Changes

May 2025 — reviewed. A literature search was conducted in May 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic.

Update

Goals

To support primary healthcare professionals to:

• Identify and offer testing to people who are at risk of hepatitis C infection.
• Refer all people who test positive for active hepatitis C infection to a specialist for ongoing monitoring and management.
• Provide appropriate information and support to all people affected by hepatitis C infection, including people who continue to be at risk of infection.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

NICE quality standards

What is it?

• Hepatitis C infection is a slow, progressive disease of the liver caused by infection with the hepatitis C virus (HCV).
  • HCV is a highly infectious, blood-borne virus of the Flaviviridae family and a member of the Hepacivirus genus.
  • There are at least six different strains (genotypes) of HCV and multiple subtypes: 
    • Genotypes 1, 2, and 3 are distributed worldwide with geographic variation in relative prevalence.
    • Genotype 4 is prevalent in North Africa, Central Africa, and the Middle East.
    • Genotypes 5 and 6 are confined to South Africa and Hong Kong, respectively.  
    • Most infections in the UK are genotype 1 and 3.
    • People can be co-infected by more than one genotype.
  • Hepatitis C is an important, underdiagnosed, and undertreated cause of morbidity and mortality in the UK.
• HCV causes both acute (also known as recently acquired) and chronic infection.
  • Acute HCV infection refers to the presence of HCV immediately following incubation, to within 6 months of acquiring the infection. Most people are usually asymptomatic. About 15–45% of people spontaneously clear the virus within 6 months of infection without any treatment, but they do not become immune to future HCV infection and will still test positive for anti-HCV antibodies. 
  • Chronic HCV infection follows acute infection in 55–85% of people, and refers to the continued presence of HCV 6 months or more after acquiring the infection. Chronic HCV infection can lead to complications, such as liver cirrhosis and hepatocellular carcinoma.

 [BASHH, 2017; UKHSA, 2017; WHO, 2018; UKHSA, 2024; WHO, 2024; UKHSA, 2025a]

How is it transmitted?

• The hepatitis C virus (HCV) is mainly transmitted by contact with infected blood or blood-derived products.
• Parenteral spread accounts for the majority of cases of HCV in the UK through sharing of needles or other injecting paraphernalia in people who inject drugs (PWID). 
  • In 2023, the prevalence of chronic HCV in PWID was 7.2%, while the proportion who had cleared the infection was 45.4% [UKHSA, 2024].
  • Other routes of transmission include:
    • Transfusion of infected blood or blood products (before 1991 and 1986, respectively, when screening of blood donors for HCV infection or heat treatment for inactivation of viruses was introduced) [NICE, 2013].
    • Re-use or inadequate sterilization of medical equipment.
    • Needlestick or other sharps injuries. 
    • Exposure to infected blood, for example, through sharing personal items that may have blood on them (such as razors or toothbrushes), tattooing and body piercing, or through occupational and other means.
  • In developing countries, where sterile medical supplies are short or non-existent, routine injections and medical/dental procedures may confer a high cumulative lifetime risk of acquiring HCV.
• Sexual transmission of HCV is uncommon in monogamous, heterosexual relationships. However, it is more common in HIV-positive people (particularly in men who have sex with men). Other risk factors include multiple sex partners, unprotected anal sex and oral-anal sex, and the presence of sexually transmitted infections (STIs). 
• Vertical transmission of HCV from mother to baby generally occurs at a low rate (4–8%), but higher rates (10.8–25%) are seen if the mother is co-infected with HIV [WHO, 2018]. HCV can be transmitted to the infant in utero or during the peripartum period [UKHSA, 2018a].

[BASHH, 2017; UKHSA, 2017; WHO, 2018; UKHSA, 2024; WHO, 2024]

How common is it?

• Worldwide, around 50 million people are estimated to be infected with the hepatitis C virus, with 1 million new infections occurring every year [WHO, 2024]. 
  • In England, about 55,900 people were estimated to be living with chronic hepatitis C in 2023, a 56.7% decrease compared to 2015 [UKHSA, 2025b]. 
  • Hepatitis C is usually asymptomatic for many years after infection; therefore, many people remain undiagnosed [UKHSA, 2017].

What are the complications?

• Acute hepatitis C virus (HCV) infection may rarely lead to fulminant hepatitis (less than 1% of all people) [BASHH, 2017; UKHSA, 2017]. Co-infection with hepatitis A can increase the risk of acute fulminant hepatitis [SIGN, 2013; BASHH, 2017].
• Chronic HCV infection can lead to liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC), if untreated [UKHSA, 2024].
  • The risk of cirrhosis ranges from 10–30% after 20 years of infection with HCV. Initially, cirrhosis may be compensated (without liver-related symptoms). Decompensation may occur later, leading to portal hypertension, variceal haemorrhages, ascites, or hepatic encephalopathy [WHO, 2018; UKHSA, 2024].
  • About 1–3% of people with liver cirrhosis progress to HCC annually [WHO, 2018].
  • The risk of progression to cirrhosis and HCC varies according to the person’s characteristics and behaviours. Excessive alcohol intake, co-infection with hepatitis B virus or HIV, and immunosuppression owing to any cause increase the risk of developing cirrhosis or HCC [WHO, 2018].
• During pregnancy, infection with HCV is associated with increased risk of adverse fetal outcomes, including fetal growth restriction and low birth weight. Most children infected with HCV will develop chronic infection [UKHSA, 2018b]. 
• The three most common comorbidities seen in people with HCV infection are depression (24%), diabetes mellitus (15%), and chronic kidney disease (10%). Others include Sjögren's syndrome, chronic renal disease, symptomatic cryoglobulinaemia, lichen planus, and rheumatoid arthritis [WHO, 2018].
  • A proportion of these comorbidities is directly attributable to HCV and are referred to as extrahepatic manifestations. The prevalence of these extrahepatic manifestations is usually independent of the degree of liver fibrosis [WHO, 2018].

What is the prognosis?

• Hepatitis C virus (HCV) can cause both acute and chronic hepatitis, ranging in severity from a mild illness to a serious, lifelong illness, including cirrhosis and cancer. 
• Acute hepatitis C virus (HCV) is usually asymptomatic, and spontaneous clearance occurs in around 15–45% of people within the first 6 months of infection without treatment. In the remaining 70–80% of people, this progresses to chronic HCV, and if left untreated, 10–30% of them will develop cirrhosis over a 20-year period [UKHSA, 2018a; UKHSA, 2024; WHO, 2024].
  • Of people with cirrhosis, around 1–3% will develop hepatocellular carcinoma each year [UKHSA, 2024; WHO, 2024]. 
• Risk factors for a poor prognosis and complications of HCV include [SIGN, 2013; BASHH, 2017; WHO, 2018; UKHSA, 2024]:
  • Age over 40 years — this is associated with more rapid progression.
  • Male sex – males are more likely to progress to cirrhosis than females.
  • Ethnicity — Black African American and Hispanic people have lower sustained viral response rates with antiviral treatments than white and Asian people. 
  • Co-infection with hepatitis A and/or hepatitis B virus. 
  • Co-infection with HIV. 
  • Body mass index greater than 25 kg per m² — associated with an increased risk of hepatic steatosis, which may lead to more severe fibrosis. 
  • Smoking — an independent risk factor for hepatitis and fibrosis. 
  • Excess alcohol consumption. 
  • Immunosuppression due to any cause.
• Treatment with direct-acting antivirals targeting different stages in the HCV lifecycle is successful for over 90% of people [UKHSA, 2024]. 

Who should I test for hepatitis C?

• Offer hepatitis screening to asymptomatic people who are at increased risk of hepatitis C virus (HCV) infection, including:
  • People who have ever injected drugs. 
  • People who received a blood transfusion before 1991 or blood products before 1986, when screening of blood donors for hepatitis C infection, or heat treatment for inactivation of viruses were introduced. 
  • People born or brought up in a country with an intermediate or high prevalence (2% or greater) of chronic hepatitis C, including Africa, Asia, the Caribbean, Central and South America, Eastern and Southern Europe, the Middle East, and the Pacific islands. 
  • Babies born to mothers infected with hepatitis C. 
  • Prisoners, including young offenders. 
  • Sex workers.
  • Looked-after children and young people, including those living in care homes. 
  • People living in hostels for the homeless or sleeping on the streets. 
  • People who have tested positive for HIV.
    • HIV-positive men who have sex with men should be offered regular testing for hepatitis C (at least annually).
  • People who have tested positive for hepatitis B. 
  • Close contacts of someone known to be chronically infected with hepatitis C, including family members, close friends, household contacts, or sexual partners. 
  • People who have had tattoos, body piercings, acupuncture, or other procedures where unsterilized equipment may have been used. 
  • People who have received medical, cosmetic, or dental treatment (or any other invasive treatment) in countries where hepatitis C is common and infection control may be poor (including people who have received blood transfusion products that have not been screened for hepatitis C).
  • Healthcare workers who have been accidentally exposed to blood where there is a risk of hepatitis C (for example, needlestick injuries). 
  • People who have ever snorted drugs (such as cocaine) and shared straws or notes.
  • People who are at risk through the sharing of contaminated items, such as razors or toothbrushes. 
• Also offer testing to:
  • People with unexplained abnormal liver function tests (persistently elevated alanine aminotransferase [ALT]). 
  • Other people who are at increased risk of HCV infection, particularly if they have non-specific or unexplained symptoms and signs.
• The following people will usually be routinely screened by specialist services:
  • People who intend to donate blood or organs/tissue. 
  • People with end-stage chronic kidney disease requiring renal replacement therapy. 
  • Healthcare workers who perform invasive or exposure-prone procedures (for example, surgeons).  
• Routine screening of pregnant women for HCV infection is currently not recommended. However, testing is recommended if the woman is at increased risk for HCV infection.
  • They should be tested at their prenatal visits. 
  • If the initial results in pregnant women with on-going risk factors for hepatitis C infection are negative, this should be repeated later on in the third trimester. 

How should I test for hepatitis C?

• Offer a pre-test discussion to people being tested for the hepatitis C virus (HCV).
  • Ask about exposure to risk factors, and when the last known risk activity took place (to help establish the 'window period' from the time of last possible exposure). Be aware that the date of infection is unknown in most cases.
    • The window between detection of HCV RNA and antibodies to HCV can be months, with an average of 60 days.
  • Explain that testing and treatment (if required) are confidential, but the result will be recorded in medical records. Explain that a negative result does not have to be disclosed in an insurance application, but a positive result does if requested by an insurance company. 
  • Ensure that informed consent has been given for the test. 
  • Discuss the potential benefits of testing: 
    • If the test is negative, reassure the person and give information and advice on measures to reduce the risk of HCV infection.
    • If the test is positive, specialist antiviral treatment can reduce the risk of complications and ensure that the infection is not transmitted to contacts. 
  • Discuss details of how the result will be given, and ask about available support if the result is positive. 
    • Check you have the correct contact details and know how the person prefers to be contacted.
    • Arrange an appointment for the result to be given, if possible.
• HCV infection is diagnosed with an antibody test and an HCV ribonucleic acid (RNA) test.  
  • Detection of antibodies indicates resolved or current infection — antibodies can be detected 5–12 weeks after infection, but may not be generated, particularly if the person is immunosuppressed.
  • Detection of HCV RNA indicates current infection — it can be detected as early as 1–3 weeks after infection.
• Send a clotted blood sample for HCV antibody testing. 
  • If the antibody test is negative in immunocompetent people, consider repeating it (especially if the person is at high risk of infection) at an appropriate time, based on when the last risk exposure occurred. Seek specialist advice if there is uncertainty about the optimal time to repeat the test. 
    • Further testing is required if the last exposure risk occurred in the preceding 3-month 'window' period.
  • If the antibody test is positive, test a second blood sample to confirm the diagnosis.
• If the antibody test is confirmed as positive, or in immunocompromized people, ensure an HCV RNA test is conducted (to check if HCV infection is active and for genotype analysis).
  • If the HCV RNA test is positive, send a repeat sample for confirmation — if a positive result is confirmed, refer the person for specialist antiviral treatment. 
  • If the HCV RNA result is negative, repeat the test after 4–6 weeks to confirm the negative status — if the negative result is confirmed, there is no active HCV infection.
    • If the antibody test was positive and HCV RNA result is negative, it means the person has a previously resolved HCV infection. However, they are not immune to future HCV infection. Give information and advice on measures to prevent re-infection. 
• If a healthcare professional has, or may have, sustained an occupational exposure to HCV (for example, from a needlestick injury): 
  • Advise that they will need HCV antibody testing at 12 and 24 weeks, and HCV RNA testing at 6, 12, and 24 weeks. This should be arranged through their Occupational Health department.
• If the person has equivocal results, or there is uncertainty in the interpretation of results, seek specialist advice. 
• If the person tests negative for HCV but remains at increased risk of infection, offer annual testing for HCV. 

What are the clinical features of hepatitis C?

• Acute Hepatitis C virus (HCV) infection is usually asymptomatic in the majority of people (over 60%), but some people experience a short, non-specific illness. Signs and symptoms may include: 
  • Fatigue, sweats (especially at night), fever, aches and pains, loss of appetite, and concentration problems. 
  • Nausea and vomiting.
  • Right upper quadrant discomfort and abdominal pain.
  • Jaundice (with dark urine and/or pale stools if cholestasis). 
• Most people are unaware of their infection, and as it can take between 2 weeks to 6 months to develop symptoms, they may not connect these symptoms to the time of risk exposure.
• In people who develop chronic HCV infection, it is often undiagnosed because it remains asymptomatic until decades after infection, when symptoms develop secondary to serious liver damage. 

Scenario: Active hepatitis C infection

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of hepatitis C.

Search dates

April 2020 - May 2025

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 1st April 2020). These were combined with filters to identify guidelines and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases.

S3     S1 OR S2
S2    AB hepatitis C OR TI hepatitis C 
S1    (MH "Hepatitis C+") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.