Prevalence of Hepatitis C Virus Infection among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis

Background Hepatitis C virus infection during pregnancy is associated with a high risk of maternal complications and poor birth outcomes. There are variable reports on the prevalence of hepatitis C virus infection among pregnant women in Ethiopia. Therefore, this study aims to estimate the pooled prevalence of hepatitis C virus infection among pregnant women in Ethiopia. Methods A comprehensive search of electronic databases including PubMed, Scopus, EMBASE, the Cochrane Library, Web of Sciences, and Google Scholar was conducted from April 03, 2020, to May 03, 2020. The quality of included article was evaluated by the JBI. Heterogeneity between the studies was assessed using Cochrane Q and I2 test. The presence of publication bias was tested by funnel plots and Egger's test. A random-effects meta-analysis was computed to determine the pooled prevalence of HCV infection among pregnant women. Results Of 502 studies, 6 studies with a total of 2117 pregnant women were included in the meta-analysis. The overall pooled prevalence of hepatitis C virus infection among pregnant women in Ethiopia was 1.83% (95% CI: 0.61, 3.06). Besides, subgroup analysis revealed that the highest HCV prevalence among pregnant women was observed in Oromia region, 5.10% (95% CI: −0.53, 10.73). Conclusions This study shows an intermediate level of HCV infection among pregnant women in Ethiopia. The finding suggests the need of implementing a routine hepatitis C virus screening program for all pregnant women, which enables women to access HCV antiviral treatment to minimize vertical transmission to the newborn infants. Moreover, national and regional health programs should mandate and monitor the screening procedures so as to reduce the risk of hepatitis C virus infection.


Background
Hepatitis C infection is an emerging worldwide public health concern affecting millions of people each year [1,2]. Hepatitis C virus (HCV) is the etiology of hepatitis C infection that can cause acute and chronic hepatitis and potentially lead to the development of cirrhosis, liver cancer, or death of infected patients [2,3].
According to World Health Organization (WHO) global health impact report of viral hepatitis, about 130 to 150 million people were affected by chronic HCV infection globally, reaching endemic proportions in sub-Saharan Africa (SSA). It is also estimated to result in 350,000 to 500,000 deaths annually [4]. e WHO estimates, about 3-4 million peoples are infected each year with most of the cases occurring in Africa [5,6]. Another evidence also indicated that an estimated 71.1 million people are infected with HCV worldwide [3]. In most African countries, HCV remains underdiagnosed and underreported even it is highly infectious [7]. e prevalence of maternal HCV infection during pregnancy ranged from 1 to 8% worldwide [8]. us, the prevention of HCV vertical transmission is very important [9]. Like other routes such as intravenous drug use or blood product transfusion, transmission during sexual, HCV can be transmitted during delivery [4,10]. e transmission of HCV from mother to child ranged from 4 to 8% [9].
Maternal HCV infection during pregnancy is associated with a high risk of maternal complications including preterm delivery, placental separation, vaginal bleeding, premature rupture of membranes, and mortality [11,12]. It is also associated with a high risk of neonatal hepatitis that can lead to liver cirrhosis and hepatocellular carcinoma in young adults [13,14]. Furthermore, infants born to women with hepatitis C infection are at risk of poor birth outcomes, including low birth weight, preterm birth, and congenital anomaly [15].
In the health system of Ethiopia, the health burden due to viral hepatitis, in general, is still given less [16,17]. ough viral hepatitis screening is recommended during routine antenatal care (ANC), regular antenatal screening of pregnant women is not common and obligatory in Ethiopia [18]. Recent findings revealed that low awareness of the hepatitis virus was reported in both the general population and healthcare professionals [16,19].
In the control of vertical transmission of HCV disease, estimating its prevalence among pregnant women is very important. ere are variable reports on the prevalence of HCV infection among pregnant women in Ethiopia; however, the variations have not been examined systematically. Moreover, there was not a nationwide study assessing the pooled prevalence of HCV infection among pregnant women. is study aims to estimate the pooled prevalence of HCV infection among pregnant women based on the available studies using systematic review and meta-analysis methods. e findings of this meta-analysis will help policymakers and other concerned bodies to provide a quantified estimate of the problem as a step toward a better understanding of the HCV epidemiology, identify gaps in HCV screening during ANC, and plan strategies to increase awareness of the general population and healthcare workers regarding the epidemiology of HCV.

Study Design and Setting.
A systematic review and metaanalysis was conducted to estimate the prevalence of HCV during pregnancy in Ethiopia. is review was conducted in Ethiopia which is found in the Horn of Africa. e country covers an area of 1, 100,000 km 2 and divided into 9 regions, namely, Tigray, Afar, Amhara, Oromia, Somali, Benishangul-Gumuz, Southern Nations Nationalities and People Region (SNNPR), Gambella, Harari, and two Administrative states (Addis Ababa city administration and Dire Dawa city administration). Currently, the population of Ethiopia is estimated to be more than 112 million [20]. In Ethiopia, there are no established programs and strategies for the vaccination of children, pregnant women, health professionals, and the general population against HCV infection. Antenatal screening for HCV to all pregnant women and vaccination of their babies at birth is recommended.

Search Strategy and Information Sources.
e search was focused on the prevalence of HCV during pregnancy in Ethiopia and carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [21]. To find studies conducted on the prevalence of HCV infection among pregnant women, systematic literature searches were conducted on PubMed, Scopus, EMBASE, the Cochrane Library, Web of Sciences, Directory of Open Access Journal, and Google scholar. e search was conducted from April 03, 2020, to May 03, 2020.

Study Selection.
During the advanced search, articles/ documents were downloaded into Endnote software version 7 × 2.1 to manage references. After excluding duplicates, titles and abstracts and full texts of the remained papers were screened to determine the relevance of the studies. e PRISMA flow diagram was used to summarize the study selection processes [22].

Exclusion Criteria.
Before exclusion, the titles, abstracts, and full texts of the studies were cautiously reviewed for eligibility. Articles that did not clearly report the prevalence of HCV among pregnant women in Ethiopia were excluded. In addition, articles published in languages other than English and outside Ethiopia were excluded. Review, case reports, editorials or commentaries, and case studies were also excluded.

Data Extraction.
Data were extracted using a standardized data extraction tool adapted from Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instruments [23]. All necessary data such as the name of the first author, year of study, year of publication, geographic region, study design, study setting, sample size, study population, serological evidence of HCV, absolute numbers of HCV infected pregnant women, and prevalence of HCV were extracted. en, all data were inserted into the data extraction template of Microsoft Office Excel 2013.

Methodological Quality of Studies.
e overall quality of all included studies was assessed using a critical appraisal checklist for observational studies adopted from JBI [23]. Full-text articles were reviewed for the following criteria: addressing the target population, adequacy of sample size, sampling methods, study population, data collection methods, definition of the variables and method of dealing with samples, data collection tools, statistical analysis tests, study objectives, illustration of the results, and presentation of the findings based on the objectives and adequacy of response rate. Each question was assigned one score with the possible range of scores being 0-8. e JBI criteria for assessing the quality of primary studies recommend including primary studies that scored ≥60% of methodological checklists in the meta-analysis.
us, all included studies were scored ≥80%.

Outcome Measures.
e main outcome required for the final meta-analysis was the "prevalence of HCV among pregnant women in Ethiopia." e prevalence was calculated by dividing the number of pregnant women with confirmed HCV infection by the total number of pregnant women who have been included in the study (sample size) multiplied by 100.

Data Synthesis and Analysis.
Data were analyzed using statistical software STATA version 11. To summarize the selected studies, tables and figures were used. e overall pooled prevalence of HCV among pregnant women was estimated using a random-effects meta-analysis. A randomeffects meta-analysis model was used to minimize the random variations between the point estimates of the primary studies since heterogeneity was exhibited. Point prevalence as well as their 95% confidence intervals (CI) was exemplified by forest plots. e degree of heterogeneity among the results of the selected studies was detected using the Cochrane test (Q) and I 2 indicator [24]. To determine the possible reasons for substantial heterogeneity, subgroup analyses were conducted by geographical location (region) where the primary studies were conducted. ough the funnel plot and Egger's test are less reliable when the number of studies is less than ten, visual inspection of the asymmetry in funnel plots and Egger test were served to assess the presence of publication bias, with p value less than 0.05 indicating significant publication bias [25].

Study Selection.
In the search of the literature, 502 potential studies were identified. Of these, 104 were duplicates and were removed. After screening the titles and abstracts, 347 irrelevant studies were excluded from the meta-analysis. Consequently, only 51 articles were considered for full-text review. After full-text review, 45 articles were removed: studies with no quantitative measures of hepatitis C virus in pregnant women; studies that were not conducted in Ethiopia; studies that provided combined HCV and hepatitis B virus prevalence; studies that did not meet the eligibility criteria. Finally, 6 articles were identified as eligible for meta-analysis. e overall selection process of studies was undertaken according to PRISMA flow diagram (Figure 1).

Study Characteristics.
Five primary studies that fulfilled the eligibility criteria were institutional-based cross-sectional studies and one was community-based cross-sectional. e studies were conducted from 2013 to 2017 and published from 2014 to 2019. e sample size among studies ranged from the smallest 222 [26] to the largest 455 [27]. e majority of the studies (n � 4) used random sampling methods whereas 2 studies used convenient sampling methods. e highest prevalence of HCV infection among pregnant women (8.08%) was reported in East Wollega Zone [28] while the lowest prevalence (0.26%) was reported from a study done in Felege Hiwot referral hospital [19]. Most of the included studies (4 out of 6) measured the prevalence of hepatitis C virus infection using the rapid test and the other 2 studies using the enzyme-linked immunosorbent assay (ELISA) test. After reviewing the methodological quality of the studies, 4 were deemed to be of good quality and 2 of medium quality, and no article was found with poor quality.

Quality Assessment.
e quality of each study included in this systematic review and meta-analysis was critically evaluated using a critical appraisal checklist for observational studies adopted from the Joanna Briggs Institute (JBI). Four of the studies (66.7%) scored ≥7 "yes" out of 8 on the quality assessment scale which is ≥87.5% and determined to be of high quality. Two of the studies (33.3%) were demeaned moderate quality as they scored 6 "yes" out of 8 on the quality scale assessment which is 75% (Table 2).

Prevalence of HCV Infection among Pregnant Women.
In the current meta-analysis, a total of 2117 pregnant women were involved. e overall pooled prevalence of HCV infection among pregnant women in Ethiopia was 1.83% (95% CI: 0.61, 3.06). e I 2 statistics for HCV infection among pregnant women was I 2 � 87.4% (p < 0.001) which indicates the presence of significant heterogeneity among the included studies. Hence, a random effect metaanalysis model was used to estimate the pooled prevalence of HCV infection among pregnant women in Ethiopia (Figure 2).
A metaregression analysis was done based on the categorical variables including sample size, year of publication, quality of included paper, and screening methods that primary studies have used. Accordingly, the analysis shows that all the variables included in the metaregression analysis had no significant effect on the pooled prevalence of HCV infection among pregnant women in Ethiopia (Table 3).

Subgroup Analysis.
Since this meta-analysis exhibited considerable heterogeneity, subgroup analysis was done using regions (where the studies were conducted) to identify the possible sources of heterogeneity among the studies. e subgroup analysis indicated that the heterogeneity level was the highest among pregnant women (I 2 � 92.9%) in Oromia    Advances in Preventive Medicine region. Furthermore, the pooled estimate of subgroup analysis revealed that the prevalence of HCV among pregnant women was the highest (5.10%) in Oromia region, compared with 0.44% in Amhara and 1.80% in SNNPR ( Figure 3).

Publication Bias.
Publication bias among the included studies for this meta-analysis was checked using visual inspection of the shape funnel plots and statistical Egger's test. e result of the tests revealed no evidence of publication bias according to Egger's test (p � 0.017) and symmetrical shape of funnel plots (Figure 4).

Discussion.
e current systematic review and metaanalysis aimed to estimate the pooled prevalence of HCV infection among pregnant women in Ethiopia. e evidence obtained from this study may help healthcare workers and other concerned bodies to identify gaps in HCV screening during ANC; improve knowledge on the epidemiology of HCV infection among pregnant women in Ethiopia; and increase awareness of the general population regarding the epidemiology of HCV.
In this systematic review and meta-analysis, the prevalence of HCV infection among pregnant women in Ethiopia is close to the WHO endemicity definition of HCV infection [7]. is finding implies, first, the need of evaluating the knowledge, skill, and readiness of healthcare workers on HCV screening of pregnant women during routine antenatal care. is may be attributed to the low awareness of the service provider at the service delivery level. Studies showed low awareness of hepatitis virus was reported in healthcare professionals [16,19]. Second, though the health system policy focuses on early detection of disease and complications during pregnancy as an element of focused antenatal care, this study indicates the need of evaluating its effectiveness. is may be attributed to less attention given to the health burden of viral hepatitis by the health system of Ethiopia. ird, due attention should be given to pregnant women so as to prevent the transmission of HCV to their newborns. us, screening of apparently healthy pregnant women can prevent the transmission and the complications HCV [8,31].
e overall pooled prevalence of HCV infection among pregnant women in Ethiopia was 1.83% (95% CI: 0.61, 3.06). Although there was no comparable meta-analysis study conducted on this specific research question, this finding is consistent with WHO intermediate definition of HCV infection (1.5%-3.5%) [7] and prevalence of HCV (3.1%) in Ethiopia estimated by a systematic review and meta-analysis  conducted on hepatitis viruses in Ethiopia [17]. is may indicate the risk of HCV infection among pregnant women is comparable with the risk of the general population. e intermediate level of HCV infection should also act as a major alert for decision and policymakers in the Ethiopian health sector. e present study covers three regions of Ethiopia. e result revealed that the prevalence of HCV among pregnant women was the highest (5.10%) in Oromia region, compared with 0.44% in Amhara and 1.80% in SNNPR. is prevalence variation in different regions of Ethiopia could be due to differences in sample size, sampling method, and screening service and difference in the efficiency of diagnostic kits used. Moreover, the variation might be due to the difference in behavioral characteristics of the study participants including sexual practices, medical exposure for the potential risk factors of HCV infection, and level of awareness and differences in cultural practices.

Limitations of the Study.
e prevalence estimates in this meta-analysis are likely to show the current situation of HCV infection among pregnant women in Ethiopia because the included studies were conducted in more recent years. e introduction of language bias is expected as articles published only in the English language were included. In addition, the heterogeneity across selected studies was high, but important sources of heterogeneity were not fully addressed. Subsequently, the question about the methodological rigor of the review may raise as the review process was conducted with a single author. Selection bias in the estimation of community prevalence may be introduced as many of the studies included in the meta-analysis recruited participants from the referral hospitals. Moreover, this metaanalysis represented only studies reported from three regions of Ethiopia, which could affect the estimated prevalence reported and its representatives.

Conclusion
is systematic review and meta-analysis confirmed the intermediate level of HCV infection among pregnant women in Ethiopia. e finding of this study suggests the need to implement a routine and universal HCV screening program for all pregnant women, which enables women to access HCV antiviral treatment to minimize vertical transmission to newborn infants. Moreover, national and