Abstract

Graphical Abstract

Open in a separate window

Introduction

Untreated hepatitis C virus (HCV) is a leading cause of hepatitis C-related liver disease, cirrhosis, and hepatocellular carcinoma [1,2]. With an estimated 71 million chronically infected patients worldwide, HCV epidemics affect all World Health Organization (WHO) regions, although prevalence is higher in region European and the Eastern Mediterranean [2], partly due to testing practices [3]. In 2019, there were an estimated 1.5 million new cases of HCV and an additional 290,000 deaths related to HCV infection [4].

In recent years, the implementation of direct-acting antivirals (DAA) has transformed the prognosis of the infection into a completely curable disease, favorably reducing HCV mortality [4], [5], [6]. In 2016, the WHO adopted the first global health sector strategy on viral hepatitis, setting targets for HCV eradication by 2030 [7]. As one of the few countries on track to reach the WHO goals by 2030 [2,6], Spain developed its 2015 Strategic Plan for the Approach to Hepatitis [8], which includes the widespread use of DAAs.

Since early 2000, HCV has been considered a sexually transmitted infection (STI), particularly in gay, bisexual, and other men who have sex with men (GBMSM) [2,5,7,9,10]. Within this key population, those with an HIV diagnosis have an increased risk of HCV acquisition [7,9,11]. Some proposed explanation includes serosorting practices during the widespread initiation of combined antiretroviral therapy in the US and Western Europe ever since the 1990s, which may lead to condomless anal sex [9]. Furthermore, the rise of sexualized drug use or chemsex [11], especially the increase in sexualized injection drug use (slam-sex or slamming) [9,12,13] has been associated with an increase in HCV cases. Additional blood-sharing risk practices include having multiple sexual partners, sharing douching materials, and/or sexual practices which may damage anal mucosa (fisting) [9].

In HIV-negative GBMSM, the observed risk has been lower than their HIV-positive peers; although their incidence is reported to be higher than general population and rising in some occidental countries [9,10,12]. Some explanations include chemsex and increased condomless serosorting practices due to HIV pre-exposure prophylaxis (PrEP) [5], overlapping the sexual networks between HIV-positive and negative GBMSM [14]. A systematic review described that, in HIV-negative GBMSM who do not use PrEP, the pooled HCV incidence was 0.12 per 1000 person-years (95% confidence interval [CI] 0.00-0.72) while in PrEP users this pooled incidence was 14.80 per 1000 person-years (9.65-20.95) [7]. Moreover, few studies have specifically looked at how social and structural factors facilitate HCV transmission, what is missing in HCV information and support for GBMSM, or the efficacy of specific HCV interventions in GBMSM [9,15].

In Spain, according to the second National Study of HCV seroprevalence (2017-2018) [16], the prevalence of HCV antibodies among 20-80s is an estimated 0.85% (95% CI: 0.64-1.08%) and the prevalence of active HCV infection is 0.22% (0.12-0.32%). According to the National Centre of Epidemiology [1], by 2020, 819 cases were notified across Spain (incidence rate of 2.36 per 100.000 citizens) but of those only 7.8% (n = 64) were confirmed as active cases. Among Spain's HIV-negative GBMSM, the data remains unclear. In order to provide clinical recommendations for HCV screening key populations, the aim of this study is to estimate the HCV antibodies prevalence and active HCV infection in HIV-negative GBMSM of Barcelona and Madrid, from March 2018 to March 2021, and their characteristics.

Methodology

Results

From March 2018 to March 2021, 3548 participants attended any of the services in Barcelona or Madrid, where 97.6% (n = 3463) were HIV-negative. Of them, 18 participants (0.52%, 95% CI: 0.33-0.82) tested positive for HCV AB, of which nine participants (0.26% 95% CI: 0.14-0.49) were diagnosed later with an active HCV (AC). Of the 2.4% (n = 85) participants who tested positive for HIV, some 3.5% (n = 3) tested also positive for HCV AB, with 2.4% (n = 2) presenting an active HCV (Figure 1).

Open in a separate window

Figure 1

Flowchart according to city of testing and type of facility. Results are presented in absolute frequency and prevalence with 95% confidence interval, according to their HIV status. AB, antibody; GBMSM, gay, bisexual, and other men who have sex with men; HCV, hepatitis C virus; STI, sexually transmitted infection.

Most HIV-negative cases with a reactive HCV test (AB/AC) had attended university education, had a subjective comfortable economic welfare, and lived an openly sexual orientation between their peers. Most of the cases had sex exclusively with men and had been tested for HIV in the last 6 months. In total, 77.8% of the cases (AB/AC) have had some STI in their lifetime, mostly syphilis and gonorrhea, and mostly had their last STI during the last year. Two of the nine diagnosed with an AC-HCV have had a previous HCV diagnosis. Between the participants, the best-known statement was the existence of several types of hepatitis named by letters of the alphabet, and the worst known was that healthcare providers recommend that GBMSM gets vaccinated against viral hepatitis A and B. Some 66.7% of AC-HCV had ever shared douching material and some 77.8% had ever participated in group sex. All AC-HCV cases reported use of drugs related to sex (AB: 77.8%). Injectable drug use was described by 83.3% of HCV AB and 66.7% of HCV-AC (Table 1a, Table 1b).

In the single Poisson model, those with HCV antibodies were associated to have ever lived with an HCV (+) person (APR: 7.84, [95% CI: 2.50-24.53]), ever using injectable drugs for sex (APR: 6.92, [1.20-39.79]) and referring an STI in the previous year (4.06, [1.09-15.12]). The adjusted models found associations with previous STIs (syphilis and chlamydia), higher amount of condomless encounters with different sexual partners, group sex, and sex work. Furthermore, presenting an active infection was strongly associated with a previous HCV diagnosis (APR: 100.82 [22.16-458.76]), also to sexualized injectable drug use (APR: 17.53 [2.70-113.76]) and to ever have shared douching material (APR: 7.45, [2.12-25.95]). Similar to AB-HCV, associations were found with a higher amount of condomless sexual partners, previous syphilis, and sharing shaving material with HCV partners, but also for sharing sniffing material for sex, and the use of gamma-hydroxybutyrate/gamma-hydroxybutirolactone (GHB/GBL) (Table 2).

Discussion

Our study results estimate that HCV seroprevalence and active infection in HIV-negative GBMSM from Barcelona and Madrid are similar to the prevalence among the general population. However, individuals with a history of HCV were positively associated with a range of sexual behaviors epidemiologically linked to an increased risk of bleeding, particularly condomless anal sex, an elevated number of penetrations in a given sexual encounter, and sexualized drug consumption. Other practices with risk of blood-sharing observed with this population include group sex participation and sharing douching, sniffing, or injection materials.

Our HCV antibody prevalence seem a bit lower than what has been observed in previous reports on HIV-negative GBMSM [7,12], although they correlate very well with previous analysis of this population conducted in community centers in Barcelona [19,20]. Systematic review from Jin et al. [7] described a general HCV seroprevalence in GBMSM of 3.4% (2.5-10.4%), independent of their HIV status, and 1.5% (1.0-2.1%) in HIV-negative GBMSM. Zheng et al. [12]’s review pooled an HCV prevalence of 5.9% (5.1-6.8%) in general GBMSM and 2.8% (1.9-4.0%) in the HIV-negative group. In Spain's GBMSM, While earlier studies reported a general prevalence of 4.2% (2.2-6.7%) [7]; they found no cases of HCV in HIV-negative GBMSM (0% [0-0.9%]); Zheng et al. [12]’s study reported a general GBMSM seroprevalence of 6.3% (3.7-9.4%), with a seroprevalence of 3.0% (0.7-6.6%) in HIV-undiagnosed GBMSM, being correlated with our results. Many factors could explain these differences, like the study's region, the sample selection method, or the inclusion of specific populations, such as people who inject drugs (PWID). In Barcelona, Saludes et al. [19] reported an HCV seroprevalence of 0.75% (0.1-1.6%) in 617 HIV-negative GBMSM recruited voluntarily from a community center, while Coll et al. [20] followed 258 HIV-undiagnosed GBMSM from 2009-2012, recruited as well from community centers, finding an HCV seroprevalence of 2.0% (0.7-4.8%), both similar with our results. Furthermore, Jin et al. [7]’s results describe that HCV seroprevalence was higher in low and lower-middle-income economies, independent of their HIV status, unlike Spain, which is close to HCV eradication [2], and other countries that have adopted DAA strategies [21]. Other studies evaluating HCV seroprevalence in GBMSM in Spain begin by recruiting HIV-positive individuals and assessing the coinfection risk. In our sample, those who received an HIV diagnosis presented an HCV antibody prevalence of 3.53% (1.21-9.87) and a prevalence of active infection of 2.35% (0.65-8.18), supporting the correlation between these two infections [7,9,11].

Both antibodies and presenting an active HCV were strongly associated with ever being in close contact with an HCV partner diagnosed, especially if they have previously shared shaving material. Moreover, presenting an active infection was strongly associated with a previous HCV diagnosis, supporting previous evidence of reinfection risk [22]. Ever being paid for sex presented significant associations in both adjusted models but may have interacted with other variables in the final models, like slamming or sharing douching material. It is important, for screening and surveillance implications, the correct identification of key populations, contact tracing when a diagnosis is made, and the linkage for regular testing in an HCV-diagnosed patient. Adu et al. [23] found that in reinfected HCV HIV (+) GBMSM, mental health counseling could reduce the risk of reinfection, so targeted interventions could be beneficial also in those HIV-negative.

PWID, in general, has been targeted as a key population for HCV eradication [2,24], with reported seroprevalence in European PWID ranging from 7-95% and national PWID's seroprevalence estimated at 66.6% [25]. Due to this previous assumption, we expected the high association of seroprevalence observed with ever using heroin or using injectable drugs, for any purpose. PWID who also identifies as GBMSM may constitute a unique group with an increased risk of HCV acquisition. Moreover, high rates of injecting drug use appear to be one of the main drivers of the HCV epidemic in this population. In our sample, the association of using injectable drugs for sex was higher than using them for any purpose. Previous analyses on this sample have been published on this subject [13], describing associations with an increased number of sex partners and meeting them in private parties. Slamming sex is a practice reported to be rising among individuals practicing chemsex [7,13,26], so screening and preventive interventions during sexual health consultation should be mandatory [27]. Previous data published in this sample observed a significant increase compared with previous Spanish reports, where 81.9% of first injectors were in a sexual context, 62.7% started with mephedrone, and 32.2% with methamphetamine [13].

Mephedrone and Crystal Methamphetamine have been recognized as two of the drugs in “4-Chem”, along with GHB/GBL and ketamine [18], with an increasing amount of research focused on their sexualized use within GBMSM communities, and their effects [28]. Although a single definition for chemsex does not yet exist [29,30], the practices associated with consuming these substances present a pathway for HCV acquisition, such as participating in group sex or the association with GHB/GBL using, besides the other chem drugs. Unlike others with a clear correlation due to the sniffed or injected pathway of administration, GHB/GBL is orally administrated. This could be explained due to the sexual context where the substances are consumed, where they could facilitate the occurrence of known risk of bleeding practices. Furthermore, social determinant variables such as peer pressure, mental health-related variables, or hegemonic masculinity could increase those related risks [28,30].

Rectal douching, or the use of enemas before sex, has been reported as a risk factor for HIV and other STIs, including HCV [31]. Sharing douching material may be a regular practice in those who practice receptive anal sex (bottoming), especially those who attend saunas or private sex parties. It is important to discuss the normative expectations of an anal sexual encounter, balancing the risk and benefits of a regular douching practice, as well as risk reduction strategies, like utilizing their own instruments and attending regular anal checkups in higher-risk populations [31].

Sexual health services are cost-effective and critical points to addressing sexual behaviors with risk of HCV acquisition [32,33]. Personalized risk reduction strategies should be recommended according to their practices, the number of sexual partners, and the preventive strategies of choice, independent of their gender or sexual orientation. Targeting recommendations in sexually active and non-monogamous individuals, with early detection of bleeding risk practices and sexualized substance use, are key elements to an effective response for current needs as well as future outbreaks and epidemics related to sex [34].

Spain's 2017 guidelines for STI management include a yearly HCV screening, with recommendations on 3-6 months of screening in those of “higher risk”, not specifying what indeed defines a “riskier” GBMSM [17]. However, although 6.4% of our total sample was tested for the first time for HIV, only 44.7% of the sample referred to being previously tested for HCV. As the 2022 mpox (monkeypox) outbreak demonstrated, there is a need for homogeneous, integrated, and articulated sexual health-related services, with sanitary, surveillance, and community entities developing effective risk communication strategies, clear and informed, but free of stigma. Considering globalized culture and patterns of human movements, it is possible that practices associated with a higher risk of HCV transmission have also increased in countries where HCV testing policies are less expanded, especially in sexual health context.

Limitations

This study has an important limitation of not including PrEP usage as a variable since the beginning of the study, which was difficult due to the particular political environment around the start of the study. PrEP in Spain was included in the sanitary system in November of 2019, and since then, the number of users has been growing, especially in Barcelona and Madrid. PrEP users who engage in condomless sex are identified as a key population for STI prevention [5,7,14], and between this group, the observed risk of acquiring HCV is reported to be higher than their nonusers' peers, for different causes previously discussed [7,14]. Spanish current guidelines in PrEP management indicates HCV screening at the first visit, without recommendations for further control [35], so better recommendations are needed. Nevertheless, PrEP use should not be seen as a causal correlation of acquiring HCV, but as a tool to improve their sexual health. Regular HCV testing in PrEP users, especially in those with practices with risk of bleeding, among counseling interventions, could impact this increased risk.

Other limitations of this study include the selection bias as a result of recruiting individuals from sexual health centers, which may overrepresent higher-risk GBMSM. However, some compensation may be achieved by designing the recruitment from health care centers and community centers in different cities, which may encompass the different profiles of users in the most populated areas of Spain, who attract GBMSM from other parts of Spain and abroad. The COVID-19 pandemic may have affected the access to sexual health services during a good part of our recruitment, as well as restrictions in mobility, which translated into fewer screening checkups, however, most of the sample was recruited before the confinement period. The cross-sectional design does not allow to define causality, so further research is encouraged. The strengths of this study include the power of the sample, the diversity of recruitment sites in highly concentrated GBMSM cities, and the deep research in bleeding risk practices, hepatitis knowledge, and substance use consumption. Our results reinforce the need to develop clear and updated indications on HCV screening, and better interventions in key populations, understanding the specific characteristics of this population in preparation for stronger services.

Conclusion

During 2018-2021, the risk of HCV infection among Barcelona and Madrid's HIV-negative GBMSM was similar to the general population, but higher in those who engage in sexual practices with bleeding risk, such as slamming, chemsex, and sharing rectal douching material. With the increase of PrEP users, HCV diagnosis between HIV-negative GBMSM may rise, due to regular testing but also to the incorporation of new sexual practices. The increased risk for HIV and STIs in GBMSM responds to multiple factors yet to be better understood. Future research is needed to elucidate the contextual, behavioral, and cultural differences of this group allowing to improve the quality of the continuum of care and strengthen the response to potential outbreaks or epidemics related to sex. Sexual health services should identify these practices early during consultation, promoting targeted risk reduction strategies, such as hepatitis A and B vaccination and regular testing. Frequent testing should be recommended in non-monogamous individuals, according to their individual needs and epidemiological context. When a diagnosis is made, contact tracing is highly recommended for cohabitants and sex partners. Further preventive interventions that address mental health and social determinants of health should be promoted, integrating community entities with healthcare and surveillance systems.

Declarations of competing interest

The authors have no competing interests to declare.

Funding

Footnotes

References