Simple Blood Test Shows Promise for Detecting Liver Fibrosis in Schistosomiasis

A simple blood test that measures the molecular fingerprints of liver scarring may offer a new way to track one of the most dangerous complications of schistosomiasis, according to a pilot study published in PLOS Neglected Tropical Diseases. Researchers in Brazil found that serum values from the Enhanced Liver Fibrosis, or ELF, test rose in step with the severity of periportal fibrosis, the distinctive pattern of liver damage caused by infection with the parasitic worm Schistosoma mansoni. The finding suggests that a routine blood draw could eventually help clinicians identify patients at risk of portal hypertension without relying solely on specialized ultrasound expertise.

Schistosomiasis mansoni remains a major public health burden in endemic regions of Brazil and other parts of the world where the parasite’s larvae, released from freshwater snails, penetrate human skin during contact with contaminated water. While the acute phase of infection often produces only vague symptoms, the long-term consequences can be severe. Eggs deposited by adult worms in the mesenteric veins trigger a chronic inflammatory reaction in the liver, leading over years to periportal fibrosis, a fibrotic thickening around the portal tracts that distorts the organ’s vascular architecture. Unlike the cirrhosis produced by alcohol or viral hepatitis, schistosomal liver damage typically spares the hepatocytes themselves, but the fibrotic obstruction of portal blood flow drives the pressure inside the portal vein dangerously upward.

The clinical stakes of this process are considerable. Portal hypertension in schistosomiasis manifests as splenomegaly, the development of collateral blood vessels, and ultimately esophageal varices that can rupture and cause life-threatening upper gastrointestinal bleeding. Detecting periportal fibrosis early, and gauging how far it has advanced, is therefore essential for deciding which patients need closer surveillance or intervention. The reference standard for assessing this fibrosis in the field is abdominal ultrasound interpreted according to the Niamey classification, a scoring system that grades the periportal thickening from pattern A, essentially normal, through patterns B and C for mild involvement, to patterns D and E for moderate and advanced disease, and pattern F for the most severe fibrotic distortion. Ultrasound, however, requires trained examiners and equipment that are not always available in the rural areas where the disease is most prevalent.

The ELF test was developed as a noninvasive alternative for quantifying liver fibrosis in conditions such as chronic hepatitis C and nonalcoholic fatty liver disease. It combines the serum concentrations of three markers of fibrotic remodeling: hyaluronic acid, a component of the extracellular matrix that accumulates as fibrosis progresses; tissue inhibitor of metalloproteinases 1, or TIMP-1, which reflects the inhibition of matrix-degrading enzymes; and procollagen III amino-terminal peptide, known as PIIINP, a byproduct of new collagen synthesis. An algorithm converts the three measurements into a single ELF score, with higher values indicating more extensive fibrosis. Because the test uses a standard blood sample and a validated analytical platform, it could in principle be deployed in settings where imaging expertise is scarce.

Despite this potential, few studies had examined whether the ELF score performs meaningfully in schistosomiasis mansoni, whose fibrotic pattern differs fundamentally from the cirrhotic scarring for which the test was calibrated. The new study, led by Rebecca Dantas Thorp and colleagues at institutions in Pernambuco, Brazil, set out to determine whether serum ELF values correlate with the periportal fibrosis pattern established by the Niamey ultrasound classification, and whether the score relates to a history of upper gastrointestinal bleeding, the most feared complication of advanced disease.

The researchers conducted a cross-sectional, bidirectional analytical study enrolling patients from an endemic area and from a reference outpatient clinic dedicated to schistosomiasis care. In total, 196 patients were evaluated, 58 percent of them women, with a mean age of 45.04 years and a standard deviation of 15.30 years. Each participant completed a structured questionnaire capturing sociodemographic and clinical information, including any prior episodes of upper gastrointestinal bleeding, and provided blood samples for ELF determination. A single examiner performed all ultrasound examinations, an approach that eliminated interobserver variability and ensured that the Niamey patterns were assigned consistently across the cohort.

The distribution of fibrosis severity in the study population spanned the full range of the Niamey scale. Eighteen patients showed pattern A plus B, indicating no or minimal periportal thickening, while 64 fell into pattern C, 56 into pattern D, 49 into pattern E, and 9 into pattern F, the most advanced category. When the researchers compared median ELF values across these groups, a clear gradient emerged: the median score rose from 8.36 in patients with pattern A plus B, to 8.40 in pattern C, 8.64 in pattern D, 8.99 in pattern E, and 9.75 in pattern F. This monotonic increase was statistically significant, with a p value of 0.0021, indicating that the probability of observing such a pattern by chance alone was low.

The team then tested whether the ELF score could discriminate between broader categories of fibrosis severity. It could. The test differentiated patients without periportal fibrosis from those with mild, moderate, and advanced disease when the Niamey patterns were grouped as A plus B versus C versus D versus E plus F, with a p value of 0.0024. It also distinguished patients with advanced fibrosis from those without fibrosis or with moderate fibrosis: the comparison of A plus B versus E plus F yielded a p value of 0.0464, and the comparison of C plus D versus E plus F was even stronger, at p equal to 0.0007. In practical terms, this means the blood test reliably flagged the patients whose livers had reached the stage of fibrosis most likely to produce clinically significant portal hypertension.

One result, however, tempered the enthusiasm. When the researchers compared mean ELF values between patients with and without a history of upper gastrointestinal bleeding, they found no statistically significant difference. This suggests that while the ELF score tracks the structural progression of periportal fibrosis as seen on ultrasound, it does not by itself identify which patients have already experienced variceal hemorrhage. Bleeding risk in schistosomiasis depends not only on the degree of fibrosis but also on the size and wall tension of the collateral vessels, factors that a fibrosis marker measured in serum cannot directly capture. The authors therefore position the ELF test as a complement to, rather than a replacement for, clinical assessment and endoscopic or imaging surveillance of varices.

Nevertheless, the study’s conclusion is significant for a disease that continues to affect millions of people in poverty-stricken rural communities. The ELF test demonstrated potential as a tool for assessing periportal fibrosis in patients with schistosomiasis mansoni, because it could differentiate those with minimal fibrosis from those with moderate or advanced fibrosis using nothing more than a blood sample. As a pilot study with a modest sample size and a cross-sectional design, it cannot yet establish whether serial ELF measurements can monitor fibrosis progression in individual patients over time, or whether the score predicts future decompensation. Those questions will require longitudinal cohorts and validation in other endemic regions. But if larger studies confirm these findings, the ELF score could become a practical, scalable screening instrument, allowing health systems in endemic areas to reserve scarce ultrasound resources for patients whose blood tests signal advancing disease, and to intervene before portal hypertension claims another life.

Subject of Research: Use of the Enhanced Liver Fibrosis serum score to assess periportal fibrosis severity in schistosomiasis mansoni

Article Title: Evaluating periportal fibrosis in schistosomiasis mansoni using the ELF [Enhanced Liver Fibrosis] score: A pilot study

Article References: Thorp, R. D., Batista, A. D., Mariz, C. A., de Araújo, L. R. M. G., Diniz, G. T. N., Barreto, A. V. M. S., de Morais, C. N. L., Silva, P. C. V., Domingues, A. L. C., & Lopes, E. P. (2026). Evaluating periportal fibrosis in schistosomiasis mansoni using the ELF [Enhanced Liver Fibrosis] score: A pilot study. PLOS Neglected Tropical Diseases, 20(10), e0014775. https://doi.org/10.1371/journal.pntd.0014775

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014775

Keywords: schistosomiasis mansoni, periportal fibrosis, ELF score, liver fibrosis, Niamey classification, portal hypertension, ultrasound, biomarkers, neglected tropical diseases, Brazil, noninvasive diagnostics, PLOS Neglected Tropical Diseases