The effect of Hepatitis B Viral Infection on Hemostatic Profile and Liver markers in Ghanaian Pregnant Women

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Abstract Background Viral hepatitis has been associated with profound alterations in the coagulation system as well as liver biomarkers. Meanwhile, during pregnancy, the coagulation system also undergoes significant changes with an increase in the majority of the clotting factors and a decrease in natural anticoagulants. This study aimed to evaluate the coagulation profile and liver biomarkers among hepatitis B-infected pregnant women in a Ghanaian population. Methods This case-control study was conducted with 90 hepatitis B pregnant women as cases and 90 hepatitis B negative pregnant women as controls. A structured questionnaire was used to obtain sociodemographic, obstetric, and clinical data from each participant. Results Levels of albumin, Fibrinogen [4.09 (3.57–5.94) vs. 6.89 (5.43–9.08), p < 0.0001], Protein C [2.46 (1.09–3.42) vs. 4.12 (2.96–6.07), p < 0.0001], and Protein S [2.61 (2.20–3.36) vs. 2.98 (2.53–3.54), p = 0.036] were significantly reduced in the hepatitis B positive pregnant women than the negative controls. However, there was high levels of AST, ALP and bilirubins in hepatitis B positive pregnant women than the controls. Also, Protein C and Protein S had significantly positive association with PT and aPTT, whereby a rise in Protein C and Protein S, resulted in an increasing PT and aPTT respectively (all p-value < 0.05). Conversely, albumin had a negative correlation with both PT and aPTT (p-value < 0.05). In a ROC analysis, aPTT had the highest area under the curve (AUC) value (AUC = 0.881) and the optimal clotting time at which aPTT indicated chronic hepatitis B was ≥ 35.7secs with sensitivity of 79.4% and specificity of 91.6%. Conclusion Pregnant women with hepatitis B infection present with significant changes in their coagulation parameters, natural anticoagulants and liver biomarkers. Furthermore, Fibrinogen, Protein C, and aPTT showed accurate diagnostic potential in identifying chronic viral hepatitis B infection and may be valuable surrogate indicators for managing chronic hepatitis-related complications.
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The effect of Hepatitis B Viral Infection on Hemostatic Profile and Liver markers in Ghanaian Pregnant Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effect of Hepatitis B Viral Infection on Hemostatic Profile and Liver markers in Ghanaian Pregnant Women Abiba Alhassan Khalifah, Wina Ivy Ofori Boadu, Francis Agyei Amponsah, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7849679/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Viral hepatitis has been associated with profound alterations in the coagulation system as well as liver biomarkers. Meanwhile, during pregnancy, the coagulation system also undergoes significant changes with an increase in the majority of the clotting factors and a decrease in natural anticoagulants. This study aimed to evaluate the coagulation profile and liver biomarkers among hepatitis B-infected pregnant women in a Ghanaian population. Methods This case-control study was conducted with 90 hepatitis B pregnant women as cases and 90 hepatitis B negative pregnant women as controls. A structured questionnaire was used to obtain sociodemographic, obstetric, and clinical data from each participant. Results Levels of albumin, Fibrinogen [4.09 (3.57–5.94) vs. 6.89 (5.43–9.08), p < 0.0001], Protein C [2.46 (1.09–3.42) vs. 4.12 (2.96–6.07), p < 0.0001], and Protein S [2.61 (2.20–3.36) vs. 2.98 (2.53–3.54), p = 0.036] were significantly reduced in the hepatitis B positive pregnant women than the negative controls. However, there was high levels of AST, ALP and bilirubins in hepatitis B positive pregnant women than the controls. Also, Protein C and Protein S had significantly positive association with PT and aPTT, whereby a rise in Protein C and Protein S, resulted in an increasing PT and aPTT respectively (all p-value < 0.05). Conversely, albumin had a negative correlation with both PT and aPTT (p-value < 0.05). In a ROC analysis, aPTT had the highest area under the curve (AUC) value (AUC = 0.881) and the optimal clotting time at which aPTT indicated chronic hepatitis B was ≥ 35.7secs with sensitivity of 79.4% and specificity of 91.6%. Conclusion Pregnant women with hepatitis B infection present with significant changes in their coagulation parameters, natural anticoagulants and liver biomarkers. Furthermore, Fibrinogen, Protein C, and aPTT showed accurate diagnostic potential in identifying chronic viral hepatitis B infection and may be valuable surrogate indicators for managing chronic hepatitis-related complications. Hematology Infectious Diseases Hepatitis B Fibrinogen Protein C Protein S PT aPTT Liver enzymes Albumin Bilirubin Pregnancy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Viral hepatitis is a critical global health issue, with infected patients facing a substantial risk of morbidity and mortality. The two most common hepatotropic viruses that cause chronic hepatitis are hepatitis B and C viruses, infecting more than 360 million people globally, with over one million death ( 1 ). In 2020, the African region represented 26% of worldwide hepatitis B and C cases and caused 125,000 related fatalities, as per the WHO ( 2 ). Ghana faces hyperendemic hepatitis B viral (HBV) infection, with estimated prevalence ranging from 8.36% (2020) to 12.30% (2016). A recent systematic review reported 7.4% as HBV prevalence in pregnant women ( 3 ). Transmission of HBV from infected mothers to their newborns, during pregnancy or childbirth, plays a significant role in sustaining the pool of chronically infected individuals worldwide ( 4 ). The liver synthesizes vital proteins for both coagulation (procoagulants) and anti-coagulation purposes ( 5 ). In the advent of chronic HBV infection, there is activation of hepatic stellate cells, resulting in the replacement of healthy hepatic parenchyma with excess extracellular matrix, termed as liver fibrosis, which can advance to a more severe form known as cirrhosis ( 6 ). Because the liver is so central in the coagulation process, patients with liver fibrosis and cirrhosis display some profound changes in the components of the coagulation cascade ( 7 ). Levels of procoagulant proteins such as fibrinogen and others are decreased, with a concomitant decrease in anticoagulant proteins such as protein C and protein S in liver fibrosis and cirrhosis subjects. This causes a state of delicate hemostatic balance, which increases the risk of such patients to bleeding or thrombosis ( 7 ). Studies have also reported prolongation of prothrombin time (PT), International normalized ratio (INR) and activated partial thromboplastin time (aPTT) following viral hepatitis with dysfibrinogenemia and thrombocytopenia ( 8 ). This is because of the loss of the integrity of both the extrinsic pathway of coagulation and the factors of the common pathway. And the degree of prolongation of this clotting time has been suggested to correlate to the degree of deficiency or inhibition of extrinsic or common pathway clotting factors, hence the severity of the liver disease ( 6 ). Normally during pregnancy, changes are often seen in the hepatic biochemical profile. Usually, there is elevation in the level of serum ALP, and this elevation may be up to 2–4 times the normal baseline level. This is because the placenta produces additional ALP during pregnancy, while the serum albumin usually drops, and this is attributed to the total plasma volume. However, the serum levels of AST, ALT, and bilirubin usually remain normal, and any elevation seen may be attributed to a liver condition ( 9 ). AST and ALT are often released into the bloodstream once there is hepatocellular damage, so AST and ALT serum level elevation correlate more with hepatic injury ( 10 ). Several studies have reported an increased risk for adverse pregnancy outcomes in pregnancies associated with maternal HBV infection ( 11 ). Hepatitis B viral infection has also been linked to elevated levels of liver function test markers as well as significant alterations in the proteins of the coagulation cascade( 7 ). Pregnancy also predisposes a woman into a hypercoagulable state, and therefore, a pregnant woman coupled with HBV infection can be at a much greater risk for liver markers and coagulation abnormalities( 12 , 13 ). In Ghana, although a positive HBV carrier status is common among pregnant women, little is known about the impact of the infection on their liver markers and hemostatic profile. Therefore, this study sought to determine hepatitis B infection’s impact on fibrinogen, protein C, protein S levels and liver markers in pregnant women. Materials and Methods Study Site This research was carried out at Afrancho Polyclinic in the Afigya Kwabre South District, Ashanti Region, Ghana. The district lies in the center of the Ashanti Region and covers about 159 km 2 area. Its proximity to urbanized Kumasi drives rapid population growth, transforming the district into a vibrant dormitory area with thriving settlements. According to the 2021 population census by the Ghana Statistical Service, the district has a total population of about 234,000. Afrancho Polyclinic offers a wide range of medical services which are categorized under units and departments such as; antenatal clinic, emergency unit, laboratory department, eye clinic, theatre unit, labor unit, mental health department, disease control unit, out-patient department, medical imaging, and others. Ethical Consideration and Informed Consent Ethical approval was obtained from the Committee on Human Research, Publication and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology (CHRPE/AP/834/22), as well as the management of Afrancho Polyclinic. The ethical approval was fixed for one year from 19th December, 2022 to 18th December, 2023. Also, both oral and written consent from all participants was obtained before their recruitment. All participants had the age to consent. Study Design and Sample Size This hospital-based case-control study was carried out from January 2022 to July 2023. Based on the HBV prevalence in Ghanaian pregnant women (6.0% by Antuamwine et al. ( 14 )), we recruited a total of hundred and eighty (180) subjects. Ninety (90) Hepatitis B-positive subjects were selected as cases and ninety (90) Hepatitis B negative subjects served as controls. Cochran’s formula was used to estimate sample size. The above subjects were pregnant women visiting the antenatal clinic at different stages of gestation and were between the ages of 18 and 45 years. Sociodemographic data were obtained with a standardized questionnaire. Their clinical history and obstetric information were also obtained from their antenatal folder. Subject Criteria Pregnant women enrolled as cases were purposively selected after being screened and found to be reactive to hepatitis B virus using the rapid chromatographic method. The control group were also selected after they were found to be non-reactive to HBV and any other viral infection. Exclusion Criteria For the cases, pregnant women showing any underlying chronic illness such as diabetes mellitus, tuberculosis, cardiovascular or any other clinical condition other than hepatitis B infection were excluded from the study. Under the control group, pregnant women who were reactive to HBV, HCV, HIV and Syphilis or any other clinical condition were also excluded. Sample Collection Each subject's venous blood (8ml) was aseptically collected via the standard vacutainer system. About 4ml was dispensed into a citrated anticoagulant bottle and gently mixed properly. 2ml was dispensed into a gel tube for Liver Function Test (LFT), and the remaining 2ml dispensed into an EDTA tube for full blood count. The citrated blood samples were immediately spun (2000rpm for 20 mins). Thereafter, portions of the platelet-poor plasma (PPP) were aliquoted and stored at -80℃ for later analysis of Fibrinogen, Protein C and Protein S. Prothrombin time (PT) and activated Partial Thromboplastin time (aPTT) were run the same day with the remaining platelet-poor plasma. The gel tube blood sample was centrifuged once clotted and the serum used for the LFT. Laboratory Investigations All reagents and test kits were purchased from reputable companies whose standard operating procedures were strictly followed. Full blood count was done with the Sysmex KX-21N hematology analyzer (Sysmex Corporation, Japan). The hepatitis B profile status of the cases (HBsAg-positive) was ascertained using an HBV-5 in 1 Combo Rapid diagnostic Test from Smartcare™, China. This HBV 5-parameter Rapid Test Kit is a lateral flow chromatographic immunoassay for the qualitative detection of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in human serum/plasma. The PT and APTT were assessed by the manual method with reagents from Fortress Diagnostics Limited, UK. Fibrinogen, Protein C, and Protein S concentrations were measured by a solid-phase Sandwich ELISA technique, with reagents from Melson Shanghai Chemical Limited, China, and the manufacturer’s instructions were strictly adhered to. The liver function tests were run using Sinnowa semi-automated chemistry analyzer, with reagents from Fortress Diagnostics, UK. Concentrations of liver parameters such as liver enzymes [Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT)], bilirubin (total, direct, and indirect), total protein, albumin, and globulin were all estimated, with strict adherence to manufacturer’s protocol. Statistical Analysis Data was entered in Excel 2016, and SPSS v.26 was utilized for analysis. Categorical data were represented as counts and proportions and subjected to comparison using either Chi-squared or Fisher's exact test. Logistic regression was used to assess how the sociodemographic characteristics predict HBV infection. Normality check was performed using Kolmogorov-Smirnov test. We represented non-normally distributed data as median (interquartile range) and subjected them to comparison using Kruskal-Wallis test. Spearman correlation was utilized to determine the association of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S levels with PT or APTT among HBV-infected pregnant women. Receiver operating characteristics (ROC) curve of aPTT, PT, Fibrinogen, Protein C, Fibrinogen/Albumin ratio (FAR), albumin, and Protein S for detecting chronic viral hepatitis B infection were drawn and respective areas under the curve (AUC) values were estimated. P < 0.05 signified statistical significance. Results Sociodemographic characteristics among the study participants Age categories were evenly distributed (p = 0.456), with 47.2% among the control cohort and 52.8% among the HBV cohort aged 18–29. Marital status (p = 0.588), employment status (p = 0.465), residence (p = 0.709), religion (p = 0.594), ethnicity (p = 0.478), gravidity (p = 0.709), parity (p = 0.891), sickling status (p = 0.225), G6PD (p = 0.943), and blood group (p = 0.52) did not differ between the two cohorts. However, a few notable differences were observed. The HBV group had a slightly higher percentage of individuals who were cohabiting (48.5%) compared to the control group (41.9%). Additionally, higher percentages of the HBV group were self-employed (54.9% vs. 45.1%) and had tertiary education (64.3% vs. 35.7%). These differences, however, did not attain statistical significance (all p > 0.05). Alcohol consumption and contraceptive use were significantly related to HBV infection. The HBV group had a higher proportion of individuals who reported alcohol consumption (75.0% vs. 25.0%) and contraceptive use (60.0% vs. 40.0%) compared to controls. The crude odds ratio (cOR) for alcohol consumption was 3.3 (95% CI: 1.0-10.7), indicating a positive association. Similarly, the cOR for contraceptive use was 2.3 (95% CI: 1.2–4.1), suggesting an increased likelihood of HBV infection among contraceptive users ( Table 1 ). Table 1 Association between sociodemographic characteristics and hepatitis B infection Variable Controls (N = 90) HBV (N = 90) cOR (95% CI) p-value Age categories 0.456 18–29 42 (47.2) 47 (52.8) Ref (1) 30–42 48 (52.7) 43 (47.3) 1.2 (0.7–2.2) Marital status 0.588 Single 6 (50.0) 6 (50.0) Ref (1) Married 70 (51.5) 66 (48.5) 0.9 (0.3-3.0) Cohabiting 13 (41.9) 18 (48.5) 1.4 (0.4–5.30 Employment status 0.465 Unemployed 46 (53.5) 40 (46.5) Ref (1) Self-employed 37 (45.1) 45 (54.9) 1.4 (0.8–2.6) Formally employed 7 (58.3) 5 (41.7) 0.8 (0.2–2.8) Educational level 0.17 None 12 (41.4) 17 (58.6) 0.4 (0.1–1.2) Primary 15 (65.2) 8 (34.8) 0.9 (0.4–2.2) Junior 25 (43.9) 32 (56.1) 0.5 (0.2–1.3) Secondary 33 (57.9) 24 (42.1) 1.3 (0.3–4.8) Tertiary 5 (35.7) 9 (64.3) Ref (1) Residence 0.709 Periurban 19 (52.8) 17 (47.2) 0.9 (0.4–1.8) Urban 71 (49.3) 73 (50.7) Ref (1) Religion 0.594 Christianity 71 (51.1) 68 (48.9) 0.8 (0.4–1.7) Islam 19 (46.3) 22 (53.7) Ref (1) Ethnicity 0.478 Akans 51 (50.5) 50 (49.5) 0.6 (0.3–1.1) Ewe/Fante/Bono 4 (33.3) 8 (66.7) 0.5 (0.1–1.8) Northerners 35 (52.2) 32 (47.8) Ref (1) Gravidity 0.709 Primigravida 19 (52.8) 17 (47.2) 0.9 (0.4–1.8) Multigravida 71 (49.3) 73 (50.7) Ref (1) Parity 0.891 Nulliparous 22 (48.9) 23 (51.1) 1.0 (0.5–2.1) Primiparous 30 (52.6) 27 (47.4) 0.9 (0.4–1.7) Multiparous 38 (48.7) 40 (51.3) Ref (1) Smoking status 0.316 No 90 (50.3) 89 (49.7) Ref (1) Yes 0 (0.0) 1 (100.0) > 100 (0-inf) Alcohol consumption 0.036 No 86 (52.4) 78 (47.6) Ref (1) Yes 4 (25.0) 12 (75.0) 3.3 (1.0-10.7) Contraceptive use 0.007 No 54 (60.0) 36 (40.0) Ref (1) Yes 36 (40.0) 54 (60.0) 2.3 (1.2–4.1) Note: Data are shown as frequency and percentages; analyzed with Chi-squared/Fisher’s test and logistic regression. P < 0.05 signified statistical significance. Abbreviations: HBV: Hepatitis B viral infection; N: Number; cOR: crude odds ratio. Bold values show statistical significance. Liver function test markers among the study groups Serum levels of AST [36.4 (32.8–47.5) vs 30.7 (26.4–39.2), p = 0.014], ALP [155.4 (138.3-304.5) vs. 115.4 (105.2-141.9), p < 0.0001], total bilirubin [5.6 (2.7–6.3) vs. 1.3 (1.0-1.9), p < 0.0001], direct bilirubin [1.7 (1.0-2.5) vs. 0.5 (0.3–0.8), p < 0.0001], and indirect bilirubin [3.3 (1.6–4.5) vs. 0.9 (0.6–1.1), p < 0.0001] were markedly elevated among acute HBV infected pregnant women relative to the control women. Similarly, Serum levels of AST [37.3 (32.0-45.6) vs. 30.7 (26.4–39.2), p < 0.0001], ALP [132.4 (116.6-197.4) vs. 115.4 (105.2-141.9), p = 0.004], GGT [30.9 (24.5–37.6) vs. 27.2 (19.4–32.1), p = 0.007], total bilirubin [2.4 (1.8–4.3) vs. 1.3 (1.0-1.9), p < 0.0001], direct bilirubin [0.9 (0.6–1.8) vs. 0.5 (0.3–0.8), p < 0.0001], and indirect bilirubin [1.5 (1.1–2.5) vs. 0.9 (0.6–1.1), p 0.05). ( Table 2 ) Comparison of PT, aPTT, INR, and albumin among the study groups PT [17.5 (16.4–19.5) vs. 16.1 (15.0-18.4) vs. 14.1 (13.1–15.7), p < 0.0001] and INR [1.55 (1.42–1.78) vs. 1.38 (1.27–1.65) vs. 1.17 (1.06–1.34), p < 0.0001] were significantly raised among acute HBV, followed by those with chronic HBV and then the controls (HBV negative pregnant women). aPTT was significantly elevated in both acute and chronic HBV compared to the HBV-negative pregnant women (p 0.05). Moreover, albumin was significantly lower in both acute [31.0 (28.0–36.0) vs. 36.0 (31.0–39.0), p = 0.005] and chronic HBV [33.0 (29.0–37.0) vs. 36.0 (31.0–39.0), p = 0.036] relative to the HBV negative pregnant women but did not differ between the acute and chronic HBV group (p > 0.05) (Fig. 1 (A-D)) . Comparison of levels of fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S among the subjects Levels of fibrinogen [4.09 (3.57–5.94) vs. 6.89 (5.43–9.08), p < 0.0001], FAR [0.14 (0.11–0.20) vs. 0.19 (0.17–0.26), p = 0.002], and protein C [2.46 (1.09–3.42) vs. 4.12 (2.96–6.07), p < 0.0001] were significantly reduced among the acute relative to the HBV negative pregnant women. Again, fibrinogen [4.33 (3.60–5.20) vs. 6.89 (5.43–9.08), p < 0.001], FAR [0.13 (0.11–0.17) vs. 0.19 (0.17–0.26), p < 0.0001], and protein C [2.10 (1.45-3.00) vs 4.12 (2.96–6.07), p 0.05). Also, protein S [2.61 (2.20–3.36) vs. 2.98 (2.53–3.54), p = 0.036] was significantly reduced among the chronic HBV group relative to the control group but was similar between either the chronic and acute HBV or the acute and controls (Fig. 2 (E-H)). Association between the levels of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S, in comparison with prothrombin time (PT) and aPTT among HBV-infected pregnant women. In a multivariate linear regression model, increasing FAR (R = 0.288, p = 0.006) and protein C (R = 0.273, p = 0.009) were associated with a significant increase in prothrombin time (PT). However, in comparison with aPTT, these increments were not statistically significant. Meanwhile, protein S (R = 0.147, p = 0.046) was the only marker which had a positive and significant association with aPTT. In contrast, decreasing albumin (R = − 0.279, p = 0.008), (R = − 0.571, p < 0.001) was associated with significant increases in PT and aPTT respectively. (Fig. 3 (A-E) & Figure 4 (F-J) ). Receiver operating characteristics (ROC) curve of aPTT, PT, Fibrinogen, Protein C, Fibrinogen/Albumin ratio (FAR), albumin, and Protein S for detecting chronic viral hepatitis B infection In a ROC analysis, aPTT (AUC = 0.881), fibrinogen (AUC = 0.867), and protein C (AUC = 0.816) could detect chronic HBV with a very high area under the curve values. FAR (AUC = 0.793) and PT (AUC = 0.786) could also detect chronic HBV with high area under the curve. However, albumin (AUC = 0.615) and protein S (AUC = 0.593) could poorly detect chronic HBV. (Fig. 5 (A-B) ). Diagnostic performance of aPTT, PT, Fibrinogen, Protein C, FAR, albumin, and Protein S in identifying chronic viral hepatitis B infection. At a cutoff of ≥ 35.7 secs, aPTT was the best measure for detecting chronic HBV infection with a sensitivity of 79.4% and a specificity of 91.6%, whiles PT and fibrinogen were both highly sensitive (92.6% and 95%) but less specific (54.7% and 62.4%), respectively. However, Albumin and Protein S were less sensitive in detecting chronic viral hepatitis B infection ( Table 3 ) Table 3 Diagnostic performance of aPTT, PT, Fibrinogen, Protein C, FAR, albumin, and Protein S in identifying chronic viral hepatitis B infection. Parameters Cut-offs Sensitivity (%) Specificity (%) PPV (%) NPV (%) LR+ Accuracy aPTT ≥ 35.7 79.4 91.6 87.1 86.1 9.4 86.5 PT ≥ 14.5 92.6 54.7 59.4 91.2 2 70.6 Fibrinogen ≤ 6.17 95.6 62.4 65 95.1 2.5 76.4 Protein C ≤ 2.55 70.6 82.1 73.8 79.6 3.9 77.3 FAR ≤ 0.16 73.5 74.2 67.6 79.3 2.8 73.9 Albumin ≤ 33.0 58.8 64.2 54.1 68.5 1.6 62.0 Protein S ≤ 2.31 50.1 89.4 61.9 65.3 2.3 64.4 Abbreviations: PPV: Positive predictive value; NPV: Negative predictive value; LR+: Positive likelihood ratio; aPTT: activated partial thromboplastin time; PT: prothrombin time; FAR: Fibrinogen/Albumin ratio Discussion Viral hepatitis infection is a major risk factor for adverse fetal-maternal complications during pregnancy. Both the acute and chronic forms of viral hepatitis have been associated with impaired liver function thereby altering the hemostatic balance. Pregnancy also presents with physiological changes in the hemostatic balance resulting in a shift towards a state of increased blood clotting tendency. However, studies on coagulation disturbances in pregnant women with concurrent viral hepatitis B infection are lacking. Hence this study assessed the coagulation profile among hepatitis B-infected pregnant women in a Ghanaian population. As far as sociodemographic characteristics are concern; age, gender, marital status and employment status were similar among cases and controls which agrees with a study conducted by Anaedobe et al .( 15 ). However, alcohol consumption and contraceptive use were statistically different in the hepatitis B patients and controls. In addition to this revelation, the number of individuals who use contraceptives were high in the HBV group as compared to the controls, a similar trend was seen in a study done by Anaedobe et al .( 15 ). Bayo et al. and Onwuiri et al . reported that behavioural factors including risky sexual acts may be more prevalent among contraceptive users which indirectly increases the risk of transmission ( 16 , 17 ). Alcohol consumption has been shown to impair the function of the immune system and this may increase the susceptibility of consumers to infection ( 16 , 18 ). In this present study, the increased levels of AST, ALP, GGT, bilirubin (total, direct and indirect) and decreased levels of albumin were observed in the HBV-infected pregnant women compared to controls. These findings are consistent with previous studies conducted by Onwuiri et al . and Abulude et al. who showed that HBsAg seropositivity was associated with high prevalence of abnormal ALP, AST, total and direct bilirubin ( 10 , 17 ). In this study, HBV-infected pregnant women presented with prolonged PT, aPTT and INR compared to controls. This finding is consistent with previous studies by Olley et al. and Xu et al . which found increased values of these tests in HBV-infected patients compared to controls ( 19 , 20 ). Studies have reported that viral liver infection results in the production of tumour necrosis factor (TNF), which contributes to liver pathology and which can lead to impaired liver synthetic function ( 21 – 23 ). This leads to a decrease in the procoagulant factors of both the intrinsic and extrinsic pathways, which disrupts the coagulation cascade and prolongs the test times ( 24 , 25 ). The levels of fibrinogen were decreased in both chronic and acute viral infections compared to controls. This finding is similar to reports by Xu et al .( 20 ) who found decreased levels of fibrinogen in HBV positive patients compared to controls. Fibrinogen is primarily synthesized in the liver and as a positive phase reactant protein, it levels rise during inflammation ( 26 ). Physiological changes in pregnancy also lead to an increase in the levels of fibrinogen levels ( 27 , 28 ). Nonetheless, hepatitis B infection results in an impaired synthetic function of the liver, leading to decrease fibrinogen levels ( 29 ). Moreover, the level of FAR was decreased in both the hepatitis groups than controls. Albumin likewise fibrinogen is mainly synthesized in the liver, hence its dysfunction decreases the levels of these markers. This is inconsistent with previous studies that showed that elevated levels of FAR can serve as a valuable predictor of severity and likelihood of death of various clinical conditions, including cancer, cardiovascular diseases, and cerebrovascular disorders ( 30 – 32 ). Both protein C and protein S serves as natural anticoagulant and like the above, are primarily synthesized in the liver, hence a dysfunctional liver impairs it synthesis. In our study, protein C levels were decreased in pregnant women with chronic and acute infection compared to controls, whiles protein S was only decreased in women with chronic viral hepatitis. Previous studies have reported decreased protein C levels in hepatitis positive-patients compared to controls which is consistent to our study ( 33 , 34 ). In contrast, Güven et al .( 35 ) observed comparable protein C and protein S levels in patients with chronic hepatitis compared to controls. These inconsistencies may be explained by the differences in sample size and study population. In the regression analysis, Fibrinogen levels did not show any significant association with both PT and aPTT. In contrast, a previous study by Leticia et al .( 6 ) showed a statistically significant positive relationship between serum fibrinogen levels and the coagulation test times, PT and aPTT. However, this study was conducted among hepatitis-infected blood donors while our study population employed pregnant women and this may account for the differences. Finally, the diagnostic performances of these coagulation indices in identifying chronic viral hepatitis B infection showed that, that aPTT, fibrinogen and protein C had excellent diagnostic accuracy for identifying chronic hepatitis B infection and thus may be valuable indicators for mitigating chronic hepatitis-related complications including cirrhosis, hepatocellular carcinoma and liver failure. PT and FAR also showed better diagnostic accuracy but were inferior to the above indices, whereas, protein S and Albumin showed the poorest diagnostic accuracy. Peng et al. ( 36 ) also observed that aPTT, PT and fibrinogen had high AUCs and were excellent indicators for early diagnosis of cirrhosis. The strength of this study is that, this is the first case-control study to have simultaneously assessed the hematobiochemical and coagulation profile among HBV-infected pregnant women. Notwithstanding the novel findings, this present study has limitations worth considering for future studies. Firstly, this study did not take into consideration the pregnancy stage, the use of conventional or nonconventional treatments, such as herbs or other interventions, or exposure of subjects to toxins at the workplace before the study as these factors can affect liver enzymes. Also, other coagulation markers including prothrombin fragment F1 and thrombin-anti-thrombin complexes were not assessed, as this could provide a better understanding of the coagulation system abnormalities. Lastly, this study was carried out at a single centre and may limit its generalizability to the entire Ghanaian population. Therefore, a multicentre study with a larger sample size is required Conclusion Pregnant women with HBV infection present with significant increases in liver function enzymes and bilirubin levels. Also, HBV causes significant changes in coagulation parameters and natural anticoagulants, however, these alterations are generally comparable in acute and chronic hepatitis B infection. aPTT, fibrinogen and protein C showed excellent diagnostic accuracy for identifying chronic hepatitis B viral-related infection and thus may be valuable supportive indicators in managing chronic hepatitis-related complications. The study therefore concludes that, pregnant women coupled with HBV infection have higher levels of liver biomarkers, prolonged PT and aPTT with reduced levels of Protein C, Protein S, and Fibrinogen. Implementing therapeutic strategies focused on preserving the functionality of the coagulation system can significantly improve supportive care for pregnant women with Hepatitis B virus. Declarations Acknowledgement We would like to present our gratitude to the entire lecturers in the Department of Medical Diagnostics at Kwame Nkrumah University of Science and Technology for their invaluable support. We would also like to extend our sincere gratitude to the Laboratory and entire staff of Afrancho Polyclinic for their enormous support in this research. Authors Contribution Conceptualization: A.A.K, W.I.O.B, E.O.A Data curation : A.A.K, W.I.O.B, A.A.A, S.T, D.A.A Formal analysis : J.F, S.T, A.A.A Investigation : A.A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A.A Methodology: A.A.K, W.I.O.B, E.O.A, ST, A.A.A Project administration : A.A.K, W.I.O.B, E.O.A Validation : A.A.K, W.I.O.B, E.O.A Visualization : A.A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A. Writing-original draft : A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A.A, E.A, A.N.B, D.N.M.A, E.O.A Writing-review, editing and approving: All authors Ethical Approval Statement Ethical approval was obtained from the Committee on Human Research, Publication and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology (CHRPE/AP/834/22), as well as the management of Afrancho Polyclinic. The ethical approval was fixed for one year from 19 th December, 2022 to 18 th December, 2023. Patient Consent Statement Both oral and written consent from all participants was obtained before their recruitment. All participants had the age to consent. Funding The author(s) received no financial support for the research, authorship and or/ publication of this article. Data Availability Statement Data and materials for study are available upon request from the corresponding authors. Consent for publication Not applicable. 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Study on correlation between coagulation indexes and disease progression in patients with cirrhosis. American journal of translational research. 2021;13(5):4614. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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09:04:52","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":132360,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/d6f94f5eee4c395cce2aa19d.html"},{"id":93571640,"identity":"e9992c41-59cd-4093-810c-dda83682aa93","added_by":"auto","created_at":"2025-10-15 09:04:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":194214,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A-D): Comparison of PT, aPTT, INR, and albumin among the study groups. \u003c/strong\u003e\u003cem\u003ePT: Prothrombin time; aPTT: Activated partial thromboplastin time; INR: international normalized ratio\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/3b2d58034921f93784e4b821.png"},{"id":93571641,"identity":"3c1af94c-2dd8-497c-ad1d-3bc465dd5c3f","added_by":"auto","created_at":"2025-10-15 09:04:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":166482,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(E-H): Comparison of levels of fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S among the subjects\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/ccdd4fd9b257204708607e33.png"},{"id":93571645,"identity":"389436b3-d81a-457c-86e4-70b1378d7019","added_by":"auto","created_at":"2025-10-15 09:04:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":305182,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A-E): Association between the levels of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, protein S and prothrombin time (PT) among HBV infected pregnant women\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/1c8fe10d2cb5a6414523189c.png"},{"id":93571642,"identity":"8f64ff5e-d12c-4bc8-95b0-591b3ea95cba","added_by":"auto","created_at":"2025-10-15 09:04:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":312820,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(F-J): Association between the levels of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, protein S and activated partial thromboplastin time (aPTT) among HBV infected pregnant women\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/c6f2f4c0089c700d27018373.png"},{"id":93573770,"identity":"6fa5c800-b8e7-4b91-bbfb-6607df7869d1","added_by":"auto","created_at":"2025-10-15 09:12:52","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":161205,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A-B): Receiver operating characteristics (ROC) curve of aPTT, PT, Fibrinogen, Protein C, FAR, Albumin and Protein S for detecting chronic viral hepatitis B infection\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/e50e48b85de174f9c4383dcc.png"},{"id":93574947,"identity":"61ed69ad-cd74-4979-a72c-bb07ead8f7b8","added_by":"auto","created_at":"2025-10-15 09:20:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2639269,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7849679/v1/dfbf23d3-6a32-4934-9d34-b76093091cb3.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eThe effect of Hepatitis B Viral Infection on Hemostatic Profile and Liver markers in Ghanaian Pregnant Women\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eViral hepatitis is a critical global health issue, with infected patients facing a substantial risk of morbidity and mortality. The two most common hepatotropic viruses that cause chronic hepatitis are hepatitis B and C viruses, infecting more than 360\u0026nbsp;million people globally, with over one million death (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2020, the African region represented 26% of worldwide hepatitis B and C cases and caused 125,000 related fatalities, as per the WHO (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Ghana faces hyperendemic hepatitis B viral (HBV) infection, with estimated prevalence ranging from 8.36% (2020) to 12.30% (2016). A recent systematic review reported 7.4% as HBV prevalence in pregnant women (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Transmission of HBV from infected mothers to their newborns, during pregnancy or childbirth, plays a significant role in sustaining the pool of chronically infected individuals worldwide (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe liver synthesizes vital proteins for both coagulation (procoagulants) and anti-coagulation purposes (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In the advent of chronic HBV infection, there is activation of hepatic stellate cells, resulting in the replacement of healthy hepatic parenchyma with excess extracellular matrix, termed as liver fibrosis, which can advance to a more severe form known as cirrhosis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBecause the liver is so central in the coagulation process, patients with liver fibrosis and cirrhosis display some profound changes in the components of the coagulation cascade (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Levels of procoagulant proteins such as fibrinogen and others are decreased, with a concomitant decrease in anticoagulant proteins such as protein C and protein S in liver fibrosis and cirrhosis subjects. This causes a state of delicate hemostatic balance, which increases the risk of such patients to bleeding or thrombosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eStudies have also reported prolongation of prothrombin time (PT), International normalized ratio (INR) and activated partial thromboplastin time (aPTT) following viral hepatitis with dysfibrinogenemia and thrombocytopenia (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This is because of the loss of the integrity of both the extrinsic pathway of coagulation and the factors of the common pathway. And the degree of prolongation of this clotting time has been suggested to correlate to the degree of deficiency or inhibition of extrinsic or common pathway clotting factors, hence the severity of the liver disease (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNormally during pregnancy, changes are often seen in the hepatic biochemical profile. Usually, there is elevation in the level of serum ALP, and this elevation may be up to 2\u0026ndash;4 times the normal baseline level. This is because the placenta produces additional ALP during pregnancy, while the serum albumin usually drops, and this is attributed to the total plasma volume. However, the serum levels of AST, ALT, and bilirubin usually remain normal, and any elevation seen may be attributed to a liver condition (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). AST and ALT are often released into the bloodstream once there is hepatocellular damage, so AST and ALT serum level elevation correlate more with hepatic injury (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSeveral studies have reported an increased risk for adverse pregnancy outcomes in pregnancies associated with maternal HBV infection (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Hepatitis B viral infection has also been linked to elevated levels of liver function test markers as well as significant alterations in the proteins of the coagulation cascade(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Pregnancy also predisposes a woman into a hypercoagulable state, and therefore, a pregnant woman coupled with HBV infection can be at a much greater risk for liver markers and coagulation abnormalities(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In Ghana, although a positive HBV carrier status is common among pregnant women, little is known about the impact of the infection on their liver markers and hemostatic profile. Therefore, this study sought to determine hepatitis B infection\u0026rsquo;s impact on fibrinogen, protein C, protein S levels and liver markers in pregnant women.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Site\u003c/h2\u003e\u003cp\u003eThis research was carried out at Afrancho Polyclinic in the Afigya Kwabre South District, Ashanti Region, Ghana. The district lies in the center of the Ashanti Region and covers about 159 km\u003csup\u003e2\u003c/sup\u003e area. Its proximity to urbanized Kumasi drives rapid population growth, transforming the district into a vibrant dormitory area with thriving settlements. According to the 2021 population census by the Ghana Statistical Service, the district has a total population of about 234,000. Afrancho Polyclinic offers a wide range of medical services which are categorized under units and departments such as; antenatal clinic, emergency unit, laboratory department, eye clinic, theatre unit, labor unit, mental health department, disease control unit, out-patient department, medical imaging, and others.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEthical Consideration and Informed Consent\u003c/h3\u003e\n\u003cp\u003eEthical approval was obtained from the Committee on Human Research, Publication and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology (CHRPE/AP/834/22), as well as the management of Afrancho Polyclinic. The ethical approval was fixed for one year from 19th December, 2022 to 18th December, 2023. Also, both oral and written consent from all participants was obtained before their recruitment. All participants had the age to consent.\u003c/p\u003e\u003c/p\u003e\n\u003ch3\u003eStudy Design and Sample Size\u003c/h3\u003e\n\u003cp\u003eThis hospital-based case-control study was carried out from January 2022 to July 2023. Based on the HBV prevalence in Ghanaian pregnant women (6.0% by Antuamwine et \u003cem\u003eal.\u003c/em\u003e (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)), we recruited a total of hundred and eighty (180) subjects. Ninety (90) Hepatitis B-positive subjects were selected as cases and ninety (90) Hepatitis B negative subjects served as controls. Cochran\u0026rsquo;s formula was used to estimate sample size. The above subjects were pregnant women visiting the antenatal clinic at different stages of gestation and were between the ages of 18 and 45 years. Sociodemographic data were obtained with a standardized questionnaire. Their clinical history and obstetric information were also obtained from their antenatal folder.\u003c/p\u003e\n\u003ch3\u003eSubject Criteria\u003c/h3\u003e\n\u003cp\u003ePregnant women enrolled as cases were purposively selected after being screened and found to be reactive to hepatitis B virus using the rapid chromatographic method. The control group were also selected after they were found to be non-reactive to HBV and any other viral infection.\u003c/p\u003e\n\u003ch3\u003eExclusion Criteria\u003c/h3\u003e\n\u003cp\u003eFor the cases, pregnant women showing any underlying chronic illness such as diabetes mellitus, tuberculosis, cardiovascular or any other clinical condition other than hepatitis B infection were excluded from the study. Under the control group, pregnant women who were reactive to HBV, HCV, HIV and Syphilis or any other clinical condition were also excluded.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSample Collection\u003c/h2\u003e\u003cp\u003eEach subject's venous blood (8ml) was aseptically collected via the standard vacutainer system. About 4ml was dispensed into a citrated anticoagulant bottle and gently mixed properly. 2ml was dispensed into a gel tube for Liver Function Test (LFT), and the remaining 2ml dispensed into an EDTA tube for full blood count. The citrated blood samples were immediately spun (2000rpm for 20 mins). Thereafter, portions of the platelet-poor plasma (PPP) were aliquoted and stored at -80℃ for later analysis of Fibrinogen, Protein C and Protein S. Prothrombin time (PT) and activated Partial Thromboplastin time (aPTT) were run the same day with the remaining platelet-poor plasma. The gel tube blood sample was centrifuged once clotted and the serum used for the LFT.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaboratory Investigations\u003c/h3\u003e\n\u003cp\u003eAll reagents and test kits were purchased from reputable companies whose standard operating procedures were strictly followed. Full blood count was done with the Sysmex KX-21N hematology analyzer (Sysmex Corporation, Japan). The hepatitis B profile status of the cases (HBsAg-positive) was ascertained using an HBV-5 in 1 Combo Rapid diagnostic Test from Smartcare\u0026trade;, China. This HBV 5-parameter Rapid Test Kit is a lateral flow chromatographic immunoassay for the qualitative detection of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in human serum/plasma. The PT and APTT were assessed by the manual method with reagents from Fortress Diagnostics Limited, UK. Fibrinogen, Protein C, and Protein S concentrations were measured by a solid-phase Sandwich ELISA technique, with reagents from Melson Shanghai Chemical Limited, China, and the manufacturer\u0026rsquo;s instructions were strictly adhered to. The liver function tests were run using Sinnowa semi-automated chemistry analyzer, with reagents from Fortress Diagnostics, UK. Concentrations of liver parameters such as liver enzymes [Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT)], bilirubin (total, direct, and indirect), total protein, albumin, and globulin were all estimated, with strict adherence to manufacturer\u0026rsquo;s protocol.\u003c/p\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData was entered in Excel 2016, and SPSS v.26 was utilized for analysis. Categorical data were represented as counts and proportions and subjected to comparison using either Chi-squared or Fisher's exact test. Logistic regression was used to assess how the sociodemographic characteristics predict HBV infection. Normality check was performed using Kolmogorov-Smirnov test. We represented non-normally distributed data as median (interquartile range) and subjected them to comparison using Kruskal-Wallis test. Spearman correlation was utilized to determine the association of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S levels with PT or APTT among HBV-infected pregnant women. Receiver operating characteristics (ROC) curve of aPTT, PT, Fibrinogen, Protein C, Fibrinogen/Albumin ratio (FAR), albumin, and Protein S for detecting chronic viral hepatitis B infection were drawn and respective areas under the curve (AUC) values were estimated. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 signified statistical significance.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eSociodemographic characteristics among the study participants\u003c/h2\u003e\n \u003cp\u003eAge categories were evenly distributed (p = 0.456), with 47.2% among the control cohort and 52.8% among the HBV cohort aged 18–29. Marital status (p = 0.588), employment status (p = 0.465), residence (p = 0.709), religion (p = 0.594), ethnicity (p = 0.478), gravidity (p = 0.709), parity (p = 0.891), sickling status (p = 0.225), G6PD (p = 0.943), and blood group (p = 0.52) did not differ between the two cohorts.\u003c/p\u003e\n \u003cp\u003eHowever, a few notable differences were observed. The HBV group had a slightly higher percentage of individuals who were cohabiting (48.5%) compared to the control group (41.9%). Additionally, higher percentages of the HBV group were self-employed (54.9% vs. 45.1%) and had tertiary education (64.3% vs. 35.7%). These differences, however, did not attain statistical significance (all p \u0026gt; 0.05).\u003c/p\u003e\n \u003cp\u003eAlcohol consumption and contraceptive use were significantly related to HBV infection. The HBV group had a higher proportion of individuals who reported alcohol consumption (75.0% vs. 25.0%) and contraceptive use (60.0% vs. 40.0%) compared to controls. The crude odds ratio (cOR) for alcohol consumption was 3.3 (95% CI: 1.0-10.7), indicating a positive association. Similarly, the cOR for contraceptive use was 2.3 (95% CI: 1.2–4.1), suggesting an increased likelihood of HBV infection among contraceptive users \u003cstrong\u003e(\u003c/strong\u003eTable\u0026nbsp;1\u003cstrong\u003e).\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAssociation between sociodemographic characteristics and hepatitis B infection\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eControls (N = 90)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHBV (N = 90)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ecOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge categories\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18–29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30–42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48 (52.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43 (47.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.7–2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarital status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.588\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarried\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70 (51.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66 (48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.3-3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCohabiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.4–5.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEmployment status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnemployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46 (53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40 (46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSelf-employed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37 (45.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45 (54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.8–2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFormally employed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.2–2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducational level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (58.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (0.1–1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.4–2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJunior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (43.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (56.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.2–1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (57.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (42.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.3–4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTertiary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeriurban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.4–1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73 (50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReligion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.594\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChristianity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71 (51.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68 (48.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.4–1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIslam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (53.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAkans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51 (50.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50 (49.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (0.3–1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEwe/Fante/Bono\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.1–1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNortherners\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35 (52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGravidity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimigravida\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.4–1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultigravida\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73 (50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (48.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (51.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.5–2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimiparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27 (47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.4–1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultiparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38 (48.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40 (51.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90 (50.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89 (49.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt; 100 (0-inf)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.036\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86 (52.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78 (47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (1.0-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eContraceptive use\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRef (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (1.2–4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eNote: Data are shown as frequency and percentages; analyzed with Chi-squared/Fisher’s test and logistic regression. P \u0026lt; 0.05 signified statistical significance.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAbbreviations: HBV: Hepatitis B viral infection; N: Number; cOR: crude odds ratio.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eBold values show statistical significance.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eLiver function test markers among the study groups\u003c/h2\u003e\n \u003cp\u003eSerum levels of AST [36.4 (32.8–47.5) vs 30.7 (26.4–39.2), p = 0.014], ALP [155.4 (138.3-304.5) vs. 115.4 (105.2-141.9), p \u0026lt; 0.0001], total bilirubin [5.6 (2.7–6.3) vs. 1.3 (1.0-1.9), p \u0026lt; 0.0001], direct bilirubin [1.7 (1.0-2.5) vs. 0.5 (0.3–0.8), p \u0026lt; 0.0001], and indirect bilirubin [3.3 (1.6–4.5) vs. 0.9 (0.6–1.1), p \u0026lt; 0.0001] were markedly elevated among acute HBV infected pregnant women relative to the control women. Similarly, Serum levels of AST [37.3 (32.0-45.6) vs. 30.7 (26.4–39.2), p \u0026lt; 0.0001], ALP [132.4 (116.6-197.4) vs. 115.4 (105.2-141.9), p = 0.004], GGT [30.9 (24.5–37.6) vs. 27.2 (19.4–32.1), p = 0.007], total bilirubin [2.4 (1.8–4.3) vs. 1.3 (1.0-1.9), p \u0026lt; 0.0001], direct bilirubin [0.9 (0.6–1.8) vs. 0.5 (0.3–0.8), p \u0026lt; 0.0001], and indirect bilirubin [1.5 (1.1–2.5) vs. 0.9 (0.6–1.1), p \u0026lt; 0.0001] were markedly raised in chronic HBV infected women compared to those uninfected. However, these liver function indicators did not differ between the acute and chronic subjects (all p \u0026gt; 0.05). \u003cstrong\u003e(\u003c/strong\u003eTable\u0026nbsp;2\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eComparison of PT, aPTT, INR, and albumin among the study groups\u003c/h2\u003e\n \u003cp\u003ePT [17.5 (16.4–19.5) vs. 16.1 (15.0-18.4) vs. 14.1 (13.1–15.7), p \u0026lt; 0.0001] and INR [1.55 (1.42–1.78) vs. 1.38 (1.27–1.65) vs. 1.17 (1.06–1.34), p \u0026lt; 0.0001] were significantly raised among acute HBV, followed by those with chronic HBV and then the controls (HBV negative pregnant women). aPTT was significantly elevated in both acute and chronic HBV compared to the HBV-negative pregnant women (p \u0026lt; 0.0001). However, aPTT was similar between acute and chronic HBV (p \u0026gt; 0.05). Moreover, albumin was significantly lower in both acute [31.0 (28.0–36.0) vs. 36.0 (31.0–39.0), p = 0.005] and chronic HBV [33.0 (29.0–37.0) vs. 36.0 (31.0–39.0), p = 0.036] relative to the HBV negative pregnant women but did not differ between the acute and chronic HBV group (p \u0026gt; 0.05) (Fig.\u0026nbsp;1\u003cstrong\u003e(A-D))\u003c/strong\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eComparison of levels of fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S among the subjects\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLevels of fibrinogen [4.09 (3.57–5.94) vs. 6.89 (5.43–9.08), p \u0026lt; 0.0001], FAR [0.14 (0.11–0.20) vs. 0.19 (0.17–0.26), p = 0.002], and protein C [2.46 (1.09–3.42) vs. 4.12 (2.96–6.07), p \u0026lt; 0.0001] were significantly reduced among the acute relative to the HBV negative pregnant women. Again, fibrinogen [4.33 (3.60–5.20) vs. 6.89 (5.43–9.08), p \u0026lt; 0.001], FAR [0.13 (0.11–0.17) vs. 0.19 (0.17–0.26), p \u0026lt; 0.0001], and protein C [2.10 (1.45-3.00) vs 4.12 (2.96–6.07), p \u0026lt; 0.0001] were significantly reduced among the chronic HBV relative to the HBV negative pregnant women. However, their levels were similar between the acute and chronic HBV groups (all p \u0026gt; 0.05). Also, protein S [2.61 (2.20–3.36) vs. 2.98 (2.53–3.54), p = 0.036] was significantly reduced among the chronic HBV group relative to the control group but was similar between either the chronic and acute HBV or the acute and controls (Fig.\u0026nbsp;2\u003cstrong\u003e(E-H)).\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAssociation between the levels of albumin, fibrinogen, fibrinogen/albumin ratio (FAR), protein C, and protein S, in comparison with prothrombin time (PT) and aPTT among HBV-infected pregnant women.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn a multivariate linear regression model, increasing FAR (R = 0.288, p = 0.006) and protein C (R = 0.273, p = 0.009) were associated with a significant increase in prothrombin time (PT). However, in comparison with aPTT, these increments were not statistically significant. Meanwhile, protein S (R = 0.147, p = 0.046) was the only marker which had a positive and significant association with aPTT. In contrast, decreasing albumin (R = − 0.279, p = 0.008), (R = − 0.571, p \u0026lt; 0.001) was associated with significant increases in PT and aPTT respectively. (Fig.\u0026nbsp;3\u003cstrong\u003e(A-E) \u0026amp;\u003c/strong\u003eFigure 4\u003cstrong\u003e(F-J)\u003c/strong\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eReceiver operating characteristics (ROC) curve of aPTT, PT, Fibrinogen, Protein C, Fibrinogen/Albumin ratio (FAR), albumin, and Protein S for detecting chronic viral hepatitis B infection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn a ROC analysis, aPTT (AUC = 0.881), fibrinogen (AUC = 0.867), and protein C (AUC = 0.816) could detect chronic HBV with a very high area under the curve values. FAR (AUC = 0.793) and PT (AUC = 0.786) could also detect chronic HBV with high area under the curve. However, albumin (AUC = 0.615) and protein S (AUC = 0.593) could poorly detect chronic HBV. (Fig.\u0026nbsp;5\u003cstrong\u003e(A-B)\u003c/strong\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnostic performance of aPTT, PT, Fibrinogen, Protein C, FAR, albumin, and Protein S in identifying chronic viral hepatitis B infection.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAt a cutoff of ≥ 35.7 secs, aPTT was the best measure for detecting chronic HBV infection with a sensitivity of 79.4% and a specificity of 91.6%, whiles PT and fibrinogen were both highly sensitive (92.6% and 95%) but less specific (54.7% and 62.4%), respectively. However, Albumin and Protein S were less sensitive in detecting chronic viral hepatitis B infection \u003cstrong\u003e(\u003c/strong\u003eTable\u0026nbsp;3\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eDiagnostic performance of aPTT, PT, Fibrinogen, Protein C, FAR, albumin, and Protein S in identifying chronic viral hepatitis B infection.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCut-offs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecificity (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePPV (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNPV (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLR+\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAccuracy\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eaPTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≥ 35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≥ 14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e92.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFibrinogen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≤ 6.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProtein C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≤ 2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≤ 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≤ 33.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProtein S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e≤ 2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eAbbreviations: PPV: Positive predictive value; NPV: Negative predictive value; LR+: Positive likelihood ratio; aPTT: activated partial thromboplastin time; PT: prothrombin time; FAR: Fibrinogen/Albumin ratio\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eViral hepatitis infection is a major risk factor for adverse fetal-maternal complications during pregnancy. Both the acute and chronic forms of viral hepatitis have been associated with impaired liver function thereby altering the hemostatic balance. Pregnancy also presents with physiological changes in the hemostatic balance resulting in a shift towards a state of increased blood clotting tendency. However, studies on coagulation disturbances in pregnant women with concurrent viral hepatitis B infection are lacking. Hence this study assessed the coagulation profile among hepatitis B-infected pregnant women in a Ghanaian population.\u003c/p\u003e\u003cp\u003eAs far as sociodemographic characteristics are concern; age, gender, marital status and employment status were similar among cases and controls which agrees with a study conducted by Anaedobe et \u003cem\u003eal\u003c/em\u003e.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). However, alcohol consumption and contraceptive use were statistically different in the hepatitis B patients and controls. In addition to this revelation, the number of individuals who use contraceptives were high in the HBV group as compared to the controls, a similar trend was seen in a study done by Anaedobe et \u003cem\u003eal\u003c/em\u003e.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Bayo et \u003cem\u003eal.\u003c/em\u003e and Onwuiri et \u003cem\u003eal\u003c/em\u003e. reported that behavioural factors including risky sexual acts may be more prevalent among contraceptive users which indirectly increases the risk of transmission (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Alcohol consumption has been shown to impair the function of the immune system and this may increase the susceptibility of consumers to infection (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn this present study, the increased levels of AST, ALP, GGT, bilirubin (total, direct and indirect) and decreased levels of albumin were observed in the HBV-infected pregnant women compared to controls. These findings are consistent with previous studies conducted by Onwuiri et \u003cem\u003eal\u003c/em\u003e. and Abulude et \u003cem\u003eal.\u003c/em\u003e who showed that HBsAg seropositivity was associated with high prevalence of abnormal ALP, AST, total and direct bilirubin (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn this study, HBV-infected pregnant women presented with prolonged PT, aPTT and INR compared to controls. This finding is consistent with previous studies by Olley et \u003cem\u003eal.\u003c/em\u003e and Xu et \u003cem\u003eal\u003c/em\u003e. which found increased values of these tests in HBV-infected patients compared to controls (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Studies have reported that viral liver infection results in the production of tumour necrosis factor (TNF), which contributes to liver pathology and which can lead to impaired liver synthetic function (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). This leads to a decrease in the procoagulant factors of both the intrinsic and extrinsic pathways, which disrupts the coagulation cascade and prolongs the test times (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe levels of fibrinogen were decreased in both chronic and acute viral infections compared to controls. This finding is similar to reports by Xu et \u003cem\u003eal\u003c/em\u003e.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) who found decreased levels of fibrinogen in HBV positive patients compared to controls. Fibrinogen is primarily synthesized in the liver and as a positive phase reactant protein, it levels rise during inflammation (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Physiological changes in pregnancy also lead to an increase in the levels of fibrinogen levels (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Nonetheless, hepatitis B infection results in an impaired synthetic function of the liver, leading to decrease fibrinogen levels (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Moreover, the level of FAR was decreased in both the hepatitis groups than controls. Albumin likewise fibrinogen is mainly synthesized in the liver, hence its dysfunction decreases the levels of these markers. This is inconsistent with previous studies that showed that elevated levels of FAR can serve as a valuable predictor of severity and likelihood of death of various clinical conditions, including cancer, cardiovascular diseases, and cerebrovascular disorders (\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBoth protein C and protein S serves as natural anticoagulant and like the above, are primarily synthesized in the liver, hence a dysfunctional liver impairs it synthesis. In our study, protein C levels were decreased in pregnant women with chronic and acute infection compared to controls, whiles protein S was only decreased in women with chronic viral hepatitis. Previous studies have reported decreased protein C levels in hepatitis positive-patients compared to controls which is consistent to our study (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). In contrast, G\u0026uuml;ven et \u003cem\u003eal\u003c/em\u003e.(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) observed comparable protein C and protein S levels in patients with chronic hepatitis compared to controls. These inconsistencies may be explained by the differences in sample size and study population.\u003c/p\u003e\u003cp\u003eIn the regression analysis, Fibrinogen levels did not show any significant association with both PT and aPTT. In contrast, a previous study by Leticia et \u003cem\u003eal\u003c/em\u003e.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) showed a statistically significant positive relationship between serum fibrinogen levels and the coagulation test times, PT and aPTT. However, this study was conducted among hepatitis-infected blood donors while our study population employed pregnant women and this may account for the differences.\u003c/p\u003e\u003cp\u003eFinally, the diagnostic performances of these coagulation indices in identifying chronic viral hepatitis B infection showed that, that aPTT, fibrinogen and protein C had excellent diagnostic accuracy for identifying chronic hepatitis B infection and thus may be valuable indicators for mitigating chronic hepatitis-related complications including cirrhosis, hepatocellular carcinoma and liver failure. PT and FAR also showed better diagnostic accuracy but were inferior to the above indices, whereas, protein S and Albumin showed the poorest diagnostic accuracy. Peng et \u003cem\u003eal.\u003c/em\u003e(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) also observed that aPTT, PT and fibrinogen had high AUCs and were excellent indicators for early diagnosis of cirrhosis.\u003c/p\u003e\u003cp\u003eThe strength of this study is that, this is the first case-control study to have simultaneously assessed the hematobiochemical and coagulation profile among HBV-infected pregnant women. Notwithstanding the novel findings, this present study has limitations worth considering for future studies. Firstly, this study did not take into consideration the pregnancy stage, the use of conventional or nonconventional treatments, such as herbs or other interventions, or exposure of subjects to toxins at the workplace before the study as these factors can affect liver enzymes. Also, other coagulation markers including prothrombin fragment F1 and thrombin-anti-thrombin complexes were not assessed, as this could provide a better understanding of the coagulation system abnormalities. Lastly, this study was carried out at a single centre and may limit its generalizability to the entire Ghanaian population. Therefore, a multicentre study with a larger sample size is required\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePregnant women with HBV infection present with significant increases in liver function enzymes and bilirubin levels. Also, HBV causes significant changes in coagulation parameters and natural anticoagulants, however, these alterations are generally comparable in acute and chronic hepatitis B infection. aPTT, fibrinogen and protein C showed excellent diagnostic accuracy for identifying chronic hepatitis B viral-related infection and thus may be valuable supportive indicators in managing chronic hepatitis-related complications. The study therefore concludes that, pregnant women coupled with HBV infection have higher levels of liver biomarkers, prolonged PT and aPTT with reduced levels of Protein C, Protein S, and Fibrinogen. Implementing therapeutic strategies focused on preserving the functionality of the coagulation system can significantly improve supportive care for pregnant women with Hepatitis B virus.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to present our gratitude to the entire lecturers in the Department of Medical Diagnostics at Kwame Nkrumah University of Science and Technology for their invaluable support. We would also like to extend our sincere gratitude to the Laboratory and entire staff of Afrancho Polyclinic for their enormous support in this research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e A.A.K, W.I.O.B, E.O.A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData curation\u003c/strong\u003e: A.A.K, W.I.O.B, A.A.A, S.T, D.A.A \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFormal analysis\u003c/strong\u003e: J.F, S.T, A.A.A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigation\u003c/strong\u003e: A.A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A.A\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eMethodology:\u003c/strong\u003e A.A.K, W.I.O.B, E.O.A, ST, A.A.A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProject administration\u003c/strong\u003e: A.A.K, W.I.O.B, E.O.A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eValidation\u003c/strong\u003e: A.A.K, W.I.O.B, E.O.A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisualization\u003c/strong\u003e: \u0026nbsp;A.A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting-original draft\u003c/strong\u003e: A.K, W.I.O.B, F.A.A, A.A.A, S.T, D.A.A, E.A, A.N.B, D.N.M.A, E.O.A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting-review, editing and approving:\u003c/strong\u003e\u0026nbsp; All authors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEthical Approval Statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Committee on Human Research, Publication and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology (CHRPE/AP/834/22), as well as the management of Afrancho Polyclinic. The ethical approval was fixed for one year from 19\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eDecember, 2022 to 18\u003csup\u003eth\u003c/sup\u003e December, 2023.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent Statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Both oral and written consent from all participants was obtained before their recruitment.\u0026nbsp;All participants had the age to consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship and or/ publication of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and materials for study are available upon request from the corresponding authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization WH. 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Proceedings of the Society for Experimental Biology and Medicine: Minireviews. 2000;223(3):241-57.\u003c/li\u003e\n\u003cli\u003eOrange JS, Salazar-Mather TP, Opal SM, Biron CA. Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection. Journal of virology. 1997;71(12):9248-58.\u003c/li\u003e\n\u003cli\u003eTiegs G, Horst AK, editors. TNF in the liver: targeting a central player in inflammation. Seminars in immunopathology; 2022: Springer.\u003c/li\u003e\n\u003cli\u003eHoffman M, editor Coagulation in liver disease. Seminars in thrombosis and hemostasis; 2015: Thieme Medical Publishers.\u003c/li\u003e\n\u003cli\u003eKenny L, Baker PN, Cunningham FG. Platelets, coagulation, and the liver. Chesley\u0026apos;s Hypertensive Disorders in Pregnancy. 2009:335-51.\u003c/li\u003e\n\u003cli\u003eGhanim B, Hoda M, Klikovits T, Winter M, Alimohammadi A, Grusch M, et al. 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Importance of anticoagulant proteins in chronic liver diseases. Turk J Gastroenterol. 2005;16(3):129-33.\u003c/li\u003e\n\u003cli\u003ePeng J, He G, Chen H, Kuang X. Study on correlation between coagulation indexes and disease progression in patients with cirrhosis. American journal of translational research. 2021;13(5):4614.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Kwame Nkrumah University of Science and Technology","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatitis B, Fibrinogen, Protein C, Protein S, PT, aPTT, Liver enzymes, Albumin, Bilirubin, Pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-7849679/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7849679/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eViral hepatitis has been associated with profound alterations in the coagulation system as well as liver biomarkers. Meanwhile, during pregnancy, the coagulation system also undergoes significant changes with an increase in the majority of the clotting factors and a decrease in natural anticoagulants. This study aimed to evaluate the coagulation profile and liver biomarkers among hepatitis B-infected pregnant women in a Ghanaian population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis case-control study was conducted with 90 hepatitis B pregnant women as cases and 90 hepatitis B negative pregnant women as controls. A structured questionnaire was used to obtain sociodemographic, obstetric, and clinical data from each participant.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eLevels of albumin, Fibrinogen [4.09 (3.57\u0026ndash;5.94) vs. 6.89 (5.43\u0026ndash;9.08), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001], Protein C [2.46 (1.09\u0026ndash;3.42) vs. 4.12 (2.96\u0026ndash;6.07), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001], and Protein S [2.61 (2.20\u0026ndash;3.36) vs. 2.98 (2.53\u0026ndash;3.54), p\u0026thinsp;=\u0026thinsp;0.036] were significantly reduced in the hepatitis B positive pregnant women than the negative controls. However, there was high levels of AST, ALP and bilirubins in hepatitis B positive pregnant women than the controls. Also, Protein C and Protein S had significantly positive association with PT and aPTT, whereby a rise in Protein C and Protein S, resulted in an increasing PT and aPTT respectively (all p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, albumin had a negative correlation with both PT and aPTT (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In a ROC analysis, aPTT had the highest area under the curve (AUC) value (AUC\u0026thinsp;=\u0026thinsp;0.881) and the optimal clotting time at which aPTT indicated chronic hepatitis B was \u0026ge;\u0026thinsp;35.7secs with sensitivity of 79.4% and specificity of 91.6%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003ePregnant women with hepatitis B infection present with significant changes in their coagulation parameters, natural anticoagulants and liver biomarkers. Furthermore, Fibrinogen, Protein C, and aPTT showed accurate diagnostic potential in identifying chronic viral hepatitis B infection and may be valuable surrogate indicators for managing chronic hepatitis-related complications.\u003c/p\u003e","manuscriptTitle":"The effect of Hepatitis B Viral Infection on Hemostatic Profile and Liver markers in Ghanaian Pregnant Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 09:04:47","doi":"10.21203/rs.3.rs-7849679/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"11bb3cb3-e3b5-4e97-a3f9-33be736bd8c2","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56209052,"name":"Hematology"},{"id":56209053,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2025-10-15T09:04:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-15 09:04:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7849679","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7849679","identity":"rs-7849679","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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