Hepatitis C (HCV) affects 0.8-1% of the UK population, with up to 70% having ongoing chronic infection.¹ The prevalence is higher within certain ethnic, cultural and socioeconomic groups. HCV is curable but if left untreated can progress to end stage liver failure or cancer (hepatocellular carcinoma).

HCV has six known genotypes,^2-7 which show geographical variance. Genotypes 1 and 3 are most commonly seen in the UK.

Therapeutic breakthroughs over the past few years have led to cure rates of more than 90%. The challenge is to deliver the benefits of these new drugs.

Risk factors

Several groups are at increased risk of HCV. People who inject drugs (PWID) are the main high-risk group in the UK. Blood to blood transmission is the main mode of infection, risk factors include:

• Sharing or reuse of needles for injection (and other drug paraphernalia)

• Tattooing or acupuncture with non-sterile equipment

• Needlestick injuries

• Blood and blood products (before 1991 in the UK)

• Medical procedures

• Contact with blood from an infected person

Male circumcision and childhood inoculations are also potential modes of transmission in the developing world.

Sexual transmission of HCV is uncommon with studies suggesting an incidence of 0-2/1,000 years of sexual contact,² although this rate is higher in cases of co-infection with HIV and men who have sex with men.³ Infected individuals should be advised to take precautionary measures; the sharing of razors and toothbrushes should be discouraged and safe sexual practices encouraged.

Acute hepatitis C infection has mild symptoms only and is likely to go undiagnosed. The estimated diagnosis rate in England is 35%, suggesting that 65% of the total HCV-positive population remains undiagnosed.⁸ Symptomatic presentation is uncommon.

HCV is often detected in response to abnormal liver enzymes and a subsequent liver screen. In this situation, patients usually only have a mild rise in transaminases. The most common method of detecting HCV is case finding in high-risk groups:

• Both current and former PWID

• Patients on opiate substitution therapy

• Patients who have received overseas healthcare

• Recipients of blood products before 1991 in the UK

• Certain immigrant groups (e.g. Eastern Europeans, Pakistanis,⁴ Egyptians⁵)

GPs can play a major role in identifying those at risk of the disease providing information and arranging testing. 

Diagnosis

Maintaining a high index of suspicion is paramount. Offering HCV testing to at-risk groups will allow early detection and referral.

Testing is usually on blood, the presence of HCV antibodies indicates exposure to HCV, but does not confirm active HCV infection. Once exposed to the virus the patient will have HCV antibodies lifelong. An HCV-positive individual should have their HCV PCR checked to confirm active infection.⁹

In groups who are difficult to reach, dried spot blood testing is a convenient method of delivering HCV testing.⁶

It allows blood sampling in the community from patients who often have difficulties with traditional phlebotomy. In addition, non-clinical workers can carry out dry blood spot testing. It is a useful screening test which has been shown to be highly sensitive and specific.⁷

Referral

All patients with evidence of active HCV infection (HCV RNA positive) should be considered for referral to local specialist hepatology or infectious diseases services. In addition, most local services will have developed referral pathways with access to clinics. Many units will offer community-based clinics using nurse specialists and treatment networks at the point of contact attempting to engage the difficult to reach cohorts.

Traditionally, active drug injection was regarded as a barrier to HCV services and treatment. This is no longer the case. Evidence suggests that engaging active PWID and providing education, awareness and support will increase their treatment success rates to those of non-injecting drug users/previous users.¹⁰

At the point of referral an assessment of the stage of disease will be made.

This can be done using noninvasive serum fibrosis markers such as the FIB⁴ panel, AST:ALT ratio and APRI.¹¹ Fibroscan is a useful adjunct, providing an additional means of non-invasive assessment of liver fibrosis,¹² this is accessed via specialist services.

Management

The objective of HCV treatment is to achieve cure. This is measured as undetectable virus RNA measured three or more months after the end of a planned treatment programme, and is known as a sustained virological response (SVR).

HCV management options have changed dramatically over the past five years, with improvement in patient experience, cure rates and tolerability. The first treatment for HCV was interferon alpha which was very poorly tolerated and associated with a less than 10% success rate.

The addition of ribavirin and then the pegylation of interferon improved cure rates throughout the 1990s and early 2000s. However, side effects  remained an issue, with treatment courses lasting up to 48 weeks for HCV genotype 1.

In the past five years the fruits of unravelling the HCV genome and identifying target proteins have led to a plethora of new drugs in three classes:

• Protease inhibitors (e.g. simprevir, boceprevir)

• NS5a inhibitors (e.g. daclatasvir, ledipasvir)

• NS5b inhibitors (e.g. sofosbuvir, dasabuvir)

The combination of two or three drugs from these classes has led to treatment cure rates of up to 97%,¹³ with treatment duration as short as eight weeks for some patients.¹⁴

An additional benefit of these agents, in particular if used without interferon, is a very good tolerability as there are few side effects.

A number of patient characteristics influence the response to therapy, perhaps the most important of which is the presence of cirrhosis. Previous treatment history also has an impact on choice and duration of therapy.

Table 1 summarises treatment options based on genotype, treatment experience and presence of cirrhosis.

Given the rapid changes, complexities of the different drugs, the impact of genotype and patient characteristics as well as drug costs treatment is initiated in specialist centres, although primary care and community-based services are increasingly involved in the delivery of treatment in shared care arrangements.

The excellent safety and tolerability of these new drugs means that a move towards more community-based treatment is highly likely, given that the main challenge is no longer curing the virus but delivering therapy to the patient.

Conclusion

HCV is a common virus affecting the liver, with the potential to lead to liver failure and cancer. This virus can now be cured in most patients and complications prevented with early identification and treatment.