Introduction

Hepatitis C virus (HCV) infection is a significant public health concern and, regrettably, a major cause of liver-related morbidity and mortality that challenges healthcare systems in many countries. Globally, 1.5 (1.3–1.8) million people are newly infected with HCV every year, and 58 (46–76) million people are living with chronic HCV infection, with a global prevalence of 0.8% (0.6–1.0%) in the general population. The highest prevalence in the Eastern Mediterranean Region is 1.6% (1.4–1.8%), 290,000 (230,000–580,000) people die from hepatitis C-related causes every year, and only 21% of people are diagnosed with HCV infection, and 62% of them receive treatment1.

Gender is an essential determinant of social outcomes, including health. Research has shown a growing interest in health-related gender differences and raises the question of gender-biased differential response that is relevant in many health fields, including the prevalence, risk factors, clinical features, and treatment of diseases. Still, the epidemiological pattern of HCV infection in research and medical practice requires further knowledge of the potential role of gender differences. Thus, assessing gender-level change in HCV prevalence may help identify population subgroups most likely to suffer an increased infection rate, thus enabling health authorities to plan targeted interventions for these changes2.

The origin of gender differences in HCV prevalence is not well understood, and some hypotheses tried to explain this difference. The salience of gender in positioning women at increased risk of exposure to HCV infection has been confirmed by some studies3,4,5,6, while others support the view that HCV infection appears to be prevalent and progresses more rapidly in males than in females7,8,9,10,11. On the other hand, some studies found gender differences are artifactual, with nearly flat rates of HCV infection12,13,14,15. Also, some studies found a decreased rate of liver cirrhosis and hepatocellular carcinoma (HCC) in females16, more progress to hepatic fibrosis in males, and more liability to adverse events of direct-acting antivirals (DAAs) in females17.

Compared to men, women are more exposed to syringes, blood, and blood products, especially during pregnancy and labor, and ear piercing, and thus run a higher risk of HCV infection. Biological sex with female predominance has been associated with differences in rates of spontaneous HCV clearance, with a possible role of sex hormones in determining host susceptibility to viral infections18. On the other hand, male predominance can be explained by differences in daily life conditions, environmental experiences, and social, cultural, and occupational aspects taken up more frequently by men than women, especially in marginalized groups and slum areas such as IV drug use, circumcision, shared use of toothbrushes or shaving razors, tattooing, wet cupping (Higama), or illegal sexual intercourse, in addition to blood transfusion emergencies19. The hormonal hypothesis and other mechanisms have been invoked, such as cellular mosaicism, genes escaping X chromosome inactivation, skewed X chromosome inactivation, and miRNAs encoded on the X chromosome20. In addition, gender differences in HCV infection rates might reflect differences in the patterns of gender-specific risky behaviors21,22.

Historically, Egypt is one of the world countries with the highest prevalence of HCV infection. Over the past decade, Egypt has continued efforts to achieve HCV control and works towards the common goal, targeted by the WHO, of the elimination of viral hepatitis by 2030. The universal access to treatment with the introduction of DAAs has resulted in a paradigm shift in HCV management and declining mortality. A large Egyptian study showed a marked decrease in mortality in Egypt23.

In Egypt, some studies indicated that anti-HCV prevalence in the general population was higher in males than in females (19.67% vs. 9.73%; p < 0.001)10, (16.1% vs. 13.4%; p < 0.001)9, and (7.5% vs. 5.3%; p < 0.001)8. While other studies found more anti-HCV prevalence in women than in men in special situations: (13.4% vs. 7.3%; p = 0.045) among family contacts of HCV-positive children24, (25.2% vs. 17.6%; p = 0.031) in patients with coronary heart disease5, and (25.1% vs. 15%; p = 0.002) in apparently healthy blood donors3.

We aimed to review and evaluate the dominance of gender in HCV infection and whether gender differences in HCV seroprevalence and HCV RNA exist amongst Egyptians that can support prevention and control programs and minimize HCV-related morbidity and mortality.

Methods

To conduct this meta-analysis, we searched PubMed, Scopus, and Web of Science (WOS) for relevant articles published from 1st January 2011 to 13th December 2021. Our protocol was registered to the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022303921).

Search strategy

We searched the target databases one by one using the following search terms: (HCV OR “hepatitis C” OR hepacivirus) AND (prevalence OR seroprevalence OR epidemiology OR incidence OR magnitude).

Eligibility criteria

Any Egyptian observational cross-sectional study containing original information regarding the prevalence of HCV on both males and females published in the English language from 2011 or later till the end of 2021 was included irrespective of the governorate, studied group, and age of participants. Studies that did not specify gender, non-Egyptian studies, studies with a mixed population with no definite data for Egyptians, studies in which prevalence was not the primary concern, editorials, reviews, abstracts, posters, commentaries, and non-human studies were excluded.

Screening, data extraction, and quality assessment

Title and abstract screening were done by four independent reviewers (MO, YA, HN, FA), and a discussion with the research team solved any disagreements. The same four independent reviewers did full-text screening for articles selected in the previous step. Data extraction for finally included studies retrieved from the full-text screening was done independently. Relevant data were extracted to a pre-prepared excel file. Quality assessment was done by two independent reviewers (MA, MA). We used The Joanna Briggs Institute (JBI)25 tool for the quality assessment of prevalence studies.

Data synthesis and analysis

Collected data were analyzed using STATA version 16 (Stata Crop LP). Heterogeneity was assessed using the I2 test and classified as high, moderate, and low heterogeneity according to I2; more than 75%, 50%, or 25%, respectively. A log odds ratio with a 95% confidence interval (CI) was used with a random effect model to compare males and females. A funnel plot was used to check for publication bias using egger's test (a p value less than 0.05 was considered significant) (Supplementary Fig. 1).

Results

Overview of included studies

Our primary search results yielded 616 studies from databases; 89 duplicated studies were excluded. By title and abstract screening, 308 studies were selected and entered the full-text screening. Only 30 studies3,4,5,8,9,10,12,13,14,15,24,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44 were finally included in our meta-analysis after full-text screening (Fig. 1) with 193,621 included participants: 97,597 male and 96,024 female. Studies ranged from modest to high quality. Characteristics of the included studies are detailed in Table 1.

Figure 1
figure 1

PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only.

Full size image
Table 1 Characteristics of finally included studies.
Full size table

The overall gender differences in the seroprevalence of HCV antibodies (all included studies)

The seroprevalence of HCV antibodies among the Egyptian population using serum antibodies test by ELISA, based on the results of the random-effects method, there were no significant differences between male and female seroprevalence of HCV. The overall seroprevalence was 0.02 (log 95% CI − 0.23, 0.28), and the heterogeneity was high (T2 = 0.35, I2 = 96.99, H2 = 33.21, p value = 0.86) as shown in Fig. 2.

Figure 2
figure 2

Forest plot of seroprevalence of HCV antibodies in males and females. There is no significant difference in seroprevalence of HCV antibodies between males and females.

Full size image

Gender differences in the prevalence of HCV PCR positivity

Eight studies used PCR to measure the prevalence of HCV; based on the results of the random-effects method of these studies, there was a statistically significant increase in the prevalence of HCV RNA positivity in males than females (0.25, log 95% CI 0.04–0.46) and the heterogeneity was high (T2 = 0.05, I2 = 78.48, H2 = 4.65, p value = 0.02) as shown in Fig. 3.

Figure 3
figure 3

Forest plot of prevalence of HCV RNA in males and females. There is statistically significant increase in prevalence of HCV RNA positivity in males than females.

Full size image

Subgroup analysis of gender differences

Children versus adults

In children, there were no statistically significant differences in the seroprevalence of HCV antibodies or prevalence of PCR positivity (Figs. 4, 5).

Figure 4
figure 4

Forest plot of seroprevalence of HCV antibodies in males and females in children. There is no significant difference between males and females in HCV antibodies prevalence.

Full size image
Figure 5
figure 5

Forest plot of prevalence of HCV RNA in males and females in children. There is no significant difference between males and females in HCV RNA prevalence in children.

Full size image

In adults, there were no significant differences in the seroprevalence of HCV antibodies between males and females. At the same time, HCV PCR testing showed a significant increase in the male prevalence of HCV PCR positivity to females (0.31, log 95% CI 0.07–0.56), and the heterogeneity was high (T2 = 0.07, I2 = 84.32, H2 = 6.38, p value = 0.01) (Figs. 6, 7).

Figure 6
figure 6

Forest plot of seroprevalence of HCV antibodies in males and females in adults. There is no significant difference in seroprevalence of HCV antibodies between males and females in adults.

Full size image
Figure 7
figure 7

Forest plot of prevalence of HCV RNA in males and females in adults. There is statistically significant increase in prevalence of HCV RNA in males than females in adults.

Full size image

General population

By studying gender prevalence differences in studies conducted on the general population (with no risk factors) after excluding studies on high-risk groups, males showed a significantly increased prevalence of both HCV antibodies and HCV PCR positivity (Supplementary Figs. 2, 3).

Discussion

Gender-based differences vary by country and region. This study presents a comprehensive update on HCV infection gender differences in Egypt. Despite the historic large-scale epidemic in Egypt, HCV antibody incidence and prevalence appear to decline rapidly, consistent with a contracting epidemic. In 2006, the national treatment strategy for the control of HCV infection in Egypt was established in response to the magnitude of the HCV problem and the disease burden in Egypt45.

Egypt is the country with the highest HCV prevalence worldwide. Six percent of individuals aged 1–59 years had a positive result on the hepatitis C antibody test, and 4% were found to have an active infection. The prevalence of hepatitis C was higher among men than women in most age groups8. This finding agreed with the results of this meta-analysis in all studies conducted on the general population (26 studies).

There is limited published data on gender-based differences in children46. The worldwide pooled seroprevalence of HCV in children in these studies was low, < 1%47. In 2015, the Egyptian Demographic and Health Surveys (EDHS) tested 10,044 children (5154 male and 4890 female) to estimate HCV prevalence in those aged 1–14. The results showed that HCV prevalence in the group aged < 15 years was 0.4%. HCV antibody seroprevalence was 0.7% with viremia of 0.2% in male children, while HCV antibody was seroprevalent in 0.2% with the presence of viremia in 0.1% of female children10. The current meta-analysis shows no significant differences between male and female children in HCV antibody prevalence or viremia.

The EDHS reported that seroprevalence of HCV antibodies was 14.7% among the adult population aged 15–59 years at 14.7% with a national viremic prevalence of 9.7%, which was higher in males than in females in all studied age groups in 200848. Similarly, the results of this meta-analysis showed that the prevalence of HCV viremia was significantly higher in males than females in adults. This difference may be attributed to males being more affected by schistosomiasis disease burden and hence were the main target of the parenteral antischistosomal therapy (PAT) campaign49 with high risk for parenteral virus transmission, including HCV. Also, the lifestyle of males makes them more exposed to various risk factors for HCV transmission50.

In 2015, there was significantly lower HCV prevalence in those aged 15–19 years compared to the 2008 data (14%), and this points to a significant decrease in new infections in the age groups 15–19 years51. Total HCV seroprevalence in the age groups 15–59 years was 10%, with a viremic prevalence of 7%. HCV seroprevalence in female adults was 8.1%, with viremia of 5.5%, while HCV seroprevalence in male adults was 12.4%, with a viremic prevalence of 9.8%8.

Study limitations

There were not enough data from the included studies to determine the sources of heterogeneity. It may be due to differences in populations, regions, geographical locations, seasons, settings (rural or urban), and used screening methods. Unmeasured covariates (such as population characteristics, presence of comorbidities, HIV status, etc.) could have contributed to variability in outcome estimates. Gender differences among high-risk populations (e.g., healthcare workers, drug users, incarcerated populations, people living with HIV, etc.) were not considered in this study to avoid overestimating the problem.

Conclusion

HCV RNA positivity is significantly higher in males than females in adults, while there are no gender differences in children.