Minimal hepatic encephalopathy in hepatosplenic schistosomiasis: High prevalence and association with portosystemic shunts in a Brazilian cross-sectional study

Abstract

BACKGROUND

Hepatic encephalopathy (HE) is a poorly understood complication in hepatosplenic schistosomiasis (HSS), a neglected cause of non-cirrhotic portal hypertension. Although portosystemic shunts (PSS) are commonly observed in HSS patients, the prevalence and clinical impact of overt HE (OHE) and minimal HE (MHE) remain understudied, particularly in resource-limited settings.

AIM

To determine OHE/MHE prevalence in HSS and its associations with PSS, clinical, and laboratory characteristics.

METHODS

This cross-sectional study included 200 HSS patients undergoing treatment at the Hospital of Universidade Federal de Pernambuco in Brazil between 2021 and 2023. Cognitive function was assessed using the animal naming test (ANT) and Mini-Mental State Examination (MMSE), while psychological status was evaluated with the Hospital Anxiety and Depression Scale. PSS was identified via ultrasound, and fibrosis severity was quantified using the Coutinho index (CI). Analyses were adjusted for education level and the presence of comorbidities. Statistical analyses were performed using R software.

RESULTS

The prevalence of OHE was 0.5%, while MHE, diagnosed via ANT, affected 24% of patients. ANT positivity was significantly associated with the presence of PSS (35.1% vs 15.1%; P = 0.0018) and higher CI scores (1.79 ± 0.26 vs 1.30 ± 0.84; P = 0.045). Patients with MHE demonstrated notably lower MMSE scores (24.06 ± 1.17 vs 26.04 ± 0.63; P = 0.0003), independent of education level. The ANT showed high diagnostic robustness, even among patients with limited formal education.

CONCLUSION

MHE is prevalent in HSS, especially with PSS, and is associated with portal hypertension severity. The ANT enables practical screening, underscoring the need for routine assessment to improve outcomes.

Key Words: Hepatic encephalopathy; Schistosoma mansoni; Portosystemic shunts; Neglected tropical diseases; Cognitive dysfunction; Neuropsychological tests; Brazil; Public health; Resource-limited settings; Coutinho index

Core Tip: This pioneering study establishes a high prevalence (24%) of minimal hepatic encephalopathy (MHE) in hepatosplenic schistosomiasis (HSS), a neglected tropical disease. We use the animal naming test as a simple, culture-fair, and education-resistant tool for MHE screening in endemic, resource-limited areas. A key innovative finding is the association between MHE, portosystemic shunts, and the Coutinho index, suggesting a combined screening approach. This mandates a paradigm shift towards routine cognitive screening in HSS to mitigate the significant burden of neurocognitive impairment in this neglected population.

INTRODUCTION

Schistosomiasis remains a leading neglected tropical disease, disproportionately impacting low-income regions with inadequate sanitation. Worldwide, 207 million people are infected with Schistosoma species, and around 779 million remain at risk[1]. Brazil is the most endemic country in the Americas, with an estimated 30 million people exposed to Schistosoma mansoni (S. mansoni)[2].

The hepatosplenic form hepatosplenic schistosomiasis (HSS), the most severe manifestation of the disease, develops in approximately 5%-10% of infections and is characterized by periportal fibrosis and non-cirrhotic portal hypertension (NCPH)[3]. Unlike cirrhosis, HSS typically spares hepatocytes, thereby usually lacking classic markers of hepatic failure - such as jaundice and ascites[4]. Nonetheless, presinusoidal portal hypertension can lead to serious complications, including esophageal varices and gastrointestinal bleeding[5]. Portosystemic shunts (PSS) develop in up to 78% of HSS patients[6], providing pathway for hepatic encephalopathy (HE), a neuropsychiatric complication traditionally associated with cirrhosis but increasingly recognized in NCPH[7,8].

HE encompasses a clinical spectrum ranging from minimal HE (MHE), characterized by subtle cognitive deficits, to overt HE (OHE), which involves more severe neurological manifestations such as confusion or coma[7]. Even MHE significantly impacts quality of life, daily function, and driving ability[9]. Despite the high prevalence of PSS in HSS patients, data on HE, and particularly on MHE, remain scarce and inconsistent, with studies reporting variable rates due to heterogeneous diagnostic methodologies[10]. In HSS patients, HE has been associated with gastrointestinal bleeding, PSS, and transjugular intrahepatic portosystemic shunt placement[5,11], and accounts for approximately 22% of deaths related to S. japonicum infections[12].

The historical neglect of neurocognitive outcomes in HSS arises from its classification as a disease of poverty, which has often relegated it behind more acute conditions in public health priorities and resulted in insufficient dedicated funding for comprehensive research[13]. Furthermore, the subtle and non-lethal nature of MHE has likely contributed to its oversight in public health agendas primarily focused on reducing mortality from bleeding varices. In recent years, there has been a paradigm shift toward a more holistic understanding of schistosomiasis morbidity, with increasing emphasis on quality of life and chronic disability. This evolving perspective, complemented by growing recognition of NCPH complications and enhanced governmental and international funding for neglected tropical disease research, has created the necessary impetus to address this critical knowledge gap[14,15]. Diagnosing MHE in HSS patients presents challenges, especially in populations with limited education. Standard assessment tools, such as the Psychometric Hepatic Encephalopathy Score (PHES) or Stroop test rely on literacy[16], while electrophysiological tests, e.g., electroencephalogram (EEG) are impractical in resource-limited settings. The ANT, however, is a simple, education-resistant tool validated for MHE detection in cirrhosis[17-21], including Brazilian cohorts[21]. Its suitability for HSS populations remains unexplored.

Study objectives

Given the substantial knowledge gap on HE in HSS patients and the practical advantages of the ANT, this study aims to: (1) Determine the prevalence of OHE and MHE in HSS patients; and (2) Assess associations between HE and factors such as PSS, fibrosis severity [Coutinho index (CI)], and relevant clinical/Laboratory markers.

MATERIALS AND METHODS

Study design and population

A cross-sectional study was conducted at the schistosomiasis referral clinic of Universidade Federal de Pernambuco, Brazil, between 2021 and 2023.

Inclusion criteria

Participants were included based on the following criteria: (1) Aged between 18 and 75 years; (2) Confirmed S. mansoni infection, evidenced by positive stool microscopy and/or a documented history of prior treatment; (3) Ultrasonographic evidence of periportal fibrosis graded as patterns D, E, or F according to the Niamey classification[19]; and (4) Presence of clinical and/or ultrasonographic signs of portal hypertension, such as splenomegaly or varices.

Exclusion criteria

Participants were excluded based on the following criteria: (1) Presence of other liver diseases, including: (a) Cirrhosis (evidenced by clinical, laboratory, and ultrasonographic findings consistent with liver failure); (b) Viral hepatitis (positive serologies for hepatitis B surface antigen, hepatitis B core antibody, or anti-hepatitis C virus); and (c) Metabolic or autoimmune liver disorders (based on clinical history or medical records); (2) Recent gastrointestinal bleeding (within the previous 8 weeks); (3) Alcohol abuse, defined as consumption exceeding two alcoholic beverages per week within the past six months; and (4) Conditions potentially affecting cognitive function, including: (a) Cognitive impairment [Mini-Mental State Examination (MMSE) score < 17]; (b) Anxiety or depression [Hospital Anxiety and Depression Scale (HAD) score ≥ 10]; (c) Use of benzodiazepines, antiepileptic drugs, or central nervous system depressants; and (d) Human immunodeficiency virus infection, syphilis (positive venereal disease research laboratory), thyroid dysfunction, or vitamin B12 deficiency.

Sample size calculation

The sample size was calculated based on a pilot study involving 40 patients, which estimated the prevalence of MHE. Using these preliminary studies, a minimum of 196 participants was required to achieve 80% statistical power with a 95% confidence interval.

Clinical and cognitive assessments

All participants underwent a thorough evaluation, including: (1) Sociodemographic data: Age, sex, self-reported ethnicity (categorized as Black/mixed-race or White), and education level, with functional illiteracy defined as ≤ 4 years of formal education; (2) Physical examination: OHE was classified according to the West Haven criteria[11]; and (3) Psychometric evaluation: (a) HAD, with a cutoff score of ≥ 8 indicating potential anxiety or depression; (b) MMSE, Brazilian version, assessing six cognitive domains; and (c) Animal naming test (ANT) with MHE defined as naming fewer than 15 animals for participants with ≥ 8 years of education, or fewer than 10 animals for those with < 8 years of education, within 60 seconds[10].

Imaging and laboratory tests

Abdominal ultrasound: Performed with a Siemens Acuson S2000 device to assess periportal fibrosis (using the Niamey classification), splenomegaly, and PSS (including splenorenal shunts, paraumbilical veins, and varices)[22].

Upper digestive endoscopy: Conducted to detect esophageal and gastric varices.

Laboratory analysis: Laboratory analysis including: (1) Fibrosis indices; (2) Liver function tests: Total bilirubin, international normalized ratio (INR), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); (3) Aspartate-to-platelet ratio index (APRI): [(AST/upper limit of normal)/platelet count (10⁹/L)] × 100; (4) Fibrosis-4 index (FIB-4): [Age (years) × AST (U/L)]/[platelet count (10⁹/L) × ]; and (5) CI: [(ALP/upper limit of normal)/platelet count (10⁹/L)] × 100[23].

Statistical analysis

Data were analyzed using R software (version 3.3.1). Descriptive statistics are presented as means ± SD or percentages. The normality of data distribution was assessed using the Kolmogorov-Smirnov test, and homogeneity of variance was evaluated with Levene's test. Group comparisons were conducted using Student's t-test for parametric data, the Mann-Whitney U test for non-parametric data, and the χ² test for categorical variables. A P value < 0.05 was considered statistically significant for all analyses.

RESULTS

Sample characterization

The final study cohort included 200 patients after excluding 170 individuals who met the predefined exclusion criteria: 78 with associated cirrhosis, 62 with fatty liver disease, 15 with recent alcohol use, 3 with MMSE scores below 17, 4 with HAD scores below 10, 3 chronic benzodiazepine users, and 5 with indeterminate syphilis.

The study population had a mean age of 56.44 ± 13.31 years, comprising predominantly middle-aged and elderly adults. Slightly over half of the participants (53%, n = 106) were women. The majority self-identified as Black (74%, n = 148), which aligns with the sociodemographic profile typical of schistosomiasis-affected populations in Brazil. Educational levels were significantly low, with an average of 4.88 ± 3.47 years of formal education. Notably, 8.5% (n = 17) were illiterate, and 58.5% (n = 117) were classified as functionally illiterate. Nearly half of the participants (47%, n = 94) had undergone splenectomy, consistent with the standard management of portal hypertension in advanced HSS.

Regarding psychological and cognitive assessments, the mean HAD score was 7.88 ± 2.16. The average MMSE score was 25.42 ± 0.81, with 36.5% (n = 73) of participants scoring below 25, indicating potential cognitive impairment (Table 1).

Table 1 Demographic and clinical characteristics of 200 patients with hepatosplenic schistosomiasis (Recife, Brazil, 2025).

Variable	mean ± SD or n (%)
Mean age (years)	56.44 ± 13.31
Female sex	106 (53.00)
Self-reported ethnicity
Black	148 (74.00)
White	52 (26.00)
Average education (years)	4.88 ± 3.47
Illiteracy	17 (8.50)
Functional illiteracy	117 (58.50)
Previous splenectomy	94 (47.00)
Mean HAD score	7.88 ± 2.16
Mean MMSE score	25.42 ± 0.81

HAD: Hospital Anxiety and Depression Scale; MMSE: Mini-Mental State Examination.

Prevalence of HE

As shown in Table 2, OHE was rare, detected in only 0.5% (n = 1) of patients, whereas MHE was identified in 24% (n = 48) of patients using ANT.

Table 2 Prevalence of hepatic encephalopathy diagnosis through animal naming test in 200 patients with hepatosplenic schistosomiasis.

Variable	n (%)
Overt hepatic encephalopathy	1 (0.50)
Minimal hepatic encephalopathy (positive animal naming test)	48 (24.00)

Association between cognitive assessment and presence of PSS

PSS identified via ultrasound were significantly more prevalent in patients diagnosed with HE (67.3%) compared to those without HE (51.6%; P = 0.0018). The detailed distribution of patients according to HE status and PSS presence is presented in Table 3.

Table 3 Distribution of 200 patients with hepatosplenic schistosomiasis with and without hepatic encephalopathy, diagnosed by animal naming, according to the presence or absence of portosystemic shunts (Recife, Brazil, 2025).

Encephalopathy portosystemic shunts	Yes (%)	No (%)	Total (%)	P value
Yes	33 (67.30)	78 (51.60)	111 (55.50)	0.0018
No	16 (32.60)	73 (48.30)	89 (44.50)
Total	49 (24.50)	151 (75.50)	200 (100)

Data are showed as n (%).

Comparison of clinical characteristics by HE status

Patients with HE were significantly more likely to be female (67.35% vs 48.34%, P = 0.03) and exhibited notably lower MMSE scores (24.06 ± 1.17 vs 26.04 ± 0.63, P = 0.0003). Additionally, a higher proportion of HE patients had MMSE scores below 25 (57.14% vs 29.8%, P = 0.001). No significant differences were observed in age, ethnicity, education level, history of upper gastrointestinal bleeding, splenectomy status, or HAD scores (Table 4).

Table 4 Clinical characteristics of 200 patients with hepatosplenic schistosomiasis, according to the presence or absence of hepatic encephalopathy diagnosed by animal naming (Recife, Brazil, 2025).

Variables	Total (%)	With HE, n = 49 (%)	Without HE, n = 151 (%)	P value
Average age (years)	56.44 ± 13.31	57.55 ± 13.96	56.08 ± 13.08	0.52
Female sex	106 (53.00)	33 (67.35)	73 (48.34)	0.03
Self-reported ethnicity
Black	148 (74.00)	38 (77.55)	110 (72.84)	0.68
White	52 (26.00)	11 (22.45)	41 (27.15)
Education (years)	4.80 ± 3.47	4.50 ± 4.35	5.21 ± 3.06	0.14
History of UGIB	127 (63.50)	34 (69.38)	93 (61.58)	0.41
Previous splenectomy	94 (47.00)	21 (42.86)	73 (48.34)	0.61
HAD questionnaire score	7.88 ± 2.16	7.69 ± 3.79	7.94 ± 2.50	0.83
Mean MMSE score	25.42 ± 0.81	24.06 ± 1.17	26.04 ± 0.63	0.0003
MMSE < 25	73 (36.50)	28 (57.14)	45 (29.80)	0.001

Data are showed as n (%) or mean ± SD. UGIB: Upper gastrointestinal bleeding; HAD: Hospital Anxiety and Depression Scale; MMSE: Mini-Mental State Examination; HE: Hepatic encephalopathy.

Comparison of laboratory parameters by HE status

The CI was significantly higher in patients with HE (1.79 ± 0.26) compared to those without HE (1.30 ± 0.84, P = 0.045). No significant differences were observed between the groups regarding total bilirubin, INR, albumin, ALP, platelet count, APRI, or FIB-4 scores (Table 5).

Table 5 Comparison between the presence of hepatic encephalopathy (according to animal naming) and laboratory parameters in 200 patients with hepatosplenic schistosomiasis (Recife, Brazil, 2025), mean ± SD.

Variables	Total	With HE, n = 49	Without HE, n = 151	P value
Total bilirubin	1.20 ± 0.76	1.19 ± 0.77	1.19 ± 0.76	0.98
INR	1.20 ± 0.05	1.22 ± 0.23	1.20 ± 0.21	0.46
Albumin	4.02 ± 0.48	3.97 ± 0.57	4.04 ± 0.44	0.40
Alkaline phosphatase	128.83 ± 74.50	150.75 ± 63.00	120.96 ± 77.00	0.06
Platelets (× 109/L)1	75846 ± 48000	75000 ± 48000	77000 ± 45000	0.87
APRI1	2.00 ± 2.17	2.21 ± 0.50	1.93 ± 1.40	0.64
FIB-41	6.24 ± 4.06	7.08 ± 0.30	5.93 ± 3.40	0.27
Coutinho index1	1.43 ± 0.78	1.79 ± 0.26	1.30 ± 0.84	0.04

¹Splenectomized patients excluded.

INR: International normalized ratio; APRI: Aspartate-to-platelet ratio index; FIB-4: Fibrosis-4 index; HE: Hepatic encephalopathy.

Comparison of ultrasonographic parameters by HE status

No significant associations were observed between HE status and Niamey classification, splenectomy status, portal vein visibility, or vascular diameters (portal vein, splenic vein) (Table 6).

Table 6 Ultrasonographic characteristics of 200 patients with hepatosplenic schistosomiasis, according to the presence or absence of hepatic encephalopathy diagnosed by Animal naming (Recife, Brazil, 2025).

Variables		Total (%)	With HE, n = 49 (%)	Without HE, n = 151 (%)	P value
Niamey classification	D	22 (11.00)	9 (18.37)	13 (8.61)	0.057
	E	128 (64.00)	25 (51.02)	103 (68.21)
	F	50 (25.00)	15 (30.61)	35 (23.18)
Prior splenectomy		94 (47.00)	21 (42.86)	73 (48.34)	0.61
Portal vein not visualized1		45 (22.50)	6 (12.24)	39 (25.83)	0.074
Longitudinal diameter of spleen (n = 106)		16.15 ± 8.44	16.07 ± 8.50	16.17 ± 8.41	0.89
Portal vein diameter (n = 155)		1.02 ± 0.49	1.03 ± 0.49	1.01 ± 0.49	0.68
Splenic vein diameter (n = 106)		0.97 ± 0.52	0.90 ± 0.53	0.96 ± 0.53	0.57

¹Portal vein thrombosis or cavernoma or technical difficulties.

Data are showed as n (%) or mean ± SD. HE: Hepatic encephalopathy.

DISCUSSION

This study presents the first estimate of type B HE in patients with HSS. We observed a prevalence of 24% for MHE and 0.5% for OHE. The significant association between HE and the presence of PSS highlights the importance of screening for MHE in this population, considering its detrimental impact on quality of life and daily functioning.

Our findings are consistent with the broad range of HE prevalence reported in NCPH. This heterogeneity across NCPH etiologies is well-documented[10,24,25]. Seminal studies, such as Webb and Sherlock’s work, reported a clinical HE prevalence of up to 36% among 76 patients with extrahepatic portal vein obstruction (EHPVO)[26]. More recent studies report lower rates, ranging from 4.3% to 35%, in cohorts of 46 and 34 patients with EHPVO[27-29] and non-cirrhotic portal fibrosis, respectively[15]. The relatively high prevalence observed in our HSS cohort may be attributed to a particular propensity for developing extensive spontaneous PSS[30].

By contrast, clinical HE is considered rare (approximately 2%) in patients with idiopathic portal hypertension (IPH) and EHPVO who have not undergone surgical shunts or precipitating events[8]. When it does occur, HE usually manifests after major gastrointestinal bleeding or shunt surgery[29]. Another study reported a 7.8% HE prevalence in 51 patients with idiopathic NCPH. It suggests that underlying etiology influences portosystemic shunting mechanisms and hemodynamic alterations, which may contribute to HE development[10]. However, direct comparisons are difficult because many previous studies did not systematically assess the relationship between HE and spontaneous PSS[31], a factor that emerging evidence suggests is crucial in the pathogenesis of HE across all NCPH etiologies[32] (Table 7).

Table 7 Comparative analysis of hepatic encephalopathy prevalence across different etiologies of non-cirrhotic portal hypertension.

Ref.	Etiology	Country	Sample size	HE prevalence (%)	HE assessment method	Key findings related to PSS
Webb and Sherlock[26], 1979	EHPVO	United Kingdom	76	35.5	Clinical	High HE prevalence but no systematic PSS correlation
Sharma et al[28], 2008	EHPVO	India	22	31.82	Neuropsychological tests, CFF, blood ammonia, MRI	MHE correlates with PSS (72.7% vs 17.4%, P = 0.001)
Mohan and Venkataraman[27], 2011	EHPVO, INCPH	India	46	4.3	A and B track and CFF	No PSS correlation
Nicoletti et al[24], 2016	PVT and INCPH	Italy	51	PVT: 37.1; INCPH: 31.3	West Haven criteria, PHES, and the scan battery	Correlation with PSS in INCPH (71.4% vs 33.3%; P = 0.02)
Riggio et al[31], 2005	Cirrhosis	Italy	12	14	Neuropsychological tests, EEG, blood ammonia, MRI	Correlation with PSS (71% vs 14%; P = 0.002)
Present study	HSS	Brazil	200	24.5	Neuropsychological tests	Strong association between HE and PSS (P = 0.0018)

A and B track test: Attention and coordination tests used for minimal hepatic encephalopathy diagnosis; HE: Hepatic encephalopathy; PSS: Portosystemic shunts; EHPVO: Extrahepatic portal vein obstruction; INCPH: Idiopathic non-cirrhotic portal hypertension; PVT: Portal vein thrombosis; CFF: Critical flicker frequency; MRI: Magnetic resonance imaging; MHE: Minimal hepatic encephalopathy; PHES: Psychometric Hepatic Encephalopathy Score; EEG: Electroencephalogram.

The ANT proved to be an effective screening tool for MHE in this population, mainly due to its simplicity and cultural suitability. Ortiz-Treviño et al[33] validated the ANT in 121 patients with cirrhotic. They reported a sensitivity of 58% and a specificity of 79% for detecting MHE, using a cutoff of fewer than 16 animals named, with the PHES serving as the gold standard[33]. Our findings support the applicability of the ANT in the NCPH population, specifically among patients with HSS. Its practicality was particularly important, given that 58.5% of our participants were functionally illiterate, a common feature in regions endemic for neglected tropical diseases[34].

Educational attainment is a well-established confounder in cognitive testing, particularly for tasks involving executive function and abstraction[35]. Although the PHES is considered the gold standard for detecting MHE in cirrhotic patients[36,37], it has notable limitations in populations with low-education levels[38], often producing false-positive results. The ANT, which assesses semantic memory rather than abstract reasoning, was therefore more suitable for our study population. This supports its role as a reliable alternative to more complex tests like the PHES, although some education-based adjustments may still be necessary[39].

Additionally, the predominance of women in our sample may have influenced the outcomes. It is plausible that women might perform differently on the ANT, potentially due to a greater burden of domestic responsibilities, less frequent contact with animals, and higher illiteracy rates in this specific context. This observation warrants further investigation to understand potential gender-related differences in test performance.

Another key finding was the association between higher CI values and positive ANT results, indicating that the CI could serve as an indirect marker of cognitive impairment in HSS patients. Barreto et al[23] identified the CI as an indicator of advanced periportal fibrosis in schistosomiasis. Our findings suggest that combining the CI, which reflects the severity of portal tract fibrosis and portal hypertension, with ANT screening may enhance the identification of patients at high risk for MHE. This is consistent with the understanding that the risk of HE in portal hypertension is linked to the severity of portosystemic shunting, which often correlates with the degree of underlying fibrosis.

Furthermore, our findings corroborate the association between MHE and PSS, as reported in other forms of portal hypertension[24,28,31,40], highlighting the need for routine MHE screening in patients with PSS[10]. In our cohort, over two-thirds of patients with HE had PSS. The number is consistent with class B of the World Gastroenterology Organization's HE classification[36]. The pathophysiology of HE in HSS is mainly related to PSS, which facilitates the accumulation of neurotoxins like ammonia, resulting in hyperammonemia and systemic inflammation[41]. These mechanisms are similar to those observed in cirrhotic HE[7] and other portal hypertensive states. Another proposed mechanism involves chronic hepatic hypoperfusion leading to parenchymal extinction, supported by findings of elevated ammonia, pro-inflammatory cytokines, and abnormal proton magnetic resonance spectroscopy in patients with IPH and EHPVO[8]. Notably, there were no significant differences in conventional liver function tests between patients with and without HE. This supports the idea that, in NCPH, including HSS, HE mainly results from vascular pathophysiology and PSS, rather than hepatocellular dysfunction[42].

Study limitations

Several limitations of this study must be acknowledged. First, the lack of cross-sectional imaging techniques, such as computed tomography or magnetic resonance imaging, limited the detailed assessment of PSS, which may have led to an underestimation of vascular abnormalities[43]. Notably, one-third of patients with PSS did not have MHE, highlighting the need for more precise vascular evaluations. This also suggests that factors such as shunt size, location, or flow dynamics could be key determinants of HE risk[44]. Additionally, neuroimaging was not performed to rule out other neurological causes of cognitive impairment.

Another limitation was the reliance on a single cognitive test: The ANT. The International Society for Hepatic Encephalopathy and Nitrogen Metabolism recommends using at least two complementary tests to improve the sensitivity of MHE detection[28]. Including additional tools, such as the EncephalApp Stroop Test or EEG, could potentially enhance diagnostic accuracy, even in resource-limited settings[45].

Clinical implications

Our findings highlight the importance of routine MHE screening in patients with HSS, particularly those with PSS. Using accessible and culturally adapted tools like the ANT, combined with laboratory markers such as the CI, can enable early detection and timely intervention, ultimately enhancing patient quality of life. This approach aligns with international guidelines that advocate for context-specific strategies in the diagnosis and management of HE[11].

CONCLUSION

This pioneering study demonstrates that HE, particularly its minimal form, is a prevalent (24%) and clinically significant complication of HSS, with a strong association to PSS. We validated the ANT as a simple, culturally adaptable screening tool suited for resource-limited endemic areas, overcoming key diagnostic challenges in populations with low-education. Additionally, the CI emerged as a promising biochemical correlate of cognitive impairment, supporting a practical, combined screening strategy that leverages both cognitive testing and an accessible laboratory marker. These findings advocate for a paradigm shift in managing advanced schistosomiasis, emphasizing the need to incorporate routine cognitive screening into standard care for HSS patients, particularly those with documented PSS. Future research should focus on validating these results in larger, multi-center cohorts; using advanced imaging for comprehensive shunt characterization; and developing targeted interventions to reduce the neurocognitive burden in this neglected population.

ACKNOWLEDGEMENTS

We thank the participants for their contributions to this study.