Infectious hepatitis

Abstract

Infectious hepatitis describes inflammation of the liver due to transmissible viruses. The five most common viruses recognised are classed alphabetically as A, B, C, D and E. These different viruses cannot be differentiated clinically, but a focused history and examination can provide clues towards aetiology, guide appropriate investigations and allow for identification of complications. Hepatitis A and E are typically enterically transmitted and generally follow a mild and self-limiting course. Hepatitis B, C and D are parenterally transmitted and collectively account for a large burden of chronic liver disease globally. This article will cover clinical assessment and management of patients with viral hepatitis A–E. Although there are numerous other types of infectious hepatitis, labelled ‘non-A–E hepatitis’, they are rare and not routinely tested for in clinical practice so are not covered in this article. We will also not cover viruses with more systemic effects which can cause hepatitis but are not specific to the liver, such as Epstein– Barr virus and cytomegalovirus.

Clinical case scenario

Sarah, a 32-year-old woman who attends the practice rarely, comes to see you in your morning clinic. She is experiencing fatigue and intermittent abdominal pain, and reveals that she injects heroin. Sarah is referred to the local addictions team for consideration of starting methadone and blood tests are performed for basic haematology and biochemistry (results in Table 1). Sarah has been advised to attend for follow up of these results and discuss further tests needed.

Table 1.

Clinical case scenario blood test results.

Investigation (units)	Result	Normal range
Haemoglobin (g/L)	136	121–151
White cell count (×10⁹)	3.8	4–11
Neutrophil count (×10⁹)	1.7	1.8–7.5
Lymphocyte count (×10⁹)	0.9	1.0–4.0
Platelet count (×10⁹)	339	150–400
Sodium (mmol/L)	138	135–145
Potassium (mmol/L)	4.3	3.5–5.0
Urea (mmol/L)	3.9	2.5–6.6
Creatinine (mmol/L)	67	50–98
Bilirubin (mmol/L)	15	3–21
ALT (U/L)	79	10–50
ALP (U/L)	42	40–125

Sarah is generally well, but the symptoms from her previous consultation continue. She last injected the previous evening. She is on no other regular medications. She is nervous about having further blood tests taken as it often takes several attempts and would like to discuss the tests that need to be taken.

Clinical presentation

Patients may consult with their GP in relation to infectious hepatitis for a variety of reasons, these include: symptoms of hepatitis, travel to high-risk areas, abnormal blood results, or screening certain patient groups, such as in pregnancy or migrants from areas of high prevalence.

History

Patients with acute infectious hepatitis can be asymptomatic or have a variety of symptoms based on disease severity, stage of illness and viral aetiology. Symptoms of acute hepatitis are summarised in Box 1. Although symptoms are usually mild, patients may very rarely present with features of acute liver failure, such as persistent vomiting, drowsiness or confusion, which should prompt urgent admission to hospital. Hepatitis A and E are predominantly enterically transmitted, although hepatitis E can, rarely, be transmitted through blood products (NHS Blood and Transplant, 2021). Risk factors for enteric transmission include travel to areas with poor sanitation, oral–anal sex and consumption of certain raw or undercooked meats (see hepatitis E section). Hepatitis B, C and D are transmitted parenterally through contact with infected blood or body fluids, as listed in Box 2 (Public Health England, 2019). Box 1.

Symptoms of acute hepatitis.

Cholestasis symptoms:

• Dark urine

• Itchy skin

• Pale stools

Gastrointestinal symptoms:

• Abdominal discomfort

• Jaundice

• Loss of appetite

• Nausea

Influenza-like symptoms:

• Fever

• Fatigue

• Muscle and joint pain

Box 2.

Routes of parenteral transmission of viral hepatitis.

• Blood transfusion

• Intravenous drug use

• Needle stick injury

• Sexual transmission

• Tattoo or body piercing

• Vertical transmission from mother to baby

Examination

Most patients with acute viral hepatitis will have few clinical signs apart from, possibly, jaundice and abdominal tenderness. However, patients with chronic viral hepatitis (B and C) can develop liver cirrhosis and portal hypertension. There are numerous stigmata of chronic liver disease such as leukonychia (due to hypoalbuminaemia), spider naevi (due to elevated oestrogen), wasting of muscle tone, and bruising, with more examples illustrated in Fig. 1. Signs of decompensated chronic liver disease include jaundice, hepatic encephalopathy, ascites and peripheral oedema. Hepatic encephalopathy in acute liver disease is typically more severe and evolves more rapidly than in chronic liver disease. Identification of any decompensation signs prompts same-day referral to a liver specialist. Specific clues indicating possible viral hepatitis include ethnicity relating to high-prevalence regions, tattoos or needle marks on people who inject drugs (PWID).

Figure 1.

Signs of chronic liver disease.

Primary care investigations

Initial investigations for all patients with suspected infectious hepatitis include full blood count (white cell count will usually be normal but could show a degree of lymphocytosis or lymphopenia (Guo et al., 2021)), urea and electrolytes, liver function tests (bilirubin, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase, albumin and prothrombin time/INR (international normalised ratio). If abnormalities are found on initial blood tests or there is a high clinical suspicion of hepatitis, a liver screen can be performed to detect common causes. Table 2 outlines the standard liver screen blood tests in addition to blood tests indicated in cases of diagnostic uncertainty or as guided by specific clinical features.

Table 2.

Liver aetiology screen.

Disease	Standard aetiology panel	Extended aetiology panel
Autoimmune
Autoimmune hepatitis	Anti-nuclear AbAnti-smooth muscle AbSerum immunoglobulins	Anti-LKM Ab
Primary biliary cirrhosis	Anti-mitochondrial Ab
Primary sclerosing cholangitis		P-ANCA
Coeliac disease		Anti-transglutaminase AbAnti-endomysial Ab
Genetic
α-1 antitrypsin		α-1 antitrypsin
Haemochromatosis	FerritinTransferrin saturation	Haemochromatosis gene testing
Wilson’s disease		CeruloplasminUrinary copper collection
Viral hepatitis
Hepatitis A		Anti-HAV IgM
Hepatitis B	HBsAg	Anti-HBc IgMAnti-HBc IgGHBV DNA PCRHBeAg
Hepatitis C	Anti-HCVHCV RNA PCR (if Ab+)
Hepatitis D		Anti-HDV
Hepatitis E		Anti-HEV IgM
Other		Thyroid function tests

If the standard aetiology panel is negative, and/or points towards a specific liver disease, further investigations with the extended aetiology panel should be considered. Ab, Antibody; Ag, Antigen; Anti-HAV IgM, Hepatitis A IgM Ab; Anti-HBc, Hepatitis B Core Ab; HBeAg, Hepatitis B e Ag; Anti-HCV, HCV Ab; Anti-HDV, HDV Ab; Anti-HEV IgM, Hepatitis E IgM Ab; Anti-LKM, Anti-liver-kidney microsome; HBsAg, Hepatitis B surface Ag; Ig, Immunoglobulin; P-ANCA, perinuclear antineutrophil cytoplasmic antibodies; PCR, polymerase chain reaction.

Reproduced from Tang CM (2019) Abnormal liver function tests. InnovAiT 12(9): 507–515. DOI: 10.1177/1755738019855092.

Specific serology testing for infectious hepatitis in primary care usually screens for hepatitis A, B and C. Hepatitis D and E are typically requested by secondary care if required. Positive serology for hepatitis A virus immunoglobulin M (IgM) indicates acute hepatitis A infection. Hepatitis B surface antigen (HBsAg) is the initial serological test for hepatitis B as an indicator of current infection. If positive, additional serological tests should be performed by secondary care to determine if the infection is acute or chronic and the degree of infectivity of the patient (virology laboratories perform IgM to core HBV (anti-HBc), indicative of recent HBV infection, automatically at some centres). Positive hepatitis B e antigen (HBeAg) is associated with high infectivity in patients with chronic hepatitis B. Hepatitis C antibody (anti-HCV) is the initial test for hepatitis C. If the patient is symptomatic or is subsequently hepatitis C virus (HCV) RNA (ribonucleic acid) positive, the patient should be referred to secondary care.

In addition to blood tests, an ultrasound scan of the abdomen should be performed to check for signs of chronic liver disease or alternative, structural diagnoses. Liver biopsy is seldom required in patients with infectious hepatitis, but may be considered for those with severe disease and unclear aetiology.

Reporting

Acute infectious hepatitis is notifiable in England (UK Health Security Agency, 2021) and Wales (Public Health Wales Health Protection Division, 2013), and all viral hepatitis infections are reportable in Northern Ireland (HSC Public Health Agency, 2021) and Scotland (National Services Scotland, 2021). Laboratories performing the diagnostic tests have a responsibility to inform the relevant public health authority. Registered medical practitioners in the UK also have a duty to notify the relevant public health authority if a notifiable disease is suspected (although not specifically for hepatitis in Scotland (Health Protection Scotland, 2010)).

Hepatitis A

Hepatitis A virus is an RNA hepatovirus which typically causes a short-lived and mild hepatitis. Older patients and individuals with underlying liver disease have a higher risk of more serious disease (Dooley et al., 2018). Hepatitis A is endemic in low- and middle-income countries in association with poor sanitation, and cases occur sporadically and in epidemics. In the UK, hepatitis A is rare with only 503 laboratory-confirmed cases in 2019 in England and Wales (Public Health England, 2021). However, the true incidence is likely higher given asymptomatic infection.

Management

Patients with hepatitis A can be managed supportively in the community, but require hospital admission if they are unwell. General measures include advice to rest, maintain hydration and avoid alcohol. To minimise risk of hepatitis A transmission to other people, patients should be advised to avoid close contact with others, regularly wash their hands and avoid institutions such as schools and workplaces. Children and school staff members should not attend school while they are unwell, for 7 days after jaundice onset or for 7 days after symptom onset if they are not jaundiced (UK Health Security Agency, 2022). Mild liver disease does not contraindicate prescription of simple analgesics, anti-emetics or anti-pruritics for symptomatic management (National Institute for Health and Care Excellence (NICE), 2021a).

Prevention

Hepatitis A can be prevented through improved sanitation, safe food practices and immunisation. Several different injectable hepatitis A vaccines are licenced for use in the UK (NICE, 2021b). Vaccination for hepatitis A is available on the NHS for the following groups of people: those who have contact with someone with hepatitis A, those at risk of exposure to hepatitis A at work (such as sewage workers), contacts of patients with hepatitis A, those planning travel to an endemic area, patients with chronic liver disease, men who have sex with men, and PWID. Patients at high risk of previous exposure, such as those from endemic areas, may not require vaccination for hepatitis A if they possess positive serology for hepatitis A virus immunoglobulin G (HAV-IgG), suggestive of immunity.

Hepatitis E

Hepatitis E is an RNA hepevirus which includes four genotypes that can affect humans. Types 1 and 2 only infect humans and are transmitted by the faecal–oral route; they typically occur in low- and middle-income countries in areas with poor sanitation. Types 3 and 4 are enzootic in animals such as pigs and deer; sporadic cases typically occur in cases of ingesting raw or undercooked meat containing the virus.

Indigenous acquisition of hepatitis E accounts for most hepatitis E cases in the UK. The clinical presentation and management of hepatitis E is similar to hepatitis A. Although hepatitis E typically causes mild self-limiting infection, pregnant women, particularly in their second and third trimester of pregnancy, are at increased risk of fulminant hepatic failure from genotypes 1 and 2. Chronic infection with hepatitis is rare but can occur in immunocompromised patients. The incidence of hepatitis E is low in the UK with 1202 laboratory-confirmed cases in 2019 (Public Health England, 2020a).

Prevention

Prevention of faecal–oral transmission is the same as for hepatitis A: with improved sanitation and safe food practices. For indigenous disease, individuals can reduce their risk of hepatitis E through avoiding eating raw or undercooked meat and shellfish (Public Health England, 2020a). Donated blood is screened for hepatitis E in the UK, due to rare cases of transmission of hepatitis E through blood products (NHS Blood and Transplant, 2021). Unlike hepatitis A, there are no licenced vaccines for hepatitis E in the UK.

Hepatitis B

Hepatitis B virus (HBV) is a DNA virus which belongs to the Hepadnaviridae family of viruses. Over 200 000 000 people worldwide are infected with a wide variation in prevalence between different countries. Hepatitis B is endemic (prevalence more than 8%) in many sub-Saharan African and southeast Asian countries (NICE, 2021c). Hepatitis B is estimated to have a very low overall prevalence in the UK (0.1–0.5%), but prevalence varies between individual communities (Health and Safety Executive, 2021). The incidence of acute hepatitis B is very low in the UK, with 381 cases of acute or probable hepatitis B being reported for England in 2018 (Public Health England, 2020b). The risk of developing chronic infection with HBV is highest when infected at birth and decreases with age. There is a stark contrast of chronicity risk following infection: 90% for babies and 5% for adults (NHS, 2019). In the UK, most chronic hepatitis B occurs in patients born in high prevalence areas (NICE, 2021c).

Management

Individuals with current hepatitis B infection, as indicated by a positive HBsAg, should be referred to a liver specialist (NICE, 2021c). Most patients with acute hepatitis B will have self-limiting disease. Active treatment is only required for patients if they develop signs of liver failure, particularly prolonged prothrombin time, and should be managed in a secondary care setting. A small number of patients will develop fulminant liver failure and potentially require transplantation (Lampertico et al., 2017). Patients with chronic hepatitis B infection will be managed by liver specialists or infectious diseases (ID) specialists at some centres. Principles of hepatitis B management are outlined in Box 3 and indications for treatment in Box 4. Box 3.

Principles of management for patients withhepatitis B.

• Determine activity of infection: All patients will have a virus level checked (HBV DNA PCR (deoxyribonucleic acid polymerase chain reaction)) at review, as well as ALT as a marker of liver inflammation

• Assessment of fibrosis: All patients with HBV should have an assessment of fibrosis. The first-line investigation is an abdominal ultrasound scan, which should ideally be performed before the patient is seen at clinic. If there is no radiological evidence of cirrhosis on ultrasound scan, other assessments of liver fibrosis may include a fibroscan, hyaluronic acid or ELF (enhanced liver fibrosis) blood test

• Medical treatment: Indications for treatment are listed in Box 4. The two broad classifications of medication options for hepatitis B are interferon and nucleos(t)ide analogues (NA). The current treatment of choice long term is the NA, tenofovir. Entecavir can be used for those with renal impairment. Treatment should always be initiated by a liver/ID specialist

• HCC surveillance: All patients with confirmed cirrhosis should have a 6-monthly abdominal ultrasound scan and serum alpha-fetoprotein surveillance for HCC. Given the increased risk of HCC from HBV, some higher risk patients may undergo HCC surveillance even without existing cirrhosis

Box 4.

Indications for treatment of hepatitis B withantiviral medication.

• Any patient with HBV DNA PCR > 2000 IU/ml, raised ALT and/or evidence of at least moderate fibrosis

• Any patient with compensated or decompensated cirrhosis with any detectable HBV DNA level

• Any patient with HBV DNA > 20 000 IU/ml and ALT raised at twice the upper limit of normal

• Patients aged over 30 years with high viral load and family history of HCC

Pregnancy and breastfeeding

All pregnant women should be screened for HBV infection in the first trimester of pregnancy (NHS, 2021). Pregnant women with HBV infection should be assessed for consideration of tenofovir treatment in the third trimester, dependent on viral load (Lampertico et al., 2017). Hepatitis B immunoglobulin and vaccination should be given within 12 hours of birth to reduce risk of perinatal transmission in HBeAg positive disease (UK Health Security Agency, 2019). Breastfeeding is not contraindicated in women who are HBsAg positive or on tenofovir treatment.

Vaccination

In the UK, vaccination against hepatitis B is currently available to all babies as part of the ‘6-in-1 vaccine’ at 8, 12 and 16 weeks of age. Vaccinations are also offered to high-risk groups as outlined on the NHS.UK website (NHS, 2019). Positive antibodies to HBV surface antigen (anti-HBs) alongside negative HBsAg and HBV core antibodies (anti-HBc) indicate vaccine-induced immunity.

Hepatitis D

Hepatitis D is an RNA virus that can only infect patients who have hepatitis B. Globally almost 5% of people with chronic HBV infection also have hepatitis D (World Health Organization (WHO), 2021). Co-infection with hepatitis D is associated with more severe acute hepatitis and chronic liver disease.

Hepatitis C

HCV is a single-stranded RNA virus from the genus Hepacivirus in the Flaviviridae family. Around 70 000 000 people are chronically infected with HCV worldwide, and it is a major cause of liver disease globally (Pawlotsky et al., 2018). Hepatitis C is a curable disease and cases of chronic hepatitis C in the UK have fallen dramatically from 174 000 people in 2015 to 118 000 in 2019 (Public Health England, 2020c). This is due to improved testing, wider awareness, and better access to more effective treatments. The WHO set an ambitious target in 2016 to reduce new chronic infections by 90% by 2030 (WHO, 2016). Local initiatives have shown to be effective, with NHS Tayside in East Scotland becoming the first region in the world to reach the WHO target for hepatitis C in 2019 (University of Dundee, 2020).

Acute hepatitis C is usually asymptomatic or causes mild symptoms, so cases are often not diagnosed. Most patients with HCV infection (50–90%) develop chronic disease (Pawlotsky et al., 2018) and are unlikely to present until they develop cirrhosis or hepatocellular carcinoma (HCC). Screening of high-risk groups is therefore needed to detect patients before they develop complications. NICE has created an extensive list of individuals to whom screening should be offered (NICE, 2020).

Management

Although hepatitis C is curable, it often affects underserved communities who may have difficulty accessing or keeping to treatment regimes. PWID are at particular risk of infection and reinfection with HCV (Public Health England, 2020c). Management should therefore be holistic through providing access to clean injecting equipment, such as needle-exchange services, offering opioid substitution treatment and supporting patients to access treatment (Public Health England, 2020c). There is no vaccine currently licenced in the UK for HCV. The principles of management in secondary care clinics are outlined in Box 5. Box 5.

Principles of management for patients with hepatitis C.

• Assessment of fibrosis: Fibrosis assessment should be undertaken in the same way as that for hepatitis B. Patients with advanced fibrosis or cirrhosis will require ongoing follow up once treatment is completed

• HCV RNA quantification: The aim of medical treatment is to achieve a sustained viral response. This is defined as undetectable HCV RNA at 12 weeks following treatment meaning that the patient is cured

• Determining HCV genotype: Once patients are diagnosed with hepatitis C, the genotype of HCV is determined as it affects choice and duration of treatment therapy. Six main genotypes of HCV exist, and types 1 and 3 are commonest in the UK

• Medical treatment: All patients with active disease, either treatment-naive or having failed previous therapy, should be considered for treatment. Those patients with liver fibrosis or cirrhosis, with extrahepatic manifestations, and those at higher risk of transmitting the disease (such as PWID or women of childbearing age who wish to get pregnant) should be considered for urgent treatment. There are a wide range of anti-viral medications used in the management of hepatitis C, which are initiated and monitored by liver/ID specialists. Treatment regimens for hepatitis C are beyond the scope of this article.

Follow up

Patients who achieve a sustained viral response and do not have evidence of fibrosis or cirrhosis do not require any specific follow up. Those patients with either fibrosis or cirrhosis require follow up like other patients with cirrhosis, with 6-monthly liver ultrasound and alpha-fetoprotein (AFP). Patients can be reinfected with hepatitis C once cured, so patients should be advised of this and measures sought to reduce reinfection risk.

Pregnancy

Hepatitis C is not included in the routine infectious disease screening of pregnancy in the UK (NHS, 2021). Women with known hepatitis C who are of childbearing age and who are looking to conceive should be offered treatment as a matter of urgency. Breastfeeding is not contraindicated in women who have active hepatitis C or who are on treatment.

Conclusion

This article has provided an approach to assessment and management of patients with a viral hepatitis infection. Although acute hepatitis A and E viral infections can occur sporadically and in epidemics in low- and middle-income countries, the incidence in the UK is low. Illness with these viruses is typically mild and patients can usually be managed with a conservative approach. Primary care clinicians should nevertheless be aware that, in rare instances, patients could develop acute liver decompensation. Hepatitis B and C infections can cause chronic liver disease and patients may not have signs or symptoms until they have cirrhosis. Testing patients from high-risk groups for hepatitis B and C infection can provide an opportunity to identify patients early in the course of the disease and initiate treatment. Although the global burden of hepatitis B and C infection is still large, there is potential for global eradication through public health preventative measures and widely available medical treatment.

Key points

Acute viral hepatitis is generally mild, but symptoms or signs of liver decompensation should prompt urgent referral to secondary care

Hepatitis A and E usually cause a self-limiting illness, but can cause more severe disease in patients who are elderly, have existing liver disease or are immunocompromised

Hepatitis B usually causes chronic disease if acquired in childhood and acute infection in adulthood

Hepatitis C is a treatable condition and shows potential for eradication

Patients with chronic hepatitis B and C are at increased risk of HCC and require 6-monthly surveillance with ultrasound and AFP

Footnotes

ORCID iD

Dr Thomas J Downes

References

Dooley

Lok

ASF

Garcia-Tsao

, et al. (eds) (2018) Sherlock’s Diseases of the Liver and Biliary System, 13th Edition. Oxford, UK: John Wiley & Sons Ltd.

Guo

Zhang

Prajapati

, et al. (2021) Lymphopenia caused by virus infections and the mechanisms beyond. Viruses 13(9): 1876. DOI: 10.3390/v13091876.

Health and Safety Executive (2021) Hepatitis B virus (HBV). Available at: www.hse.gov.uk/biosafety/blood-borne-viruses/hepatitis-b.htm (accessed 12 January 2022).

Health Protection Scotland (2010) Notification of infectious disease or health risk state form. Available at: www.hps.scot.nhs.uk/web-resources-container/notification-of-infectious-disease-or-health-risk-state-form/ (accessed 25 January 2022).

HSC Public Health Agency (2021) Notifiable diseases. Available at: www.niinfectioncontrolmanual.net/notifiable-diseases (accessed 25 January 2022).

Lampertico

Agarwal

Berg

, et al. (2017) EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. Journal of Hepatology 67(2): 370–398. DOI: 10.1016/j.jhep.2017.03.021.

National Services Scotland (2021) National infection prevention and control manual. Available at: www.nipcm.hps.scot.nhs.uk/a-z-pathogens/#h (accessed 12 December 2021).

NHS (2019) Overview: Hepatitis B. Available at: www.nhs.uk/conditions/hepatitis-b/ (accessed 25 January 2022).

NHS (2021) Screening for hepatitis B, HIV and syphilis. Available at: www.nhs.uk/pregnancy/your-pregnancy-care/screening-for-hepatitis-b-hiv-and-syphilis/ (accessed 25 January 2022).

10.

NHS Blood and Transplant (2021) Tests we carry out on your blood. Available at: www.blood.co.uk/the-donation-process/further-information/tests-we-carry-out/ (accessed 25 January 2022).

11.

NICE (2020) Clinical knowledge summary. Hepatitis C: Who should I test for hepatitis C? Available at: https://cks.nice.org.uk/topics/hepatitis-c/ (accessed 25 January 2022).

12.

NICE (2021a) Clinical knowledge summary. Hepatitis A: Scenario: Managing hepatitis A infection. Available at: https://cks.nice.org.uk/topics/hepatitis-a/management/managing-hepatitis-a-infection/ (accessed 25 January 2022).

13.

NICE (2021b) Clinical knowledge summary. Hepatitis A: What issues should I consider before giving hepatitis A vaccine? Available at: https://cks.nice.org.uk/topics/hepatitis-a/prescribing-information/hepatitis-a-vaccine/ (accessed 25 January 2022).

14.

NICE (2021c) Clinical knowledge summary. Hepatitis B. Available at: https://cks.nice.org.uk/topics/hepatitis-b/ (accessed 25 January 2022).

15.

Pawlotsky

Negro

Aghemo

, et al. (2018) EASL recommendations on treatment of hepatitis C 2018. Journal of Hepatology 69(2): 461–511. DOI: 10.1016/j.jhep.2018.03.026.

16.

Public Health England (2019) Hepatitis B: Clinical and public health management. Available at: www.gov.uk/guidance/hepatitis-b-clinical-and-public-health-management (accessed 25 January 2022).

17.

Public Health England (2020a) Hepatitis E: Symptoms, transmission, treatment and prevention. Available at: www.gov.uk/government/publications/hepatitis-e-symptoms-transmission-prevention-treatment/hepatitis-e-symptoms-transmission-treatment-and-prevention (accessed 25 January 2022).

18.

Public Health England (2020b) Acute hepatitis B (England): Annual report for 2018. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/877344/hpr3019_ct-hbv18_V3.pdf (accessed 25 January 2022).

19.

Public Health England (2020c) Hepatitis C in the UK 2020: Working to eliminate hepatitis C as a major public health threat. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/943154/HCV_in_the_UK_2020.pdf (accessed 25 January 2022).

20.

Public Health England (2021) Laboratory reports of hepatitis A infections in England and Wales. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/982962/hpr0715_HAV19_v2.pdf (accessed 25 January 2022).

21.

Public Health Wales Health Protection Division (2013) About the notification of infectious disease in Wales. Available at: www.wales.nhs.uk/sites3/page.cfm?orgid=457&pid=48544 (accessed 25 January 2022).

22.

RCGP. Clinical topic guide: Gastroenterology. Available at: www.rcgp.org.uk/mrcgp-exams/gp-curriculum/clinical-topic-guides#gastroenterology (accessed 1 July 2022).

23.

Tang

(2019) Abnormal liver function tests. InnovAiT 12(9): 507–515. DOI: 10.1177/1755738019855092.

24.

UK Health Security Agency (2019) Hepatitis B: The green book, chapter 18. Available at: www.gov.uk/government/publications/hepatitis-b-the-green-book-chapter-18 (accessed 25 January 2022).

25.

UK Health Security Agency (2021) Notifiable diseases and causative organisms: How to report. Available at: www.gov.uk/guidance/notifiable-diseases-and-causative-organisms-how-to-report (accessed 25 January 2022).

26.

UK Health Security Agency (2022) Chapter 3: Public health management of specific infectious diseases. Available at: www.gov.uk/government/publications/health-protection-in-schools-and-other-childcare-facilities/chapter-3-public-health-management-of-specific-infectious-diseases (accessed 30 May 2022).

27.

University of Dundee (2020) NHS Tayside first region in the world to eliminate hepatitis C. Available at: www.dundee.ac.uk/stories/nhs-tayside-first-region-world-eliminate-hepatitis-c (accessed 25 January 2022).

28.

WHO (2016) Combating hepatitis B and C to reach elimination by 2030. Available at: www.who.int/publications/i/item/combating-hepatitis-b-and-c-to-reach-elimination-by-2030 (accessed 25 January 2022).

29.

WHO (2021) Hepatitis D. Available at: www.who.int/news-room/fact-sheets/detail/hepatitis-d (accessed 25 January 2022).