiding unnecessary medication and getting vaccinated against both hepatitis A and B.

Treatment

Until 2012, the treatment for hepatitis C was ‘dual therapy’ with pegylated interferon-α injections and ribavirin tablets for 24-to-48 weeks. Dual therapy had many side-effects and results were average, at best <50 per cent for genotype 1 HCV. More successful drug treatments for hepatitis C, known as direct-acting antivirals (DAAs), have become available in recent years. In the majority of cases, DAAs offer a cure for hepatitis C. International trials report successful eradication of the HCV virus in more than 95 per cent of patients prescribed DAA therapies. DAAs are directed at multiple target sites in the HCV virus, inhibiting or preventing many viral proteins from being produced by the HCV virus. These drugs include inhibitors of the HCV non-structural proteins NS3/4A (protease inhibitors), NS5A and NS5B (polymerase inhibitors), and direct micro-RNA targeting agents.

DAA drug regimens which are interferon-free usually consist of two or three oral drugs in combination, sometimes in a single tablet form. They are usually prescribed once or twice a day for 12-to-24 weeks, and in some instances for only eight weeks in patients without advanced liver disease. Treatments which use a combination of drugs including interferon are still available, however, DAA therapies are now the standard of care for HCV infection (HSE, 2018).

HCV elimination

The first global health sector strategy on viral hepatitis (2016-2021) was published by the World Health Organisation (WHO) in 2016. It sets the goal of eliminating viral hepatitis as a major public health threat by 2030 by reaching the target of 90 per cent of those infected being diagnosed, and 80 per cent of those eligible having been treated. The strategy calls for action across the entire continuum of hepatitis care, from primary prevention of infection, to diagnosis, linkage to care, and treatment.

An Expert Advisory Group established by the Department of Health (DoH) was set up in 2014 to examine the feasibility of a multi-annual public health treatment plan for patients in Ireland with HCV infection, based on clinical prioritisation criteria. The DoH subsequently published A Public Health Plan for the Therapeutic Treatment of Hepatitis C in 2015, recommending the establishment of the HSE National Hepatitis C Treatment Programme (NHCTP), which was set up so that people with hepatitis C in Ireland are offered free, effective antiviral drug regimens that ensure quality and governance in keeping with international best practice. The HSE NHCTP aims to provide treatment across a range of healthcare settings to all persons living with HCV in Ireland, with a view to successfully eliminating HCV in Ireland and making it a rare disease by 2030.

Improving detection

A HCV antibody test is used to screen for past exposure and current infection. It detects the presence of antibodies to the virus, indicating exposure to HCV. Screening for hepatitis C can be carried out at GP practices, sexual health clinics, GUM clinics and drug treatment centres. There are eight hospitals where patients can receive treatment for hepatitis C in Ireland: The Mater, Beaumont, St James’s, and St Vincent’s Hospitals in Dublin, Galway University Hospital, Cork University Hospital, St Luke’s Hospital, Kilkenny, and Our Lady’s Children’s Hospital, Crumlin. Treatment is also available in some drug treatment clinics in Dublin.

People with strong risk factors who should be tested for hepatitis C are:

Those who have ever injected drugs.

Those who have used unprescribed or illicit drugs by a route other than injecting, if there is a possibility of transmission of infection by the route of administration.

Prisoners or former prisoners.

Homeless people who have a history of engaging in risk behaviours associated with HCV transmission, or who have had a potential HCV risk exposure.

Migrants from a country with an intermediate and high prevalence of HCV (anti-HCV ≥2 per cent).

People who are HIV-positive.

Infants of HCV-RNA positive women.

Men who have sex with men.

People on renal dialysis or who have had a kidney transplant.

Recipients of blood or blood components in Ireland prior to October 1991 who have not yet been tested.

Recipients of anti-D immunoglobulin in Ireland between 1 May 1977 and the end of July 1979, and 1 March 1991 to 18 February 1994 who have not yet been tested.

Recipients of plasma-derived clotting factor concentrates in Ireland prior to 1992 who have not yet been tested (HSE, 2017).

Screening should also be carried out for:

Those with a tattoo, particularly those who received tattoos a number of decades ago, in non-professional settings, prisons, countries with a high prevalence of HCV, or in circumstances where infection control was poor.

Household contacts of a person who is HCV-positive in circumstances where household transmission is more likely to have occurred.

Recipients of organ transplants in Ireland prior to the introduction of routine screening.

Recipients of blood components and blood products overseas in any country where a quality-assured blood donor screening programme may not have been in place.

People who have received medical or dental treatment in countries where HCV is common (anti-HCV prevalence ≥2 per cent) and infection control may be poor.

Sexual partners of known HCV cases: If the case or contact is also HIV positive and if the HCV-infected case is an injecting drug user.

Sexual contacts of persons who inject drugs, but where HCV status is unknown or where there is evidence (HSE, 2017).

In certain circumstances, screening is mandated by legislation, ie, donors. In other circumstances, failure to agree to screening may prohibit a person such as healthcare workers from undertaking certain activities in order to maintain patient safety (HSE, 2017).

A key requirement for Ireland to meet its goal of hepatitis C elimination by 2030 is for undiagnosed cases to be detected through screening and subsequently linked to care and treatment. Those most at risk of HCV are often from marginalised groups in society who may experience barriers to accessing healthcare services such as screening. In Ireland, those most at risk of infection are the homeless and drug users. One-in-three homeless persons in Ireland is hepatitis C-positive, compared to about one in 10,000 in the general population (HSE, 2017).

Interventions shown to have a positive impact on the uptake of screening among high-risk groups include targeted case-finding in primary care, support and training for primary care practitioners, and offering alternative testing and provision of outreach testing. Delivery of services in non-specialist community settings has been found to be particularly effective. Targeted HCV testing interventions have been shown to be more effective compared to no targeted interventions or routine practice in increasing the number of people tested, cases detected, referrals to a specialist, attendance at a specialist, and cases commencing treatment. Practitioner-based targeted testing interventions where a health or social care professional was given support to offer risk assessment and/or testing were found to be most effective. Recommended settings for testing include mobile clinics, community settings, harm-reduction programmes and low-threshold service centres (HSE, 2017).

Healthcare professionals must take every opportunity to offer HCV screening to those at risk and should be aware that a person may fall into a risk group for HCV unrelated to their reason for presentation to a health service. Individuals may have more than one risk factor for HCV and this should be considered when determining the need for repeat testing rather than one-off screening. HCV testing should be considered in those with an unexplained rise in ALT. Screening should be undertaken voluntarily and with gained consent. When offering HCV screening, healthcare professionals should counsel on the testing process, receiving results, and the importance of returning for test results. Confidentiality should be maintained during the offer of screening and delivery of results. An offer of a test or a negative test result provides an opportunity to counsel about prevention and harm reduction.

On diagnosis of HCV infection, newly-diagnosed persons should be referred for specialist assessment. Patients should be informed of subsequent diagnostic tests required, treatment options available, and be provided with information on HCV, including how to reduce the risk of transmission to others. They should be counselled on the importance of linkage to care and directed to services that can provide support and counselling as needed. Continuity of care should be maintained as the patient transitions between services, settings, or circumstances (HSE, 2017).

Although it is unlikely a vaccine would provide complete immunity, findings suggest that a hepatitis C vaccine would be an essential part of a prevention strategy to meet the WHO’s goal of eradicating hepatitis C by 2030. Meanwhile, until such a vaccine becomes available, every preventative measure must be taken through ongoing education, screening and treatment programmes to reduce and eliminate hepatitis C.

References on request