Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study

Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study | 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 Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study Amal Farahat Allam, Hoda Farag, Amel Shehab, Ahmed El Sahy, Safia Khalil, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3552503/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Aug, 2024 Read the published version in Journal of Parasitic Diseases → Version 1 posted 5 You are reading this latest preprint version Abstract Background The implication of human Schistosoma mansoni ( S. mansoni ) infection in concomitance with other risk factors such as hepatitis C virus (HCV) and hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC) is still under controversy. This work aimed to evaluate the role of S. mansoni infection in association with hepatitis B virus (HBV), hepatitis C virus (HCV) and other risk factors in the development and/or progress of HCC. Methods The present study was carried out on 90 HCC patients recruited from Kafr El-Sheikh Liver Disease Research Institute. After obtaining their informed consents, socio-demographic and clinical data were collected and patients were examined for S. mansoni by Kato-Katz and indirect hemagglutination (IHA) techniques. Alpha-fetoprotein (AFP) level was determined. The Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system were used to evaluate the pathological features of the studied patients. Results All participants were negative for active S. mansoni by Kato-Katz. Based on IHA, the participants were categorized into two groups: group I: sixty-two patients negative for S. mansoni and group II: twenty-eight schistosomiasis positive . The patients’ age ranged between 40->60 years with a mean of 57.07± 8.12 years. HCC was more prevalent in the age range of >50-60 years in both groups. Males were more than females and rural participants were more than urban patients in both groups. Most of the patients (88.9%) had HCV while 7.8% had HBV. A higher proportion of HCC patients showed concomitant HCV and S. mansoni (92.6%) than the S. mansoni negative group. Alpha-fetoprotein (AFP) level was higher in group II than that in group I with no significant difference. Statistical analysis showed no difference between the two studied groups regarding Child scores. On the contrary, BCLC class D was significantly higher among HCC positive schistosomiasis cases compared to the negative group. Conclusion Concomitant S. mansoni with HCV and HBV potentiate HCC progression. Hepatocellular carcinoma S. mansoni HCV HBV Alpha-fetoprotein Introduction Schistosomiasis is a chronic disease caused by the genus Schistosoma of the trematode parasites. It is endemic in 78 countries, infecting more than 207 million people worldwide and provoking above 200,000 deaths yearly (Calvisi, 2020 ). Human infection occurs after exposure to contaminated water with schistosome cercariae which penetrate the skin and become schistosomula. They penetrate the wall of a nearby vein and are carried out in the blood circulation, eventually reaching the portal venous system, where they mature and lay eggs. These eggs are either trapped in the tissues and provoke a granulomatous reaction or are passed in the feces, then hatch in water to miracidia which invade the snail and are developed into cercariae to start a new cycle causing schistosomiasis which affects several organs, including the genitourinary, digestive, and nervous systems causing a spectrum of serious diseases (Davis, 1996 ) Different Schistosoma species are involved in the development and/or progression of some tumor types, including colorectal carcinoma, prostate adenocarcinoma, giant follicular lymphoma, and hepatocellular carcinoma (Calvisi, 2020 ). Hepatocellular carcinoma (HCC) is the sixth most widespread cancer in the world and is responsible for approximately one million deaths per year. Most of HCC develops in the presence of chronic liver diseases mostly related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in addition to intestinal schistosomiasis (Ohata et al. 2004 ; Rashed et al, 2020 ; Hu et al. 2022 ). Egypt ranks the 15th worldwide and the 3rd country in Africa regarding HCC. HCC constitutes 70% of all liver tumors, with an increase in the incidence rate in the last years (Shaker et al. 2013 ; El-Tonsy et al. 2016 ; Rashed et al, 2020 ). This requires the investigation of the potential risk factors for its development. In rural areas, S. mansoni remained a major chronic disease for many years (Barakat, 2013 ). It develops a series of pathology including hepatic fibrosis and it can help in development of neoplasia due to chronic granulomatous inflammatory reactions (Elbaz and Esmat, 2013 ). There is controversy and limited evidence in the available literature about the real role of S. mansoni alone or in association with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the development of hepatic carcinoma. It was reported that 70–90% of patients with chronic hepatitis, cirrhosis or HCC have co-infection of schistosomiasis and HCV (Rashed et al. 2020 ; Strickland, 2006 ). It was suggested that the combination of chronic S. mansoni infection and HBV or HCV may cause a higher risk of HCC. Understanding these associations may clarify the development and progress of HCC and subsequently draw attention and more effort to its prevention and control (El-Tonsy et al. 2013 ; Toda et al. 2015 ; El-Tonsy et al. 2016 ; Alboraie et al. 2019 ). Screening tools of HCC were commonly performed by measuring AFP levels in combination with ultrasonography that increased its sensitivity to 100% (Tateyama et al. 2011 ). It is a large serum glycoprotein, belonging to the eccentric class of onco-development protein (Bruno Daniele et al. 2004 ). Normally, its level decreases sharply after birth and continues at a low level afterwards. AFP level was studied among HCC patients in combination with other factors to find out if it is correlated with the progress of the disease (Hu et al. 2022 ). The severity of HCC is evaluated using the modified Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system (Pugh et al. 1973 ; Forner et al. 2010 ). Child Pugh-score relies on clinical and laboratory evaluation including liver functions, serum albumin, international normalization ratio (INR) and prothrombin time to assess the severity of liver cirrhosis. BCLC identifies the stages of HCC based on the number and the size of tumors in the liver associated with liver function and overall performance status (Vogel et al. 2018 ). It helps in the decision of treatment for HCC patients (Jelic and Sotiropoulos, 2010 ; Jun et al. 2017 ). To shed more light on this controversial issue, this work aimed to evaluate the role of Schistosoma mansoni infection in association with HBV and HCV and other risk factors in the development and/or progress of HCC. Materials and Methods Study Subjects and Ethical Considerations To perform this study, approvals from the Egyptian Ministry of Health and Population, the administration of Health Affairs in Kafr El-Sheikh governorate and the Research Ethics Committee of the Medical Research Institute (MRI), Alexandria University were obtained. The study was conducted on 90 HCC patients from Kafr El Sheikh and nearby Gharbia governorates attending or admitted to Kafr El Sheikh Liver Disease Research Institute during the period from September 2018 to September 2019. They were diagnosed by ultrasound (US) and confirmed by Triphasic Computed Tomography (CT). All participants were asked to freely volunteer and informed consent was obtained prior to their inclusion in the study. Based on a predesigned questionnaire, brief demographic and retrospective clinical signs were collected including age, gender, residency and medical records concerning upper gastrointestinal bleeding (GIB). Laboratory Investigations Stool and blood (2ml/patient) samples were collected from all patients and examined for active S. mansoni infection by Kato-Katz (Katz et al. 1972 ) and IHA (Bilharziose Fumouze Diagnostics/SERFIB, France). Accordingly, the patients were categorized into two groups; group I included HCC patients negative for schistosomiasis and group II included HCC patients with schistosomiasis. They were also examined for HCV antibodies by enzyme-linked immunosorbent assay (ELISA) technique (Human diagnostics, Germany and HCV Murex 40 Anhet laboratories, USA). The results of HBsAg and the other routine laboratory tests that were processed for each HCC patient were collected from the institute’s records. Among these tests: liver enzymes, alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), bilirubin (total and direct), albumin, thromboplastin activity and international normalization ratio (INR) in plasma using Biomed-Liquiplastin kit. No patients had concomitant parasite infections and any serological evidence, or a history of recent or old hepatitis A or D virus infections. Serum AFP level was performed for each patientusing ELISA technique (AFP ElISA kit UK)(Chang et al. 2015 ; Sauzay et al. 2016 ). Evaluation of HCC Severity The severity of liver cirrhosis was evaluated in each patient with a modified Child-Pugh score (Pugh et al. 1973 ). The BCLC stages were determined based on tumor features and liver function tests (Forner et al. 2010 ). Accordingly, patients were classified as A (early), B (intermediate), C (advanced) and D (terminal) (Toda et al. 2015 ). All the data were obtained from medical records. Statistical Analysis Data analysis was completed using IBM SPSS software package version 20.0. ( Armonk, NY: IBM Corp)(Kirkpatrick and Feeney, 2013 ). Qualitative data was described using numbers and percentages. The Kolmogorov-Smirnov test was used to verify the normality of distribution of quantitative data using range (minimum and maximum), mean and standard deviation, median and interquartile range (IQR). The significance of the obtained results was judged at the 5% level. Tests of Chi-square, Fisher’s Exact, Mann Whitney and student t-test were used to compare between the two studied groups (Altman, 1992 ). Results All 90 HCC patients were negative for S. mansoni by Kato-Katz. Based on IHA; 62 HCC/S. mansoni negative patients were classified as group I and 28 S. mansoni positives were in group II. The mean age of all HCC patients was 57.07 ± 8.12 years, with no significant difference between HCC alone and HCC S. mansoni co-infection. The larger proportion of HCC patients were in the age between 50–60 years among both groups. Regarding gender, HCC was about four times more prevalent in males compared to females; 78.9% (71/90) versus 21.1% (19/90) respectively. Among positive S. mansoni HCC patients: the male to female ratio was 3:1 (75% vs 25%). HCC was more common among patients from rural than urban areas in both groups with no statistically significant difference ( p > 0.05). As for upper gastrointestinal bleeding, patients with S. mansoni had significantly higher bleeding than those negative for S. mansoni (64.3% versus 16% respectively, p < 0.001) (Table 1 ). Table 1 Baseline features of the 90 HCC patients Parameter (Group I) HCC/ S. mansoni -ve (n = 62) (Group II) HCC /S. mansoni +ve (n = 28) Test of Sig. P No. % No. % Age (years) 40–50 10 16.1 2 7.1 2.654 0.265 >50–60 25 40.3 16 57.1 >60 27 43.5 10 35.7 Mean ± SD 56.68 ± 8.44 57.93 ± 7.43 U = 815.500 0.647 Gender Male 50 80.6 21 75.0 χ 2 = 0.369 0.544 Female 12 19.4 7 25.0 Residence Rural 38 61.3 19 67.9 χ 2= 0.358 0.550 Urban 24 38.7 9 32.1 Upper GIB 10 16.1 18 64.3 χ 2 = 20.872 * 0.01) * Statistically significant at p ≤ 0.05 GIB: gastrointestinal bleeding Among the two studied groups, HCV was more prevalent than HBV (88.9% vs 7.8% respectively). Similar patterns of HCV and HBV were observed in both groups; HCV was 87.1% in group I versus 92.6% in group II and HBV was 8.1% vs 7.1% among group I and group II respectively. There was no statistically significant difference between the two studied groups, p > 0.05 (Table 2 ). Table 2 Distribution of the two studied groups according to HCV antibodies and HBsAg Variables (Group I) HCC /S. mansoni -ve (n = 62) (Group II) HCC /S. mansoni +ve (n = 28) Total (n = 90) • χ 2 FE p No. % No. % No. % HCV Ab 54 ∗ 87.1 26 92.6 80 88.8 1.866 0.264 HBsAg 5 ∗ 8.1 2 7.1 7 7.8 0.023 1.000 χ 2 : Chi-square test, FE: Fisher Exact. p: p -value for comparing between the studied groups * Two patients were negative for HCV antibodies and HBsAg and one case had both HCV and HBsAg and they were not included in the calculations Table 3 revealed that all HCC patients had high liver enzymes levels regarding alanine aminotransferase (SGPT), aspartate aminotransferase (SGOT), total bilirubin (T.BIL), direct bilirubin (D.BIL), albumin (ALB), prothrombin time (P.T) with no statistically significant difference between the two groups. Regarding the international normalization ratio (INR), it was statistically significantly higher in HCC/ S. mansoni positives (groups II) compared to HCC/ S. mansoni negatives (group I). Mean serum AFP level was elevated among all studied patients (1239.8 ± 2918). The mean value of AFP in group II (1830.5 ± 3735.3 IU/ml) was higher than that in group I (973.0 IU/ml) yet not significant. Table 3 Comparison of the laboratory investigation results between the two studied groups Parameters (Group I) HCC /S. mansoni -ve (n = 62) (Group II) HCC /S. mansoni +ve (n = 28) Total (n = 90) Test of Sig. p SGPT Min. – Max. 24.0–156.0 29.0–117.0 24.0–156.0 U = 839.0 0.800 Mean ± SD. 65.73 ± 31.84 61.54 ± 24.67 64.42 ± 29.72 Median (IQR) 56.0(46.8–71.0) 54.50(41.3–78.3) 56.0(46.0–74.5) SGOT Min. – Max. 15.0–205.0 34.0–130.0 15.0–205.0 U = 780.0 0.443 Mean ± SD. 76.60 ± 41.65 67.14 ± 26.87 73.66 ± 37.78 Median (IQR) 62.0(49.8–93.3) 60.0(49.3–84.8) 62.0(49.8–87.3) T. BIL Min. – Max. 0.40–20.30 0.68–10.90 0.40–20.30 U = 723.50 0.207 Mean ± SD. 3.44 ± 4.0 2.41 ± 2.36 3.12 ± 3.59 Median (IQR) 2.12(1.1–3.8) 1.55(0.94–2.5) 1.98(1.1–3.5) D. BIL Min. – Max. 0.09–17.90 0.13–6.10 0.09–17.90 U = 738.0 0.257 Mean ± SD. 1.83 ± 2.84 1.16 ± 1.31 1.62 ± 2.48 Median (IQR) 0.89(0.46–1.8) 0.71(0.40–1.3) 0.80(0.41–1.5) ALB Min. – Max. 2.40–4.40 2.20–4.90 2.20–4.90 t = 0.377 0.707 Mean ± SD. 3.20 ± 0.47 3.16 ± 0.56 3.19 ± 0.50 Median (IQR) 3.20(2.9–3.5) 3.15(2.8–3.5) 3.20(2.9–3.5) P.T Min. – Max. 11.50–20.50 11.50–19.70 11.50–20.50 t= 1.400 0.165 Mean ± SD. 14.05 ± 1.91 14.67 ± 2.0 14.25 ± 1.95 Median (IQR) 13.70(12.9–14.9) 14.20(13.3–15.4) 13.90(12.9–15.1) INR Min. – Max. 1.01–1.94 1.01–2.10 1.01–2.10 U = 631.0 * 0.039 * Mean ± SD. 1.28 ± 0.24 1.38 ± 0.26 1.31 ± 0.25 Median (IQR) 1.20(1.1–1.4) 1.36(1.2–1.5) 1.24(1.1–1.4) AFP (IU/ml) Min. – Max. 1.50–15433.0 2.30–16800.0 1.50–16800.0 U = 776.50 0.425 Mean ± SD. 973.0 ± 2452.9 1830.5 ± 3735.3 1239.8 ± 2918.2 Median (IQR) 87.55(12.2–618.0) 89.55(12.3–1346.3) 87.55(12.2 − 809.3) χ 2 : Chi-square test, FE: Fisher Exact. p: p- value for comparing between the studied groups SGPT: alanine aminotransferase, SGOT: aspartate aminotransferase, T.BIL: total bilirubin, D.BIL: direct bilirubin, ALB albumin, P.T: prothrombin time, INR: international normalization ratio. Child-Pugh Scoring System and BCLC among the Two Studied Groups In Table 4 , based on the Child-Pugh scoring system, a smaller proportion of group II had mild cirrhosis compared to group I, while a greater proportion of group II had moderate cirrhosis with no statistically significant difference. Marked cirrhosis was found in equal proportion in the two groups without any level of significance. Regarding the BCLC staging system, in class A (early), more cases in group I revealed a higher percentage compared to those in group II (24.2% versus 7.1% respectively) with a borderline statistically significant difference. There was no statistically significant difference between group I and group II in classes B and C. However, HCC/ S. mansoni co-infection revealed a higher percentage in class D (terminal) compared to group I with a statistically significant difference ( p < 0.05). Table 4 Child-Pugh scoring system and BCLC among the HCC studied groups Variables (Group I) HCC /S. mansoni -ve (n = 62) (Group II) HCC /S. mansoni +ve (n = 28) Total (n = 90) χ 2 p No. % No. % No. % Child Pugh score (level of cirrhosis) A (Mild) 17 27.4 5 17.9 22 24.4 0.955 0.328 B (Moderate) 31 50.0 17 60.7 48 53.3 0.890 0.346 C (Marked) 14 22.6 6 21.4 20 22.2 0.015 0.903 BCLC A (Early) 15 24.2 2 7.1 17 18.9 3.660 0.056 B (Intermediate) 28 45.2 13 46.4 41 45.6 0.012 0.911 C (Advanced) 10 16.1 3 10.7 13 14.4 0.458 FE p=0.747 D (Terminal) 9 14.5 10 35.7 19 21.1 5.204 * 0.023 * χ 2 : Chi-square test FE: Fisher Exact p: p- value for comparing between the studied groups *: Statistically significant at p ≤ 0.05 Discussion HCC is commonly a disease of infectious origin; consequently, it could be preventable (El-Tonsy et al. 2013 ). In the present study, the association of S. mansoni with HBV and/or HCV was investigated as a risk factor for the development of HCC. A total of 90 HCC cases were eligible for this study; they were categorized into HCC patients negative for schistosomiasis (62 patients) and HCC patients positive for schistosomiasis (28 patients). In this study, the larger proportion of HCC positive for S. mansoni was in the age group 50–60 years with no statistical significance. Abdel-Wahab et al. ( 2007 ) and El-Zayadi et al. ( 2005 ) revealed different findings and the predominant age was 40–59 years, this was explained by the different localities, the risk of exposure and the study periods. As for gender, HCC was more prevalent in males than females (3:1) in the two groups with no significant difference. Concordant results were obtained by El-Zayadi et al. ( 2005 ) and El-Tonsy et al. ( 2016 ) concerning gender. Considering residence, the rural areas dwelled patients showed that HCC was 1.5 times higher than those living in urban areas (63% vs 36% respectively) with no statistically significant difference. These findings agreed with those of Abdel-Wahab et al. ( 2007 ) and El-Tonsy et al. ( 2016 ), which attributed the high prevalence in rural areas to the use of insecticides, pollution, and aflatoxins. Regarding the clinical data, gastrointestinal hemorrhage in patients with HCC is common and is a major contributor to mortality (Srivastava et al. 2000 ). The present results revealed that upper GIB was highly significant among positive S. mansoni group compared to the negative one. Consistently, it was reported that schistosomiasis fibrosis is associated with several vascular changes within the host. The peripheral destruction of the portal vein system with the obstruction of some medium-sized branches explains the presence of portal hypertension (one of the S. mansoni infection complications) which leads to upper GIB (Johnson, 2006 ; Kumar et al. 2008 ; Andrade, 2009 ). During the present study period, 88.9% and 7.8% of HCC patients had HCV and HBV correspondingly without statistically significant difference among the two groups, despite the higher proportion of HCC patients showing concomitant HCV and S. mansoni . The development of a vaccine against HBV explains its lower prevalence. Similar results were reported by Abdel-Wahab et al. ( 2007 ), Shaker et al. ( 2013 ) and Zampino et. al. ( 2015 ). Regarding, S. mansoni and HCV co-infection, El-Zayadi et al. ( 2005 ) and Toda et al. ( 2015 ) described that Schistosoma infection may modify the sequence of hepatitis C and lead to more significant complications and faster progression to HCC than patients with no schistosomiasis parasite burden. Instead, Hassan et al. ( 2001 ) concluded that HCV infection increases the risk of HCC whereas S. mansoni infection does not. Currently, Egypt succeeded to transform HCV from a health system stigma to a global success story through the 100 million healthy lives initiative launched in October 2018. Hopefully this may lead to lowering the prevalence of HCC. Regarding the liver enzyme levels (SGPT, SGOT), total bilirubin, direct bilirubin and albumin, they were higher in HCC S. mansoni positives compared to S. mansoni negatives yet not statistically significant. Regarding the INR, there was a statistically significant difference between both groups. The concomitant infection or over infection with HCV in patients with schistosomiasis could be the cause of provocation of liver damage and subsequently reduction in coagulation factors production leading to prolonged prothrombin time. Similarly, Kamal et al., 2000a reported more fibrosis in liver biopsies in S. mansoni and HCV concomitant infections compared to HCV mono- infection. The present results showed that AFP values ranged between 1.5 and 16800 IU/ml in all cases. Although the AFP level in the two studied groups showed no statistical difference, its mean value in the S. mansoni positive group was higher than that in the negative one (1830.5 and 973.0 IU/ml respectively). It was reported that the increased levels in high risk patients provide HCC diagnostic clues. Yet, normal level does not exclude its presence. It was reported that 10–30% of HCC patients have negative AFP expression. On the contrary, many investigators believe that AFP is significant in predicting HCC recurrence and evaluating the biologic features of tumors and treatment regimens (Kamal et al. 2000a ; Hu et al. 2022 ). It was pointed out that AFP prevalence among HCC is accompanied by certain controversies and needs novel directions for prospective studies (Lee et al. 2019 ; Hu et al. 2022 ). In the current study, the Child-Pugh classification revealed no significant difference between the two studied groups. However, BCLC classification showed significant statistical difference between the two groups regarding class (D). Therefore, the concomitant association of HCV and schistosomiasis may have increased the severity of liver pathology and progress of HCC. As for the role of S. mansoni in inducing HCC, cumulating findings of human clinical investigations and experimental research in animal models on a molecular level suggest S. mansoni is potentially associated with HCC. This association was explained by its activation of the proto-oncogenes; c-Jun signal transducer and transcription 3, whose role in liver inflammation and carcinogenesis is well established (Calvisi, 2020 , Shousha et al, 2021). This study together with others suggest thatchronic inflammation resulting from prolonged parasitic infections may encourage carcinogenesis by three mechanisms; first, chronic inflammation that damages host cell and gene expression by supporting the release of reactive oxygen and nitrogen species; second, insertion of oncogenes into the host genome particularly in the presence of hepatitis B and hepatitis C, stimulation of mitosis and inhibition of tumor suppressors; third, reduction of immune response and induction of immune suppression (el-Zayadi et al. 2005 ; El-Tonsy et al. 2013 ; Toda et al. 2015 ; Abdelghani et al. 2020 ). In conclusion, although in the current study, the co-occurrence of S. mansoni with HCV and HBV quickens hepatic dysplastic changes and accelerates cancer progression yet; these associations are still being sorted out. So, further studies on large cohorts of HCC patients are essential. Declarations The authors declare no conflict of interest. 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Kumar R, Saraswat MK, Sharma BC, Sakhuja P, Sarin SK (2008) Characteristics of hepatocellular carcinoma in India: a retrospective analysis of 191 cases. QJM 101(6): 479-485. DOI: 10.1093/qjmed/hcn033 Lee CW, Tsai HI, Lee WC, Huang SW, Lin CY, et al (2019) Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal? Journal of Clinical Medicine 8(10), 1736–. doi:10.3390/jcm8101736. Ohata K, Hamasaki K, Toriyama K, Ishikawa H, Nakao K, Eguchi K (2004) High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Gastroenterol Hepatol 19(6),670-675. https://doi.org/10.1111/j.1440-1746.2004.03360.x Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8): 646-649. doi: 10.1002/bjs.1800600817. Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S (2020) Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst 16;32(1):5. doi: 10.1186/s43046-020-0016-x. PMID: 32372179. Sauzay C, Alexandra Petit A, Bourgeois AM, Barbare JC, Chauffert B, et al (2016) Alpha-fetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta 1; 463:39-44. doi: 10.1016/j.cca.2016.10.006. Shaker MK, Abdella HM, Khalifa MO, El Dorry AK (2013) Epidemiological characteristics of hepatocellular carcinoma in Egypt: a retrospective analysis of 1313 cases. Liver Int 33(10), 1601-1606. DOI: 10.1111/liv.12209. Shousha HI, Abdelaziz AO, Nabeel MM, Omran DA, Abdelmaksoud AH, Elbaz TM, Salah A, Harb STE, Hosny KA, Osman A, Atef M, Gaber A, Zayed NA, Yosry AA, Leithy R (2022). Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade. Pathog Glob Health 116(2), 119-127. DOI: 10.1080/20477724.2021.1975081. Srivastava DN, Gandhi D, Julka PK, Tandon RK (2000) Gastrointestinal hemorrhage in hepatocellular carcinoma: management with transhepatic arterioembolization. Abdom Imaging 25: 380–384. DOI: 10.1007/s002610000056 Strickland GT (2006) Liver disease in Egypt: Hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors. Hepatol 43(5):915-922. Tateyama M, Yatsuhashi H, Taura N, et al (2011) Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 46(1), 92–100. Toda KS, Kikuchi L, Chagas AL, Tanigawa RY, Paranaguá-Vezozzo DC, et al (2015) Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review. J Clin Transl Hepatol 3(4), 260-264. doi: 10.14218/JCTH.2015.00027 Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, et al (2018) ESMO Guidelines Committee. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29 (Suppl 4): iv238-iv255. doi: 10.1093/annonc/mdy308. Zampino R, Pisaturo MA, Cirillo G, Marrone A, Macera M, et al (2015) Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration. Ann Hepatol. 14(1):75-82. Cite Share Download PDF Status: Published Journal Publication published 21 Aug, 2024 Read the published version in Journal of Parasitic Diseases → Version 1 posted Editorial decision: Minor revisions needed 14 Jul, 2024 Reviewers agreed at journal 21 May, 2024 Reviewers invited by journal 10 Apr, 2024 Editor assigned by journal 03 Nov, 2023 First submitted to journal 02 Nov, 2023 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3552503","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":289697512,"identity":"afc43914-ec0e-4f51-9e41-0b82ff98d011","order_by":0,"name":"Amal Farahat Allam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYHACxgMMBQwM/MyM7R8+MDAkEKXnAIMBA4Nke/MxxhkkaTE4cyyNmYcYLfzTDj848MPALprhRo7ZY9s2uzx+9gbGDx9zcGuRuJ1mcLDHIDm3cUaOuXFuW3KxZM8BZsmZ2/BYczvB4ACPAXNus0SOgXRuG3PihhsJbMy8eLTI307/cPCPQX1uG0iLZVs9YS0Gt3MMDvMYHM7t4TmWJs3YdpiwFsPbOQWHZQyO585gbz5s2HPueOLMnoPNeP0idzt948M3FdW5+w8zNj74UVad2M/efPDDR3zeRwGMbGCygVj1IPCHFMWjYBSMglEwUgAA0ClbS8MYrqUAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-4965-9469","institution":"Alexandria University","correspondingAuthor":true,"prefix":"","firstName":"Amal","middleName":"Farahat","lastName":"Allam","suffix":""},{"id":289697513,"identity":"177a7bde-11fa-461a-99c6-83611cbc9e49","order_by":1,"name":"Hoda Farag","email":"","orcid":"","institution":"Alexandria University Medical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Hoda","middleName":"","lastName":"Farag","suffix":""},{"id":289697514,"identity":"66b439f2-6c94-4c3b-a6a1-d1d6a5920200","order_by":2,"name":"Amel Shehab","email":"","orcid":"","institution":"Alexandria University Medical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Amel","middleName":"","lastName":"Shehab","suffix":""},{"id":289697515,"identity":"1d72dc97-1369-4df1-9448-22f3600102c0","order_by":3,"name":"Ahmed El Sahy","email":"","orcid":"","institution":"Alexandria University Medical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"El","lastName":"Sahy","suffix":""},{"id":289697516,"identity":"49925e04-2a56-49ac-ae0a-9853e01178a9","order_by":4,"name":"Safia Khalil","email":"","orcid":"","institution":"Alexandria University Medical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Safia","middleName":"","lastName":"Khalil","suffix":""},{"id":289697517,"identity":"b817fa55-7aa4-4d2f-872a-2466b5353aa0","order_by":5,"name":"Naglaa Abd El-Latif","email":"","orcid":"","institution":"Alexandria University Medical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Naglaa","middleName":"Abd","lastName":"El-Latif","suffix":""}],"badges":[],"createdAt":"2023-11-03 15:29:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3552503/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3552503/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12639-024-01721-y","type":"published","date":"2024-08-21T15:56:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63300003,"identity":"86721efb-5cbe-4c4d-bbed-003a5218692c","added_by":"auto","created_at":"2024-08-26 16:08:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":745522,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3552503/v1/e6bc1240-3d74-421b-8c23-371ef5d6fa47.pdf"}],"financialInterests":"","formattedTitle":"Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSchistosomiasis is a chronic disease caused by the genus Schistosoma of the trematode parasites. It is endemic in 78 countries, infecting more than 207\u0026nbsp;million people worldwide and provoking above 200,000 deaths yearly (Calvisi, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Human infection occurs after exposure to contaminated water with schistosome cercariae which penetrate the skin and become schistosomula. They penetrate the wall of a nearby vein and are carried out in the blood circulation, eventually reaching the portal venous system, where they mature and lay eggs. These eggs are either trapped in the tissues and provoke a granulomatous reaction or are passed in the feces, then hatch in water to miracidia which invade the snail and are developed into cercariae to start a new cycle causing schistosomiasis which affects several organs, including the genitourinary, digestive, and nervous systems causing a spectrum of serious diseases (Davis, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e1996\u003c/span\u003e) Different Schistosoma species are involved in the development and/or progression of some tumor types, including colorectal carcinoma, prostate adenocarcinoma, giant follicular lymphoma, and hepatocellular carcinoma (Calvisi, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHepatocellular carcinoma (HCC) is the sixth most widespread cancer in the world and is responsible for approximately one million deaths per year. Most of HCC develops in the presence of chronic liver diseases mostly related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in addition to intestinal schistosomiasis (Ohata et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; Rashed et al, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Hu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEgypt ranks the 15th worldwide and the 3rd country in Africa regarding HCC. HCC constitutes 70% of all liver tumors, with an increase in the incidence rate in the last years (Shaker et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; El-Tonsy et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Rashed et al, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). This requires the investigation of the potential risk factors for its development. In rural areas, \u003cem\u003eS. mansoni\u003c/em\u003e remained a major chronic disease for many years (Barakat, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). It develops a series of pathology including hepatic fibrosis and it can help in development of neoplasia due to chronic granulomatous inflammatory reactions (Elbaz and Esmat, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). There is controversy and limited evidence in the available literature about the real role of \u003cem\u003eS. mansoni\u003c/em\u003e alone or in association with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the development of hepatic carcinoma. It was reported that 70\u0026ndash;90% of patients with chronic hepatitis, cirrhosis or HCC have co-infection of schistosomiasis and HCV (Rashed et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Strickland, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). It was suggested that the combination of chronic \u003cem\u003eS. mansoni\u003c/em\u003e infection and HBV or HCV may cause a higher risk of HCC. Understanding these associations may clarify the development and progress of HCC and subsequently draw attention and more effort to its prevention and control (El-Tonsy et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Toda et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; El-Tonsy et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Alboraie et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eScreening tools of HCC were commonly performed by measuring AFP levels in combination with ultrasonography that increased its sensitivity to 100% (Tateyama et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). It is a large serum glycoprotein, belonging to the eccentric class of onco-development protein (Bruno Daniele et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). Normally, its level decreases sharply after birth and continues at a low level afterwards. AFP level was studied among HCC patients in combination with other factors to find out if it is correlated with the progress of the disease (Hu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe severity of HCC is evaluated using the modified Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system (Pugh et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e1973\u003c/span\u003e; Forner et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). Child Pugh-score relies on clinical and laboratory evaluation including liver functions, serum albumin, international normalization ratio (INR) and prothrombin time to assess the severity of liver cirrhosis. BCLC identifies the stages of HCC based on the number and the size of tumors in the liver associated with liver function and overall performance status (Vogel et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). It helps in the decision of treatment for HCC patients (Jelic and Sotiropoulos, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Jun et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo shed more light on this controversial issue, this work aimed to evaluate the role of \u003cem\u003eSchistosoma mansoni\u003c/em\u003e infection in association with HBV and HCV and other risk factors in the development and/or progress of HCC.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Subjects and Ethical Considerations\u003c/h2\u003e \u003cp\u003e To perform this study, approvals from the Egyptian Ministry of Health and Population, the administration of Health Affairs in Kafr El-Sheikh governorate and the Research Ethics Committee of the Medical Research Institute (MRI), Alexandria University were obtained. The study was conducted on 90 HCC patients from Kafr El Sheikh and nearby Gharbia governorates attending or admitted to Kafr El Sheikh Liver Disease Research Institute during the period from September 2018 to September 2019. They were diagnosed by ultrasound (US) and confirmed by Triphasic Computed Tomography (CT).\u003c/p\u003e \u003cp\u003e All participants were asked to freely volunteer and informed consent was obtained prior to their inclusion in the study. Based on a predesigned questionnaire, brief demographic and retrospective clinical signs were collected including age, gender, residency and medical records concerning upper gastrointestinal bleeding (GIB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory Investigations\u003c/h2\u003e \u003cp\u003eStool and blood (2ml/patient) samples were collected from all patients and examined for active \u003cem\u003eS. mansoni\u003c/em\u003e infection by Kato-Katz (Katz et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e1972\u003c/span\u003e) and IHA (Bilharziose Fumouze Diagnostics/SERFIB, France). Accordingly, the patients were categorized into two groups; group I included HCC patients negative for schistosomiasis and group II included HCC patients with schistosomiasis. They were also examined for HCV antibodies by enzyme-linked immunosorbent assay (ELISA) technique (Human diagnostics, Germany and HCV Murex 40 Anhet laboratories, USA).\u003c/p\u003e \u003cp\u003eThe results of HBsAg and the other routine laboratory tests that were processed for each HCC patient were collected from the institute\u0026rsquo;s records. Among these tests: liver enzymes, alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), bilirubin (total and direct), albumin, thromboplastin activity and international normalization ratio (INR) in plasma using Biomed-Liquiplastin kit. No patients had concomitant parasite infections and any serological evidence, or a history of recent or old hepatitis A or D virus infections.\u003c/p\u003e \u003cp\u003eSerum AFP level was performed for each patientusing ELISA technique (AFP ElISA kit UK)(Chang et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Sauzay et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of HCC Severity\u003c/h2\u003e \u003cp\u003eThe severity of liver cirrhosis was evaluated in each patient with a modified Child-Pugh score (Pugh et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e1973\u003c/span\u003e). The BCLC stages were determined based on tumor features and liver function tests (Forner et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). Accordingly, patients were classified as A (early), B (intermediate), C (advanced) and D (terminal) (Toda et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). All the data were obtained from medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData analysis was completed using IBM SPSS software package version 20.0. \u003cb\u003e(\u003c/b\u003eArmonk, NY: IBM Corp)(Kirkpatrick and Feeney, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Qualitative data was described using numbers and percentages. The Kolmogorov-Smirnov test was used to verify the normality of distribution of quantitative data using range (minimum and maximum), mean and standard deviation, median and interquartile range (IQR). The significance of the obtained results was judged at the 5% level. Tests of Chi-square, Fisher\u0026rsquo;s Exact, Mann Whitney and student t-test were used to compare between the two studied groups (Altman, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1992\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAll 90 HCC patients were negative for \u003cem\u003eS. mansoni\u003c/em\u003e by Kato-Katz. Based on IHA; 62 HCC/S. \u003cem\u003emansoni\u003c/em\u003e negative patients were classified as group I and 28 \u003cem\u003eS. mansoni\u003c/em\u003e positives were in group II. The mean age of all HCC patients was 57.07\u0026thinsp;\u0026plusmn;\u0026thinsp;8.12 years, with no significant difference between HCC alone and HCC \u003cem\u003eS. mansoni\u003c/em\u003e co-infection. The larger proportion of HCC patients were in the age between 50\u0026ndash;60 years among both groups. Regarding gender, HCC was about four times more prevalent in males compared to females; 78.9% (71/90) versus 21.1% (19/90) respectively. Among positive \u003cem\u003eS. mansoni\u003c/em\u003e HCC patients: the male to female ratio was 3:1 (75% vs 25%). HCC was more common among patients from rural than urban areas in both groups with no statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). As for upper gastrointestinal bleeding, patients with \u003cem\u003eS. mansoni\u003c/em\u003e had significantly higher bleeding than those negative for \u003cem\u003eS. mansoni\u003c/em\u003e (64.3% versus 16% respectively, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline features of the 90 HCC patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(Group I)\u003c/p\u003e \u003cp\u003eHCC/\u003cem\u003eS. mansoni\u003c/em\u003e\u003c/p\u003e \u003cp\u003e-ve (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e(Group II)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni\u003c/em\u003e \u003c/p\u003e \u003cp\u003e+ve (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTest of Sig.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2.654\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.265\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;50\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e56.68\u0026thinsp;\u0026plusmn;\u0026thinsp;8.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e57.93\u0026thinsp;\u0026plusmn;\u0026thinsp;7.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;815.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eResidence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2=\u003c/sup\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUpper GIB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;20.872\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eU: Mann Whitney test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eχ\u003csup\u003e2\u003c/sup\u003e: Chi-square test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003ep: p\u003c/em\u003e-value for comparing between the studied groups, not significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.01)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* Statistically significant at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eGIB: gastrointestinal bleeding\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the two studied groups, HCV was more prevalent than HBV (88.9% vs 7.8% respectively). Similar patterns of HCV and HBV were observed in both groups; HCV was 87.1% in group I versus 92.6% in group II and HBV was 8.1% vs 7.1% among group I and group II respectively. There was no statistically significant difference between the two studied groups, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of the two studied groups according to HCV antibodies and HBsAg\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(Group I)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni\u003c/em\u003e\u003c/p\u003e \u003cp\u003e-ve (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e(Group II)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni\u003c/em\u003e\u003c/p\u003e \u003cp\u003e+ve (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90) \u003csup\u003e\u0026bull;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003eFE\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCV Ab\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e87.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e92.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e88.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.866\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBsAg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eχ\u003csup\u003e2\u003c/sup\u003e: Chi-square test, FE: Fisher Exact. \u003cem\u003ep: p\u003c/em\u003e-value for comparing between the studied groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003e*\u003c/sup\u003eTwo patients were negative for HCV antibodies and HBsAg and one case had both HCV and HBsAg and they were not included in the calculations\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e revealed that all HCC patients had high liver enzymes levels regarding alanine aminotransferase (SGPT), aspartate aminotransferase (SGOT), total bilirubin (T.BIL), direct bilirubin (D.BIL), albumin (ALB), prothrombin time (P.T) with no statistically significant difference between the two groups. Regarding the international normalization ratio (INR), it was statistically significantly higher in HCC/\u003cem\u003eS. mansoni\u003c/em\u003e positives (groups II) compared to HCC/\u003cem\u003eS. mansoni\u003c/em\u003e negatives (group I). Mean serum AFP level was elevated among all studied patients (1239.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2918). The mean value of AFP in group II (1830.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3735.3 IU/ml) was higher than that in group I (973.0 IU/ml) yet not significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the laboratory investigation results between the two studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(Group I)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni \u003c/em\u003e\u003c/p\u003e \u003cp\u003e -ve (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(Group II)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni \u003c/em\u003e\u003c/p\u003e \u003cp\u003e +ve (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTest of Sig.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGPT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.0\u0026ndash;156.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.0\u0026ndash;117.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.0\u0026ndash;156.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e839.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65.73\u0026thinsp;\u0026plusmn;\u0026thinsp;31.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61.54\u0026thinsp;\u0026plusmn;\u0026thinsp;24.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.42\u0026thinsp;\u0026plusmn;\u0026thinsp;29.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56.0(46.8\u0026ndash;71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54.50(41.3\u0026ndash;78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56.0(46.0\u0026ndash;74.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSGOT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.0\u0026ndash;205.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.0\u0026ndash;130.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15.0\u0026ndash;205.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e780.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76.60\u0026thinsp;\u0026plusmn;\u0026thinsp;41.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67.14\u0026thinsp;\u0026plusmn;\u0026thinsp;26.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e73.66\u0026thinsp;\u0026plusmn;\u0026thinsp;37.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62.0(49.8\u0026ndash;93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60.0(49.3\u0026ndash;84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e62.0(49.8\u0026ndash;87.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT. BIL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.40\u0026ndash;20.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.68\u0026ndash;10.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.40\u0026ndash;20.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e723.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.41\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.12(1.1\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.55(0.94\u0026ndash;2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.98(1.1\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eD. BIL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.09\u0026ndash;17.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13\u0026ndash;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u0026ndash;17.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e738.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.89(0.46\u0026ndash;1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.71(0.40\u0026ndash;1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.80(0.41\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.40\u0026ndash;4.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.20\u0026ndash;4.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.20\u0026ndash;4.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003et\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.20(2.9\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.15(2.8\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.20(2.9\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP.T\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.50\u0026ndash;20.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.50\u0026ndash;19.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.50\u0026ndash;20.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003et=\u003c/p\u003e \u003cp\u003e1.400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.70(12.9\u0026ndash;14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.20(13.3\u0026ndash;15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.90(12.9\u0026ndash;15.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eINR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01\u0026ndash;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.01\u0026ndash;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.01\u0026ndash;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e631.0\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003e0.039\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.20(1.1\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.36(1.2\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.24(1.1\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAFP (IU/ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin. \u0026ndash; Max.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.50\u0026ndash;15433.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.30\u0026ndash;16800.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.50\u0026ndash;16800.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e776.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e973.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2452.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1830.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3735.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1239.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2918.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87.55(12.2\u0026ndash;618.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e89.55(12.3\u0026ndash;1346.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e87.55(12.2 \u0026minus;\u0026thinsp;809.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eχ\u003csup\u003e2\u003c/sup\u003e: Chi-square test, FE: Fisher Exact. \u003cem\u003ep: p-\u003c/em\u003evalue for comparing between the studied groups\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSGPT: alanine aminotransferase, SGOT: aspartate aminotransferase, T.BIL: total bilirubin, D.BIL: direct bilirubin, ALB albumin, P.T: prothrombin time, INR: international normalization ratio.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eChild-Pugh Scoring System and BCLC among the Two Studied Groups\u003c/h2\u003e \u003cp\u003eIn Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, based on the Child-Pugh scoring system, a smaller proportion of group II had mild cirrhosis compared to group I, while a greater proportion of group II had moderate cirrhosis with no statistically significant difference. Marked cirrhosis was found in equal proportion in the two groups without any level of significance.\u003c/p\u003e \u003cp\u003eRegarding the BCLC staging system, in class A (early), more cases in group I revealed a higher percentage compared to those in group II (24.2% versus 7.1% respectively) with a borderline statistically significant difference. There was no statistically significant difference between group I and group II in classes B and C. However, HCC/\u003cem\u003eS. mansoni\u003c/em\u003e co-infection revealed a higher percentage in class D (terminal) compared to group I with a statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChild-Pugh scoring system and BCLC among the HCC studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(Group I)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni\u003c/em\u003e\u003c/p\u003e \u003cp\u003e-ve (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e(Group II)\u003c/p\u003e \u003cp\u003eHCC\u003cem\u003e/S. mansoni\u003c/em\u003e\u003c/p\u003e \u003cp\u003e+ve (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChild Pugh score\u003c/b\u003e (level of cirrhosis)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA (Mild)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e24.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB (Moderate)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e53.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.346\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC (Marked)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e22.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBCLC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA (Early)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e18.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3.660\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB (Intermediate)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e45.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.911\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC (Advanced)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003csup\u003eFE\u003c/sup\u003ep=0.747\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD (Terminal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e35.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e21.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5.204\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.023\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eχ\u003csup\u003e2\u003c/sup\u003e: Chi-square test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFE: Fisher Exact \u003cem\u003ep: p-\u003c/em\u003evalue for comparing between the studied groups *: Statistically significant at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHCC is commonly a disease of infectious origin; consequently, it could be preventable (El-Tonsy et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). In the present study, the association of \u003cem\u003eS. mansoni\u003c/em\u003e with HBV and/or HCV was investigated as a risk factor for the development of HCC. A total of 90 HCC cases were eligible for this study; they were categorized into HCC patients negative for schistosomiasis (62 patients) and HCC patients positive for schistosomiasis (28 patients).\u003c/p\u003e \u003cp\u003eIn this study, the larger proportion of HCC positive for \u003cem\u003eS. mansoni\u003c/em\u003e was in the age group 50\u0026ndash;60 years with no statistical significance. Abdel-Wahab et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) and El-Zayadi et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) revealed different findings and the predominant age was 40\u0026ndash;59 years, this was explained by the different localities, the risk of exposure and the study periods. As for gender, HCC was more prevalent in males than females (3:1) in the two groups with no significant difference. Concordant results were obtained by El-Zayadi et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) and El-Tonsy et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) concerning gender.\u003c/p\u003e \u003cp\u003eConsidering residence, the rural areas dwelled patients showed that HCC was 1.5 times higher than those living in urban areas (63% vs 36% respectively) with no statistically significant difference. These findings agreed with those of Abdel-Wahab et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) and El-Tonsy et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), which attributed the high prevalence in rural areas to the use of insecticides, pollution, and aflatoxins.\u003c/p\u003e \u003cp\u003eRegarding the clinical data, gastrointestinal hemorrhage in patients with HCC is common and is a major contributor to mortality (Srivastava et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). The present results revealed that upper GIB was highly significant among positive \u003cem\u003eS. mansoni\u003c/em\u003e group compared to the negative one. Consistently, it was reported that schistosomiasis fibrosis is associated with several vascular changes within the host. The peripheral destruction of the portal vein system with the obstruction of some medium-sized branches explains the presence of portal hypertension (one of the \u003cem\u003eS. mansoni\u003c/em\u003e infection complications) which leads to upper GIB (Johnson, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Kumar et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Andrade, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2009\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring the present study period, 88.9% and 7.8% of HCC patients had HCV and HBV correspondingly without statistically significant difference among the two groups, despite the higher proportion of HCC patients showing concomitant HCV and \u003cem\u003eS. mansoni\u003c/em\u003e. The development of a vaccine against HBV explains its lower prevalence. Similar results were reported by Abdel-Wahab et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), Shaker et al. (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) and Zampino et. al. (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Regarding, \u003cem\u003eS. mansoni\u003c/em\u003e and HCV co-infection, El-Zayadi et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) and Toda et al. (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) described that \u003cem\u003eSchistosoma\u003c/em\u003e infection may modify the sequence of hepatitis C and lead to more significant complications and faster progression to HCC than patients with no schistosomiasis parasite burden. Instead, Hassan et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2001\u003c/span\u003e) concluded that HCV infection increases the risk of HCC whereas \u003cem\u003eS. mansoni\u003c/em\u003e infection does not. Currently, Egypt succeeded to transform HCV from a health system stigma to a global success story through the 100\u0026nbsp;million healthy lives initiative launched in October 2018. Hopefully this may lead to lowering the prevalence of HCC.\u003c/p\u003e \u003cp\u003eRegarding the liver enzyme levels (SGPT, SGOT), total bilirubin, direct bilirubin and albumin, they were higher in HCC \u003cem\u003eS. mansoni\u003c/em\u003e positives compared to \u003cem\u003eS. mansoni\u003c/em\u003e negatives yet not statistically significant. Regarding the INR, there was a statistically significant difference between both groups. The concomitant infection or over infection with HCV in patients with schistosomiasis could be the cause of provocation of liver damage and subsequently reduction in coagulation factors production leading to prolonged prothrombin time. Similarly, Kamal et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2000a\u003c/span\u003e reported more fibrosis in liver biopsies in \u003cem\u003eS. mansoni\u003c/em\u003e and HCV concomitant infections compared to HCV mono- infection.\u003c/p\u003e \u003cp\u003eThe present results showed that AFP values ranged between 1.5 and 16800 IU/ml in all cases. Although the AFP level in the two studied groups showed no statistical difference, its mean value in the \u003cem\u003eS. mansoni\u003c/em\u003e positive group was higher than that in the negative one (1830.5 and 973.0 IU/ml respectively). It was reported that the increased levels in high risk patients provide HCC diagnostic clues. Yet, normal level does not exclude its presence. It was reported that 10\u0026ndash;30% of HCC patients have negative AFP expression. On the contrary, many investigators believe that AFP is significant in predicting HCC recurrence and evaluating the biologic features of tumors and treatment regimens (Kamal et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2000a\u003c/span\u003e; Hu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). It was pointed out that AFP prevalence among HCC is accompanied by certain controversies and needs novel directions for prospective studies (Lee et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Hu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the current study, the Child-Pugh classification revealed no significant difference between the two studied groups. However, BCLC classification showed significant statistical difference between the two groups regarding class (D). Therefore, the concomitant association of HCV and schistosomiasis may have increased the severity of liver pathology and progress of HCC.\u003c/p\u003e \u003cp\u003eAs for the role of \u003cem\u003eS. mansoni\u003c/em\u003e in inducing HCC, cumulating findings of human clinical investigations and experimental research in animal models on a molecular level suggest \u003cem\u003eS. mansoni\u003c/em\u003e is potentially associated with HCC. This association was explained by its activation of the proto-oncogenes; c-Jun signal transducer and transcription 3, whose role in liver inflammation and carcinogenesis is well established (Calvisi, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2020\u003c/span\u003e, Shousha et al, 2021). This study together with others suggest thatchronic inflammation resulting from prolonged parasitic infections may encourage carcinogenesis by three mechanisms; first, chronic inflammation that damages host cell and gene expression by supporting the release of reactive oxygen and nitrogen species; second, insertion of oncogenes into the host genome particularly in the presence of hepatitis B and hepatitis C, stimulation of mitosis and inhibition of tumor suppressors; third, reduction of immune response and induction of immune suppression (el-Zayadi et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; El-Tonsy et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Toda et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Abdelghani et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn conclusion, although in the current study, the co-occurrence of \u003cem\u003eS. mansoni\u003c/em\u003e with HCV and HBV quickens hepatic dysplastic changes and accelerates cancer progression yet; these associations are still being sorted out. So, further studies on large cohorts of HCC patients are essential.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors thank all the staff members of Kafr El Sheikh Liver Disease Research Institute for providing the required data, clinical advice, and unending cooperation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAbdelghani E, Zerpa R, Iliescu G, Escalante CP (2020) Schistosomiasis and liver disease: Learning from the past to understand the present. Clin Case Rep 8(8):1522-1526. doi: 10.1002/ccr3.2922. PMID: 32884787; PMCID: PMC7455423.\u003c/li\u003e\n \u003cli\u003eAbdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, et al (2007) Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. 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DOI:10.1053/j.gastro.2004.09.023\u003c/li\u003e\n \u003cli\u003eCalvisi DF (2020) Schistosoma mansoni and Hepatocellular Carcinoma: Is It All About c-Jun and Signal Transducer and Activator of Transcription 3? Hepatology 72(2):375-378. doi: 10.1002/hep.31392.\u003c/li\u003e\n \u003cli\u003eChang TS, Wu YC, Tung SY, Wei KL, Hsieh YY, et al (2015) Alpha-fetoprotein measurement benefits hepatocellular carcinoma surveillance in patients with cirrhosis. Am J Gastroenterol. 110(6):836-44; quiz 845. doi: 10.1038/ajg.2015.100.\u003c/li\u003e\n \u003cli\u003eDavis A (1996) Schistosomiasis. In: Cook G, ed. Manson\u0026rsquo;s Tropical Diseases. 20th ed. London: WB Saunders: 1413\u0026ndash;1456.\u003c/li\u003e\n \u003cli\u003eElbaz T, Esmat G (2013) Hepatic and Intestinal Schistosomiasis. 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Rev Inst Med Trop Sao Paulo 14(6), 397-400.\u003c/li\u003e\n \u003cli\u003eKirkpatrick LA, Feeney BC (2013) A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif.: Wadsworth, Cengage Learning.\u003c/li\u003e\n \u003cli\u003eKumar R, Saraswat MK, Sharma BC, Sakhuja P, Sarin SK (2008) Characteristics of hepatocellular carcinoma in India: a retrospective analysis of 191 cases. QJM 101(6): 479-485. DOI: 10.1093/qjmed/hcn033\u003c/li\u003e\n \u003cli\u003eLee CW, Tsai HI, Lee WC, Huang SW, Lin CY, et al (2019) Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal? Journal of Clinical Medicine 8(10), 1736\u0026ndash;. doi:10.3390/jcm8101736.\u003c/li\u003e\n \u003cli\u003eOhata K, Hamasaki K, Toriyama K, Ishikawa H, Nakao K, Eguchi K (2004) High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection. 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Hepatol 43(5):915-922.\u003c/li\u003e\n \u003cli\u003eTateyama M, Yatsuhashi H, Taura N, et al (2011) Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 46(1), 92\u0026ndash;100.\u003c/li\u003e\n \u003cli\u003eToda KS, Kikuchi L, Chagas AL, Tanigawa RY, Paranagu\u0026aacute;-Vezozzo DC, et al (2015) Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review. J Clin Transl Hepatol 3(4), 260-264. doi: 10.14218/JCTH.2015.00027\u003c/li\u003e\n \u003cli\u003eVogel A, Cervantes A, Chau I, Daniele B, Llovet JM, et al (2018) ESMO Guidelines Committee. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29 (Suppl 4): iv238-iv255. doi: 10.1093/annonc/mdy308.\u003c/li\u003e\n \u003cli\u003eZampino R, Pisaturo MA, Cirillo G, Marrone A, Macera M, et al (2015) Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration. Ann Hepatol. 14(1):75-82.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-parasitic-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jopd","sideBox":"Learn more about [Journal of Parasitic Diseases](https://www.springer.com/journal/12639)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jopd/default.aspx","title":"Journal of Parasitic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Hepatocellular carcinoma, S. mansoni, HCV, HBV, Alpha-fetoprotein","lastPublishedDoi":"10.21203/rs.3.rs-3552503/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3552503/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eThe implication of human \u003cem\u003eSchistosoma mansoni\u003c/em\u003e (\u003cem\u003eS. mansoni\u003c/em\u003e) infection in concomitance with other risk factors such as hepatitis C virus (HCV) and hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC) is still under controversy. This work aimed\u003c/p\u003e\n\u003cp\u003eto evaluate the role of \u003cem\u003eS. mansoni\u003c/em\u003e infection in association with hepatitis B virus (HBV), hepatitis C virus (HCV) and other risk factors in the development and/or progress of HCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e The present study was carried out on 90 HCC patients recruited from Kafr El-Sheikh Liver Disease Research Institute. After obtaining their informed consents, socio-demographic and clinical data were collected and patients were examined for \u003cem\u003eS. mansoni \u003c/em\u003eby Kato-Katz and indirect hemagglutination (IHA) techniques. Alpha-fetoprotein (AFP) level was determined. The Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system were used to evaluate the pathological features of the studied patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eAll participants were negative for active \u003cem\u003eS. mansoni\u003c/em\u003e by Kato-Katz. Based on IHA, the participants were categorized into two groups: group I: sixty-two patients negative for \u003cem\u003eS. mansoni\u003c/em\u003e and group II: twenty-eight schistosomiasis positive\u003cem\u003e.\u003c/em\u003e The patients’ age ranged between 40-\u0026gt;60 years with a mean of 57.07± 8.12 years. HCC was more prevalent in the age range of \u0026gt;50-60 years in both groups. Males were more than females and rural participants were more than urban patients in both groups. Most of the patients (88.9%) had HCV while 7.8% had HBV. A higher proportion of HCC patients showed concomitant HCV and \u003cem\u003eS. mansoni\u003c/em\u003e (92.6%) than the \u003cem\u003eS. mansoni\u003c/em\u003enegative group. Alpha-fetoprotein (AFP) level was higher in group II than that in group I with no significant difference. Statistical analysis showed no difference between the two studied groups regarding Child scores. On the contrary, BCLC class D was significantly higher among HCC positive schistosomiasis cases compared to the negative group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eConcomitant \u003cem\u003eS. mansoni\u003c/em\u003e with HCV and HBV potentiate HCC progression.\u003c/p\u003e","manuscriptTitle":"Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-15 13:28:33","doi":"10.21203/rs.3.rs-3552503/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revisions needed","date":"2024-07-14T23:24:03+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-05-21T05:20:38+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-10T12:26:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-11-03T07:23:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Parasitic Diseases","date":"2023-11-02T11:15:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-parasitic-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jopd","sideBox":"Learn more about [Journal of Parasitic Diseases](https://www.springer.com/journal/12639)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jopd/default.aspx","title":"Journal of Parasitic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"aafa41db-f0a4-4311-90c6-df20c6a786be","owner":[],"postedDate":"April 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T15:58:44+00:00","versionOfRecord":{"articleIdentity":"rs-3552503","link":"https://doi.org/10.1007/s12639-024-01721-y","journal":{"identity":"journal-of-parasitic-diseases","isVorOnly":false,"title":"Journal of Parasitic Diseases"},"publishedOn":"2024-08-21 15:56:56","publishedOnDateReadable":"August 21st, 2024"},"versionCreatedAt":"2024-04-15 13:28:33","video":"","vorDoi":"10.1007/s12639-024-01721-y","vorDoiUrl":"https://doi.org/10.1007/s12639-024-01721-y","workflowStages":[]},"version":"v1","identity":"rs-3552503","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3552503","identity":"rs-3552503","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}