Schistosomiasis is an infectious disease caused by trematode parasites of the genus Schistosoma. According to the World Health Organization (WHO), it is estimated that about 250 million people in the world are infected with the disease, nearly 800 million people are at risk of infection, and more than 200,000 people die of schistosomiasis every year.1, 2 In China, the endemic species of schistosome that primarily infects humans is Schistosoma japonicum. Schistosomiasis japonica has been a major public health problem affecting human health and economic development in the past decades. The latest national epidemiological data showed that there were still 29,517 advanced cases of schistosomiasis japonica at the end of 2020. Moreover, approximately 842,500 patients had been previously infected with S. japonicum nationwide, of whom 83.3% had chronic schistosomiasis.3 Our previous studies confirmed that past cases have no possibility of re-infection after antiparasitic treatment and that liver fibrosis continues to progress and eventually develops into advanced schistosomiasis.4 Some studies have also shown that although chemotherapy with praziquantel is readily available and has good efficacy, liver fibrosis remains the most serious consequence of S. japonicum chronic infection, with an incidence of nearly 20% in infected patients.5 Hence, nearly one million patients with chronic schistosomiasis are at risk of later developing liver fibrosis. Unlike Schistosoma haematobium which causes urinary tract morbidities, S. japonicum causes gastrointestinal and liver diseases. In the human host, some schistosome eggs excreted by adult parasites that have settled in the mesenteric venous plexuses are transported by mesenteric circulation to the liver, where they are trapped in small portal branches. A granulomatous cell-mediated response to egg antigens occurs around the eggs, resulting in the excessive production and deposition of collagen along the portal vein and tract branches by activated hepatic stellate cells. Repeated embolization of eggs over time, especially in cases of high-burden infection, leads to hepatosplenic schistosomiasis (HSS) or also known as Symmers' fibrosis, a form of hepatopathy that results in periportal fibrosis (PPF) with portal hypertension. HSS represents one of the most common chronic sequelae of this infection.6, 7 Patients with periportal fibrosis retain hepatocellular function, differentiating the disease from cirrhosis and other liver diseases (Table 1).8 Confluent granulomata around trapped helminth ova → portal “pipe-stem” fibrosis around portal vessels; liver parenchyma preserved Liver cell necrosis followed by nodular hepatocellular regeneration and fibrous septa and bands involving the entire liver parenchyma Presinusoidal block; normal occluded hepatic venous pressure Sinusoidal block; increased occluded hepatic venous pressure Liver function preserved Liver function impaired Normal hepatic vein pressure gradient Increased hepatic vein pressure gradient The presence and severity of liver fibrosis determines the prognosis and clinical management. Therefore, the early diagnosis and long-term dynamic monitoring of liver fibrosis are clinically important. According to the consensus on the diagnosis and therapy of liver fibrosis (2019) issued by the Chinese Medical Association, liver biopsy remains the gold standard for the diagnosis of liver fibrosis. The hepatic venous pressure gradient (HVPG) is significantly related to the stage of liver fibrosis and is the gold standard for the diagnosis and risk classification of portal hypertension. Liver biopsy is an invasive examination that causes discomfort to patients. Additionally, cases may result in complications, such as bleeding and sepsis, that are not easily accepted by patients. Moreover, the uneven distribution of fibrosis in the liver often leads to sampling errors, resulting in the underestimation of stages of fibrosis and missed diagnosis of liver cirrhosis. The histological analysis relies on the experience and skills of pathologists and has a subjective tendency, which is easy to produce differences within and among observers. In addition to the aforementioned technical shortcomings, the high cost of tissue biopsies limits widespread application. HVPG measures the pressure difference between the portal vein and the intra-abdominal vena cava by comparing the difference between the wedge pressure of the hepatic vein and the free pressure of the hepatic vein. Compared to the wedge pressure of the hepatic vein, the pressure gradient of the hepatic vein eliminates the influence of intra-abdominal pressure on the measurement results and therefore better reflects the pressure of the portal vein. However, in prehepatic or intrahepatic presinusoidal portal hypertension, the wedge pressure of the hepatic vein cannot reflect the increase in portal vein pressure as the blood flowing to the hepatic vein travels through the unaffected sinuses with a large volume and low resistance. Therefore, the hepatic vein wedge and pressure were normal in these patients. Portal hypertension caused by advanced schistosomiasis does not cause changes in wedge pressure or free pressure of the hepatic vein. Therefore, HVPG may not be effective in diagnosing and monitoring hepatic fibrosis in patients with advanced schistosomiasis. Considering these limitations, most studies have focused on noninvasive methods for detecting liver fibrosis. Serum markers can directly or indirectly reflect liver fibrosis. Studies have explored the diagnostic performance of individual and combinations of serum markers for the assessment of liver fibrosis in S. japonica (Supporting Information: Table 1). Hou et al. selected seven biomarkers to evaluate diagnostic efficacy and found that hyaluronic acid (HA) resulted in a high area under receiver operating characteristic curve (AUROC) of 0.938 (95% confidence interval [CI], 0.886–0.990) for significant fibrosis (F ≥ 2). Using a combination of aspartate aminotransferase and platelet ratio index and HA/100, the AUROC was 0.958 (95% CI, 0.914–1.000) for F ≥ 2.9 Another study constructed a new index using biomarkers to diagnose significant fibrosis. The international normalized ratio × HA/100 yielded a higher AUROC of 0.921 and therefore, the new index was considered a useful tool for identifying significant fibrosis in patients with schistosomiasis.10 However, serum markers have several limitations, including overestimating or underestimating the stage of fibrosis in certain conditions, as well as the inability to discriminate between intermediate stages of fibrosis. Due to the advantages of noninvasiveness and high repeatability, abdominal ultrasound plays an important role in the diagnosis of hepatosplenic schistosomiasis (Supporting Information: Figure 1). However, ultrasound is limited by the need for adequate experience and training, in addition to its low accuracy during the initial stages of the disease. Transient elastography (TE) is an ultrasound-based noninvasive technology for diagnosing liver fibrosis based on the assessment of liver stiffness measurement (LSM). The diagnostic value of LSM using TE for assessing liver fibrosis has been widely investigated in patients with various chronic liver diseases. A study showed that LSM is a reliable parameter for predicting significant to advanced liver fibrosis and cirrhosis in patients with advanced schistosomiasis japonica.5 LSM using TE is a noninvasive, convenient, and economical method for fibrosis risk evaluation; however, it has a few limitations. First, LSM cannot be accurately measured in patients with high body mass index or ascites because the mechanical waves cannot correctly propagate to the tissue. Moreover, TE evaluation does not allow the region of interest (ROI) to be placed in a specific area. Given the nature and distribution of fibrosis in HSS (fibrosis is not diffused by the liver parenchyma), LSM measured by TE will be subject to sampling error. Acoustic radiation force impulse elastography (point shear wave elastography, pSWE; two-dimensional shear wave elastography, 2DSWE) can also be used to diagnose HSS, enabling the detection of fibrosis in an ROI and yielding better diagnostic accuracy than conventional TE.11 A recent study that explored the application of pSWE in the context of schistosomiasis showed that pSWE was able to differentiate between mild and significant PPF at higher velocities (1.40 m/s).12 With the application of artificial intelligence technology in the medical field, an emerging technology called radiomics that is widely used in disease diagnosis can provide the automated quantification of image features from a large number of medical images. A recent prospective multicenter study investigating the diagnostic performance of the newly developed deep learning radiomics of elastography (DLRE) in 2D-SWE images for liver fibrosis staging in patients with HBV infection showed that DLRE was more accurate than 2D-SWE in assessing cirrhosis and advanced fibrosis, and more accurate than biomarkers in assessing all three liver fibrosis stages in patients with CHB.13 However, no studies on the use of radiomics technology have been conducted to evaluate periportal fibrosis caused by schistosomiasis. Although the noninvasive diagnosis of PPF has been extensively explored, there is still a lack of accepted and easy-to-use standards. Future studies should focus on establishing the role of noninvasive techniques in the diagnosis of liver fibrosis in schistosomiasis japonica, identifying fibrosis regression following antiparasitic therapy, and predicting the progression of the disease. Tao Wang and Kun Yang drafted the manuscript. HaiYong Hua, JianFeng Zhang, Wei Li, and Kun Yang critically revised the manuscript for important intellectual content. All the authors have read and approved the final version of the manuscript. This study was funded by the National Natural Science Foundation of China (Grant No.: 82173586) and Jiangsu Provincial Department of Science and Technology (Grant No.: BZ2020003). The authors declare no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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Jan 1, 2024
Chengfang Wang + 2