Guidance

Hepatitis A immunoglobulin (issued 2024)

Updated 7 November 2024

Applies to England

Overview

Subgam (human normal immunoglobulin) (HNIG) from Bio Products Laboratory (BPL) is centrally supplied by the UK Health Security Agency (UKHSA) for post-exposure use against hepatitis A virus (HAV) infection.

Other subcutaneous immunoglobulin (SCIg) products that may be available locally in NHS trusts can also be used (see alternative HNIG products section).

Assessment of eligibility for HNIG for hepatitis A post exposure prophylaxis should be made following the UKHSA hepatitis A: public health management guidance.

Indications and request for stock

HNIG has limited use now and hepatitis A vaccine is usually recommended with or without HNIG.

UKHSA recommends the use of HNIG in addition to hepatitis A vaccine for post exposure use for the prevention of infection in eligible household and other close contacts in specific circumstances outlined in the hepatitis A: public health management guidance.

UKHSA issues HNIG for eligible close contacts on request via the duty doctor service. 

UKHSA Subgam stock is held by a limited number of stockholders: Manchester, Birmingham and Cambridge Public Health Laboratories (PHL), and can be issued nationally by Colindale from Movianto.

For all issues a UKHSA risk assessment and issue form should be completed by the issuer (stockholder or UKHSA duty doctor).

Recommendations

The mainstay of hepatitis A post-exposure prophylaxis in non-immune close contacts is hepatitis A vaccine. Human normal immunoglobulin (HNIG) may provide short term immunity in the first 7 days post initiation of prophylaxis and is most effective soon after exposure.

HNIG can be given to close contacts up to 14 days after exposure if they are eligible, that is, fully susceptible to hepatitis A, aged over 60 years or immunosuppressed.

Consideration should also be given to offering HNIG to close contacts at risk of severe disease (that is, those with chronic liver disease or pre-existing chronic hepatitis B or C infection) up to 28 days post exposure, if they are fully susceptible.

The total antibody level induced by active immunisation (vaccine) may be many orders of magnitude greater than can be provided by passive immunisation (HNIG). For this reason HNIG is not given more than 7 days after the first dose of hepatitis A vaccine, or to an individual who is already primed by partial or previous immunisation.

Definitions of close contacts, fully susceptible, primed and immune, and time after exposure to inform assessment of eligibility for HNIG are summarised below, along with information on administration and dosage of HNIG.

Assessment of need for HNIG should be made in conjunction with the national guidance on prevention and control of hepatitis A infection is available in the hepatitis A: public health management guidance.

Definition of a close contact

Individuals who are at high risk of being exposed to hepatitis A through close contact, equivalent to household type exposure, with the index case during the infectious period.

A risk assessment should be undertaken to identify close contacts, with particular consideration of those that have shared food and toilet facilities with the index case, equivalent to a household type exposure.

There should be a low threshold for considering someone a close contact.

Close contacts may include:

• a person living in the same household as the index case or regularly sharing food or toilet facilities with the index case during the infectious period, including extended family members and friends who frequently visit the household – this may also include those in shared accommodation with shared kitchen or toilet facilities
• any person who has been involved in nappy changing or assistance with toileting including nursery school staff and childminders during the infectious period of the index case, where the index case is a child in nappies or requiring assistance with toileting
• a person who has had sexual contact with the index case during the infectious period
• same room contacts in a pre-school child-care setting and reception class if the index case is a child, such as those working or being cared for in the same room as the index case during the infectious period
• in long stay care facilities, those sharing toilet facilities or food with the index case, and those who were assisted with activities of daily living (such as eating and toileting) by the index case during the infectious period
• people who inject drugs and share injecting paraphernalia with the index case

The risk of transmission in all settings should be assessed on a case by case basis by the local senior health protection lead.

Immune status of a close contact

Close contacts should be assessed to determine whether they are immune, primed or fully susceptible. 

Close contacts should be considered immune (not susceptible) and do not require vaccine or HNIG if they have a:

• reliable history or evidence of a complete course of hepatitis A vaccine in the past 10 years (for example, 2 monovalent doses or equivalent), or
• reliable history or evidence of one dose of monovalent vaccine (or equivalent) within the past 12 months, or
• reliable history of hepatitis A infection or previous laboratory-confirmed hepatitis A (previous anti-HAV IgG (IgG antibody to the hepatitis A virus) positive, or HAV RNA (ribonucleic acid) positive)

Close contacts that have any other history of receiving a hepatitis A vaccine that does not fit the criteria above should be considered ‘susceptible but primed’ and require post-exposure vaccine but not HNIG (regardless of age or co-morbidities). For example:

• reliable history or evidence of one dose of hepatitis A vaccine at any point more than 12 months ago, or
• reliable history or evidence of a complete course (for example, 2 monovalent doses) of hepatitis A vaccine more than 10 years ago

Close contacts that meet the following criteria should be considered ‘fully susceptible’ and require post-exposure vaccine and should be considered for HNIG:

• no history or evidence of hepatitis A vaccine, and
• no reliable history of hepatitis A infection or laboratory-confirmed hepatitis A (previous anti-HAV IgG positive, or HAV RNA positive)

Rapid testing for anti-HAV IgG

Rapid anti-HAV IgG testing prior to administration of HNIG can be done, if feasible and immunity is suspected.  Such testing can be used to avoid  unnecessary administration of a blood product which carries theoretical risks of transmission of unidentified infectious agents.

However, anti-HAV testing is not a pre-requisite for HNIG issue and anti-HAV IgG testing should not delay the administration of post-exposure vaccine

The decision on whether to conduct anti-HAV IgG testing prior to HNIG issue requires consideration of several factors, including time since exposure, intensity of exposure, likelihood of pre-existing immunity and the time it will take to carry out an anti-HAV IgG test and get the result.

For example, it may be reasonable to consider anti-HAV testing in older persons born overseas in a hepatitis A endemic country as there is a higher likelihood of them being anti-HAV IgG positive compared to a UK born older person.

Conversely, testing may be less helpful and introduce delays where there has been continuous close contact from before the onset of jaundice (for example, household contacts). For these individuals, administration without testing may be warranted to achieve maximum potential benefit from HNIG.

Anti-HAV IgG testing will not be helpful in individuals who have had recent post-exposure vaccination, as IgG detected could be due to the immune response to vaccine rather than past natural infection. Anti-HAV IgG testing can therefore be considered prior to HNIG issue, provided results will be available within 3 days, and if:

• it is less than 10 days since last exposure
• it is less than 7 days since HAV vaccine

If an anti-HAV IgG result is negative or equivocal, HNIG can be given.

Definition of time since exposure

In the case of continuous exposure (such as contacts in a shared household), the limit for administering prophylaxis should be timed from the onset of jaundice, or onset of symptoms such as fatigue, nausea, fever in the absence of jaundice.

In the case of single exposure in the infectious period, time since exposure should be calculated from day of the exposure to the index case in their infectious period.

In the case of intermittent exposure (such as contacts from school or hospital) time since exposure is defined as the last day of exposure to the index case in their infectious period.

Where jaundice is not reported, the date of onset of dark urine or pale stools should be used. If there are no symptoms of jaundice, dark urine or pale stools, onset of other symptoms (such as fatigue, nausea, and fever) should be used.

Route of administration

For patients managed in the community, intramuscular (IM) HNIG is recommended.   Subgam® can be issued from UKHSA stockholders on request. The current Summary of Product Characteristics (SPC) covering these products do not mention IM administration. Given the clinical imperative to treat these contacts urgently, it is reasonable to use available HNIG products IM so long as use via this route is acknowledged to be off-label.

There are no specific contraindications to IM use listed. The functional biological activity of these produces is expected to be equivalent. In the absence of data from the manufacturers, users are asked to report back to UKHSA any concerns over tolerability with IM use.

Dosage

The volume of Subgam is being recommended to provide levels of antibody equivalent to that achieved with products meeting the World Health Organization (WHO) standard.

Less than 10 years old:  500mg by intramuscular injection

10 years old and older:  1,000mg by intramuscular injection

Hepatitis A vaccine may be administered simultaneously with human normal immunoglobulin but should be given at separate injection sites.

Alternative HNIG products available in NHS Trusts

Most large NHS trusts should have stock of HNIG products which can be used as an alternative to Subgam. This facilitates timely administration and allows UKHSA to reserve limited stock of Subgam for use in the community. If the NHS Trust is using their own stock for  hepatitis A post-exposure prophylaxis, this should follow a risk assessment supported by the local Health Protection Team, sharing patient details and agreeing the indication for immunoglobulin.

List of Products

Please note these products are often labelled as SCIg and therefore overlooked as HNIG products when a pharmacist is looking for them – so best to suggest they search for the product names:

• Cutaquig
• Cuvitru
• Hizentra
• Hizentra PFS
• Subgam
• Gammanorm

Dosage

The SPCs for these products give the total immunoglobulin (Ig) protein content in mg/ml and were all over 150mg/ml. However, this does not necessarily reflect the amount of hepatitis A specific antibody present. But testing of recent batches of these products indicate that anti-HAV IgG concentration in all the above products exceed 100iu/ml which has historically been the acceptable seroprotective lower limit of IgG for against hepatitis A.  Therefore, we suggest these products are treated as equivalent to Subgam and the fixed age-based doses that are suggested for Subgam are used for the other products listed above. For SCIg products not listed above, please only use if the total immunoglobulin content is at least 150mg/ml.

Further guidance on prevention and control of hepatitis A infection is available in the hepatitis A: public health management guidance