In the absence of up-to-date data on HEV seroprevalence in Malaysians, archived serum samples of the Subang Men's Health Study were screened. The study sample for the Subang Men's Health Study was recruited from an affluent township located in Subang Jaya, Selangor, Malaysia. Malaysia is a multi-ethnic country with a population consisting of 69% Malay, 23% Chinese, 7% Indian and 1% mostly indigenous people of Borneo (30). The official religion of Malaysia is Islam, practiced by more than 60% of the population.
In this study, the seroprevalence of HEV-specific IgG antibody detected with the Wantai HEV IgG assay in a sample of men of the Subang Men's Health Study was 11.5%, extremely high compared to that reported in previous studies in Malaysia. Comparatively, the HEV IgG seroprevalence in this study was over 3-fold higher than that of blood donors reported recently (3.1%) (21) and a study conducted nearly two decades ago on a relatively small sample of 100 donors (2%) in Malaysia (22). The findings of this study provide additional evidence of sexual dimorphism in HEV seropositivity. Other local studies on mixed male and female samples reported that males had nearly 3-fold higher odds of having anti-HEV IgG than females (odds ratio [OR] = 2.86; 95% CI 0.95–8.64) (20). Likewise, in two other studies from the Asian region, males were found to have an over 2-fold higher HEV seropositivity rate than their female counterparts (OR = 2.2; 95% CI 1.8–2.8) (31, 32). The high HEV-specific IgG antibody seroprevalence found in this study provides insights into personalized HEV prevention and control approaches that could be developed among the male population. The findings further heighten the ideology of masculinity norms and infectious disease, in particular, HEV infection. In light of the fact that behaviours traditionally associated with masculinity may put some men at increased risk for HEV infection, future HEV prevention interventions should adopt a gender discourse that incorporates men and the meaning of masculinity.
This study also evidenced an increase in the HEV IgG seroprevalence rate by age. The finding of an increasing trend in HEV IgG antibody prevalence with age in this study is consistent with a meta-analysis on HEV seroprevalence in Asia and western countries (24, 33–35) The increase in anti-HEV IgG seroprevalence with increasing age suggests a cumulative lifetime exposure to HEV (21). An important finding of this study is that there is a greater than 3-fold increase in the risk of high HEV seropositivity in men above the age of 60 relative to those 40–50 years old. The alarming increase in HEV seropositivity in men aged greater than 60 emphasizes the importance of older men being made known of the risk of acquiring HEV. As seroprevalence was higher in older people, it is particularly important to perform HEV screening in older men. The study findings also provide enlightenment to health care authorities in prioritizing targeted age groups for HEV infection prevention and control measures. The Centers for Disease Control and Prevention (CDC) recommends that HEV infection should be considered in any person with symptoms of viral hepatitis who tests negative for serologic markers of hepatitis A, hepatitis B, hepatitis C, and other hepatotropic viruses. Additionally, any symptomatic person who has travelled either to or from an HEV-endemic area or outbreak-afflicted region should also be evaluated for HEV infection (36).
The ethnic disparities in the HEV IgG seroprevalence rate found in this study are also in concordance with those previously reported in Malaysia (21). This study found that of the three major ethnic groups in Malaysia, the majority of HEV IgG seropositivity occurred among people of Chinese descent, and only two Malay men were found to be positive for anti-HEV IgG antibodies. Ingestion of pig-derived food products, particularly raw or undercooked pig meats, has been proposed as a possible source of HEV transmission (37). The low risk of HEV seropositivity among Malays could be due to their non-consumption of pork and the absence of activities involving contact with pork products. The results suggest that exposure to HEV is common in the general Chinese population. Therefore, raising public awareness with a focus on imparting knowledge about the prevention and transmission of HEV should be a priority to decrease the risk of HEV infection in the community.
This study has several limitations and requires cautious interpretation. First, we investigated the seroprevalence of anti-HEV antibodies from archived samples, and thus our results may not reflect the current seroprevalence of men in the study population. A future study using more recent samples is warranted to better estimate the level of anti-HEV antibodies in the current population. Second, the blood donor samples were from the Subang Men's Health Study and, despite being a random sample, may not be representative of the male population in Malaysia. Therefore, there is a need to initiate larger-scale screening for HEV antibodies in the wider population. The third limitation is that the Subang Men's Health Study did not collect samples from females in the population; therefore, we are unable to draw valid comparisons between male and female anti-HEV antibody prevalence. Nonetheless, findings from the large and randomized archived sample from the Subang Men's Health Study provide insight into the magnitude of HEV infection in the male population in an affluent urban population in Malaysia, which has been under-reported to date. Lastly, it is equally important to acknowledge the potential for false positives in serological testing. Future studies should consider diagnosis using nucleic acid amplification techniques (NAT or NAAT) to detect HEV RNA.