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Abstract
Objectives Since February 2017, an increase of acute hepatitis A (AHA) cases has been notified in North of France. We aimed to report clinical and virological features of 49 cases treated in three hospitals in Lille European Metropolis (LEM).
Methods All adult patients treated for AHA in 3 LEM hospitals between 20 February and 5 July 2017 were included. Demographic characteristics, exposure risk factors to hepatitis A virus (HAV), AHA manifestations and concomitant sexually transmitted infections (STI) were retrospectively recorded.
Results Forty-nine cases of AHA were diagnosed among which 34 (69%) were hospitalised. Severe AHA occurred in 7 (14%) patients. The median age of cases was 36 years. All cases except 1 were men and 32 (65%) were identified as men having sex with men (MSM). Eleven (23%) patients were HIV-infected, 5 were under HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 had a history of at least one STI. Only three patients had received HAV vaccine. Proportion of patients tested for syphilis, chlamydial and gonococcal infections was 75% (18/24) in those seen by sexual health specialists and 21% (6/29) in those seen by other specialists. At least one concomitant STI was diagnosed in 13 out of 24 tested patients (54%). RT-PCR sequencing was available for 38 cases and confirmed co-circulation of 3 different strains of subgenotype IA (VRD 521 2016: n=24, RIVM-HAV16-090: n=13, V16-25801: n=1), already identified in several European countries.
Conclusions We are facing an outbreak of AHA among MSM in the North of France with a high rate of hospitalisation. Analysis of cases highlighted missed opportunities of vaccination and lack of concomitant STI screening. Awareness among healthcare providers and MSM should be increased and HAV vaccination promoted.
- hepatitis A
- gay men
- epidemiology (clinical)
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Introduction
The hepatitis A virus (HAV) is usually transmitted via the fecal–oral route. In developed countries, acute hepatitis A (AHA) is mainly travel-related. In men having sex with men (MSM), sexual transmissions of HAV and AHA outbreaks have been described.1 An outbreak is currently affecting MSM across Europe.2 In this context, France is facing an increase of AHA cases. In the Hauts-de-France region, 151 cases have been notified since the beginning of 2017.3 The Lille European Metropolis (LEM) concentrates 1.2 of the 6 million inhabitants of the region. We aimed to report features of 49 cases treated in three hospitals in LEM from February to July 2017.
Patients and methods
Study population
We conducted a retrospective observational study in three hospitals of LEM: Tourcoing Hospital, Lille University Regional Hospital and Seclin-Carvin Hospital. All adult patients treated for AHA between 20 February and 5 July were included. Cases were identified using laboratory databases. A case of AHA was defined by the presence of hepatitis A-specific immunoglobulin M antibodies (HAV IgM) in the serum detected by ELISA.
Data collection
Demographic characteristics, medical history, exposure risk factors to HAV within 6 weeks before diagnosis, AHA manifestations and outcome were registered. In 12 patients, additional data on sexual practices were collected using a standard questionnaire. Concomitant sexually transmitted infections (STI) were recorded.
Molecular analysis
Forty serum were sent to the National Consultant Laboratory for HAV for molecular analysis. HAV RNA was tested by an in-house RT-PCR assay as described.4
Statistical analysis
Continuous variables were expressed as median (IQR). Categorical variables were expressed as percentages. Analyses were conducted using statview.
Results
Baseline characteristics
During the study period, 49 patients were diagnosed with AHA. Before the AHA outbreak, from disease case reporting, the baseline number of AHA cases was five per 4-month period. Patient characteristics are summarised in table 1. All patients except 1 were men and 32 (65%) were identified as MSM. Eleven (23%) HIV-infected patients were under antiretroviral therapy, with undetectable RNA virus, except for one. Twenty-seven (55%) patients were tested and were negative for hepatitis E (HEV). Four patients had a history of hepatitis B (HBV) and two of hepatitis C. Twenty-three (47%) patients were vaccinated against HBV. Five patients were receiving HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 of STI.
Demographic characteristics and clinical features of patients presenting with AHA during an outbreak among MSM in northern France
In 43 cases, HAV vaccination had never been offered. HAV vaccine had been prescribed to three patients but not performed due to unavailability, a median time of 10 months before the outbreak occurred. One patient, infected with HIV, had received two doses of vaccine 5 years ago but was a non-responder. Two patients had received one dose of vaccine during the AHA incubation period.
Exposure to HAV risk factors
Twenty-eight (49%) patients, all MSM, reported condomless sexual intercourse. Thirteen patients had travelled abroad, but only 4 (8%) in HAV endemic countries. Nine patients reported close contact with a confirmed AHA case. The related case was a sexual partner for eight patients. Five patients reported consumption of shellfish.
A completed questionnaire on sexual practices was available for 12 patients identified as MSM. Of these, 7 (58%) reported frequent condomless anal sex, 11 (92%) condomless oral sex and 11 (92%) group sex. In four cases, the sexual intercourse exposure occurred in a backroom or bathhouse.
AHA manifestations and outcomes
Median duration of follow-up was 3 weeks in non-HIV, and 21 weeks in HIV-infected patients. Thirty-four (69%) patients were hospitalised, 10 (20%) in an intensive care unit for monitoring of liver failure. Seven (14%) patients suffered from severe AHA but none developed a fulminant hepatitis. One patient was diagnosed with recurrent hepatitis. No additional hepatitis serological tests were performed.
Concurrent infections
HBV and HCV serological tests were performed in 46 (94%) patients. HCV RNA levels in 11 (22%) patients indicated non-acute infections. HBV and HCV serological tests were repeated during the follow-up respectively in 1 and 10 patients, revealing no seroconversion. Thirty-six of 38 (96%) of patients not already known to be HIV-positive were tested for HIV, revealing one chronic HIV infection (CD4 cell count 343/mm3 viral load of 5.1 log10).
Other STI testing was offered to 24 (49%) patients. The proportion of tested patients varied from 75% (18/24) in patients seen by sexual health specialists to 21% (6/29) in those seen by other specialists. None of the patients treated by other specialists was referred for STI testing. At least 1 STI was diagnosed in 13/24 (54%) patients tested (table 1). Six of eight (four rectal and two urethral) chlamydial infections diagnosed were asymptomatic and two were rectal lymphogranuloma venereum. Seven asymptomatic (six rectal and one urethral) gonococcal infections were diagnosed. Nine patients were diagnosed with latent syphilis.
HAV genotyping
HAV sequencing was undertaken on specimens from 40 patients. Three different strains of subgenotype IA were reported: VRD_521_2016 in 24 cases, RIVM-HAV16-090 in 13 cases and V16-25801 in one case. In two cases, sequencing failed.
Discussion
We reported an ongoing outbreak of AHA in MSM in the LEM area with a high rate of hospitalisation. Analysis of cases highlighted numerous missed opportunities of vaccination and screening for concurrent STIs.
Our patients were almost exclusively male, with two-thirds identified as MSM. In France, notification of AHA cases has been mandatory since 2005, but sexual preference is not recorded. An increase in the male to female ratio is an early indication of a possible outbreak in MSM. The molecular analysis revealed three different strains recently detected in MSM from various European countries, supporting the hypothesis of an epidemic spread of HAV through MSM-specific networks that is driven by sexual contact.2 Almost half of our patients reported high sexual risk behaviour and a history of STI. Previous investigations of AHA outbreaks affecting MSM have identified anonymous sex partners, group sex, oral–anal or digital-anal sex, visiting bathhouses and saunas and STI history as risk factors.1 5 6
In our study, concurrent STIs were frequent and mainly asymptomatic, increasing the risk of missed diagnosis and spread. HIV prevalence was also high as seen in previous studies.5 6 The European Centre for disease prevention and control has highlighted that all AHA cases among MSM should be referred for further STI/HIV testing and that prevention measures should be strengthened.2 Links between specialities should be promoted.
AHA is preventable with a highly effective vaccine.7 In France, HAV vaccination in MSM has been recommended since 2000.1 Our study highlights the lack of follow-up of existing guidance. Assessment of HAV vaccination coverage among MSM has revealed low coverage8 9 and in our study, the majority of patients stated that vaccination was never offered. One additional obstacle is the limited availability of HAV vaccine in Europe.2 In response, French sanitary authorities recommended prioritising vaccination among HAV non-immune MSM.10
The impact of HAV infection can be considerable, justifying vaccination among those at risk. In our study, hospitalisation rates were high and >10% of our patients developed severe liver failure, concordant with previously published case series.6
Our study has several limitations. We included only three hospitals and patients included may be the most seriously affected, resulting in some underestimation of case numbers. Rare cases presenting at a very early stage with undetectable anti-HAV IgM and those seen in primary care would also have been missed. No acute HBV or HCV infections were reported but some cases could have been undiagnosed as repeat serological tests were not done. Furthermore, missing data on sexual behaviour and reasons for absence of HAV vaccination have hampered interpretation.
Since the end of the study period, 23 new HAV cases have been identified. To contain the outbreak, awareness among healthcare providers and MSM should be increased and vaccination promoted. STI screening in MSM diagnosed with HAV is essential. Sexual preference information on HAV notifications could improve surveillance of the relative importance of sexual exposure in HAV transmission.
Footnotes
Handling editor Gwenda Hughes
Contributors AB and AM: analysed the data and wrote the manuscript. AK, SE and LB: contributed to the data collection. All authors contributed to the interpretation of the results and the final draft of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.