Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study

doi:10.21203/rs.3.rs-3552503/v1

Download PDF

Research Article

Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study

https://doi.org/10.21203/rs.3.rs-3552503/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 21 Aug, 2024

Read the published version in Journal of Parasitic Diseases →

You are reading this latest preprint version

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. mansoninegative 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

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.

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).

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
Parameter	No.	%	No.	%	Test of Sig.	P
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	χ² = 0.369	0.544
Female	12	19.4	7	25.0	χ² = 0.369	0.544
Residence
Rural	38	61.3	19	67.9	χ²⁼0.358	0.550
Urban	24	38.7	9	32.1	χ²⁼0.358	0.550
Upper GIB	10	16.1	18	64.3	χ² = 20.872^*	< 0.001^*
U: Mann Whitney test
χ²: Chi-square test
p: p-value for comparing between the studied groups, not significant (p > 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) ^•		χ²	^FEp
Variables	No.	%	No.	%	No.	%	χ²	^FEp
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
χ²: 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)
χ²: 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)		χ²	p
	No.	%	No.	%	No.	%	χ²	p
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	^FEp=0.747
D (Terminal)	9	14.5	10	35.7	19	21.1	5.204^*	0.023^*
χ²: Chi-square test

FE: Fisher Exact p: p-value for comparing between the studied groups *: Statistically significant at p ≤ 0.05

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.

The authors declare no conflict of interest.

Acknowledgments

The authors thank all the staff members of Kafr El Sheikh Liver Disease Research Institute for providing the required data, clinical advice, and unending cooperation.

Abdelghani 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.
Abdel-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. Hepatogastroenterol 54(73): 157-162.
Alboraie M, Youssef N, Sherief AF, Afify S, Wifi MN, et al (2019) Egyptian liver library: An indexed database for liver disease evidence in Egypt. Arab Enterol 2(6),109-113. https://doi.org/10.1016/j.ajg.2019.05.004
Altman GA (1992) Practical statistics for medical research. London, Chapman and Hall. pp. 404–408.
Andrade ZA (2009) Schistosomiasis and liver fibrosis. Parasite immunol 31(11): 656-663. https://doi.org/10.1111/j.1365-3024.2009.01157.x
Barakat RMR (2013) Epidemiology of Schistosomiasis in Egypt: Travel through Time: Review. J Adv Res 4(5), 425-432.
Bruno Daniele B, Bencivenga A, Megna AS, Tinessa V (2004) Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterol 127(5): 108-112. DOI:10.1053/j.gastro.2004.09.023
Calvisi 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.
Chang 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.
Davis A (1996) Schistosomiasis. In: Cook G, ed. Manson’s Tropical Diseases. 20th ed. London: WB Saunders: 1413–1456.
Elbaz T, Esmat G (2013) Hepatic and Intestinal Schistosomiasis. J Adv Res 4(5): 445–452. doi: 10.1016/j.jare.2012.12.001
El-Tonsy MM, Hussein HM, Helal Tel S, Tawfik RA, Koriem KM, et al (2016) Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective. J Parasit Dis 40(3): 976-980. doi: 10.1007/s12639-014-0618-0.
El-Tonsy MM, Hussein HM, Helal TES, Tawﬁk RA, Koriem KM, et al (2013) Schistosoma mansoni infection: Is it a risk factor for development of hepatocellular carcinoma? Acta Tropica 128: 542– 547. https://doi.org/10.1016/j.actatropica.2013.07.024
El-Tonsy MM, Hussein HM, Helal TES, Tawfik RA, Koriem KM, Hussein HM (2016) Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective J Parasit Dis 40(3), 976-980. doi: 10.1007/s12639-014-0618-0.
el-Zayadi AR, Badran HM, Barakat EM, Attia Mel D, Shawky S, et al (2005) Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 11(33): 5193-5198. DOI: 10.3748/wjg.v11.i33.5193
Forner A, Reig ME, de Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30(1): 61-74. doi: 10.1055/s-0030-1247133
Hassan MM, Zaghloul AS, El-Serag HB, Soliman O, Patt YZ, et al (2001) The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients. J Clin Gastroenterol 33(2): 123-126. DOI: 10.1097/00004836-200108000-00006.
Hu X, Chen R, Wei Q, Xu X. (2022) The landscape of alpha fetoprotein in hepatocellular carcinoma: Where are we? Int J Biol Sci. 18(2):536-551. doi: 10.7150/ijbs.64537. PMID: 35002508; PMCID: PMC8741863.
Jelic S, Sotiropoulos GC (2010) Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21 (Suppl 5) v59–64. doi: 10.1093/annonc/mdq166
Johnson P (2006) Malignant tumours of the liver. In B. Bacon, G. O’Grady, A. Di Bisceglie & J. Lake (Eds.), Comprehensive Clinical Hepatology, 2nd edn (p.p.453–485). Philadelphia, PA: Elsevier Mosby publications.
Jun CH, Yoon JH, Cho E, Shin SS, Cho SB, et al (2017) Barcelona clinic liver cancer-stage C hepatocellular carcinoma: A novel approach to subclassification and treatment. Medicine (Baltimore) 96(17): e6745. doi: 10.1097/MD.0000000000006745.
Kamal S, Madwar M, Bianchi L, Tawil AE, Fawzy R, et al (2000a) Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni. Liver 20(4): 281-289. DOI: 10.1034/j.1600-0676.2000.020004281.x
Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14(6), 397-400.
Kirkpatrick LA, Feeney BC (2013) A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif.: Wadsworth, Cengage Learning.
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.

Download PDF

Journal Publication

published 21 Aug, 2024

Read the published version in Journal of Parasitic Diseases →

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

Schistosoma mansoni Infection and Hepatocellular Carcinoma: A Comorbidity Study

Status:

Journal Publication

Version 1

Abstract

Introduction

Materials and Methods

Study Subjects and Ethical Considerations

Laboratory Investigations

Evaluation of HCC Severity

Statistical Analysis

Results

Child-Pugh Scoring System and BCLC among the Two Studied Groups

Discussion

Declarations

Acknowledgments

References

Status:

Journal Publication

Version 1