Hepatitis A

Source:
Clinical Knowledge Summaries
Publication date:
01 December 2016

Abstract

Hepatitis A Last revised in December 2016 Next planned review by December 2019 Summary Back to topHepatitis A: Summary Hepatitis A is inflammation of the liver caused by infection with the hepatitis A virus, and transmission is by the faecal-oral route.Hepatitis A infection is usually self-limiting, causes an illness which usually lasts less than 2 months, has no long-term sequelae, has no chronic carrier state, and does not cause chronic liver disease.The clinical features of acute hepatitis A are common to all forms of viral hepatitis, and are characterized by different phases:Prodromal phase includes flu-like symptoms, gastrointestinal symptoms (such as anorexia, nausea, vomiting, and abdominal right upper quadrant discomfort), and occasionally headache, cough, pharyngitis, constipation, diarrhoea, itch, and urticaria. Usually, there are no specific signs on examination.Icteric phase includes jaundice, pale stools and dark urine (if there is cholestasis), pruritus, fatigue, anorexia, nausea, and vomiting — symptoms often improve once jaundice occurs. Hepatomegaly, splenomegaly, lymphadenopathy, and hepatic tenderness are often present on examination.Convalescent phase includes malaise and hepatic tenderness.Confirmed hepatitis A infection is defined by:An acute illness with a discrete onset of symptoms,andJaundice or elevated serum aminotransferase levels,andLaboratory-confirmed IgM antibodies to hepatitis A virus.Management of a person with confirmed or probable hepatitis A infection includes admission to hospital if they are severely unwell. If admission is not needed:Providing symptomatic supportive care for pain, nausea, or itch if needed.Notifying the local Health Protection Unit promptly — if an outbreak is suspected, or the person is a food handler, notify immediately.Providing information and advice about hepatitis A, including the need to avoid alcohol during the acute illness.Offering referral to a genito-urinary medicine clinic or drug rehabilitation centre, if appropriate.Monitoring liver function tests and prothrombin time, the frequency of which depends on clinical judgement, the person's symptoms and liver function test results.Advising the person to seek medical attention if their symptoms worsen.Prevention of transmission of hepatitis A involves advising:The person to avoid work, school, or nursery, until they are no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice).The person and all close contacts about thorough hand washing after using the toilet, changing nappies, and helping with child toileting; ensuring good general personal hygiene; avoid handling food or thorough hand washing before food preparation; practising safe sex until they are no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice); avoiding sharing drug paraphernalia.People at high risk of hepatitis A infection should be offered hepatitis A vaccination if they are not already immune. Have I got the right topic? Back to topHave I got the right topic? From birth onwards.This CKS topic covers the management of hepatitis A, and its prevention, in children and adults.This CKS topic does not cover the initial assessment and management of people presenting with jaundice.There are separate CKS topics on Hepatitis B, Hepatitis C, and Immunizations - travel.The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care. How up-to-date is this topic? Back to topHow up-to-date is this topic? Back to top Changes Changes December 2016 — minor update. Information added on concomitant administration of Havrix®.January to April 2014 — reviewed. A literature search was conducted in January 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made. Back to top Previous changes Previous changes September 2013 — minor update to the text to reflect current recommendations regarding metoclopramide.February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency. Prescriptions have been updated to reflect the revised dosing. Issued in July 2011.September 2010 — minor update. Additional information has been included in the Prescribing information section. Issued in September 2010.April to August 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence. Back to top Update Update Back to top New evidence New evidence Evidence-based guidelinesPHE (2017) Hepatitis A: the green book. Public Health England. www.gov.uk [Free Full-text]PHE (2017) Hepatitis A infection: prevention and control guidance. Public Health England. www.gov.uk [Free Full-text]BASHH (2015) 2015 BASHH CEG guidance on tests for sexually transmitted infections. British Association for Sexual Health and HIV.www.bashh.orgNewsome, P.N., et al. (2017) Guidelines on the management of abnormal liver blood tests. Gut epub ahead of print. HTAs (Health Technology Assessments)No new HTAs since 1 January 2014.Economic appraisalsNo new economic appraisals relevant to England since 1 January 2014.Systematic reviews and meta-analysesNo new systematic review or meta-analyses since 1 January 2014.Primary evidenceNo new randomized controlled trials published in the major journals since 1 January 2014. Back to top New policies New policies No new national policies or guidelines since 1 January 2014. Back to top New safety alerts New safety alerts No new safety alerts since 1 January 2014. Back to top Changes in product availability Changes in product availability No changes in product availability since 1 January 2014. Goals and outcome measures Back to topGoals and outcome measures Back to top Goals Goals To support primary healthcare professionals to:Offer hepatitis A vaccination to people at risk.Prevent hepatitis A infection in people at risk.Diagnose and manage people with hepatitis A infection.Provide self-care advice to people with hepatitis A, their carers and families, to reduce the risk of transmission of infection.Admit people with hepatitis A to hospital, when appropriate.Monitor people in primary care appropriately until infection has resolved. Back to top Outcome measures Outcome measures No outcome measures were found during the review of this topic. Back to top Audit criteria Audit criteria No audit criteria were found during the review of this topic. Back to top QOF indicators QOF indicators No QOF indicators were found during the review of this topic. Back to top QIPP - Options for local implementation QIPP - Options for local implementation Non-steroidal anti-inflammatory drugs (NSAIDs)Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients).If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis [CSM, 2005; NICE, 2008].Co-prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008; NICE, 2009a; NICE, 2009b].Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with ACE inhibitors or angiotensin receptor blockers (ARBs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.[NICE, 2015] Back to top NICE quality standards NICE quality standards No NICE quality standards were found during the review of this topic. Background information Back to topBackground information Back to top Definition What is it? Hepatitis A infection is inflammation of the liver caused by infection with the hepatitis A virus.Hepatitis A virus is a non-enveloped single-stranded RNA virus, which is classified in the hepatovirus genus of the Picornaviridae family. The virus replicates in hepatocytes (liver cells), interfering with cell function and causing inflammation of the liver.Hepatitis A is usually a self-limiting illness with a good prognosis. It typically has four clinical phases — incubation, prodromal, icteric, and convalescent.In adults, 70–95% of infections result in clinical illness.In children younger than 5 years of age, 80–95% of infections are asymptomatic.In the UK, hepatitis A usually presents as:Sporadic cases.Community-wide outbreaks (from person-to-person transmission).Point-of-source outbreaks (related to contaminated food, although this is uncommon).[HPA, 2009; WHO, 2009; NaTHNaC, 2013; PHE, 2013a; PHE, 2014] Back to top Prevalence How common is it? Hepatitis A is uncommon in the UK and other high-income countries.In 2012, the Health Protection Agency (HPA) received notification of 248 acute infectious hepatitis cases in England and Wales. Hepatitis A was the causal organism in 73 (about 29%) of these cases. The majority occurred after overseas travel.The incidence of hepatitis A in the European Union has steadily decreased, due to improved living conditions and reduced exposure to infection, especially in early childhood. Outbreaks in the European Union generally follow the introduction of the virus from endemic countries through 'seeding events' via non-immunized travellers.Worldwide, approximately 1.5 million cases of hepatitis A are reported every year, but the true incidence is likely to be 3–10 times higher.Hepatitis A is endemic in many low-income countries, where standards of sanitation and food hygiene may be poor. The highest risk areas for UK travellers are the Indian sub-continent (particularly India, Pakistan, Bangladesh, and Nepal), sub-Saharan Africa and North Africa, parts of the Far East (excluding Japan), South and Central America, and the Middle East.Infection in adults is uncommon in countries where hepatitis is endemic, as most people are exposed to the virus at a young age and acquire lifelong immunity.[Payne and Coulombier, 2009; NaTHNaC, 2013; PHE, 2013a; PHE, 2013b] Back to top Transmission How is hepatitis A transmitted? Transmission of hepatitis A is by the faecal-oral route.The mean incubation period is 28–30 days, with a range of 15–50 days, when the person is asymptomatic.In countries where hepatitis A is highly endemic, it is mainly transmitted by close contact or via faeces-contaminated food and water.In countries where hepatitis A is uncommon, new infections occur mostly among travellers returning from places where the virus is highly endemic, causing small outbreaks among unvaccinated children or adults, or among men who have sex with men, or injecting drug users (risk of faecal contamination of drug injecting equipment).Hepatitis A virus is excreted in bile, and shed in the faeces of infected people.Faecal shedding of virus has been demonstrated for 14–21 days before, and up to 8 days after, the onset of jaundice. Shedding may continue for longer in infected infants and children (virus RNA has been detected in the faeces of newborn babies for as long as 6 months after infection), and in people who are immunocompromised.Vertical transmission of hepatitis A from mother to child is very rare (in case reports).[HPA, 2009; Urbanus et al, 2009; NaTHNaC, 2013; PHE, 2013a; PHE, 2014] Back to top Risk factors People at high risk of hepatitis A People at high risk of hepatitis A infection include:Travellers to areas with a high prevalence (especially people visiting friends and relatives, long-term travellers, and people visiting areas with poor sanitation and food hygiene). For country-by-country recommendations for hepatitis A and other travel vaccines, see www.nathnac.org.People with clotting factor disorders (those receiving factor VIII and factor IX concentrates are at higher risk of potential blood product contamination).Men who have sex with men, and people with risky sexual behaviours (sexual practices involving oral-anal or digital-rectal contact, those who have multiple sexual partners, anonymous partners, sex in public places, and group sex).Injecting drug users and their close contacts (at risk of poor standards of personal hygiene, with possible faecal contamination of shared drug equipment and other paraphernalia).People at occupational risk (such as laboratory workers, staff of large residential institutions, sewage workers, and people who work with primates.[BASHH, 2008; HPA, 2009; Urbanus et al, 2009; NaTHNaC, 2013; PHE, 2013a] Back to top Complications and prognosis What are the complications and prognosis of hepatitis A? Complications of hepatitis A infection:Up to 15% of people may relapse at an interval of 4–15 weeks after the original illness.Cholestasis occurs in 8% of people (features include severe pruritus, diarrhoea, weight loss, and malabsorption), with eventual complete recovery.Fulminant liver failure occurs in less than 0.4% of people, but can present with sudden, severe vomiting, irritability and confusion, leading to coagulopathy and hepatic encephalopathy.It usually manifests during the first four weeks of illness and is more common in people with concurrent chronic liver disease including chronic hepatitis B or C infection.It has a mortality rate of 40% without liver transplantation.Overall, hepatitis A infection has an estimated mortality rate of 0.1% for children younger than 15 years of age, 0.3% for people 15–39 years of age, and 2.1% for adults 40 years of age or older.Prognosis of hepatitis A infection:Usually causes a self-limiting illness which lasts less than 2 months. Complete clinical recovery may take up to 6 months after the onset of the illness.Has no long-term sequelae, does not cause chronic liver disease, and has no chronic carrier state.Results in lifelong immunity.[Spira, 2003; Sjogren, 2006; BASHH, 2008; Curry, 2009; Urbanus et al, 2009; Wasley et al, 2009; WHO, 2009; NaTHNaC, 2013; PHE, 2013a] Diagnosis Back to topDiagnosis of hepatitis A Back to top Diagnosis How do I know my patient has it? Confirmed infection with hepatitis A is defined by:An acute illness with a discrete onset of symptoms (see Clinical features), andJaundice or elevated serum aminotransferase levels (see Investigations), andLaboratory-confirmed IgM antibodies to hepatitis A virus (see Interpretation of serology results).Probable infection is defined by:An acute illness with a discrete onset of symptoms, andIts occurrence in a person who has an epidemiological link with someone with laboratory-confirmed hepatitis A (for example a household or sexual contact during the 15–50 days before the onset of symptoms). Back to top Basis for recommendation Basis for recommendation Recommendations on definitions of confirmed and probable infection are based on Guidance for the prevention and control of hepatitis A infection produced by the Health Protection Agency [HPA, 2009] and information in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013a]. Back to top Clinical features What are the clinical features of hepatitis A infection? The clinical features of acute hepatitis A are common to all forms of acute viral hepatitis, and it cannot easily be distinguished by history, examination, or by routine biochemistry tests. Suspicion may be increased, however, by a history of a specific exposure or risk.The clinical features of the prodromal phase of hepatitis (may last from 2 days to more than 2 weeks) include:Flu-like symptoms (such as general fatigue, malaise, joint and muscle pain, low-grade fever up to 39°C).Gastrointestinal symptoms (such as anorexia, nausea, vomiting, and right upper quadrant abdominal discomfort).There may be accompanying headache, cough, sore throat, constipation, diarrhoea, itch, or urticaria.Usually, there are no specific signs on examination.The clinical features of the icteric phase of hepatitis (usually lasts 1–3 weeks, but can persist for more than 12 weeks) include:Jaundice, pale stools and dark urine if cholestasis.Pruritus (present in 40% of those with jaundice).Fatigue, anorexia, nausea, and vomiting — symptoms often improve once jaundice occurs.Hepatomegaly (85%), splenomegaly (15%), lymphadenopathy (5%), and hepatic tenderness are often present on examination.The clinical features of the convalescent phase of hepatitis (may take up to 6 months) include:Malaise, anorexia, muscle weakness, and hepatic tenderness. Back to top Basis for recommendation Basis for recommendation The clinical phases of hepatitis A infection are described in Guidance for the prevention and control of hepatitis A infection produced by the Health Protection Agency [HPA, 2009], a review published by the National Travel Health Network and Centre [NaTHNaC, 2013], a review by the World Health Organization [WHO, 2009], expert opinion in two chapters of the textbook Principles and practice of infectious diseases [Curry, 2009; Wasley et al, 2009], a review of combined hepatitis A and hepatitis B vaccination for travellers [Spira, 2003], a Guideline on the management of the viral hepatitides A, B and C published by the British Association for Sexual Health and HIV [BASHH, 2008], and information in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013a]. Back to top Investigations What investigations should I do? Request hepatitis serology — if hepatitis A is suspected, this should be specifically stated on the request form. For more information see Interpretation of serology results.Check liver function tests (test results return to normal within 12 months).Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may be significantly increased (usually higher than 1000 IU/L).Bilirubin may be elevated (up to 500 micromols/L).Prothrombin time may be prolonged (5 seconds or more suggests hepatic decompensation). Back to top Interpretation of serology results Interpretation of serology results Hepatitis A serology testing usually checks for hepatitis A virus immunoglobulin M (HAV-IgM) and hepatitis A virus immunoglobulin G (HAV-IgG). If serology shows:Positive HAV-specific IgM, acute hepatitis A infection is likely.HAV-IgM is detectable about 3 weeks after exposure, increases in titre over 4–6 weeks, then declines to non-detectable levels (generally within 6–12 months of infection).If serology is taken in the first 7–10 days of symptoms, there is a small risk of a false negative result, so serology should be repeated 1–2 weeks later.There is a small risk of a false positive result, especially in the elderly.Positive HAV-non-specific IgM, repeat the test.Positive HAV-IgG, this indicates current or past hepatitis A infection, or immunity from previous vaccination.HAV-IgG is detectable 5–10 days after the onset of symptoms and persists, conferring lifelong immunity. Back to top Basis for recommendation Basis for recommendation Hepatitis serology requestsThe recommendation to state any suspicion of hepatitis A on the laboratory request form when ordering hepatitis serology is based on expert opinion from a CKS external reviewer. Hepatitis A may not be routinely included in hepatitis serology screens in all laboratories in the UK, so it should be specifically requested when suspected. The clinical features of acute hepatitis A cannot easily be distinguished from other forms of acute hepatitis, and people may have co-infection with hepatitis B or C, so a full hepatitis screen is recommended [British Liver Trust, 2009].Liver function testsThe information on deranged liver function tests is based on the National guideline on the management of the viral hepatitides A, B and C [BASHH, 2008] and on UK standards for microbiology investigations: investigation of hepatitis [PHE, 2014]. High levels of alanine transaminase (ALT) and aspartate transaminase (AST) are an indicator of liver cell damage. In general, the level of ALT is thought to be a more specific indicator of liver inflammation, as AST may be raised in other conditions, such as heart disease.Interpretation of serology resultsRecommendations for the interpretation of hepatitis A serology results are largely based on Guidance for the prevention and control of hepatitis A infection, and UK standards for microbiology investigations. Hepatitis A virus acute infection serology, both published by the Health Protection Agency [HPA, 2009; HPA, 2011].The recommendation to repeat HAV-IgM levels 1–2 weeks later, if the person has had an initial negative result but is in the first 7–10 days of symptoms (to exclude a false-negative result), is based on expert opinion in a hepatitis A review article [Cuthbert, 2001] and the expert opinion of a CKS external reviewer.Elderly people may have been previously infected with hepatitis A in childhood, and may have a false positive serology result [HPA, 2009; HPA, 2011]. Back to top Differential diagnosis What else might it be? The differential diagnosis of hepatitis A includes:Viral hepatitis caused by other viruses (such as hepatitis B, C, D, and E), Epstein-Barr virus (infectious mononucleosis), or cytomegalovirus (CMV).Alcohol-induced hepatitis.Drug-induced liver disease, such as following paracetamol use.Acute HIV infection.Autoimmune hepatitis.Hepatitis caused by bacteria, such as Leptospirosis and Coxiella burnetii.Granulomatous disorders.Wilson's disease. Back to top Basis for recommendation Basis for recommendation The information about differential diagnosis is based on a textbook of the liver and pancreas, and a chapter about the clinical aspects of viral hepatitis in the Oxford textbook of medicine [Forbes and Jackson, 2003; Hodgson, 2010]. Management Back to topManagement Scenario: Prevention of infection with hepatitis A: covers who should be offered pre-exposure vaccination, who should be offered pre-vaccination testing, and hygiene advice for people at high risk.Scenario: Managing hepatitis A infection: covers the management of confirmed or probable hepatitis A infection; including referral, follow up, and the prevention of further transmission.Scenario: Contact with hepatitis A: covers the management of people who have been in contact with someone with hepatitis A. Back to top Scenario: Prevention of infection with hepatitis A Scenario: Prevention of infection with hepatitis A From birth onwards. Back to top Hepatitis A vaccination Who should be offered vaccination for hepatitis A? For people at high risk of hepatitis A infection:Consider pre-vaccination serology testing for hepatitis A virus immunoglobulin G (HAV-IgG) to check for immunity in people from highly endemic areas, those with a prior history of hepatitis or jaundice, and in men who have sex with men.If immunity to hepatitis A is demonstrated following initial serology testing, there is no need to vaccinate the person. For information on hepatitis serology testing, see Interpretation of serology results.For all other people at high risk, who are not known to be immune, offer hepatitis A vaccination.Give two doses of monovalent hepatitis A vaccine at zero and 6–12 months to provide long-term protection.For detailed information on the hepatitis A vaccine, see Prescribing information. Back to top Basis for recommendation Basis for recommendation Pre-vaccination testing of particular high-risk groupsThe recommendation to consider pre-vaccination testing for people from areas of high endemicity of hepatitis A, or with a past history of jaundice or hepatitis, is taken from a review article which states that it may be cost-effective to screen these high-risk people to check whether they are already hepatitis A immune. These groups are at especially high risk of having been exposed to hepatitis A previously and therefore may already be immune to infection, resulting in the costs of pre-vaccination testing being favourably offset by the savings in time and money by not having to vaccinate this group of people unnecessarily [Steele et al, 2009].The recommendation to consider pre-vaccination testing for men who have sex with men is based on a guidance from the British Association of Sexual Health and HIV, which states that 'screening for pre-existing hepatitis A exposure before vaccination has been found to be cost-effective' [BASHH, 2008]. It refers to an audit of different vaccination strategies for men who have sex with men attending a large sexual health clinic in London. The authors concluded that screening men who have sex with men for hepatitis A virus immunoglobulin G (HAV-IgG) in an area of relatively low prevalence of hepatitis A, is the most cost-effective approach [O'Riordan et al, 2007].Vaccination for travellers to areas of moderate or high endemicityThe recommendation to offer hepatitis A vaccination to travellers to areas at risk is based on expert opinion in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013c] and expert opinion in a review article by the National Travel Health Network and Centre [NaTHNaC, 2013].Young children rarely become significantly ill from hepatitis A infection, but immunization is considered to be important for children older than 1 year of age to protect public health, because children are extremely efficient at disease transmission. The risks of disease for children younger than 1 year of age are low, and the hepatitis A vaccine is not licensed for this age group [PHE, 2013c].Vaccination for people with chronic liver disease, clotting factor disorders, injecting drug users, and those at occupational riskThe recommendation to offer hepatitis A vaccination to people with chronic liver disease, clotting factor disorders, injecting drug users, and those at occupational risk is based on expert opinion in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013c], and expert opinion in a review article about vaccination for people with inherited bleeding disorders [Steele et al, 2009].People with chronic liver disease (including chronic hepatitis B or C infection) are at greater risk of more severe fulminant liver disease from hepatitis A infection [BASHH, 2008; WHO, 2012].Vaccination for men who have sex with men and those with risky sexual behavioursExpert opinion regarding the recommendation to offer hepatitis A vaccination to those at risk from sexual transmission varies. Overall, CKS has followed the consensus of opinion that pre-exposure vaccination of men who have sex with men is potentially beneficial.Guidance from the World Health Organization position paper on hepatitis A vaccines recommends that targeted vaccination of high-risk groups including men who have sex with men should be considered, as it produces individual benefit. There is, however, little evidence that high coverage among targeted groups can be achieved, and such an approach may not reduce infection rates in the general population in areas of low endemicity, such as the UK [WHO, 2012].Expert opinion in Immunisation against infectious diseases (the 'Green Book') published by Public Health England recommends pre-exposure vaccination to men who have sex with men, particularly when outbreaks are occurring [PHE, 2013c]. Similarly, Guidance for the prevention and control of hepatitis A Infection issued by the Health Protection Agency, recommends pre-exposure vaccination for men who have sex with men [HPA, 2009].Expert opinion in a review article by the National Travel Health Network and Centre recommends vaccination for people whose sexual behaviour is likely to put them at increased risk of infection, including men who have sex with men [NaTHNaC, 2013].However, the British Association for Sexual Health and HIV recommends that, as current evidence suggests that most men who have sex with men are not at increased risk of hepatitis A infection, universal vaccination in this group cannot be firmly recommended. It suggests that vaccination is offered in large cities where outbreaks have been reported, particularly when there are increased rates of infection [BASHH, 2008]. Back to top Advice for people at high risk of infection What advice should I give to people at high risk of hepatitis A infection? Advise all people at high risk of hepatitis A infection to:Thoroughly wash their hands after using the toilet and before food preparation.Ensure good personal hygiene.Practice safe sex to reduce the risk of sexual transmission.Get vaccinated against hepatitis B at the same time, if appropriate. For more information, see the CKS topic on Hepatitis B.Advise travellers to moderately or highly endemic areas to:Avoid food and water potentially contaminated by human faeces — in particular, foods grown close to the ground (such as strawberries and salad vegetables), and under-cooked or raw molluscs that feed by filtering large volumes of sewage-polluted waters (such as mussels, oysters and clams). For additional information on the prevention of food and water-borne diseases, see www.nathnac.org/pro/factsheets/food.htm.Advise people at occupational risk of infection to:Use appropriate protective gloves, boots, and face protection, as required by their individual job role.For more information on advice for people with hepatitis A to reduce the risk of transmission to others, see Information and advice. Back to top Basis for recommendation Basis for recommendation General adviceThe recommendations to advise thorough hand washing, good personal hygiene, and safe sexual practices aim to reduce the risk of person to person transmission of hepatitis A by the faecal-oral route. People with risky sexual behaviours such as oral-anal or digital-rectal sexual contact may be at particular risk, as are injecting drug users with poor personal hygiene, or those using unhygienic equipment [BASHH, 2008; HPA, 2009; NaTHNaC, 2013].The recommendation to offer hepatitis B vaccination to people at high risk of hepatitis A in all groups (except those at risk of occupational exposure), is based on expert opinion in the chapters about hepatitis A and hepatitis B in Immunisation against infectious diseases (the 'Green Book') published by Public Health England. It is prudent to offer hepatitis B vaccination at the same time as hepatitis A vaccination to maximise the chance of prophylaxis against both diseases. Combined hepatitis A and B vaccines are available and may be offered, if appropriate [PHE, 2013a; PHE, 2013d].Advice to travellersThe recommendation to avoid potentially contaminated food and water is based on expert opinion in Guidance for the prevention and control of hepatitis A infection published by the Health Protection Agency [HPA, 2009], expert opinion in a review article produced by the National Travel Health Network and Centre [NaTHNaC, 2013], and expert opinion inImmunisation against infectious diseases(the 'Green Book') published by Public Health England [PHE, 2013a].Advice to people at occupational riskThis is what CKS considers to be pragmatic advice based on good medical practice in primary care. Back to top Scenario: Managing hepatitis A infection Scenario: Managing hepatitis A infection From birth onwards. Back to top Managing hepatitis A infection How should I manage a person with confirmed or probable hepatitis A infection? Admit any person with hepatitis A infection to hospital if they are severely unwell.If hospital admission is not required and the diagnosis is confirmed by serology testing:Provide symptomatic supportive care for pain, nausea, or itch as required.Notify the Health Protection Unit (HPU) promptly to facilitate appropriate surveillance and contact tracing.If an outbreak is suspected, or the person is a food handler, notify the HPU immediately.Provide the person with information and advice about hepatitis A, including the need to avoid alcohol during the acute illness, and how to prevent transmission of infection.Consider referring the person to a:Genito-urinary medicine department (or other specialist sexual health service), if screening for sexually transmitted infections is appropriate, and/orDrug rehabilitation agency (if appropriate). Back to top Basis for recommendation Basis for recommendation Admission of all people with hepatitis A infection if unwellThe recommendation to admit people to hospital when severely unwell is based on expert opinion in guidance by the British Association of Sexual Health and HIV [BASHH, 2008], and is a pragmatic approach for managing people in primary care.Notifying the Health Protection Unit (HPU)The recommendation to notify the local Health Protection Unit promptly is based on expert opinion in Guidance for the prevention and control of hepatitis A infection published by the Health Protection Agency. Hepatitis A is a notifiable disease, and the HPU can provide help and advice in managing the person and any contacts at risk of transmission of infection [HPA, 2009].The HPU may initiate fact-finding, and collate the required data for risk factors, partner notification and contact tracing. This includes notifying any sexual contacts or needle-sharing partners during the infectious period (commonly defined as two weeks before to one week after the onset of jaundice, if present) [BASHH, 2008; HPA, 2009].The recommendation to notify the HPU immediately if an outbreak is suspected or the person is a food handler, is taken from expert opinion in the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008] and expert opinion in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013a]. Prompt notification will allow a timely risk assessment of other food handlers in the same location, and allow for post-exposure prophylaxis to be offered to colleagues or traceable customers, if appropriate.Referral to a genito-urinary medicine department or a drug rehabilitation agencyThis recommendation is based on expert opinion in the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008], and what CKS considers to be good clinical practice. Back to top Symptomatic supportive care What symptomatic and supportive care should I offer? Advise the person to rest when necessary if they are unwell.If pain relief is required, options include:Paracetamol — normal dosages can be used, unless there is evidence of moderate or severe liver impairment. If serum bilirubin is greater than 300 micromols/L or prothrombin time is greater than 3 seconds, reduce the dosage to a maximum of 1 gram two or three times a day.Ibuprofen.A weak opioid (such as codeine) if liver impairment is mild. Avoid codeine in severe liver impairment (enhanced sedative effects and reduced drug clearance).If treatment of nausea is required, options include:Metoclopramide (maximum duration of treatment 5 days) or cyclizine at normal dosages, if liver impairment is mild.Seek specialist advice on the choice and dosage of anti-emetic if the person has more severe liver impairment.If treatment of itch is required, options include:Simple measures (such as maintaining a cool, well-ventilated environment, wearing loose clothing, and avoiding hot baths or showers).Chlorphenamine at normal dosage at night (avoid in severe liver impairment). The dosage can be increased to every 4–6 hours if itch is severe.Ursodeoxycholic acid, colestyramine, and corticosteroids are other treatment options — seek specialist advice before prescribing.For more detailed information, see the section on Prescribing information. Back to top Basis for recommendation Basis for recommendation Advice to restThis is recommended in guidance published by the British Association of Sexual Health and HIV [BASHH, 2008], and is what CKS considers to be pragmatic advice based on good medical practice in primary care.Treatment of painThese recommendations are based on the opinion of CKS expert reviewers and the textbook Drugs and the liver [North-Lewis, 2008].Treatment of nauseaMost CKS expert reviewers suggested offering metoclopramide or cyclizine in normal dosages in mild liver disease, but emphasized the need to exercise caution in more severe liver impairment.Following a review by the European Medicines Agency, metoclopramide should not be taken for longer than 5 days [EMA, 2013]. The EMA review confirmed the well-known risks of neurological effects such as short-term extrapyramidal adverse effects. This risk is higher in children, although tardive dyskinesia was reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The EMA states that the risks outweighed the benefits of metoclopramide in conditions requiring long-term treatment. There have also been very rare cases of serious cardiovascular adverse effects, particularly after injection of the drug.Treatment of itchThe recommendation to try simple measures is based on the opinion of one CKS expert reviewer.The recommendation to consider offering chlorphenamine first-line is based on the opinion of CKS expert reviewers. There was a difference of opinion regarding the use of ursodeoxycholic acid, colestyramine, and corticosteroids, and liver-associated itch can be difficult to treat, therefore CKS recommends seeking specialist advice if chlorphenamine is ineffective or there is severe liver impairment. Back to top Follow up and monitoring What follow up and monitoring should occur for people with hepatitis A? Monitor liver function tests and prothrombin time, the frequency of which depends on clinical judgement, the person's symptoms and liver function test results:Initially check liver function 3–5 days after the diagnosis, then weekly until liver function tests start to improve. Monitoring can then be reduced to fortnightly and then monthly until liver function normalizes (usually takes 4–12 weeks).If the person is symptomatic or has jaundice, monitor twice a week. If liver function is worsening, consider admission if the person is unwell, or seek specialist advice to guide monitoring and management if needed.If the person has significantly abnormal liver function tests (for example aspartate aminotransferase [AST] or alanine aminotransferase [ALT] levels greater than 2000 IU/L, bilirubin greater than 300 micromols/L, or prothrombin time greater than 3 seconds), monitor tests every 1–2 days. Consider admission if the person is unwell, or seek specialist advice to guide monitoring and management if needed.Advise the person to seek medical attention if symptoms worsen.Admit the person to hospital if they are severely unwell (vomiting, dehydrated, showing signs of hepatic decompensation), or seek specialist advice to guide monitoring and management if needed. Back to top Basis for recommendation Basis for recommendation Monitoring of liver function tests and prothrombin timeThe recommendations regarding monitoring of liver function and prothrombin time are based on expert opinion in the UK national guideline on the management of the viral hepatitides A, B, and C, produced by the British Association for Sexual Health and HIV and the opinion of CKS expert reviewers. There is no specific anti-viral treatment for hepatitis A, so regular monitoring during the acute illness can help to identify rare complications such as fulminant liver failure which requires hospital admission and specialist management [BASHH, 2008].Decision to admit to hospital or seek advice if unwellThese recommendations are what CKS considers to be pragmatic advice based on good medical practice in primary care. Back to top Information and advice What information and advice should I give to someone with hepatitis A? Provide a person with confirmed hepatitis A infection with patient information resources that may be helpful. In particular, advise the person to:Avoid drinking alcohol during the acute illness, as this can increase the risk of liver damage.Avoid work, school, or nursery, until they are no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice).Give advice to minimize the risk of transmission to partners and contacts. The person and all close contacts should:Ensure thorough hand washing after using the toilet, including supervising young children who may have difficulty with personal hygiene.Wash their hands immediately after changing nappies or helping with child toileting (including handling a potty).Ensure good general personal hygiene.Avoid handling food, if possible, or thorough hand washing before food preparation, for contacts of cases.Avoid unprotected sexual intercourse, including oro-anal and oro-genital contact, until the person is no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice).Avoid sharing needles and other drug paraphernalia. For information on managing intravenous drug users, see the CKS topic on Opioid dependence.Advise pregnant women (and those planning to become pregnant) with acute hepatitis A infection that:There may be an increased risk of miscarriage and premature labour requiring specialist obstetric input and monitoring.Breastfeeding is safe, providing thorough hand washing and personal hygiene is maintained. Back to top Basis for recommendation Basis for recommendation Patient information resources and general adviceThe recommendation to avoid alcohol during the acute illness is based on expert opinion in the textbook Principles and practice of infectious diseases [Curry, 2009] and in the textbook Oxford textbook of medicine [Hodgson, 2010].The recommendation to avoid work, school, or nursery while the person is infectious is taken from Guidance for the prevention and control of hepatitis A infection, and Guidance on infection control in schools and other childcare settings, both published by the Health Protection Agency [HPA, 2009; HPA, 2010].Advice to minimize the risk of transmissionThese recommendations are largely based on expert opinion in the UK national guideline on the management of the viral hepatitides A, B, and C, produced by the British Association for Sexual Health and HIV [BASHH, 2008], and expert opinion in Guidance for the prevention and control of hepatitis A infection published by the Health Protection Agency [HPA, 2009].The advice about thorough hand washing, good personal hygiene, and safe sexual practices aims to reduce the risk of person-to-person transmission of hepatitis A by the faecal-oral route. Close contacts may already have acquired hepatitis A and be excreting the virus, so strict hygiene is important to prevent further transmission [BASHH, 2008; HPA, 2009].The infectious period is commonly defined as during the prodromal illness and the first week of jaundice, if present [BASHH, 2008].Advice for pregnant women (and those planning to become pregnant)The recommendation about the risks of infection in pregnancy are based on expert opinion mentioned in the UK national guideline on the management of the viral hepatitides A, B, and C, produced by the British Association for Sexual Health and HIV [BASHH, 2008], but study data are often limited to small, retrospective case studies [Elinav et al, 2006; Sookoian, 2006].The recommendation about breastfeeding is based on expert opinion published in guidelines produced by the American College of Obstetricians and Gynecologists [American College of Obstetricians and Gynecologists, 2007], and expert opinion published in the UK national guideline on the management of the viral hepatitides A, B, and C, produced by the British Association for Sexual Health and HIV [BASHH, 2008]. There is no evidence that hepatitis A is transmitted in breast milk, and infection is not a contraindication to breastfeeding. Back to top Patient information resources Patient information resources British Liver Trust (www.britishlivertrust.org.uk)A national charity that raises awareness of, and provides information and education on, all forms of liver disease.Children's Liver Disease Foundation (www.childliverdisease.org)A national charity that provides information for the public and health professionals about all liver diseases of childhood, and provides a support service for young people living with liver disease and their families.Health and Safety Executive (www.hse.gov.uk)Aims to protect people against risks to health or safety arising out of work activities.Public Health England (www.hpa.org.uk)Provides advice and information on infectious diseases to the general public, healthcare professionals, and the government. Back to top Scenario: Contact with hepatitis A Scenario: Contact with a person with hepatitis A From birth onwards. Back to top Management How do I manage someone who has been in contact with a person with hepatitis A? If a person presents who has been in contact with someone with known hepatitis A infection:Contact the local Health Protection Unit (HPU) immediately, who will advise on further management if the person has not previously received hepatitis A vaccine — this may include giving hepatitis A vaccination if exposure is within one week of the onset of jaundice, and arranging for the administration of human normal immunoglobulin, depending on the timing and circumstances of contact. Back to top Basis for recommendation Basis for recommendation The management of people who have been in contact with someone with known hepatitis A infection is based on expert opinion in Guidance for the prevention and control of hepatitis A infection, published by the Health Protection Agency [HPA, 2009], and expert opinion in Immunisation against infectious diseases (the 'Green Book') published by Public Health England [PHE, 2013a].The advice to contact the local Health Protection Unit (HPU) reflects its expertise in assessing each individual case as to who may benefit from post-exposure prophylaxis, identifying the possible source of infection, and identifying and controlling suspected outbreaks, with huge potential public health implications [HPA, 2009].Hepatitis A vaccine may be given up to 14 days after exposure providing this was within the infectious period (commonly defined as during the prodromal illness two weeks before the onset of jaundice, to one week after the onset of jaundice, if present). The period of infectivity may be prolonged in people with HIV or in people who are immunocompromised [BASHH, 2008].Human normal immunoglobulin may be indicated for contacts of cases of hepatitis A, and for control during outbreaks of infection. It provides immediate protection against infection if given within 14 days of exposure, and the effect lasts for 4–6 months [PHE, 2013a]. Prescribing information Back to topPrescribing information Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF) . Back to top Hepatitis A vaccine What issues should I consider before giving hepatitis A vaccine? Back to top Types of vaccine What types of hepatitis A vaccine are available? There are several hepatitis A vaccines that are licensed for use in the UK. All are inactivated, and prepared from different strains of the hepatitis A virus:Avaxim®Epaxal®Havrix Monodose®Havrix Junior Monodose®Vaqta Paediatric®There are also combined hepatitis A and B vaccines:Twinrix® (adult and paediatric formulations)Ambirix® (paediatric formulation)[PHE, 2013a] Back to top Immunization schedule What is the immunization schedule for the hepatitis A vaccine? The hepatitis A monovalent vaccine is given as two doses, 6–12 months apart.If the second dose has been missed there is no need to restart immunization. Give the second dose as soon as possible after the missed dose.Antibodies may not be detectable for 12–15 days following administration of monovalent hepatitis A vaccine. However, the vaccine may provide some protection before antibodies can be detected.Immunity theoretically persists for more than 20 years after the second dose. A further booster dose is recommended at 25 years for people at ongoing risk of infection.The schedule for the combined hepatitis A and B vaccine varies between products:Twinrix® is given as three doses, at 0, 1, and 6 months.If Twinrix® is given as a rapid schedule (on days 0, 7, and 21), a booster dose is needed at 1 year.Ambirix® is given as two doses, 6–12 months apart.For travellers, the first dose of hepatitis A single or combined vaccine should be given at least 2 weeks before travelling (but can be given up to the day of departure).Havrix Monodose® can be given concomitantly with monovalent and combination vaccines comprised of measles, mumps, rubella and varicella. When concomitant administration is considered necessary the vaccines must be given at different injection sites. Havrix Monodose® must not be mixed with other vaccines in the same syringe [ABPI Medicines Compendium, 2016].[NaTHNaC, 2013; PHE, 2013a] Back to top People with HIV What hepatitis A vaccination schedule should be used for people with HIV? People with HIV and who are immunocompromised can be given hepatitis A vaccines, but they may have a poorer immune response than immunocompetent people, related to their CD4 count at the time of immunization.Monovalent hepatitis A vaccineIf the person's CD4 count is greater than 300 cells/mL:Use the standard vaccination schedule of two doses, given 6–12 months apart.If the person's CD4 count is less than 300 cells/mL:Give three doses of hepatitis A vaccine, over a period of 6–12 months.If the person is travelling abroad and the CD4 count is less than 200 cells/mL, seek specialist advice as additional human normal immunoglobulin may be needed before they travel.Combined hepatitis A and B vaccineGive three doses of Twinrix® vaccine at 0, 1, and 6 months.People at ongoing risk of infection should be given a booster dose of hepatitis A vaccine every 5 years.[Geretti et al, 2008; PHE, 2013a] Back to top Contraindications When is the hepatitis A vaccine contraindicated? Do not give hepatitis A vaccine if the person has:A current severe febrile illness.Experienced a confirmed anaphylactic reaction to a previous dose of hepatitis A vaccine, or to any component of the vaccine.Epaxal® should not be given to people who have had a confirmed anaphylactic reaction to egg.Avaxim®, Twinrix®, and Ambirix® should not be given to people who have had a confirmed anaphylactic reaction to neomycin.[ABPI Medicines Compendium, 2011; ABPI Medicines Compendium, 2012a; ABPI Medicines Compendium, 2012b; ABPI Medicines Compendium, 2012c; ABPI Medicines Compendium, 2013a; PHE, 2013a; ABPI Medicines Compendium, 2016] Back to top Pregnancy and breastfeeding Can the hepatitis A vaccine be used during pregnancy and breastfeeding? Hepatitis A vaccines may be given to pregnant or breastfeeding women, when clinically indicated [PHE, 2013a].The available evidence does not indicate any risk associated with vaccinating pregnant or breastfeeding women with inactivated viral vaccines [Plotkin et al, 2004]. Back to top Administration How should I administer the hepatitis A vaccine? Obtain written or verbal consent at the time of vaccination.Check that the vaccine is correct and has not expired. Only swab the site of application with alcohol if it is dirty, and let the alcohol evaporate before administration of the vaccine.For adults and children older than 1 year of age, administer the vaccine by intramuscular injection into the deltoid muscle or the anterior aspect of the thigh.Avoid the gluteal muscle as it is unlikely the needle will penetrate through the adipose tissue into the muscle, and this may cause a poor immunological response to the vaccine. In addition, there is a risk of damage to underlying structures (such as the sciatic nerve).For children younger than 1 year of age, administer the vaccine by intramuscular injection into the anterolateral aspect of the thigh.Use a 23-gauge needle (blue) for adults and older children.Use either a 23-gauge needle (blue) or a 25-gauge needle (orange) for younger children.Use a 21-gauge needle (green) for people who weigh more than 90 kg.If the person has a bleeding disorder, use the subcutaneous route, to reduce the risk of bleeding.Record the site of administration. If an additional vaccine is required on the same day, use separate limbs if possible, or inject at sites at least 2.5 cm apart in the same limb.[Vaccine Administration Task Force, 2001; PHE, 2013a] Back to top Adverse effects What are the adverse effects of the hepatitis A vaccine? Adverse effects of hepatitis A vaccines are usually mild and confined to the first few days after immunization. The most common reactions are mild, transient soreness, and erythema. Induration or a small, painless nodule may form at the injection site — this usually disappears and is of no consequence.General symptoms (such as fever, malaise, fatigue, headache, nausea, and loss of appetite) are also reported less frequently.[PHE, 2013a] Back to top Analgesia What issues should I consider before prescribing analgesia? For prescribing information on paracetamol, ibuprofen, and codeine, see the CKS topic on Analgesia - mild-to-moderate pain.For more detailed prescribing information on nonsteroidal anti-inflammatory drugs, see the CKS topic on NSAIDs - prescribing issues. Back to top Anti-emetics What issues should I consider before prescribing anti-emetics? MetoclopramideMetoclopramide is generally well tolerated. However:Extrapyramidal reactions (usually dystonic) can occur. Most reactions occur within 36 hours of starting and disappear within 24 hours of stopping treatment. The incidence of dystonic reactions is more common in young adults under the age of 20 years.Raised serum prolactin levels with prolonged treatment can cause galactorrhoea, irregular periods, and gynaecomastia.Neuroleptic malignant syndrome has very rarely been reported with metoclopramide use.Metoclopramide should not be used in people [ABPI Medicines Compendium, 2013b]:Aged under 20 years.With gastrointestinal obstruction, perforation or haemorrhage.The maximum duration of therapy with metoclopramide is 5 days [EMA, 2013].Following a review by the European Medicines Agency, metoclopramide should not be prescribed for more than 5 days. The EMA review confirmed the well-known neurological risks such as short-term extrapyramidal adverse effects. This risk is higher in children, although tardive dyskinesia was reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The EMA states that the risks outweighed the benefits of metoclopramide treatment in conditions requiring long-term treatment. There have also been very rare cases of serious cardiovascular adverse effects, particularly after injection.Metoclopramide should be used with caution in people with [North-Lewis, 2008; ABPI Medicines Compendium, 2013b; Micromedex, 2014]:Liver dysfunction — metoclopramide can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using metoclopramide in people with more severe hepatic impairment, as reduced clearance may increase the risk of gynaecomastia and extrapyramidal adverse effects. The dose should be reduced by 50% in people with cirrhosis.Renal impairment — metoclopramide and its metabolites are predominately excreted via the kidneys. In people with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2), avoid metoclopramide or use a reduced dose. Accumulation of metoclopramide increases the risk of extrapyramidal adverse effects.Epilepsy.Pregnancy — published fetal exposure data are limited, but there is no evidence of an increase in congenital malformations in exposed pregnancies, but a possible higher incidence of premature delivery in one small cohort study [UKTIS, 2013].Breastfeeding — the UK Drugs in Lactation Advisory Service states that metoclopramide is compatible with breastfeeding for short-term, low-dose use (dose not exceeding 30 mg a day), but there is insufficient evidence, or clinical experience of use, to guarantee safe use in breastfeeding. See the UKMI lactation advisory service website for more information.CyclizineCyclizine should be used with caution in people with [North-Lewis, 2008; ABPI Medicines Compendium, 2012d; Micromedex, 2014]:Liver dysfunction — cyclizine can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using cyclizine in people with moderate hepatic impairment. It must be avoided in people with severe hepatic impairment, such as those with cirrhosis or encephalopathy who may decompensate, because of its sedative effects.Urinary retention, prostatic hypertrophy, angle-closure glaucoma, or pyloroduodenal obstruction — if possible, avoid using sedating antihistamines such as cyclizine because of their significant antimuscarinic activity (particularly in elderly people).Epilepsy — avoid cyclizine if possible, as it can reduce the seizure threshold.Severe heart failure — avoid using cyclizine if possible, as it may decrease cardiac output.Pregnancy — the published data for the safety of cyclizine are limited, but there are no reports of an increased risk of congenital malformations [UKTIS, 2013].Breastfeeding — the UK Drugs in Lactation Advisory Service states that there is no published evidence of the safety of cyclizine use in breastfeeding, but it may be considered for occasional, short-term use when breastfeeding. Repeated use may cause a risk of sedation of the infant, and may interfere with lactation. See the UKMI lactation advisory service website for more information.The most commonly reported adverse effects are nervous system disorders [ABPI Medicines Compendium, 2012d]:Elderly people are particularly susceptible (and so lower doses are recommended).Sedating antihistamines may cause drowsiness.Anticholinergic adverse effects may also occur, for example blurred vision and dry mouth.Cyclizine is a recognized substance of misuse for its euphoric or hallucinatory effects, and extra vigilance is needed when prescribing [RPSGB, 2006]. Back to top Anti-pruritics What issues should I consider before prescribing anti-pruritics? ChlorphenamineSedating antihistamines should be used with caution in people with [North-Lewis, 2008; ABPI Medicines Compendium, 2012e; Micromedex, 2014]:Liver dysfunction — chlorphenamine can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using chlorphenamine in people with moderate hepatic impairment. It must be avoided in people with severe hepatic impairment, such as those with cirrhosis or encephalopathy who may decompensate, because of its sedative effects.Urinary retention, prostatic hypertrophy, angle-closure glaucoma, or pyloroduodenal obstruction — if possible, avoid using sedating antihistamines because of their significant antimuscarinic activity (particularly in elderly people).Epilepsy — avoid chlorphenamine if possible, as it may reduce the seizure threshold.Pregnancy — chlorphenamine is considered to be suitable for use during pregnancy. There is extensive clinical experience of chlorphenamine use in pregnancy, with reports of several thousand exposures and no evidence of an increased risk of fetal toxicity [UKTIS, 2009].Breastfeeding — the UK Drugs in Lactation Advisory Service states that if a sedating antihistamine is needed, chlorphenamine is preferred due to extensive clinical experience of safe use in breastfeeding. There is a possible risk of sedation in the infant, who should be monitored for drowsiness. The Summary of Product Characteristics for chlorphenamine states that it should not be used in breastfeeding unless considered medically essential [ABPI Medicines Compendium, 2012e]. See the UKMI lactation advisory service website for more information.The most commonly reported adverse effects are nervous system disorders [ABPI Medicines Compendium, 2012e]:Elderly people are particularly susceptible (and so lower doses are recommended).Sedating antihistamines may cause drowsiness.Anticholinergic adverse effects may also occur, for example blurred vision and dry mouth. Supporting evidence Back to topSupporting evidence Hepatitis A infectionWhere relevant, a discussion of the evidence to support the recommendations is provided in the basis for recommendations. The evidence for the primary care interventions described in this CKS topic are based on expert opinion from national guidelines [BASHH, 2008; HPA, 2009; NaTHNaC, 2013; PHE, 2014] and review articles.The rationale for the use of the hepatitis A vaccine is based on expert opinion in the guideline Immunisation against infectious diseases (the 'Green Book'), published by Public Health England [PHE, 2013a]. How this topic was developed Back to topHow this topic was developed This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website. Back to top Search strategy Search strategy Scope of searchA literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of hepatitis A.Search datesMay 2010 - January 2014Key search termsVarious combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.exp Hepatitis A/, hepatitis A.tw.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 Health Protection Agency World Health Organization National Guidelines Clearinghouse Guidelines International Network TRIP database GAIN NHS Scotland National Patient Pathways New Zealand Guidelines Group 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 University of Michigan Medical School Michigan Quality Improvement Consortium Singapore Ministry of Health National Resource for Infection Control Patient UK Guideline links UK Ambulance Service Clinical Practice Guidelines 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 AssessmentSources 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 & amp; Therapeutics Bulletin TRIP database Central Services Agency COMPASS Therapeutic NotesSources of national policy Department of Health Health Management Information Consortium(HMIC)Patient experiences Healthtalkonline BMJ - Patient Journeys Patient.co.uk - Patient Support GroupsSources of medicines informationThe 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 Back to top Stakeholder engagement Stakeholder engagement Our policyThe 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 processThe 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.StakeholdersKey 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 engagementClarity 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 selectionScoping of topicSelection of clinical scenariosFirst draft internal reviewSecond draft internal reviewExternal reviewFinal draft and pre-publicationOur lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals. Back to top Evidence exclusion criteria Evidence exclusion criteria Our policyScoping 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 studiesOriginal research is not written in EnglishPossible exclusions for reviewed literature:Sample size too small or study underpoweredBias evident or promotional literaturePopulation not relevantIntervention/treatment not relevantOutcomes not relevantOutcomes have no clear evidence of clinical effectivenessSetting not relevantNot relevant to UKIncorrect study typeReview articleDuplicate reference Back to top Organizational, behavioural and financial barriers Organizational, behavioural and financial barriers Our policyThe CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.FeasibilityStudies 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 AnalysisStudies 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 populationCurrent interventionsLikely uptake of new intervention or recommendationCost of the current or new intervention mixImpact on other costsCondition-related costsIn-direct costs and service impactsTime dependenciesCost-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. Back to top Declarations of interest Declarations of interest Our policyClarity 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 interestsPersonal family interestPersonal non-financial interestNon-personal financial gain or benefitAlthough 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. References Back to topReferences ABPI (2011) SPC for AVAXIM. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI Medicines Compendium (2012a) Summary of product characteristics for Ambirix suspension for injection. Electronic Medicines Compendium. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2012b) SPC for Epaxal. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2012c) SPC for Twinrix Adult Vaccine, suspension for injection in pre-filled syringe. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2012d) SPC for Valoid tablets. Electronic Medicines Compendium. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI Medicines Compendium (2012e) Summary of product characteristics for Piriton Tablets. Electronic Medicines Compendium. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2013a) SPC for VAQTA Paediatric. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2013b) SPC for Maxolon Tablets 10mg. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] ABPI (2016) SPC for Havrix Monodose Vaccine. Datapharm Communications Ltd.. www.medicines.org.uk [Free Full-text] American College of Obstetricians and Gynecologists (2007) Viral hepatitis in pregnancy. American College of Obstetricians and Gynecologists.. www.acog.org BASHH (2008) United Kingdom national guideline on the management of the viral hepatitides A, B & C 2008. British Association for Sexual Health and HIV.. www.bashh.org [Free Full-text] British Liver Trust (2009) A professional's guide to hepatitis B. British Liver Trust.. www.britishlivertrust.org.uk [Free Full-text] CSM (2005) Updated advice on the safety of selective COX-2 inhibitors. Committee on Safety of Medicines.. www.mhra.gov.uk [Free Full-text] Curry, M.P. and Chopra, S. (2009) Mandell, Douglas, and Bennett's principles and practice of infectious diseases - online. In: Mandell, G., Bennett, J., Dolin, R. (Eds.) Chapter 115: acute viral hepatitis.Churchill Livingstone. Cuthbert,J.A. (2001) Hepatitis A: old and new. Clinical Microbiology Reviews. 14(1), 38-58. [Abstract] Elinav,E., Ben-Dov,I.Z., Shapira,Y., et al. (2006) Acute hepatitis A infection in pregnancy is associated with high rates of gestational complications and preterm labor. Gastroenterology. 130(4), 1129-1134. [Abstract] EMA (2013) European Medicines Agency recommends changes to the use of metoclopramide. European Medicines Agency.. www.ema.europa.eu [Free Full-text] Forbes,C.D. and Jackson,W.F. (2003) Color atlas and text of clinical medicine. In: (Eds.) Liver and pancreas.London: Mosby. Geretti,A.M., BHIVA Immunization Writing Committee, Brook,G., Cameron,C., et al. (2008) British HIV Association guidelines for immunization of HIV-infected adults 2008. HIV Medicine. 9(10), 795-848. Hodgson,H.J.F. (2010) Oxford textbook of medicine. In: Warrell,D.A., Cox,T.M., Firth,J.D., Ogg,G.S (Eds.) Viral hepatitis - clinical aspects.Oxford: Oxford University Press., 2452-2460. HPA (2009) Guidance for the prevention and control of hepatitis A infection. Health Protection Agency.. www.hpa.org.uk [Free Full-text] HPA (2010) Guidance on infection control in schools and other child care settings. Health Protection Agency.. www.hpa.org.uk [Free Full-text] HPA (2011) UK standards for microbiology investigations. Investigation of red rash. Health Protection Agency.. www.hpa.org.uk [Free Full-text] Micromedex (2014) Micromedex. Truven Health Analytics Inc.. NaTHNaC (2013) Hepatitis A. Travel health information sheets (health professionals). National Travel Health Network and Centre.. www.nathnac.org [Free Full-text] NICE (2008) Osteoarthritis. The care and management of osteoarthritis in adults (NICE guideline) [Replaced by CG177]. National Institute for Health and Clinical Excellence.. www.nice.org.uk NICE (2009a) Rheumatoid arthritis: the management of rheumatoid arthritis (NICE guideline). National Institute for Health and Clinical Excellence.. www.nice.org.uk [Free Full-text] NICE (2009b) Low back pain: early management of persistent non-specific low back pain (NICE guideline). National Institute for Health and Clinical Excellence.. www.nice.org.uk [Free Full-text] NICE (2015) Key therapeutic topics - medicines management options for local implementation. National Institute for Health and Clinical Excellence.. www.nice.org.uk [Free Full-text] North-Lewis,P. (Eds.) (2008) Drugs and the liver. London: Pharmaceutical Press.. O'Riordan,M., Goh,L. and Lamba,H. (2007) Increasing hepatitis A IgG prevalence rate in men who have sex with men attending a sexual health clinic in London: implications for immunization policy. International Journal of STD & AIDS. 18(10), 707-710. [Abstract] Payne,L. and Coulombier,D. (2009) Hepatitis A in the European Union: responding to challenges related to new epidemiological patterns. Eurosurveillance. 14(3), 19101. PHE (2013a) Immunisation against infectious disease - "The Green Book". Chapter 17 - Hepatitis A. Public Health England.. www.gov.uk [Free Full-text] PHE (2013b) Statutory notifications of infectious diseases (Noids) England and Wales 1982-2012. Annual totals for diseases notifiable under Health Protection (Notification) regulations 2010. Public Health England.. www.hpa.org.uk [Free Full-text] PHE (2013c) Hepatitis A: the green book, chapter 17. Chapter 17. Public Health England.. www.gov.uk/ [Free Full-text] PHE (2013d) Immunisation against infectious disease - "The Green Book". Chapter 18 - Hepatitis B. Public Health England.. www.gov.uk [Free Full-text] PHE (2014) UK standards for microbiology investigations. Investigation of hepatitis. Health Protection Agency.. www.hpa.org.uk [Free Full-text] Plotkin,S.A., Orenstein,W.A., Offit,P.A. (Eds.) (2004) Vaccines. edn. Philadelphia: Saunders. RPSGB (2006) Substances of misuse. Royal Pharmaceutical Society of Great Britain.. Sjogren,M.H. (2006) Sleisenger and Fordtran's gastrointestinal and liver disease. In: Feldman,M., Friedman,L.S., Brandt,L.J. (Eds.) Hepatitis A.Philadelphia, PA: Saunders Elsevier. Sookoian,S. (2006) Liver disease during pregnancy: acute viral hepatitis. Annals of Hepatology. 5(3), 231-236. [Abstract] Spira,A.M. (2003) A review of combined hepatitis A and hepatitis B vaccination for travelers. Clinical Therapeutics. 25(9), 2337-2351. [Abstract] Steele,M., Cochrane,A., Wakefield,C., et al. (2009) Hepatitis A and B immunization for individuals with inherited bleeding disorders. Haemophilia. 15(2), 437-447. [Abstract] UKTIS (2009) Use of chlorphenamine in pregnancy. UK Teratology Information Service.. www.uktis.org [Free Full-text] UKTIS (2013) Treatment of nausea and vomiting in pregnancy. TOXBASE. UK Teratology Information Service.. www.toxbase.org Urbanus,A.T., van Houdt,R., van de,L.aar,T.J. and Coutinho,R.A. (2009) Viral hepatitis among men who have sex with men, epidemiology and public health consequences. Euro Surveillance. 14(47). [Abstract] Vaccine Administration Task Force (2001) UK guidance on best practice in vaccine administration. Shire Hall Communications.. www.rcn.org.uk Wasley,A-M., Feinstone,S.M. and Bell,B.P. (2009) Chapter 173: hepatitis A virus. Mandell, Douglas, and Bennett's principles and practice of infectious diseases - online. Churchill Livingstone.. www.expertconsultbook.com WHO (2009) The global prevalence of hepatitis A virus infection and susceptibility: a systematic review. World Health Organization.. www.who.int [Free Full-text] WHO (2012) WHO position paper on hepatitis A vaccines - June 2012. Weekly Epidemiological Record. 87(28-29), 261-276.