The Potential of Shear Wave Elastography for Assessing Liver Fibrosis in Patients with Gaucher Disease: A Promising Approach

The Potential of Shear Wave Elastography for Assessing Liver Fibrosis in Patients with Gaucher Disease: A Promising Approach | 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 The Potential of Shear Wave Elastography for Assessing Liver Fibrosis in Patients with Gaucher Disease: A Promising Approach Ge Zhang, Xinyu Wu, Shiyu Wang, Zhong xia Sun, Weiyan Zheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9335107/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objective: Patients with Gaucher disease frequently exhibit hepatosplenomegaly and high echogenicity in liver sonograms, resembling the findings in patients with hepatitis B cirrhosis and metabolic-associated fatty liver disease. Conventional two-dimensional ultrasound has not demonstrated significant advantages in diagnosing this condition. Therefore, the objective of this study was to investigate the potential of shear wave elastography as a non-invasive diagnostic tool for the early detection of Gaucher disease and to assess the feasibility of this approach. Method: A comparative analysis was conducted to evaluate the sizes of the liver and spleen, as well as the shear wave elastography values, among 33 patients diagnosed with Gaucher disease, 30 patients suffering from hepatitis B cirrhosis, 41 patients with metabolic associated fatty liver disease,and 50 normal subjects. Furthermore, the correlation between the severity scores of patients with Gaucher disease and their hepatic elasticity values was analyzed. Results: The liver stiffness and spleen thickness observed in patients with Gaucher disease were significantly higher than those in normal subjects and individuals with metabolic associated fatty liver disease ( P < 0.001). However, liver stiffness in patients with Gaucher disease was lower than that in patients diagnosed with hepatitis B cirrhosis (P < 0.05). Furthermore, the oblique diameter of the right liver in patients diagnosed with Gaucher disease was found to be greater than individuals with hepatitis B cirrhosis ( P < 0.05). Correlation analysis demonstrated a significant relationship between the severity scores and the magnitude of liver stiffness in patients with Gaucher disease ( r = 0.5193, P < 0.001). Conclusion: Two-dimensional shear wave elastography plays a crucial role in assessing the severity of Gaucher disease and differentiating it from healthy individuals, metabolic associated fatty liver disease, and patients with hepatitis B cirrhosis. This non-invasive test has the potential to reduce the number of unnecessary invasive procedures for patients while significantly enhancing the diagnostic efficiency for this disease. Gaucher disease Shear wave elastography Liver fibrosis Rare disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Gaucher disease (GD) is an extremely rare autosomal recessive inherited metabolic disorder and one of the most common lysosomal storage diseases. It primarily results from reduced enzyme activity due to mutations in the gene encoding glucocerebrosidase, the enzyme responsible for the breakdown of glucosylceramide. This deficiency leads to the accumulation of glucosylceramide, the substrate for glucocerebrosidase, in monocytes and macrophages across various organs, including the liver, spleen, and bone marrow. Ultimately, this accumulation results in the formation of characteristic Gaucher cells(GC). [1] The prevalence of GD varies significantly across global populations, with a general prevalence rate of approximately 1 in 50,000. Notably, this rate is considerably higher in the Jewish population, estimated at about 1 in 850.[2, 3] In China, the incidence of GD is markedly lower than the global average, categorizing it as a rare disease, often referred to as a 'super-rare disease.' Currently, there is no documented incidence or research regarding GD in China. Based on epidemiological statistics from Asian countries, it is estimated that the total number of patients with GD in China is approximately 1000, with only about 200 to 300 patients having a confirmed diagnosis of GD[4].The phenotype of GD is classified into three types based on the urgency of disease onset, the degree of internal organ involvement, and the presence or absence of neurological symptoms. These classifications include chronic (non-neurological, adult, type I), acute (type II, neurological), and subacute (type III, neurological)[5]. GD is a significant metabolic disorder that can lead to debilitating or even fatal outcomes if not identified and treated promptly[6]. The most common and notable clinical manifestations of GD include liver and spleen enlargement, which may be accompanied by hypergammaglobulinemia, hyperferritinemia, and abnormalities in lipid metabolism[7]. These symptoms often result in the misdiagnosis of other hematological disorders, such as chronic liver disease, due to the absence of characteristic features in the presentation and the clinician's heightened sensitivity to the awareness of rare diseases. It has been demonstrated that the risk of liver disease in patients with GD is a significant and potentially life-threatening concern. The primary mechanism underlying this liver involvement is hepatic fibrosis. Therefore, assessing hepatic fibrosis is crucial for identifying the severity of hepatic lesions in patients with GD[8]. Liver biopsy is considered the gold standard for diagnosing hepatic fibrosis; however, due to its invasive nature, this assessment is not feasible in patients with GD who exhibit severe intolerance reactions, such as a tendency to bleed. Shear wave elastography (SWE) has proven to be an effective method for quantifying the extent of liver fibrosis in chronic liver disease. It offers several advantages over other non-invasive imaging techniques, including magnetic resonance elastography, such as ease of integration into clinical routines, low cost, and relatively short examination times. SWE allows for the elastographic assessment of various regions within the liver, thereby facilitating the quantification of hepatic fibrosis across a wide spectrum of chronic liver diseases. From these data, threshold values can be derived to differentiate the stages of fibrosis. Furthermore, the European Federation of Ultrasound Societies in Medicine and Biology has published guidelines for the clinical application of ultrasound elastography, which further validates the utility of SWE in assessing hepatic fibrosis[9]. The primary objective of this investigation is to synthesize the manifestations of GD as observed in ultrasonographic imaging and to assess the potential value of SWE for the non-invasive diagnosis of GD at its earliest stages. In addition, this study will evaluate the feasibility and efficacy of this approach. Materials and methods Case Group: A total of 33 samples from patients diagnosed with GD were collected from January 2020 to December 2025 at the Department of Hematology of the First Affiliated Hospital of Zhejiang Medical University in China. The case group consisted of patients who met the following criteria: (1) All patients were diagnosed with GD based on either marrow aspiration or glucosidase activity test results. (2) All 33 patients underwent GD-DS3. (3) Additionally, all patients received standardized abdominal ultrasonography and liver SWE. The exclusion criteria were as follows: (1) Inability to complete the coordinated ultrasound examination. (2) No history of liver or spleen-related diseases, or other hematological or chronic conditions. Table 1 Basic information of 33 Gaucher disease patients. Patient no. Gender Age Years since diagnosis (years) GD-DS3 Spleen Liver enlarged removed nodules enlarged 1 F 45 29 8 0 1 1 0 2 F 33 1 14 1 0 resection 1 3 F 21 14 14 1 0 resection 1 4 F 4 3 3 0 0 0 1 5 F 56 5 12 0 0 1 1 6 M 20 10 6.5 0 0 1 1 7 F 56 4 6.5 0 1 1 0 8 M 57 3 8.5 0 0 0 1 9 F 35 1 4 0 0 1 0 10 F 28 20 5 0 0 1 0 11 M 55 15 10.5 0 0 resection 0 12 F 38 2 9 0 1 1 1 13 F 13 2 10.5 1 0 resection 0 14 F 66 5 6.5 0 0 1 0 15 F 66 17 10 0 0 1 1 16 F 51 7 11 1 0 resection 1 17 M 53 7 8.5 0 0 0 0 18 F 11 4 9 0 0 0 1 19 F 24 5 6 0 0 0 0 20 21 22 23 24 25 26 27 28 29 30 31 32 33 M F M M F F F F F F M F F F 15 45 23 54 3 46 32 69 25 22 43 9 22 37 11 13 3 7 1 8 10 6 0.5 6 0.5 2 2 0.6 7 4 10 7 9 13 8.5 11 6.5 5 5.5 10 10 13 0 0 1 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 1 resection 1 1 resection 1 0 1 1 1 1 resection 1 0 1 1 0 1 1 0 1 0 0 0 1 1 1 F:female,M:male, GD-DS3: Gaucher Disease Severity Score System, 0: No, 1༚Yes Control group: A total of 30 patients diagnosed with hepatitis B cirrhosis were randomly selected from a pool of cases that met the diagnostic criteria established by the European Association for the Study of the Liver[10]. Similarly, 41 cases of metabolic-associated fatty liver disease(MAFLD)were randomly chosen from a pool of cases that fulfilled the criteria for MAFLD diagnosis as delineated by an international panel of experts[11]. Additionally, 50 individuals without any liver disease were randomly selected to serve as a control group. All patients underwent a comprehensive ultrasound examination of the liver and spleen, which included shear wave elasticity imaging of the liver. The exclusion criteria were as follows: (1) Inability to complete a cooperative ultrasound examination; (2) No history of hematologic or chronic diseases. ༈Table 1 ༉ Ultrasound parameters: All patients underwent evaluation using a color Doppler ultrasound diagnostic instrument (GE’s LOGIQ-E20), with all findings documented by the same physician. This study examined parameters including the diameter of the right hepatic diagonal of the liver and the thickness of the spleen, while also assessing fundamental ultrasound characteristics such as echo intensity and the presence of space-occupying lesions. The oblique diameter of the right liver exceeding 14 cm was deemed indicative of hepatomegaly, while a spleen thickness greater than 4 cm suggested splenomegaly[12](Fig. 1 、 Fig. 2 ).The procedure for measuring liver SWE using ultrasound is as follows: the patient is positioned horizontally in a supine posture. The operator places the probe perpendicular to the hepatic peritoneum in the right intercostal space, ensuring that large blood vessels are avoided. The measurement depth is selected to be approximately 1.5 cm, with the probe positioned at a depth not exceeding 5 cm. The sampling frame, which should be pre-set and not altered, is positioned in the right lobe of the liver, specifically in the S6 segment, although the optimal locations may also include the S5 segment or the 7th or 8th segments. The elasticity value of liver stiffness was obtained by instructing the patient to hold their breath for 3 to 5 seconds while breathing calmly. The data collected after filling the sampling frame with the selected color represented the elasticity value of liver stiffness. Various factors, including the positioning of the sampling frame, the operator's technique, the patient's breathing patterns, and the thickness of the adipose tissue, may influence the elasticity value. To account for these potential variations, each patient underwent 10 measurements, and the mean value was calculated at the conclusion of the study. (Fig. 3 ) Gaucher Disease Severity Score System(GD-DS3): All GD patients were evaluated for severity using the GD-DS3 scale, as described by Neal J. Weinreb[13]. This study received approval from the Institutional Review Board of the First Hospital of Zhejiang University School of Medicine, and informed consent was obtained from the participants or their guardians. Statistical analysis methods: Statistical analysis was performed using SPSS 27.0 software. Shapiro-Wilk normality test was conducted for each indicator, with p -value > 0.05 indicating normal distribution of the data. Measurement data were expressed as mean ± standard deviation \(\:\stackrel{-}{x}\) ± s , while enumeration data were presented as frequencies. Independent samples t-test was used to analyze the indicators in each group, with t-values and p-values calculated to assess the statistical significance of inter-group differences. Pearson correlation analysis was employed to explore the relationship between GD-DS3 and liver stiffness, with corresponding evaluation of the obtained r -values and p -values. A p -value less than 0.05 was considered statistically significant, while an r -value greater than 0.8 indicated a strong correlation between GD-DS3 and liver stiffness. Results A total of 33 patients with Gaucher disease, including 8 males and 25 females, 6 were minors and the remaining 27 were adults, aged 3–69 years. Hepatomegaly was found in 18(55%) patients, and splenomegaly was also found in 18(72%) patients (excluding resected spleens), of which 8(24%) underwent splenectomy due to significantly enlarged spleens, while 5(15%) patients had splenomegaly accompanied by multiple roundish nodules with sizes ranging from a minimum of about 0.9 mm to a maximum of about 5.6 cm, which were hypoechoic, with well-defined borders and no significant blood flow signals(Fig. 4 ). 33 patients were treated with enzyme replacement therapy. The basic information of the patients and some of their ultrasound characteristics are shown in(Table 1 ). The liver elasticity values were 4.49 ± 0.78 kPa in normal subjects, 10.04 ± 3.25 kPa in patients with hepatitis B type cirrhosis, 5.61 ± 1.39kPa in patients with MAFLD and 8.09 ± 3.42kPa in patients with GD. Multiple comparisons demonstrated a significant difference in liver elasticity values between patients with GD and normal subjects ( P < 0.001), as well as between patients with GD and those with MAFLD ( P < 0.001) (Table 2 ). Furthermore, the average spleen thickness in normal subjects was 3.55 ± 0.30 mm, in patients with MAFLD it was 3.63 ± 0.29 mm, and in patients with GD it was 5.91 ± 3.26mm. Multiple comparisons revealed a remarkable difference in spleen thickness between patients with GD and normal subjects ( P < 0.001), as well as between patients with GD and those with MAFLD ( P < 0.001) (Table 3 ). The oblique diameter of the right liver values were 13.21 ± 0.88 in patients with hepatitis B type cirrhosis and 13.98 ± 1.39 in patients with GD .The oblique diameter of the right liver in GD only shows statistical significance when compared with that in patients with hepatitis B( P < 0.05)(Table 4 ). Correlation analysis using Pearson's method showed a significant correlation between the GD-DS3 and the live stiffiness ( r = 0.5193, P < 0.001) (Fig. 5 ). Table 2 Comparison of SWE between the case group and the control groups Case Group Control Groups GD Normals MAFLD Liver cirrhosis SWE(kPa) 8.09 ± 3.42 4.49 ± 0.78 5.61 ± 1.39 10.04 ± 3.25 t 5.966 3.918 -2.314 p <0.001 ** <0.001 ** <0.05 * MAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease Asterisks ( * ) indicate statistically significant differences between the case group and the control groups ( * P < 0.05, ** P < 0.001) Table 3 Comparison of spleen thickness between the case group and the control groups Case Group Control Groups GD Normals MAFLD Liver cirrhosis spleen thickness 5.91 ± 3.26 3.55 ± 0.3 3.63 ± 0.29 4.94 ± 0.69 t 3.617 3.481 1.462 p <0.001 ** 0.05 MAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease Asterisks ( * ) indicate statistically significant differences between the case group and the control groups ( * P < 0.05, ** P < 0.001) Table 4 Comparison of the oblique diameter of the right liver values between the case group and the control groups Case Group Control Groups GD Normals MAFLD Liver cirrhosis The oblique diameter of the right liver values 13.98 ± 1.39 13.6 ± 0.59 13.4 ± 0.88 13.2 ± 0.88 t 1.498 1.931 2.603 p >0.05 >0.05 <0.05 * MAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease Asterisks ( * ) indicate statistically significant differences between the case group and the control groups ( * P < 0.05) Discussion Early diagnosis of GD often necessitates invasive and complex procedures, including pathological biopsies, molecular genetic tests, and enzyme activity assays, which can result in prolonged diagnostic timelines. Some physicians may exhibit reluctance to diagnose and treat GD with enzyme replacement therapy (ERT) due to limited experience, or they may misdiagnose other conditions due to the presence of splenomegaly, leading to further diagnostic challenges. Moreover, a considerable number of patients with GD struggle to tolerate the complications associated with splenic hyperfunction and the compression of peripheral organs. The risk of infection significantly increases following splenectomy, which may further exacerbate the severity of other complications. Therefore, early detection and effective intervention in the progression of GD are of paramount importance[7].Ultrasound as a simple and rapid test can guide hematologists to be able to non-invasively identify common splenomegaly and thrombocytopenia disorders, thus eliminating unnecessary imaging and laboratory tests, and ultrasound elastography can be used to quantitatively assess the extent of cirrhosis, as well as its potential use as a marker to monitor the severity of GD disease. It has been reported that almost all patients with GD exhibit some degree of liver damage, characterized by hepatomegaly, which may occur with or without abnormalities in liver function, cirrhosis, portal hypertension, and, in severe cases, even hepatocellular carcinoma[7, 14]. Patlas et al. studied 103 pediatric patients with GD, finding that the incidence of hepatomegaly was 100%[15]. In our study, more than half of the patients presented with hepatomegaly, which may be pathophysiologically attributed to the infiltration of inflammatory factors into the lobular centers of the liver or the replacement of a significant portion of hepatic parenchyma by GC, leading to massive accumulation and subsequent macroscopic enlargement of the liver[16–19].In his studies utilizing a mouse model, Manoj identified several molecules present in the circulation of mice with the Gba1 mutation (D409V/null). In vitro chemotaxis studies and flow cytometry revealed that the serum from D409V/null mice contained chemotactic agents for various immune cells. The influx of these cells, coupled with the increase in specific chemokines, contributed to the enlargement of the liver[20]. Conversely, several subjects in our study did not exhibit hepatomegaly, which may be attributed to several factors: first, they may have undergone long-term enzyme replacement therapy (ERT), leading to a reduction in the accumulation of GC; second, the duration of the disease may be relatively short, resulting in insufficient infiltration of GC in the liver or minimal hepatocyte damage. The initial presentation of many patients with GD often involves a self-perceived enlarged abdomen. This mass is, in fact, an enlarged spleen. Some patients opt for splenectomy prior to enzyme replacement therapy to mitigate the risks associated with significantly elevated splenic function. The causes of splenomegaly and hepatomegaly are fundamentally similar, as both conditions may arise from splenic enlargement due to the accumulation of large aggregates of GC or inflammatory mediators. It has been documented in the medical literature that patients with GD frequently present with intra-splenic hyperechoic nodules on ultrasonography, which account for approximately one-fifth to one-third of cases[21].According to the findings of our study, the potential causes can be attributed to three main factors: (i) the formation of clusters of nodules resulting from the concentrated aggregation of GC within the spleen, and (ii) the occurrence of ischemia due to prolonged inflammation infiltration, which subsequently leads to the formation of infarct foci. (iii)additionally, it is important to acknowledge that other common types of intra-splenic hyperechoic nodules, such as splenic hemangioma and splenic aneurysm, may also be present[22]. Due to the reduced platelet count in patients with Gaucher disease, splenic nodules are at a higher risk of bleeding complications following puncture. Therefore, these nodules were not pathologically examined to determine their nature. Consequently, close monitoring of these patients during the follow-up process is essential, which should include an evaluation of the size, echogenicity, blood flow, and any significant changes in the ultrasound manifestations of the intra-splenic nodules. The results of the study indicated that liver elasticity values in patients with GD were significantly higher than those in normal subjects and MAFLD (P < 0.001). This increased stiffness may be attributed to the establishment of a fibrotic microenvironment by GC in the liver, along with various pathophysiological mechanisms. The formation of liver fibrosis in GD can be explained by the infiltration of Gaucher cells. Prolonged infiltration may lead to chronic low-grade inflammation of the liver, which can progress to cirrhosis. Furthermore, abnormalities in the immune system due to the destruction of GC also contribute to cirrhosis. This may result from T-cell impairment or chronic stimulation of the immune response. Additionally, cytokine secretion by activated macrophages, either directly or indirectly, can induce GC leading to hepatic fibrosis in some patients[7]. Alterations in iron metabolism in patients with GD are significant contributors to liver fibrosis. Elevated iron levels in hepatocytes and Kupffer cells in these patients result in secondary iron overload. Furthermore, increased iron levels may promote the formation of reactive oxygen species, which can lead to hepatocellular injury and potentially cause liver fibrosis[23, 24]. Literature has reported that some patients develop type 2 diabetes mellitus or metabolic syndrome with hepatic lipid deposition following ERT[25]. The gradual accumulation of significant amounts of fat adversely affects the blood and oxygen supply as well as the metabolic functions of the liver, leading to hepatocellular swelling, inflammatory infiltration, and cellular degeneration and necrosis. This progression can result in steatohepatitis, followed by hepatic fibroplasia, and ultimately, fatty liver cirrhosis. The aforementioned pathophysiological processes may underlie the development of hepatic fibrosis in patients with GD. GD is caused by a reduction in glucocerebrosidase activity, leading to a significant accumulation of glucocerebrosides. A substantial body of literature demonstrates that elevated levels of glucocerebrosides have a protective effect on the liver[26, 27]. The present study found that liver stiffness in GD patients is lower than that in cirrhotic populations, although it remains higher than normal levels. The increase in glucocerebrosides may underlie the reduced risk of excessive liver injury in GD patients. The hepatoprotective effects of glucocerebrosides can be attributed to several mechanisms. One such mechanism involves glucocerebrosides acting as a glycolipid ligand presented to natural killer T (NKT) cells and dendritic cells (DCs) via CD1 molecules. glucocerebrosides can also exert immunomodulatory effects on these target cells, either directly or indirectly, by altering their interactions with other subpopulations of immune cells. Additionally, Yaron llan's research reports in animal models have all confirmed glucocerebrosides' significant protective effect on the liver: Margalit and colleagues found that glucocerebrosides attenuated ConA-induced hepatitis in mice, and its effect was associated with reduced serum interferon (IFN)- γ levels and decreased STAT1 transcription factor expression[28].These experimental data suggest that glucocerebrosides may play a beneficial role in the treatment of patients with chronic liver disease. There is also an explanation that may be related to ERT treatment, which eliminates GC in the liver tissue, but there are some areas where it is difficult for the drug to act by injecting blood into the targeted tissue due to fibrosis, i.e., it will not eliminate GC in the areas where fibrous tissue is present. As a rare disease in the clinic, GD has a low demand in the drug market and high drug development and production costs, resulting in extremely expensive therapeutic drugs, so effective and accurate assessment of the severity of the disease and guidance for the clinical stage of rationalizing the use of drugs play a crucial role in alleviating the financial difficulties of patients' families.GD-DS3 is an effective assessment of the severity of GD, as reported by Weinreb, N. J., et al[13].However, they did not include ultrasound elastography, which is a non-invasive assessment of liver fibrosis imaging, in their scoring criteria and only included assessment of liver and spleen size. André, Lollert et al. concluded that there is a correlation between MRE and GD-DS3, while MRE has the disadvantages of long detection time, inability to wear metal objects, and high cost of the examination. In our study, we conducted a correlation analysis between liver stiffness values and GD-DS3 in patients with GD using ultrasonic SWE. Our findings revealed a significant positive correlation with GD-DS3, which aligns with the results obtained by Serai et al. in their correlation analysis utilizing acoustic radial force impulse point SWE. However, the correlation reported by Serai et al. was relatively low ( P = 0.03) when compared to our results.[29] They attributed this discrepancy to prolonged treatment with ERT, which normalized certain blood indices. However, some patients in their cohort may have experienced more severe liver damage, preventing ERT from effectively reaching those areas due to significant fibrosis. Consequently, the liver elasticity values remained elevated, resulting in a lower correlation. In contrast, our analysis indicates that the subjects from our province have only recently had access to ERT through health insurance. Prior to this, many patients could not afford treatment since the onset of the disease, leading to a shorter duration of systematic treatment. As a result, some patients have not yet shown significant recovery, which may contribute to higher scores and elevated liver elasticity values, indicating a strong correlation between the two. Additionally, a subset of our population, including two children with very mild disease onset, exhibited relatively low GD-DS3 and liver elasticity values, further enhancing the observed correlation. Limitations The final results may not fully represent the entire population due to the rare nature of the diseases examined in this paper, the limited number of researchers involved, and individual differences within some experimental groups. Nevertheless, the conclusions drawn from this study align closely with those of previous research. To facilitate more rigorous and comprehensive investigations, we will continue to gather data from a larger cohort of patients across the nation. Conclusion In addition to its role in assessing disease severity, 2D-SWE has the potential to emerge as the preferred noninvasive test for differentiating GD from healthy subjects, MAFLD, and liver cirrhosis. Consequently, the efficiency of clinical diagnosis and the reduction of unnecessary patient burden will be significantly enhanced. Declarations Acknolwledgements Not applicable. Authors’ contribution: Concept: GZ, XW; Data Collection and Processing: GZ, SW; Analysis and Interpretation: GZ, Literature Search: ZS; Writing: GZ; WZ provided advice on data analysis and interpretation of the results. All authors read and approved the final manuscript Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose Ethics approval and consent to participate The study was performed in accordance with the Ethics Guidelines of the Helsinki Declaration and was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine. Written informed consent to participate was obtained from all of the participants in the study. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details 1234 Department of Ultrasound, The First Affiliated Hospital of Zhejiang University School of Medicine, 310000 Hangzhou, China 1* Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, 310000 Hangzhou, China References Tomer A, Yaron I, Deborah E, Ari Z. Liver involvement in Gaucher disease - Review and clinical approach. Blood Cells Mol Dis. 2016;68(0). Neal J W. The international cooperative Gaucher group (ICCG) Gaucher registry. Best Pract Res Clin Haematol. 2023;36(4). Pramod K M, Maria Domenica C, Elena L, Hayri O, Sara MP, Hanna R, et al. A reappraisal of Gaucher disease-diagnosis and disease management algorithms. Am J Hematol. 2010;86(1). 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Immunol Cell Biol. 2009;87(7). André L, Christian H, Michael L, Jochem K, Miriam B-H, Julia B H, et al. Acoustic radiation force impulse point shear wave elastography of the liver and spleen in patients with Gaucher disease type 1: Correlations with clinical data and markers of disease severity. Mol Genet Metab. 2020;130(2). Suraj D S, Anjani P N, T AB, Carlos E P, Stavra X, Alexander J T. Correlating liver stiffness with disease severity scoring system (DS3) values in Gaucher disease type 1 (GD1) patients. Mol Genet Metab. 2018;123(3). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 14 Apr, 2026 Editor assigned by journal 10 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 06 Apr, 2026 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9335107","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625828175,"identity":"cd6f5ac4-7803-4548-9db1-19f2337e45c6","order_by":0,"name":"Ge Zhang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Ge","middleName":"","lastName":"Zhang","suffix":""},{"id":625828179,"identity":"9c829735-e549-4d9a-9cb8-5ca4dd89687e","order_by":1,"name":"Xinyu Wu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xinyu","middleName":"","lastName":"Wu","suffix":""},{"id":625828185,"identity":"9a78fc0a-e8a8-44dd-9364-1e8d3ad69e60","order_by":2,"name":"Shiyu Wang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Shiyu","middleName":"","lastName":"Wang","suffix":""},{"id":625828202,"identity":"f8547430-6ed2-40b0-a205-c4b61332dc73","order_by":3,"name":"Zhong xia Sun","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhong","middleName":"xia","lastName":"Sun","suffix":""},{"id":625828210,"identity":"45da474a-df05-49e7-8a98-238a210e9cba","order_by":4,"name":"Weiyan Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDACCQglx8bM//BBQkUN8VqM+dl5mA0enDlGvJbEmf08bJIPW5gJ65Cf3Xzs4de2w4wbDvMeq0hsYGPgb+9OwKuFcc6xdGPZtsPMBof50m4k7pBhkDhzdgNeLcwSOWbSktsOsxkcZjC7kXiGjcFAIhe/FjaJ/G8gLTwgLQWJbcyEtfBI5LBJftx2WEKymceMgSgtEhJpZtKM/9IN+JnZkiUSzhzjIegX+RnJzyR/nLGub+M/fPDjj4oaOf72XvxaQICZh6EZ4VKCykGA8QdDHVEKR8EoGAWjYIQCADJdRrv4G7ExAAAAAElFTkSuQmCC","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Weiyan","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2026-04-06 14:54:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9335107/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9335107/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107490445,"identity":"6fbfae47-6dda-4fe8-bcd8-d8cfad242fe0","added_by":"auto","created_at":"2026-04-22 02:52:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1836959,"visible":true,"origin":"","legend":"\u003cp\u003eThe maximum oblique diameter of the right lobe of the liver was measured in both the control group and case group; \u003cstrong\u003e(a)\u003c/strong\u003e Patient number 2, diagnosed with GD, exhibited the maximum oblique diameter of the right lobe was 14.7;\u003cstrong\u003e (b) \u003c/strong\u003ePatient number 7, classified as normal, demonstrated a stiffness of 12.9; \u003cstrong\u003e(c) \u003c/strong\u003ePatient number 13, diagnosed with MAFLD, recorded a stiffness of 11.9; and \u003cstrong\u003e(d) \u003c/strong\u003ePatient number 26, suffering from liver cirrhosis, showed a stiffness of 12.4.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/2b875aa75e0dcfdceee3c5ab.png"},{"id":107450545,"identity":"6e67b272-5c6b-4966-ac36-ff12e1764605","added_by":"auto","created_at":"2026-04-21 15:13:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1576067,"visible":true,"origin":"","legend":"\u003cp\u003eThe spleen thickness was measured in both the control and the case group. \u003cstrong\u003e(a)\u003c/strong\u003e Patient number 5, diagnosed with GD, exhibited a stiffness of 2.9;\u003cstrong\u003e (b)\u003c/strong\u003e Patient number 30, classified as normal, demonstrated a stiffness of 4.7;\u003cstrong\u003e (c)\u003c/strong\u003e Patient number 15, diagnosed with MAFLD, recorded a stiffness of 3.8; and\u003cstrong\u003e (d)\u003c/strong\u003e Patient number 4, suffering from liver cirrhosis, showed a stiffness of 5.4.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/d6bda0ab7a0396baa044cbfe.png"},{"id":107704480,"identity":"375ed3d3-ec55-40d9-8552-11048ec2cc5f","added_by":"auto","created_at":"2026-04-24 08:45:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1291028,"visible":true,"origin":"","legend":"\u003cp\u003eThe quantitative evaluation of liver tissue using SWE was conducted for both the control and case group. \u003cstrong\u003e(a)\u003c/strong\u003e Patient number 2, diagnosed with GD, exhibited a stiffness of 9.8 kPa; \u003cstrong\u003e(b)\u003c/strong\u003e Patient number 7, classified as normal, demonstrated a stiffness of 3.5 kPa; \u003cstrong\u003e(c)\u003c/strong\u003e Patient number 13, diagnosed with MAFLD, recorded a stiffness of 6.2 kPa and\u003cstrong\u003e (d) \u003c/strong\u003ePatient number 26, suffering from liver cirrhosis, showed a stiffness of 6.1 kPa.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/67c8bfc09b2bb56facc074ad.png"},{"id":107450548,"identity":"26fb1569-75b8-42e9-91c8-e93412d19b51","added_by":"auto","created_at":"2026-04-21 15:13:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":400883,"visible":true,"origin":"","legend":"\u003cp\u003eIntrasplenic nodules in the case group:\u003cstrong\u003e (a)\u003c/strong\u003e Patient number 1 exhibited a nodule measuring 1.5 ×1.1 cm; \u003cstrong\u003e(b) \u003c/strong\u003ePatient number 7 had a nodule measuring 0.9 × 1.2 cm; \u003cstrong\u003e(c) \u003c/strong\u003ePatient number 26 exhibited a nodule measuring 1.5 × 1.2 cm.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/59b32c5618a0cd594b5804e7.png"},{"id":107704482,"identity":"2e4bd03c-801e-4158-a049-b521f2e66f30","added_by":"auto","created_at":"2026-04-24 08:45:36","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":23085,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between GD-DS3 and liver stiffiness in case group. (correlation coefficient, \u003cem\u003er\u003c/em\u003e= 0.5193, \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/c33d3fcd739529ebeadc3294.png"},{"id":107708505,"identity":"860d2c54-ce7d-46a4-a75b-b8aebfa4ba1a","added_by":"auto","created_at":"2026-04-24 09:27:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4386342,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9335107/v1/f199a869-6f08-491e-9158-7af79da3f783.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Potential of Shear Wave Elastography for Assessing Liver Fibrosis in Patients with Gaucher Disease: A Promising Approach","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGaucher disease (GD) is an extremely rare autosomal recessive inherited metabolic disorder and one of the most common lysosomal storage diseases. It primarily results from reduced enzyme activity due to mutations in the gene encoding glucocerebrosidase, the enzyme responsible for the breakdown of glucosylceramide. This deficiency leads to the accumulation of glucosylceramide, the substrate for glucocerebrosidase, in monocytes and macrophages across various organs, including the liver, spleen, and bone marrow. Ultimately, this accumulation results in the formation of characteristic Gaucher cells(GC). [1]\u003c/p\u003e \u003cp\u003eThe prevalence of GD varies significantly across global populations, with a general prevalence rate of approximately 1 in 50,000. Notably, this rate is considerably higher in the Jewish population, estimated at about 1 in 850.[2, 3] In China, the incidence of GD is markedly lower than the global average, categorizing it as a rare disease, often referred to as a 'super-rare disease.' Currently, there is no documented incidence or research regarding GD in China.\u003c/p\u003e \u003cp\u003eBased on epidemiological statistics from Asian countries, it is estimated that the total number of patients with GD in China is approximately 1000, with only about 200 to 300 patients having a confirmed diagnosis of GD[4].The phenotype of GD is classified into three types based on the urgency of disease onset, the degree of internal organ involvement, and the presence or absence of neurological symptoms. These classifications include chronic (non-neurological, adult, type I), acute (type II, neurological), and subacute (type III, neurological)[5].\u003c/p\u003e \u003cp\u003eGD is a significant metabolic disorder that can lead to debilitating or even fatal outcomes if not identified and treated promptly[6]. The most common and notable clinical manifestations of GD include liver and spleen enlargement, which may be accompanied by hypergammaglobulinemia, hyperferritinemia, and abnormalities in lipid metabolism[7]. These symptoms often result in the misdiagnosis of other hematological disorders, such as chronic liver disease, due to the absence of characteristic features in the presentation and the clinician's heightened sensitivity to the awareness of rare diseases.\u003c/p\u003e \u003cp\u003eIt has been demonstrated that the risk of liver disease in patients with GD is a significant and potentially life-threatening concern. The primary mechanism underlying this liver involvement is hepatic fibrosis. Therefore, assessing hepatic fibrosis is crucial for identifying the severity of hepatic lesions in patients with GD[8]. Liver biopsy is considered the gold standard for diagnosing hepatic fibrosis; however, due to its invasive nature, this assessment is not feasible in patients with GD who exhibit severe intolerance reactions, such as a tendency to bleed. Shear wave elastography (SWE) has proven to be an effective method for quantifying the extent of liver fibrosis in chronic liver disease. It offers several advantages over other non-invasive imaging techniques, including magnetic resonance elastography, such as ease of integration into clinical routines, low cost, and relatively short examination times. SWE allows for the elastographic assessment of various regions within the liver, thereby facilitating the quantification of hepatic fibrosis across a wide spectrum of chronic liver diseases. From these data, threshold values can be derived to differentiate the stages of fibrosis. Furthermore, the European Federation of Ultrasound Societies in Medicine and Biology has published guidelines for the clinical application of ultrasound elastography, which further validates the utility of SWE in assessing hepatic fibrosis[9].\u003c/p\u003e \u003cp\u003eThe primary objective of this investigation is to synthesize the manifestations of GD as observed in ultrasonographic imaging and to assess the potential value of SWE for the non-invasive diagnosis of GD at its earliest stages. In addition, this study will evaluate the feasibility and efficacy of this approach.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase Group:\u003c/h2\u003e \u003cp\u003eA total of 33 samples from patients diagnosed with GD were collected from January 2020 to December 2025 at the Department of Hematology of the First Affiliated Hospital of Zhejiang Medical University in China. The case group consisted of patients who met the following criteria: (1) All patients were diagnosed with GD based on either marrow aspiration or glucosidase activity test results. (2) All 33 patients underwent GD-DS3. (3) Additionally, all patients received standardized abdominal ultrasonography and liver SWE. The exclusion criteria were as follows: (1) Inability to complete the coordinated ultrasound examination. (2) No history of liver or spleen-related diseases, or other hematological or chronic conditions.\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\u003eBasic information of 33 Gaucher disease patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatient no.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c3\" namest=\"c2\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eYears since diagnosis (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGD-DS3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSpleen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLiver enlarged\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eremoved\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003enodules\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eenlarged\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eresection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eresection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eresection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eresection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eresection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e26\u003c/p\u003e \u003cp\u003e27\u003c/p\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e29\u003c/p\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e31\u003c/p\u003e \u003cp\u003e32\u003c/p\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eM\u003c/p\u003e \u003cp\u003eM\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eM\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e45\u003c/p\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e54\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e46\u003c/p\u003e \u003cp\u003e32\u003c/p\u003e \u003cp\u003e69\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e43\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e0.5\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e0.5\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e8.5\u003c/p\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e6.5\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e5.5\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003eresection\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003eresection\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003eresection\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eF:female,M:male, GD-DS3: Gaucher Disease Severity Score System, 0: No, 1༚Yes\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eControl group:\u003c/h3\u003e\n\u003cp\u003eA total of 30 patients diagnosed with hepatitis B cirrhosis were randomly selected from a pool of cases that met the diagnostic criteria established by the European Association for the Study of the Liver[10]. Similarly, 41 cases of metabolic-associated fatty liver disease(MAFLD)were randomly chosen from a pool of cases that fulfilled the criteria for MAFLD diagnosis as delineated by an international panel of experts[11]. Additionally, 50 individuals without any liver disease were randomly selected to serve as a control group. All patients underwent a comprehensive ultrasound examination of the liver and spleen, which included shear wave elasticity imaging of the liver. The exclusion criteria were as follows: (1) Inability to complete a cooperative ultrasound examination; (2) No history of hematologic or chronic diseases. ༈Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e༉\u003c/p\u003e\n\u003ch3\u003eUltrasound parameters:\u003c/h3\u003e\n\u003cp\u003eAll patients underwent evaluation using a color Doppler ultrasound diagnostic instrument (GE\u0026rsquo;s LOGIQ-E20), with all findings documented by the same physician. This study examined parameters including the diameter of the right hepatic diagonal of the liver and the thickness of the spleen, while also assessing fundamental ultrasound characteristics such as echo intensity and the presence of space-occupying lesions. The oblique diameter of the right liver exceeding 14 cm was deemed indicative of hepatomegaly, while a spleen thickness greater than 4 cm suggested splenomegaly[12](Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e、\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).The procedure for measuring liver SWE using ultrasound is as follows: the patient is positioned horizontally in a supine posture. The operator places the probe perpendicular to the hepatic peritoneum in the right intercostal space, ensuring that large blood vessels are avoided. The measurement depth is selected to be approximately 1.5 cm, with the probe positioned at a depth not exceeding 5 cm. The sampling frame, which should be pre-set and not altered, is positioned in the right lobe of the liver, specifically in the S6 segment, although the optimal locations may also include the S5 segment or the 7th or 8th segments. The elasticity value of liver stiffness was obtained by instructing the patient to hold their breath for 3 to 5 seconds while breathing calmly. The data collected after filling the sampling frame with the selected color represented the elasticity value of liver stiffness. Various factors, including the positioning of the sampling frame, the operator's technique, the patient's breathing patterns, and the thickness of the adipose tissue, may influence the elasticity value. To account for these potential variations, each patient underwent 10 measurements, and the mean value was calculated at the conclusion of the study. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGaucher Disease Severity Score System(GD-DS3): All GD patients were evaluated for severity using the GD-DS3 scale, as described by Neal J. Weinreb[13].\u003c/p\u003e \u003cp\u003e This study received approval from the Institutional Review Board of the First Hospital of Zhejiang University School of Medicine, and informed consent was obtained from the participants or their guardians.\u003c/p\u003e\n\u003ch3\u003eStatistical analysis methods:\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS 27.0 software. Shapiro-Wilk normality test was conducted for each indicator, with \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026gt;\u0026thinsp;0.05 indicating normal distribution of the data. Measurement data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn;\u003cem\u003es\u003c/em\u003e, while enumeration data were presented as frequencies. Independent samples t-test was used to analyze the indicators in each group, with t-values and p-values calculated to assess the statistical significance of inter-group differences. Pearson correlation analysis was employed to explore the relationship between GD-DS3 and liver stiffness, with corresponding evaluation of the obtained \u003cem\u003er\u003c/em\u003e-values and \u003cem\u003ep\u003c/em\u003e-values. A \u003cem\u003ep\u003c/em\u003e-value less than 0.05 was considered statistically significant, while an \u003cem\u003er\u003c/em\u003e-value greater than 0.8 indicated a strong correlation between GD-DS3 and liver stiffness.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 33 patients with Gaucher disease, including 8 males and 25 females, 6 were minors and the remaining 27 were adults, aged 3\u0026ndash;69 years. Hepatomegaly was found in 18(55%) patients, and splenomegaly was also found in 18(72%) patients (excluding resected spleens), of which 8(24%) underwent splenectomy due to significantly enlarged spleens, while 5(15%) patients had splenomegaly accompanied by multiple roundish nodules with sizes ranging from a minimum of about 0.9 mm to a maximum of about 5.6 cm, which were hypoechoic, with well-defined borders and no significant blood flow signals(Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). 33 patients were treated with enzyme replacement therapy. The basic information of the patients and some of their ultrasound characteristics are shown in(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe liver elasticity values were 4.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78 kPa in normal subjects, 10.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25 kPa in patients with hepatitis B type cirrhosis, 5.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39kPa in patients with MAFLD and 8.09\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42kPa in patients with GD. Multiple comparisons demonstrated a significant difference in liver elasticity values between patients with GD and normal subjects (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as between patients with GD and those with MAFLD (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Furthermore, the average spleen thickness in normal subjects was 3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30 mm, in patients with MAFLD it was 3.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 mm, and in patients with GD it was 5.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26mm. Multiple comparisons revealed a remarkable difference in spleen thickness between patients with GD and normal subjects (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as between patients with GD and those with MAFLD (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The oblique diameter of the right liver values were 13.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 in patients with hepatitis B type cirrhosis and 13.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39 in patients with GD .The oblique diameter of the right liver in GD only shows statistical significance when compared with that in patients with hepatitis B(\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Correlation analysis using Pearson's method showed a significant correlation between the GD-DS3 and the live stiffiness (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.5193, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\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\u003eComparison of SWE between the case group and the control 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=\"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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControl Groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMAFLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eLiver cirrhosis\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\u003eSWE(kPa)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.09\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e10.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.918\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e-2.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.05\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\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=\"6\"\u003eMAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAsterisks (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e) indicate statistically significant differences between the case group and the control groups (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\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 spleen thickness between the case group and the control groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl Groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMAFLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver cirrhosis\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\u003espleen thickness\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.462\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.05\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAsterisks (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e) indicate statistically significant differences between the case group and the control groups (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\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\u003eComparison of the oblique diameter of the right liver values between the case group and the control groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl Groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMAFLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver cirrhosis\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\u003eThe oblique diameter of the right liver values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.498\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.05\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\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=\"5\"\u003eMAFLD: metabolic associated fatty liver disease, SWE༚shear wave elastography, GD༚Gaucher disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAsterisks (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e) indicate statistically significant differences between the case group and the control groups (\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEarly diagnosis of GD often necessitates invasive and complex procedures, including pathological biopsies, molecular genetic tests, and enzyme activity assays, which can result in prolonged diagnostic timelines. Some physicians may exhibit reluctance to diagnose and treat GD with enzyme replacement therapy (ERT) due to limited experience, or they may misdiagnose other conditions due to the presence of splenomegaly, leading to further diagnostic challenges. Moreover, a considerable number of patients with GD struggle to tolerate the complications associated with splenic hyperfunction and the compression of peripheral organs. The risk of infection significantly increases following splenectomy, which may further exacerbate the severity of other complications. Therefore, early detection and effective intervention in the progression of GD are of paramount importance[7].Ultrasound as a simple and rapid test can guide hematologists to be able to non-invasively identify common splenomegaly and thrombocytopenia disorders, thus eliminating unnecessary imaging and laboratory tests, and ultrasound elastography can be used to quantitatively assess the extent of cirrhosis, as well as its potential use as a marker to monitor the severity of GD disease.\u003c/p\u003e \u003cp\u003eIt has been reported that almost all patients with GD exhibit some degree of liver damage, characterized by hepatomegaly, which may occur with or without abnormalities in liver function, cirrhosis, portal hypertension, and, in severe cases, even hepatocellular carcinoma[7, 14]. Patlas et al. studied 103 pediatric patients with GD, finding that the incidence of hepatomegaly was 100%[15]. In our study, more than half of the patients presented with hepatomegaly, which may be pathophysiologically attributed to the infiltration of inflammatory factors into the lobular centers of the liver or the replacement of a significant portion of hepatic parenchyma by GC, leading to massive accumulation and subsequent macroscopic enlargement of the liver[16\u0026ndash;19].In his studies utilizing a mouse model, Manoj identified several molecules present in the circulation of mice with the Gba1 mutation (D409V/null). In vitro chemotaxis studies and flow cytometry revealed that the serum from D409V/null mice contained chemotactic agents for various immune cells. The influx of these cells, coupled with the increase in specific chemokines, contributed to the enlargement of the liver[20]. Conversely, several subjects in our study did not exhibit hepatomegaly, which may be attributed to several factors: first, they may have undergone long-term enzyme replacement therapy (ERT), leading to a reduction in the accumulation of GC; second, the duration of the disease may be relatively short, resulting in insufficient infiltration of GC in the liver or minimal hepatocyte damage.\u003c/p\u003e \u003cp\u003eThe initial presentation of many patients with GD often involves a self-perceived enlarged abdomen. This mass is, in fact, an enlarged spleen. Some patients opt for splenectomy prior to enzyme replacement therapy to mitigate the risks associated with significantly elevated splenic function. The causes of splenomegaly and hepatomegaly are fundamentally similar, as both conditions may arise from splenic enlargement due to the accumulation of large aggregates of GC or inflammatory mediators. It has been documented in the medical literature that patients with GD frequently present with intra-splenic hyperechoic nodules on ultrasonography, which account for approximately one-fifth to one-third of cases[21].According to the findings of our study, the potential causes can be attributed to three main factors: (i) the formation of clusters of nodules resulting from the concentrated aggregation of GC within the spleen, and (ii) the occurrence of ischemia due to prolonged inflammation infiltration, which subsequently leads to the formation of infarct foci. (iii)additionally, it is important to acknowledge that other common types of intra-splenic hyperechoic nodules, such as splenic hemangioma and splenic aneurysm, may also be present[22]. Due to the reduced platelet count in patients with Gaucher disease, splenic nodules are at a higher risk of bleeding complications following puncture. Therefore, these nodules were not pathologically examined to determine their nature. Consequently, close monitoring of these patients during the follow-up process is essential, which should include an evaluation of the size, echogenicity, blood flow, and any significant changes in the ultrasound manifestations of the intra-splenic nodules.\u003c/p\u003e \u003cp\u003eThe results of the study indicated that liver elasticity values in patients with GD were significantly higher than those in normal subjects and MAFLD \u003cem\u003e(P\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This increased stiffness may be attributed to the establishment of a fibrotic microenvironment by GC in the liver, along with various pathophysiological mechanisms. The formation of liver fibrosis in GD can be explained by the infiltration of Gaucher cells. Prolonged infiltration may lead to chronic low-grade inflammation of the liver, which can progress to cirrhosis. Furthermore, abnormalities in the immune system due to the destruction of GC also contribute to cirrhosis. This may result from T-cell impairment or chronic stimulation of the immune response. Additionally, cytokine secretion by activated macrophages, either directly or indirectly, can induce GC leading to hepatic fibrosis in some patients[7]. Alterations in iron metabolism in patients with GD are significant contributors to liver fibrosis. Elevated iron levels in hepatocytes and Kupffer cells in these patients result in secondary iron overload. Furthermore, increased iron levels may promote the formation of reactive oxygen species, which can lead to hepatocellular injury and potentially cause liver fibrosis[23, 24]. Literature has reported that some patients develop type 2 diabetes mellitus or metabolic syndrome with hepatic lipid deposition following ERT[25]. The gradual accumulation of significant amounts of fat adversely affects the blood and oxygen supply as well as the metabolic functions of the liver, leading to hepatocellular swelling, inflammatory infiltration, and cellular degeneration and necrosis. This progression can result in steatohepatitis, followed by hepatic fibroplasia, and ultimately, fatty liver cirrhosis. The aforementioned pathophysiological processes may underlie the development of hepatic fibrosis in patients with GD.\u003c/p\u003e \u003cp\u003eGD is caused by a reduction in glucocerebrosidase activity, leading to a significant accumulation of glucocerebrosides. A substantial body of literature demonstrates that elevated levels of glucocerebrosides have a protective effect on the liver[26, 27]. The present study found that liver stiffness in GD patients is lower than that in cirrhotic populations, although it remains higher than normal levels. The increase in glucocerebrosides may underlie the reduced risk of excessive liver injury in GD patients. The hepatoprotective effects of glucocerebrosides can be attributed to several mechanisms. One such mechanism involves glucocerebrosides acting as a glycolipid ligand presented to natural killer T (NKT) cells and dendritic cells (DCs) via CD1 molecules. glucocerebrosides can also exert immunomodulatory effects on these target cells, either directly or indirectly, by altering their interactions with other subpopulations of immune cells. Additionally, Yaron llan's research reports in animal models have all confirmed glucocerebrosides' significant protective effect on the liver: Margalit and colleagues found that glucocerebrosides attenuated ConA-induced hepatitis in mice, and its effect was associated with reduced serum interferon (IFN)- γ levels and decreased STAT1 transcription factor expression[28].These experimental data suggest that glucocerebrosides may play a beneficial role in the treatment of patients with chronic liver disease. There is also an explanation that may be related to ERT treatment, which eliminates GC in the liver tissue, but there are some areas where it is difficult for the drug to act by injecting blood into the targeted tissue due to fibrosis, i.e., it will not eliminate GC in the areas where fibrous tissue is present.\u003c/p\u003e \u003cp\u003eAs a rare disease in the clinic, GD has a low demand in the drug market and high drug development and production costs, resulting in extremely expensive therapeutic drugs, so effective and accurate assessment of the severity of the disease and guidance for the clinical stage of rationalizing the use of drugs play a crucial role in alleviating the financial difficulties of patients' families.GD-DS3 is an effective assessment of the severity of GD, as reported by Weinreb, N. J., et al[13].However, they did not include ultrasound elastography, which is a non-invasive assessment of liver fibrosis imaging, in their scoring criteria and only included assessment of liver and spleen size. Andr\u0026eacute;, Lollert et al. concluded that there is a correlation between MRE and GD-DS3, while MRE has the disadvantages of long detection time, inability to wear metal objects, and high cost of the examination. In our study, we conducted a correlation analysis between liver stiffness values and GD-DS3 in patients with GD using ultrasonic SWE. Our findings revealed a significant positive correlation with GD-DS3, which aligns with the results obtained by Serai et al. in their correlation analysis utilizing acoustic radial force impulse point SWE. However, the correlation reported by Serai et al. was relatively low (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03) when compared to our results.[29] They attributed this discrepancy to prolonged treatment with ERT, which normalized certain blood indices. However, some patients in their cohort may have experienced more severe liver damage, preventing ERT from effectively reaching those areas due to significant fibrosis. Consequently, the liver elasticity values remained elevated, resulting in a lower correlation. In contrast, our analysis indicates that the subjects from our province have only recently had access to ERT through health insurance. Prior to this, many patients could not afford treatment since the onset of the disease, leading to a shorter duration of systematic treatment. As a result, some patients have not yet shown significant recovery, which may contribute to higher scores and elevated liver elasticity values, indicating a strong correlation between the two. Additionally, a subset of our population, including two children with very mild disease onset, exhibited relatively low GD-DS3 and liver elasticity values, further enhancing the observed correlation.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThe final results may not fully represent the entire population due to the rare nature of the diseases examined in this paper, the limited number of researchers involved, and individual differences within some experimental groups. Nevertheless, the conclusions drawn from this study align closely with those of previous research. To facilitate more rigorous and comprehensive investigations, we will continue to gather data from a larger cohort of patients across the nation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn addition to its role in assessing disease severity, 2D-SWE has the potential to emerge as the preferred noninvasive test for differentiating GD from healthy subjects, MAFLD, and liver cirrhosis. Consequently, the efficiency of clinical diagnosis and the reduction of unnecessary patient burden will be significantly enhanced.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknolwledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contribution:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept: GZ, XW; Data Collection and Processing: GZ, SW; Analysis and Interpretation: GZ, Literature Search: ZS; Writing: GZ; WZ provided advice on data analysis and interpretation of the results. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed in accordance with the Ethics Guidelines of the Helsinki Declaration and was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine. Written informed consent to participate was obtained from all of the participants in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1234\u003c/sup\u003eDepartment of Ultrasound, The First Affiliated Hospital of Zhejiang University School of Medicine, 310000 Hangzhou, China\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1*\u003c/sup\u003eDepartment of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, 310000 Hangzhou, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTomer A, Yaron I, Deborah E, Ari Z. 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Ultrasonic Medicine. 5th ed. Beijing: Science and Technology Documentation Press. 2006.\u003c/li\u003e\n\u003cli\u003eNeal J W, Maria D C, Timothy M C, Edward H G, Gregory A G, Wuh-Liang H, et al. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med. 2009;12(1).\u003c/li\u003e\n\u003cli\u003eFrancesca C, Maria Domenica C, Silvia F, Anna Ludovica F, Fabio N. Liver involvement in Gaucher disease: A practical review for the hepatologist and the gastroenterologist. Dig Liver Dis. 2020;52(4).\u003c/li\u003e\n\u003cli\u003eMichael P, Irith H-H, Aya A, Deborah E, Ari Z. Spectrum of abdominal sonographic findings in 103 pediatric patients with Gaucher disease. Eur Radiol. 2002;12(2).\u003c/li\u003e\n\u003cli\u003eR H L, D G W, D J L, N C F, J P S, E E, T M C. Massive hepatic fibrosis in Gaucher's disease: clinico-pathological and radiological features. QJM. 2000;93(4).\u003c/li\u003e\n\u003cli\u003ePatrick B D, Timothy M C. Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des Devel Ther. 2012;6(0).\u003c/li\u003e\n\u003cli\u003eT M C. Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. J Inherit Metab Dis. 2002(0).\u003c/li\u003e\n\u003cli\u003eH H, J L, H P, A K, V M, M E. Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process. J Inherit Metab Dis. 2009;32(4).\u003c/li\u003e\n\u003cli\u003eManoj Kumar P, Nicholas A J, You-Hai X, Wujuan Z, Kenneth D R S, Gregory A G. Gaucher disease: chemotactic factors and immunological cell invasion in a mouse model. Mol Genet Metab. 2013;111(2).\u003c/li\u003e\n\u003cli\u003eMuriel W, Ari Z, Tama D, Oren S, Stella L, David M S, Ophira S. Are transient and shear wave elastography useful tools in Gaucher disease? Blood Cells Mol Dis. 2017;68(0).\u003c/li\u003e\n\u003cli\u003eChristine S, Timothy M C, Vanessa L-S, Elizabeth M, Karima Y, Olivier M, et al. Splenic Artery Aneurysms, A Rare Complication of Type 1 Gaucher Disease: Report of Five Cases. J Clin Med. 2019;8(2).\u003c/li\u003e\n\u003cli\u003eMartine R, Andr\u0026eacute; B P vK, Joanne V, Dorine W S, Carla E M H. Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications. Blood Rev. 2016;30(6).\u003c/li\u003e\n\u003cli\u003eAnneloes E B, Laura vD, Erik M A, Aart J N, Ralph S, Peter L M J, et al. Liver fibrosis in type I Gaucher disease: magnetic resonance imaging, transient elastography and parameters of iron storage. PLoS One. 2013;8(3).\u003c/li\u003e\n\u003cli\u003eRodrigo T S, M\u0026aacute;rio R \u0026Aacute;-d-S, Ida Vanessa D S. Concerning 'Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease' by Nascimbeni et al. Liver Int. 2020;41(1).\u003c/li\u003e\n\u003cli\u003eMaya M, Samir AG, Ruslana A, Eran E, Athalia K, Victoria D, et al. Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes. Am J Physiol Gastrointest Liver Physiol. 2005;289(5).\u003c/li\u003e\n\u003cli\u003eYaron I, Deborah E, Ari Z. Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent. Immunol Cell Biol. 2009;87(7).\u003c/li\u003e\n\u003cli\u003eAndr\u0026eacute; L, Christian H, Michael L, Jochem K, Miriam B-H, Julia B H, et al. Acoustic radiation force impulse point shear wave elastography of the liver and spleen in patients with Gaucher disease type 1: Correlations with clinical data and markers of disease severity. Mol Genet Metab. 2020;130(2).\u003c/li\u003e\n\u003cli\u003eSuraj D S, Anjani P N, T AB, Carlos E P, Stavra X, Alexander J T. Correlating liver stiffness with disease severity scoring system (DS3) values in Gaucher disease type 1 (GD1) patients. Mol Genet Metab. 2018;123(3).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gaucher disease, Shear wave elastography, Liver fibrosis, Rare disease","lastPublishedDoi":"10.21203/rs.3.rs-9335107/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9335107/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with Gaucher disease frequently exhibit hepatosplenomegaly and high echogenicity in liver sonograms, resembling the findings in patients with hepatitis B cirrhosis and metabolic-associated fatty liver disease. Conventional two-dimensional ultrasound has not demonstrated significant advantages in diagnosing this condition. Therefore, the objective of this study was to investigate the potential of shear wave elastography as a non-invasive diagnostic tool for the early detection of Gaucher disease and to assess the feasibility of this approach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comparative analysis was conducted to evaluate the sizes of the liver and spleen, as well as the shear wave elastography values, among 33 patients diagnosed with Gaucher disease, 30 patients suffering from hepatitis B cirrhosis, 41 patients with metabolic associated fatty liver disease,and 50 normal subjects. Furthermore, the correlation between the severity scores of patients with Gaucher disease and their hepatic elasticity values was analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe liver stiffness and spleen thickness observed in patients with Gaucher disease were significantly higher than those in normal subjects and individuals with metabolic associated fatty liver disease (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.001). However, liver stiffness in patients with Gaucher disease was lower than that in patients diagnosed with hepatitis B cirrhosis \u003cem\u003e(P\u003c/em\u003e \u0026lt; 0.05). Furthermore, the oblique diameter of the right liver in patients diagnosed with Gaucher disease was found to be greater than individuals with hepatitis B cirrhosis (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05). Correlation analysis demonstrated a significant relationship between the severity scores and the magnitude of liver stiffness in patients with Gaucher disease (\u003cem\u003er\u003c/em\u003e = 0.5193, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo-dimensional shear wave elastography plays a crucial role in assessing the severity of Gaucher disease and differentiating it from healthy individuals, metabolic associated fatty liver disease, and patients with hepatitis B cirrhosis. This non-invasive test has the potential to reduce the number of unnecessary invasive procedures for patients while significantly enhancing the diagnostic efficiency for this disease.\u003c/p\u003e","manuscriptTitle":"The Potential of Shear Wave Elastography for Assessing Liver Fibrosis in Patients with Gaucher Disease: A Promising Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 15:13:03","doi":"10.21203/rs.3.rs-9335107/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-04-14T04:23:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T09:46:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T08:53:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2026-04-06T14:44:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd573ffc-8b7b-4a56-a7a3-02e99e24b2b2","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T15:13:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 15:13:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9335107","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9335107","identity":"rs-9335107","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}