Research and analysis

Hepatitis D national surveillance report: 2010 to 2020 (data up to end of 2020)

Published 28 July 2023

This report was commissioned by Gilead Sciences, Inc.

Executive summary

Hepatitis delta, also known as hepatitis D is caused by the hepatitis D virus (HDV), which requires the hepatitis B virus (HBV) for its replication. Coinfection of both HDV and HBV can cause the most severe form of chronic viral hepatitis due to more rapid progression towards cirrhosis, hepatocellular carcinoma and liver-related death. The most common routes of transmission are exposure to the blood of an infected person either directly or via blood products.

This report summarises data from the UK Health Security Agency (UKHSA) sentinel surveillance of blood-borne viruses (SSBBV) and focuses on testing over the past 11 years (January 2010 to December 2020). All sites submitting testing data between 2010 to 2020 was used.

Overall, 39,907 individuals were reported from 13 laboratories as having a HDV test during 2010 to 2020. The majority of HDV testing occurred among males and those aged 30 to 44 years. Where ethnicity data was available, under half of those who were tested were of white or white British ethnic origin.

Most HDV tests were reported via reference laboratories with minimal information on where the test was requested. However, for tests with requester details, most occurred in secondary care with general practice and sexual health services the most frequent requestors in primary care services.

The numbers of individuals tested for HDV remained relatively stable between 2010 and 2019, with a dramatic decline in testing observed in 2020 (66% decrease from 2019), likely due to the impact of the COVID-19 pandemic. Declines in testing were observed across all age groups, genders and service types and settings.

Between 2010 to 2020, 1,727 new HDV infections were reported to UKHSA through the SSBBV, averaging 157 cases per year. Over half of reported positive results were amongst men (58%) and median age at diagnosis was 37, with males slightly older at diagnosis than females (38 years for males versus 36 years for females). Of those with known ethnicity (62%), the majority of individuals found to be HDV positive were among those of White Other ethnic background (including White Irish), followed by those of Black or Black British African ethnic background.

Background

Hepatitis delta, also known as hepatitis D, is an inflammatory condition of the liver associated with HDV, which requires HBV for its replication (1) and cannot occur in the absence of HBV.

HDV, like hepatitis A, B, C, and E, is a notifiable organism that means under the Health Protection (Notification) Regulations 2010, diagnostic laboratories are required to notify UKHSA of the identification of these organisms in a human sample within 7 days (2).

Hepatitis D may infect those who already have chronic HBV infection (super-infection) or co-infect people simultaneously with HBV (co-infection). For those co-infected, HDV is associated with greater severity of the initial acute hepatitis and can cause acute liver failure. Those with super-infection are more likely to progress to a more severe form of chronic viral hepatitis that frequently leads to cirrhosis, and hepatocellular carcinoma. However, the initial super-infection may present as a flare up of a previously stable chronic HBV infection (3).

HDV can be transmitted parenterally, including percutaneously through broken skin (for example injection or tattooing with contaminated instruments) or through direct contact with infected blood or blood products (3). Perinatal transmission appears to be less common. Groups at higher risk of HDV infections include people who inject drugs (PWID), people with hepatitis C virus or HIV infection. The risk of HBV and HDV co-infection also appears to be potentially higher in recipients of haemodialysis, gay, bisexual and other men who have sex with men (GBMSM) and commercial sex workers (1).

HDV prevalence is primarily diagnosed and monitored by the detection of total antibodies to HDV (anti-HDV) among hepatitis B surface antigen (HBsAg) carriers. Detectable anti-HDV indicates prior HDV exposure or ongoing HDV infection. Molecular assays for HDV ribonucleic acid (RNA) should be performed in anti-HDV positive individuals to confirm the presence of ongoing HDV infection and viral load quantified where possible; however, commercial HDV RNA assays are not widely available (1).

The American Association for the Study of Liver Diseases (AASLD) recommend anti-HDV screening and periodic retesting of HBsAg-positive persons at risk for HDV (4) while the European Association for the Study of the Liver (EASL) recommend screening on initial evaluation of all patients with chronic HBV infection (5). In the UK, there is an absence of clear national clinical guidelines and the epidemiology and testing practices for HDV is not well understood. New therapeutic agents for HDV are licensed and in development so it is important to enumerate and characterise the population who may benefit from these treatments to inform drug development programmes, The National Institute for Health and Care Excellence (NICE) technology appraisals and future clinical guidelines on diagnosis and management of HDV.

This surveillance report provides valuable real-world data (RWD) on the burden of HDV in England which is essential for strategic planning around achieving the goal of elimination of viral hepatitis as a public health threat by 2030.

Laboratory surveillance of hepatitis

Routine laboratory reports

HBV and HDV are notifiable organisms and all laboratories in England performing a primary diagnostic role must notify UKHSA of positive HDV or HBV results, in accordance with the Health Protection (Notification) Regulations 2010. Notifications are reported through the Second Generation Surveillance System (SGSS) at UKHSA. Reports include basic demographics (name, date of birth, sex and NHS number, a unique identifier for all individuals registered with the NHS within England) and variable amounts of risk factor information (for example history of injecting drug use, testing within prison services, receiving tattoos, piercings or blood products).

UKHSA sentinel blood-borne virus surveillance system (SSBBV)

The UKHSA SSBBV collects information on all testing undertaken for hepatitis A, B, C, D and E, as well as HIV and human T-lymphotropic virus (HTLV) within participating sentinel NHS and private laboratories across England. Information on the testing carried out in participating centres is collected irrespective of test result and can therefore be used as a basis for estimating diagnosed prevalence among those tested, monitor trends in testing, and investigate seroconversion for incidence estimations. SSBBV is derived from a network of laboratories and since 2014 covers over 80% of the population from all 9 UKHSA regions that test for hepatitis D, E and HTLV. Information on HDV testing between 2010 to 2020 has been collected from 13 sentinel surveillance laboratories across England (Appendix 1) (6).

Given the small number of tests, lack of widely available HDV RNA assays, and absence of HDV testing programmes, for the purposes of this report ‘HDV Positive’ individuals are considered to include all those with:

• definitive laboratory evidence of HDV RNA

Or

• HDV antigen positive

Or

• detection of antibody to HDV (total antibody or immunoglobulin M (IgM) or immunoglobulin G (IgG))

Thus these individuals do not necessarily represent incident or active infections, and should be interpreted accordingly (Appendix 2).

Ethnicity is collated through linking to the Hospital Episodes Statistics (HES), using NHS number (Appendix 2). HDV results from SGSS were not used in this report as the development of laboratory reporting of HDV results into the system are still ongoing. This report provides summary data for individuals one year or older who had HDV tests reported to the SSBBV from January 2010 to December 2020.

Characteristics of individuals tested for HDV

During 2010 to 2020, results of 52,867 HDV tests from 13 laboratories in 40,415 individuals were available for analysis. Tests with equivocal (51) or no result (728) were excluded from the analysis of characteristics of individuals HDV tested, leaving 52,097 tests with a positive (3,785) or negative (48,312) result, conducted on 39,907 individuals. Of these, 68% (27,153 out of 39,907) were linked to a previous laboratory report of hepatitis B (source: SGSS, SSBBV). Individuals not linked may be explained by under-reporting of HBV to UKHSA or HDV testing occurring regardless of HBV testing results.

Characteristics of individuals tested for HDV are provided in Table 1. The age and sex of individuals tested for HDV were well reported (98.1% complete). Where known, males accounted for 55.0% (21,526 out of 39,144) of individuals tested; test positivity for males was 4.5% (964 out of 21,526) versus 4.0% (711 out of 17,618) for females. The highest proportion of tests was in the 30 to 44 year old age group (18,534, 46.4%), which also had the highest positivity (4.7%). Median age at testing was 37 years old (interquartile range (IQR): 30 to 47), with males older at time of testing (39 years for males versus 35 years for women).

Where ethnicity data was available (63.3%, 25,244 ), the majority of individuals tested for HDV were classified as Black or Black British: African origin (19%), White Other (including White Irish) (18.5%) or White British (15.8%) (Table 2). The proportion positive varied slightly by ethnic group and was highest in those classified as White other (5.7%) followed by Asian or Asian British: South Asian origin (5.4%).

Table 1. Characteristics of individuals [Note 1] tested for HDV in participating centres, 2010 to 2020

Characteristics	Number of individuals tested	Total HDV positive [Note 2]	Percentage of HDV positive [Note 2]
Total	39,907	1,727	4.3
Male	21,526	964	4.5
Female	17,618	711	4
Sex unknown	763	52	6.8
Aged 1 to 29 years	9,601	390	4.1
Aged 30 to 44 years	18,534	865	4.7
Aged 45 to 59 years	8,227	346	4.2
Aged 60 years and over	3,426	115	3.4
Age unknown	119	11	9.2
Ethnic group: Asian or Asian British – South Asian	2,606	142	5.4
Ethnic group: Asian or Asian British – Chinese	2,997	37	1.2
Ethnic group: Asian or Asian British – Any other Asian background	1,552	75	4.8
Ethnic group: Black or Black British – African	4,804	255	5.3
Ethnic group: Black or Black British – Caribbean or Any other Black, Black British, or Caribbean background	1,500	57	3.8
Mixed or multiple ethnic groups	758	34	4.5
Ethnic group: White – White British	3,976	80	2
Ethnic group: White – Other [Note 3]	4,666	267	5.7
Other Ethnic Groups – Any other ethnic group	2,385	130	5.5
Unknown ethnic origin	14,663	650	4.4

Note 1: Excludes samples for children aged under one years.
Note 2: The positive result is the first reported by participating laboratories and may not reflect an individual’s first diagnosis, a positive result includes evidence of HDV RNA or HDV antigen positive or detection of antibody to HDV (total antibody or IgM or IgG).
Note 3: White Other includes White Irish.

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 13 sentinel surveillance laboratories across England (Appendix 1).

Data is shown by region of the requesting service in Table 2. London had the highest number of persons presenting for a HDV test, which may be reflective of London having a higher burden of hepatitis B compared to the rest of the UK.

Table 2. Number of individuals [Note 1] tested and testing positive HDV in participating centres, 2010 to 2020

Region [Note 2]	Number of tests [Note 3]	Number of individuals tested	Total HDV positive [Note 4]	Percentage of HDV positive [Note 2] [Note 4]
East Midlands	2,578	2,369	76	3.2
East of England	6,413	4,745	144	3
London	18,644	15,441	722	4.7
North East	1,648	1,408	46	3.3
North West	4,182	3,532	207	5.9
South East	6,154	5,073	168	3.3
South West	2,252	1,940	64	3.3
West Midlands	2,396	2,040	123	6
Yorkshire and Humber	4,826	4,354	176	4
Unknown	9	9	1	11.1

Note 1: Excludes samples for children aged under one years.
Note 2: Region of requesting service.
Note 3: Includes all tests until a person is diagnosed positive, no tests are counted after a positive test, an individual can test in more than one region.
Note 4: The positive result is the first reported by participating laboratories and may not reflect an individual’s first diagnosis, a positive result includes evidence of HDV RNA or HDV antigen positive or detection of antibody to HDV (total antibody or IgM or IgG).

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 13 sentinel surveillance laboratories across England (Appendix 1).

The type of service which requested the HDV test was identified using the record location of the requestor. Excluding reference testing, the majority of tests were from secondary care, with the most common secondary care setting being ‘other ward type’ (includes cardiology, coroner, dermatology, haematology, ultrasound, X-ray), (44.1%, 2,932 out of 6,652), followed by specialist liver services (32.6%, 2,173 out of 6,652) (Table 3). Among primary care settings, the most common service requestor was general practice (59.3%, 2,219 out of 3,744), followed by sexual health services (30.6%, 1,147 out of 3,744).

Positivity was higher among those tested through primary care services (3.8%) compared to secondary care services (2.9%) (Table 3). Positivity overall was highest in drug dependency services, HIV services and private services, but these 3 categories each had very few tests. Amongst services with higher numbers of tests, positivity was highest in sexual health services (4.9%).

Table 3. Number of individuals [Note 1] tested and testing positive for HDV in participating centres by service type, 2010 to 2020

Service type [Note 2]	Total number of tests [Note 3]	Total number of individuals tested	Total number positive [Note 4]	Percentage positive [Note 4]
Primary care: Accident and emergency	245	236	5	2.1
Primary care: Drug dependency services [Note 5]	-	-	-	-
Primary care: General practitioner	2,219	1939	66	3.4
Primary care: Occupational health	80	74	0	0
Primary care: Prison services	52	43	1	2.3
Primary care: Sexual health services	1,147	944	46	4.9
Total primary care [Note 6]	3,744	3,171	119	3.8
Secondary care: Antenatal	302	272	4	1.5
Secondary care: IVF	611	594	20	3.4
Secondary care: General medical or surgical departments	175	159	2	1.3
Secondary care: Obstetrics and gynaecology	109	99	1	1
Secondary care: Other ward type [Note 7]	2,932	2,524	73	2.9
Secondary care: Paediatric services	21	21	1	4.8
Secondary care: Renal	147	73	0	0
Secondary care: Specialist HIV services	12	11	1	9.1
Secondary care: Specialist liver services	2,173	2,047	62	3
Secondary care: Unspecified ward [Note 8]	170	165	1	0.6
Total secondary care [Note 6]	6,652	5,615	165	2.9
Reference	38,391	32,723	1,427	4.4
Laboratory	205	191	1	0.5

Note 1: Excludes samples for children aged under one years.
Note 2: Requesting service type of 158 tests were unknown.
Note 3: Includes all tests until a person is diagnosed positive, no tests are counted after a positive test, a person can be counted more than once.
Note 4: The positive result is the first reported by participating laboratories and may not reflect an individual’s first diagnosis, a positive result includes evidence of HDV RNA or HDV antigen positive or detection of antibody to HDV (total antibody or IgM or IgG).
Note 5: Data for pharmacy testing is not presented due to low numbers.
Note 6: Totals for individuals testing in primary and secondary care, does not equal the sum of the individuals testing in each setting within primary and secondary care, as an individual can test in more than one setting.
Note 7: Other ward types includes cardiology, coroner, dermatology, haematology, ultrasound, X-ray.
Note 8: These are hospital services which are currently being investigated to identify specific service type and may include any of the secondary care services mentioned above.

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 13 sentinel surveillance laboratories across England (Appendix 1).

Trends in HDV testing, 2010 to 2020

Trends in testing were analysed using data from 6 of the 13 sentinel laboratories where complete and consistent data have been available from January 2010 to December 2020. Trend data does not reflect cumulative data.

Six sentinel laboratories consistently reported HDV testing each year between 2010 to 2020, with 40,733 tests performed (1,514 positive, 39,219 negative) on 35,906 individuals.

The annual number of individuals tested ranged from 3,168 (in 2010) to 4,828 (in 2016), between 2010 and 2019 (Figure 1), with numbers substantially falling in 2020. In general, positivity has decreased over time. Due to small numbers of individuals tested for HDV markers, HDV RNA, HDV antigen positive and HDV antibody are aggregated in this report, and therefore it is not possible to report trends in proportion positive by specific HDV markers such as total antibody or antigen. The number of males tested was consistently higher than females tested (Figure 2a).

Figure 1. Number of individuals [Note 1] tested [Note 2] for HDV by year [Note 3] and proportion positive [Note 4] in England, 2010 to 2020

Note 1: Excludes samples for children aged under one years.
Note 2: Includes all tests until a person is diagnosed positive, no tests are counted after a positive test, a person can be counted more than once.
Note 3:Trend data does not reflect cumulative data as only locations that have consistently reported between 2010 and 2020 are included in trend data to remove any artificial changes in testing.
Note 4: The positive result is the first reported by participating laboratories and may not reflect an individual’s first diagnosis a positive result includes evidence of HDV RNA or HDV antigen positive or detection of antibody to HDV (total antibody or IgM or IgG).

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 6 sentinel surveillance laboratories across England.

The majority of tests for HDV were sent to UKHSA by reference laboratories with no further detail on where the test was originally requested. However, when focusing on primary and secondary care, the number of individuals tested from secondary care was consistently higher than primary care over time (Figure 2b). The number of individuals tested in secondary care peaked in 2015 (473) while in primary care the peak was observed in 2019 (200).

Figure 2a. Number of individuals [Note 1] tested [Note 2] for HDV by year [Note 3] and sex in England, 2010 to 2020

Figure 2b. Number of individuals [Note 1] tested [Note 2] for HDV by year [Note 3] and service type [Note 4] in England, 2010 to 2020

Note 1: Excludes samples for children aged under one years.
Note 2: Includes all tests until a person is diagnosed positive, no tests are counted after a positive test, a person can be counted more than once.
Note 3: Trend data does not reflect cumulative data as only locations that have consistently reported between 2010 and 2020 are included in trend data to remove any artificial changes in testing. The scale of the y-axis differ between graphs.
Note 4: Where service type was reported. The scale of the y-axis differ between graphs.

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 6 sentinel surveillance laboratories across England.

HDV infections in England

Between 2010 to 2020, 1,727 new HDV infections were reported to UKHSA through the SSBBV, averaging 157 cases per year (range: 44 to 215) (Table 4). Of those individuals with known sex, there were more HDV positive males than females (57.6%, 964 out of 1675). Median age at diagnosis was 37 years (IQR: 30 to 45), with males slightly older at diagnosis than females (38 years for males versus 36 years for females). Of those with known ethnicity (62.4%, 1,077 out of 1,727), the majority of individuals found to be HDV positive were among those of White Other ethnic background (including White Irish), followed by those of Black or Black British African ethnic background. 41.8% of HDV positive individuals attended a service in London (Table 4).

Table 4. Characteristics of individuals [Note 1] at first HDV positive result in England, 2010 to 2020

Characteristics	Total HDV positive [Note 2]	Percentage of HDV positive [Note 2]
Total	1,727	-
Male	964	55.8
Female	711	41.2
Sex unknown	52	3
Aged 1 to 29 years	390	22.6
Aged 30 to 44 years	865	50.1
Aged 45 to 59 years	346	20
Aged 60 years and over	115	6.7
Age unknown	11	0.6
Ethnic group: Asian or Asian British – South Asian	142	8.2
Ethnic group: Asian or Asian British – Chinese	37	2.1
Ethnic group: Asian or Asian British – Any other Asian background	75	4.3
Ethnic group: Black or Black British – African	255	14.8
Ethnic group: Black or Black British – Caribbean or Any other Black, Black British, or Caribbean background	57	3.3
Ethnic group: Mixed or multiple ethnic groups	34	2
Ethnic group: White – White British	80	4.6
Ethnic group: White – Other [Note 3]	267	15.5
Ethnic group: Other Ethnic Groups – Any other ethnic group	130	7.5
Unknown ethnic origin	650	37.6
East Midlands	76	4.4
East of England	144	8.3
London	722	41.8
North East	46	2.7
North West	207	12
South East	168	9.7
South West	64	3.7
West Midlands	123	7.1
Yorkshire and Humber	176	10.2
Unknown region	1	0.1
Year of diagnosis: 2010 to 2015	1095	63.4
Year of diagnosis: 2016 to 2020	632	36.6

Note 1: Excludes samples for children aged under one years.
Note 2: The positive result is the first reported by participating laboratories and may not reflect an individual’s first diagnosis, a positive result includes evidence of HDV RNA or HDV antigen positive or detection of antibody to HDV (total antibody or IgM or IgG).
Note 3: White Other includes White Irish.

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data is from 13 sentinel surveillance laboratories across England (Appendix 1).

Of the 1,727 individuals identified as HDV positive, 77.5% (1,339) were assigned a HDV status by the UKHSA virus reference department (VRD) (Table 5). Of those with an assigned status, 42.7% were compatible with HDV infection and 38.3% were viraemic.

Table 5. Virus reference department classification of individuals with laboratory evidence of HDV, 2010 to 2020

Virus Reference Department classification [Note 1]	Number of individuals	Percentage
Compatible with HDV infection	572	42.7
Viraemic	154	11.5
Low level reactivity may represent evidence of long past HDV infection or it may be false reactivity unrelated to HDV	513	38.3
Past infection	89	6.7
Possible acute HDV infection	1	0.1
Significance of low level anti-HDV reactivities unknown	5	0.4
Significance unknown	3	0.2
Testing incomplete	2	0.2
Missing	388	-

Note 1: If VRD classification not assigned on first positive sample, VRD classification assignment obtained from the next subsequent positive sample.

Of all individuals found to be HDV positive between 2010 to 2020 in England, 84 are known to have died (death notification from NHS Spine and through linking to the Office for National Statistics (ONS) death registrations). Deaths most commonly occurred in males (54 out of 84), with 5.6% of male cases having died compared to 3.9% of female cases. More individuals of White ethnicity died than any other ethnic group (47.6%, 40 out of 84). The median time between first positive HDV test and death was 831 days (IQR: 198 to 1571).

Sixty-three deaths had information available on their underlying cause of death as noted on the death certificate. Underlying cause of death were grouped according to International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes (Appendix 3). None had viral hepatitis coded as the underlying cause of death, however, more than one-third died with a liver related condition (14 out of 63 liver cancer, 2 out of 63 end-stage liver disease, 4 out of 63 non-alcoholic liver disease, 2 out of 63 alcoholic liver disease).

RNA testing

Between 2010 to 2020, of the 1,727 individuals identified as HDV positive, 598 individuals had had a subsequent RNA test, of which 70.7% (423) were RNA positive. RNA testing data were from 4 laboratories (Appendix 1): Colindale VRD (reference laboratory) represented 85.6% of RNA testing reported to UKHSA. Among individuals tested for HDV RNA, positivity was highest in the Yorkshire and Humber region (84.3%), followed by the East of England (80.0%) and West Midlands (80%) (Table 6).

Table 6. Number of tests, individuals [Note 1] tested and individuals testing positive for HDV RNA by region, 2010 to 2020

Region	Number of individuals tested	Number positive	Proportion positive (%) [Note 2]
East Midlands	25	16	64
East of England	60	48	80
London	206	162	78.6
North East	13	9	69.2
North West	118	56	47.5
South East	55	37	67.3
South West	30	20	66.7
West Midlands	40	32	80
Yorkshire and Humber	51	43	84.3

Note 1: Excludes samples for children aged under one years.
Note 2: The proportion positive is calculated using number of individuals.

Data source: Sentinel Surveillance of Blood Borne Virus Testing. Data on RNA testing is from 4 sentinel surveillance laboratories across England (Appendix 1).

New diagnoses of HBV infection and HDV testing

Between 2010 to 2020, 49,100 individuals had no previous record of testing positive for HBsAg in the SSBBV and are therefore classified as newly diagnosed with HBV within SSBBV. Of those newly diagnosed, 26.9% (13,230 out of 49,100) were linked to a subsequent HDV test in SSBBV at any point following their positive HBV result. The median time between HBsAg positive test and a HDV test was 89 days. The number of newly diagnosed HBV individuals linked to a subsequent HDV test decreased over time (Figure 3). Between 2010 to 2020, the proportion linked to a HDV test ranged from 13.9% to 32.9%.

Figure 3. Number of individuals [Note 1] newly diagnosed with HBV by year [Note 2] and tested for HDV in England, 2010 to 2020

Note 1: Excludes samples for children aged under one years.
Note 2: Trend data does not reflect cumulative data as only locations that have consistently reported between 2010 and 2020 are included in trend data to remove any artificial changes in testing.

Data source: Sentinel Surveillance of Blood Borne Virus Testing.

Impact of COVID-19

During 2020, the ongoing COVID-19 pandemic had major impacts on healthcare, migration, and social interactions resulting in a reduction and/or reconfiguration of testing among those at high risk of blood borne viruses and clinical services providing care. Overall, when comparing testing which occurred in 2019 with 2020, a decline in testing was observed across all blood borne viruses. Declines in testing and diagnoses will be multifactorial, including but not restricted to redeployment of staff, disruption to services, impact of social and physical distancing measures resulting in fewer opportunities for onward transmission, and disruption to laboratory consumables due to increases in demand during the pandemic. It is important to note that the data and findings from 2020 are unlikely to represent the true burden of disease.

Limitations

SSBBV is derived from a network of laboratories that cover over 80% of the population from all 9 regions tested for hepatitis D in 2020 but this coverage varies annually. It is possible that we may not have identified a person’s initial HDV test if they had tested outside the sentinel sites or before SSBBV started. HDV results from data sources such as SGSS were not used in the report as the development of laboratory reporting of HDV results into the system are still ongoing. However, with over 80% coverage, the participating laboratories in the SSBBV system are broadly representative of most laboratories providing HDV testing.

Ideally, HDV RNA is measured in anti-HDV positive individuals to confirm the presence of ongoing HDV infection. Given the small number of tests, individuals tested for HDV RNA and/or HDV antigen positive and/or HDV total antibody and/or IgM and/or IgG are aggregated and therefore do not necessarily represent current infections nor incident infections.

Furthermore, it is important to note when interpreting individuals with newly diagnosed HBV infection and HDV testing it is possible that we may not have identified a person’s initial HBV positive test if they had tested outside the sentinel sites or before SSBBV started. Therefore, the lack of a subsequent HDV test in SSBBV for these individuals may be due to HDV testing occurring at time of initial diagnosis and not thereafter.

Conclusions

In summary, the data indicate the majority of HDV testing occur in males and those aged 30 to 44, with the highest proportion positive in those of White Other (including White Irish) ethnic background, followed by those of South Asian ethnic background. Most tests are linked to reference laboratories and therefore, the service type they were initially requested from is not known, however, among tests where service type was known, most testing occurs in secondary care. As seen for other blood borne viruses, a decline in testing is observed for HDV in 2020 due to the impact of the COVID-19 pandemic (5, 6).

The majority of individuals tested for HDV between 2010 to 2020 (68%) had laboratory evidence of HBV infection. However, the disparity between new HBV diagnoses reported in participating sentinel centres between 2010 to 2020 and those subsequently tested for HDV, suggests not all HBV cases are being tested for HDV, despite guidelines recommending universal testing on initial HBV diagnosis. Furthermore, 30% of individuals with evidence of HDV infection had an RNA result, although SSBBV does not cover all laboratory reporting it covers a high proportion of reference testing, suggesting not all samples where there may be a clinical indication are being referred on for RNA testing. The failure to confirm HDV RNA positivity further reduces opportunities to identify patients most likely to benefit from emerging therapeutics.

To further understand the population in which HDV testing is occurring in England and to inform a targeted strategy to improve testing across services, a more detailed audit of current testing practices is required. The introduction of routine molecular reflex testing should also be considered.

References

1. World Health Organization (WHO). ‘Hepatitis D fact sheet’. July 2021

2. UKHSA. ‘Notifiable diseases and causative organisms’

3. Ahn J, Gish RG. ‘Hepatitis D virus: a call to screening. Gastroenterology and hepatology’. National Center for Biotechnology Information (NCBI) October 2014: volume 10 issue 10, page 647

4. American Association for the Study of Liver Diseases (AASLD). ‘Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance’. April 2018

5. European Association for the Study of the Liver. ‘EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection’. Journal of hepatology. August 2017: volume 67 issue 2, pages 370 to 398

6. UKHSA. ‘Sentinel surveillance of blood borne virus testing in England: 2020’. December 2020

7. UKHSA. ‘The impact of the COVID-19 pandemic on prevention, testing, diagnosis and care for sexually transmitted infections, HIV and viral hepatitis in England’. 2020

8. Mitchell HD, Vilaplana TG, Mandal S, Ratna N, Glancy M, Shah A, Simmons R, Penman C, Kirsebom F, Costella A, Brown AE. ‘Effects of COVID-19 Pandemic Response on Service Provision for Sexually Transmitted Infections, HIV, and Viral Hepatitis, England’. Emerging Infectious Diseases March 2022: volume 28 issue 3, page 739

Appendices

Appendix 1: laboratories reporting HDV tests to SSBBV

Thirteen laboratories reporting HDV testing data to UKHSA include:

• Colindale Virus Reference Department (reference laboratory)
• St Thomas’ Hospital
• Homerton Hospital
• University College London
• Addenbrookes Hospital Cambridge
• William Harvey Hospital Ashford
• Bristol UKHSA laboratory
• Micropathology (reference laboratory)
• Freemans Hospital Newcastle
• Leeds General Infirmary
• Diana, Princess of Wales Hospital Grimsby
• Birmingham Heartlands Hospital
• Queen Alexandra Hospital Portsmouth

Six laboratories reporting complete and consistent HDV testing data included in trend analysis include:

• Colindale Virus Reference Department (reference laboratory)
• Homerton Hospital
• Addenbrookes hospital Cambridge
• Micropathology (reference laboratory)
• Freemans Hospital Newcastle
• Queen Alexandra Hospital Portsmouth

Four laboratories reported RNA testing data:

• Colindale Virus Reference Department (reference laboratory)
• William Harvey Hospital Ashford
• Micropathology (reference laboratory)
• Addenbrookes Hospital Cambridge

Appendix 2: notes on methods

Methods

Data source: UKHSA sentinel surveillance of blood-borne viruses system (SSBBV)

The UKHSA SSBBV collects information on all testing undertaken for hepatitis A, B, C, D and E, as well as HIV and HTLV within participating sentinel NHS and private laboratories across England. Information on the testing carried out in participating centres is collected irrespective of test result and can therefore be used as a basis for estimating prevalence among those tested. Individuals are de-duplicated and linked to all their test results, using a combination of coded surname (soundex), first initial, date of birth, National Health Service (NHS) number and clinic number. Alongside the test result, SSBBV records demographic information and the service requesting the test. Coverage varies annually, but in 2020, SSBBV captured front line testing by laboratories covering over 80% of the general population from all 9 UKHSA regions which offer reference laboratory testing for hepatitis D, E and HTLV.

Sentinel surveillance also collects data on testing for hepatitis B surface antigen (HBsAg), but has lower coverage than HDV, covering approximately 40% of the population from all 9 UKHSA regions that test for HBV.

Data source: Second Generation Surveillance System (SGSS)

Positive hepatitis B results from local NHS laboratories are reported to the UKHSA national laboratory SGSS. This data includes laboratory reports for both acute and chronic hepatitis B infections. Individuals tested for HDV in participating sentinel laboratories were linked to SGSS to assess whether they had laboratory evidence of previous HBV infection.

Data source: Hospital Episodes Statistics (HES)

Data from HES was used to obtain information regarding each patient’s self-declared ethnicity. We divided individuals into four broad ethnic groups: White, Asian, Black and Other/Mixed ethnic background.

Data source: Office for National Statistics (ONS) cause of death registry

The registry of deaths at ONS, includes all reported deaths in England since 1937. Cause of death is coded according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) as underlying cause.

Exclusions:

• persons aged under one year due to the possibility of false-positive results from maternal antibodies
• persons with laboratory definitive evidence of HDV infection prior to 1 January 2010
• persons tested in Wales, Scotland, Northern Ireland or Channel Islands.
• quality control samples

Definitions:

An individual with a positive HDV result or HDV infection in this report is defined as:

• an individual with laboratory definitive evidence of HDV RNA

Or

• HDV antigen positive

Or

• detection of antibody to HDV (total antibody or IgM or IgG)

Date of first positive test of any of the above HDV markers is taken as the date of diagnosis for the case.

Appendix 3

Table A1. Cause of death groupings with ICD-10 codes

Cause of death grouping	ICD-10 codes
Viral hepatitis	B15-19
End stage liver disease	I850, I983, K704, K720, K721, K729, K767, R18
Liver cancer	C22
Alcoholic liver disease	K70, excluding K704
Non-alcoholic liver disease	K71-K77, excluding K720, K721, K729, K767
External causes	S00-99, T00-98, V01-99, W00-W99, X00-X99, Y00-Y98
Other	All other ICD-10 codes