Metabolic Dysfunction-associated Steatotic Liver Disease in Adolescent and Young Adult Patients Undergoing Bariatric Surgery: When to Biopsy?

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Alyssa Stetson, Rachel Herdes, Michael Kochis, Christa Bizimana, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6480681/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in adolescent and young adults (AYA) with obesity. However, the role of liver biopsy during metabolic bariatric surgery (MBS) is debated. Methods: This is a retrospective chart review of AYA patients < 22 years old who underwent MBS between 2014-2023 at two institutions. A policy of selective liver biopsy was used for the majority of the study, but both sites had periods of routine biopsy. Selective biopsy was based on preoperative factors associated with MASLD. Patients with steatosis, fibrosis, or steatohepatitis on histology were considered to have a diagnosis of MASLD. Preoperative laboratory markers were evaluated for association with MASLD using multivariate regression. Results: Among 240 patients, 121 (50%) underwent biopsy, with 63 (53%) performed during routine biopsy periods. The remaining 56 biopsies (32%) were in the 177 patients who underwent MBS during a selective period. There was no difference in rate of positive biopsy between routine (47, 75%) and selective (44, 79%) groups (p=0.61). Steatohepatitis was present in 28 (23.5%) of patients and ≥ Stage 2 fibrosis in 13 (10.9%) of patients. Elevated BMI, ALT, and HbA1c were associated with a diagnosis of MASLD. Among 28 routine-biopsy patients with normal preoperative laboratory markers, 16 (57.1%) had MASLD on biopsy. Conclusion: In our cohort, selective biopsy was no more effective than chance at identifying patients with MASLD, suggesting a high rate of missed diagnoses. This presents an opportunity to standardize biopsy protocols including consideration of routine liver biopsy in AYA patients undergoing MBS. metabolic and bariatric surgery (MBS) liver biopsy metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) adolescent and young adult (AYA) Figures Figure 1 Key points Preoperative findings do not identify which patients should undergo liver biopsy during MBS. A policy of selective liver biopsy fails to diagnose AYA patients with MASLD. Routine intraoperative liver biopsy could capture additional patients with MASLD, ensuring they undergo appropriate management and surveillance Introduction Metabolic and bariatric surgery (MBS) is now recognized as the most effective treatment for severe obesity and obesity-related medical problems in adolescent and young adult (AYA) patients [ 1 , 2 ]. However, metabolic dysfunction-associated steatotic liver disease (MASLD) is comparatively challenging to follow as there is no simple method of diagnosis [ 3 – 5 ]. Previously known as non-alcoholic fatty liver disease, MASLD is defined as hepatic steatosis > 5% by imaging or biopsy and the presence of a cardiometabolic risk factor [ 6 ]. While most patients with MASLD are asymptomatic, MASLD contributes to the population with chronic liver disease and patients with fibrosis secondary to MASLD are at increased risk of liver-related mortality [ 7 – 9 ]. MASLD is the most common liver disease in AYA patients with an estimated prevalence of approximately 30% among those with obesity. The spectrum of disease can range from isolated steatosis to fibrosis or cirrhosis [ 2 , 10 ]. While studies have identified factors predictive of MASLD, including elevated liver function tests (LFTs), waist-hip ratio, waist circumference, diabetes, insulin resistance, and elevated triglycerides, the results of these studies are heterogeneous and fail to demonstrate a laboratory or anthropometric test that can adequately differentiate which patients undergoing MBS should have an intraoperative liver biopsy performed [ 11 ]. Improvements have been made in the use of imaging for diagnosis, but the role of these tests remains limited given a need for insurance approval, varied diagnostic accuracy, and risks of repeat radiation exposure [ 2 , 12 , 13 ]. Ultrasound is low-cost and non-invasive, and increased echogenicity can support a diagnosis of MASLD, but lacks sensitivity and specificity, especially at lower grades of steatosis [ 14 ]. Controlled attenuation parameter (CAP) may be a simple and more accurate alternative, although this also has limitations with sensitivity and specificity, especially in the setting of severe obesity [ 15 – 17 ]. Magnetic resonance imaging (MRI) proton density fat fraction is a validated approach to diagnosing and staging hepatic steatosis but is expensive and not widely available [ 18 – 20 ]. Therefore, while serum transaminases are currently used as a surrogate for diagnosis and monitoring, many patients require diagnosis through liver biopsy. Biopsy practices in AYA patients undergoing MBS are not standardized. While the American Association for Study of Liver Disease (AASLD) has recommendations for appropriate timing of liver biopsy in adults, these may not apply to younger populations and do not specifically address when to perform a biopsy during MBS [ 21 , 22 ]. An argument against biopsy is that tissue diagnosis would not necessarily affect management of MASLD, since patients undergoing MBS are already receiving the most effective treatment possible [ 23 ]. However, given the prevalence of MASLD in patients with obesity, the long-term negative ramifications of untreated MASLD, the possibility that patients with severe fibrosis are less likely to achieve resolution even after MBS, and the fact that patients are already under anesthesia, some centers choose to perform routine biopsy for AYA patients undergoing MBS [ 11 , 24 ]. In this study, we investigate the preoperative factors associated with a diagnosis of MASLD and the biopsy protocols of two centers. We hypothesized that liver biopsy would identify patients with MASLD who otherwise would be undiagnosed. Methods Study population We performed a retrospective chart review of AYA patients (age < 22) who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at two tertiary centers between 01/01/2014–12/31/2023. Site #1 is integrated within adult hospitals but has a dedicated pediatric weight loss center, while Site #2 is a standalone children’s hospital. Institutional Review Board approval was granted at both sites. Liver Biopsy At Site #1, liver biopsy was routinely performed during MBS through 6/2018, then was selectively performed. At Site #2, liver biopsy was selectively performed except between 5/1/2018–9/30/2018 when it was routine (Supplementary Fig. 1). Liver biopsy is performed via laparoscopic wedge of the peripheral left lobe of the liver. Sites stopped routinely performing liver biopsies based on guidelines from the adult population. At both centers, the decision to pursue a selective biopsy was made at the discretion of the care team based on preoperative risk factors in consultation with the patient and family. Both institutions had variable indications for the threshold at which to perform biopsy. For the purpose of analysis, patients were grouped into three cohorts: underwent routine liver biopsy, underwent selective liver biopsy, and did not undergo liver biopsy. When evaluating biopsy protocols, we compared patients who underwent selective liver biopsy to those that did not. When evaluating characteristics predictive of a histologic diagnosis of MASLD, we combined all patients who had undergone liver biopsy (both selective and routine). Preoperative laboratory values included in the analysis of factors associated with a histologic diagnosis of MASLD were alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, cholesterol, triglycerides, low density lipoprotein (LDL), high-density lipoprotein (HDL), and glycated hemoglobin (HbA1C). Data collection Data were independently collected at each site, de-identified, and compiled. Laboratory markers were classified as elevated based on the following cutoffs: ALT > 26 U/L for males and 22 U/L for females, AST ≥ 40 U/L, cholesterol > 120 mg/dL, LDL ≥ 110 mg/dL, HDL 5.7%. [ 25 ]. An imaging diagnosis of MASLD was made if steatosis with or without the presence of fibrosis or cirrhosis, was noted on CT, ultrasound, or MRI. On histology, samples were labeled with an internalized scoring system based on elements of the NAFLD activity score (NAS) involving steatosis, hepatocyte ballooning, and lobular inflammation where Grade I is mild (5–33%), Grade II is moderate (34–66%), and Grade III is severe (67–100%). Histologic MASLD was defined as the presence of steatosis, fibrosis, or steatohepatitis on histology. Statistical Analysis Continuous variables were compared using an independent sample, 2-tailed t-test. Discrete variables were analyzed with a chi-squared test. We used multiple regression to assess for relationships between preoperative variables and whether a biopsy was performed as well as a diagnosis of MASLD. Patients missing preoperative laboratory values were excluded from univariate analyses. Statistical analysis was performed using STATA (Version. 17.0; StataCorp, College Station, TX). Significance was defined as a p value of < .05. Results Group Demographics Our cohort included 241 patients. One patient was excluded due to incomplete information in the medical chart, so analysis was performed on 240 patients. Site #1 contributed 112 patients (46.7%), and the remainder by Site #2. Two-thirds (65.8%) of the patients were female and the majority of patients were white (47.5%) and not Hispanic (57.9%). Median preoperative lab values are displayed in Supplementary Table 1. Median age at surgery was 17.6 years, and median BMI was 48.1 kg/m 2 (Table 1 ). There were no complications within thirty days related to liver biopsy for any patient. Characteristics associated with a diagnosis of MASLD A total of 119 patients had a biopsy performed (routine or selective) (Table 3 ). Within this cohort, 81% had a diagnosis of MASLD based on either histology or imaging: 63.9% had a histologic diagnosis without imaging findings, 12.6% had both a radiographic and histologic diagnosis, and 4.2% had only imaging findings without histologic changes (Fig. 1 ). Patients underwent imaging due to concerns for the presence of MASLD. There were 28 patients (23.5%) with steatohepatitis and 13 patients (10.9%) with ≥ Grade 2 fibrosis. Among patients who underwent routine biopsy, 74.6% of had a diagnosis of MASLD. We performed a subset analysis of the 75 patients with a diagnosis of MASLD on biopsy but who had negative imaging. Patients who were older at time of surgery were more likely to have MASLD detected on imaging (p = 0.044) but other demographic characteristics (sex, race, ethnicity) and risk factors for MASLD (BMI and laboratory values) did not differ significantly between those with imaging findings of MASLD and those without (Supplementary Table 2). Of the 104 patients included in univariable analysis, 88 (80%) had a histologic or imaging diagnosis of MASLD. Preoperative elevated ALT (p < 0.001), elevated AST (p = .009), and insulin resistance (p = .008) were associated with a diagnosis of MASLD. On multivariable analysis, only elevated preoperative ALT (p = .01) remained significant. The sensitivity and specificity of ALT for diagnosing MASLD was 90.7% and 46.5% respectively, with an area under the curve of 0.77 (95% confidence interval 0.65, 0.88). In our cohort, among the 75 patients with an elevated ALT, 7 patients (9.3%) did not have a diagnosis of MASLD and among the 32 patients with elevated AST, 2 (6.3%) did not have a diagnosis of MASLD. The biopsy reports for these patients noted either no abnormalities (4/9) or mild non-specific changes (5/9). There were 78 patients who underwent some form of preoperative imaging, with 72 (92%) patients undergoing abdominal ultrasound and 4 patients undergoing cross-sectional imaging. Twenty-six patients (33%) had negative imaging but were diagnosed with MASLD on histology, one of which had undergone computed tomography (CT). Of these 26 patients, 3 (11.5%) had grade 3 steatosis and 10 (38%) had fibrosis. Relationship between choice to perform biopsy and diagnosis of MASLD Of 240 patients, 177 underwent surgery when selective biopsies were being performed. Of these patients, 56 (31.6%) had a biopsy performed with a diagnosis rate of MASLD of 78.6% (44/56). Patients who were male, had surgery at Site #2, or had elevated ALT, AST, or total bilirubin had a greater likelihood of undergoing a biopsy (Table 2 ). Of the 54 patients included in univariable analysis, elevated preoperative AST (p < .001), ALT (p = .05) and total bilirubin (p = 0.01) were associated with biopsy. On multivariable analysis, only elevated AST was associated with selective biopsy being performed (p < .001). There was no significant difference in the likelihood of a positive biopsy between the routine group (47/63, 75%) and selective group (44/56, 79%) (Chi-square = .25, p = 0.61). Among patients who underwent a routine biopsy, and had a normal ALT, AST, and total bilirubin, 16/28 (57.1%) had a diagnosis of MASLD on biopsy. Discussion In adults, MASLD has become the most frequent indication for liver transplant, and emerging data suggest that a diagnosis of MASLD in adolescence increases risk of hepatic morbidity in adulthood [ 26 , 27 ] [ 28 , 29 ]. Confirming a diagnosis of MASLD through liver biopsy can inform patients and providers of the presence of end-organ damage and ensure that patients are referred to a hepatologist for surveillance. In our cohort, rates of diagnosis of MASLD were not significantly different between the group who underwent routine biopsy and underwent selective biopsy. Furthermore, no concerning laboratory markers were identified among patients who were found to have MASLD on routine biopsy. This demonstrates how challenging it is for care teams to accurately predict which patients should be biopsied. Presuming a similar overall prevalence of MASLD between patients who underwent surgery during routine and selective biopsy periods, our calculations suggest that of the 121 patients who were not chosen for biopsy, 75–80% of them would be expected to have undiagnosed pathology. This raises the question of whether a diagnosis was missed in 90–95 children among the cohort of 121 patients. Notably, biopsy was obtained after patients had undergone a two-week liquid diet fast in preparation for MBS, which has been shown to significantly decrease the protein-density fat fraction [ 30 ]. Therefore, their baseline degree of steatosis was likely higher than what was captured during biopsy at time of surgery. Consistent with our finding that elevated ALT and AST were associated with the decision to perform a biopsy, elevated ALT is considered the most highly predictive laboratory value for a diagnosis of MASLD and is commonly incorporated into NAFLD scoring systems[ 31 ]. However, it is an imperfect measure, with one study finding an ALT as high as 231 U/L is necessary to create an area under the curve > 90 [ 32 , 33 ] – for comparison, the interquartile range in our cohort was 19–45 with only two patients having an ALT ≥ 231. The heterogeneity of proposed cut-offs reported in the literature (ranging from 26–39 in males and 17–31 in females) and the false negative rate of around 25% also demonstrate that ALT is insufficient as a standalone marker [ 33 – 35 ]. Furthermore, elevated LFTs in a patient with obesity can lead to the false assumption of an underlying diagnosis of MASLD. While no patients with elevated LFTs in our cohort were found to have another form of hepatic disease, six patients had mild non-specific changes that could later be diagnosed as an etiology distinct from MASLD. Obesity, MASLD, and insulin resistance are intrinsically linked, comprising the diagnosis of metabolic syndrome, with liver dysfunction likely both contributing to and resulting from insulin resistance [ 36 ]. Given this, the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines recommend screening overweight children ages 9–11 with insulin resistance for hepatic steatosis [ 37 ]. However, while insulin resistance in the setting of obesity is associated with increased risk of MASLD, an elevated Hb1Ac is not sufficiently sensitive or specific to be used to make a diagnosis of MASLD. Imaging has been used to diagnose steatosis, but like elevated ALT, has limitations. Conventional imaging modalities of ultrasound, CT, and CAP have overall sensitivities and specificities ranging from 60–100% and are less equipped to diagnose moderate steatosis or discern mild steatosis from no steatosis [ 38 – 40 ]. Elastography has an AUC of of 0.78–0.96 but is also more predictive with severe fibrosis [ 41 ]. MRI can reliably be used for detection and grading of steatosis but is limited by availability and cost [ 18 ]. In our cohort, imaging failed to detect MASLD in approximately one-third of patients, including those with severe steatosis or some degree of fibrosis, highlighting its limited sensitivity. Older age at the time of surgery was associated with increased likelihood of detection ( p = 0.044), which underscores that imaging alone should not be relied upon as a diagnostic tool for MASLD in AYA patients. Currently, the International Society for Pediatrics recommends that adolescents with diabetes be screened using ALT (≥ 22 for females, ≥ 26 for males), with referral to a gastroenterologist if liver enzymes remain elevated despite weight loss and glycemic control [ 42 ]. However, AYA patients undergoing MBS represent a unique population in that they have a high pretest probability for MASLD and will already be under general anesthesia and in a position to easily undergo surgical biopsy. The additional risk of bleeding with biopsy is very low, estimated at under 0.3% [ 43 , 44 ]. The risk of bile leak is also exceedingly rare, with only case reports in the literature, and the risk of causing adhesions secondary to liver biopsy is minimal compared to the risk of adhesions secondary to the bariatric procedure [ 45 ]. Choice to perform liver biopsy is not standardized in AYA patients [ 46 ]. We found that only elevated AST was associated with selective biopsy. Other studies in adults have proposed algorithms to predict for MASLD and/or to indicate a biopsy is warranted; these scoring systems include the BMI, age, ALT, triglycerides (BAAT) score, Fibrosis-4 (FIB4) index, Korea-NAFLD (K-NAFLD) score, Fatty Liver Index (FLI), FibroTest, FibroMeter, NashTest, and NAFLD Fibrosis Score (NFS) [ 31 ] [ 47 – 52 ]. If centers wish to pursue a practice of selective biopsy, the development of similar scoring systems in pediatrics could help ensure a higher capture rate of a diagnosis of MASLD. Management of pediatric obesity is a rapidly evolving field, and the implications of MASLD on the long-term health of children are still not fully understood. However, accurate identification of children who are most at risk and subsequent staging of this disease is critical as we work to bridge that knowledge gap [ 22 ]. First, it will allow for tailored surveillance of this population, just as the screening schedule for many other conditions depends on disease severity. Second, accurate staging of MASLD can provide guidance on when to take additional steps to ensure weight-loss and to reduce or prevent further end-organ damage, including with additional surgery or the use of medications [ 53 , 54 ]. Lastly, improved knowledge of the natural history of this disease will help us understand the relationship between obesity, MASLD, and future health outcomes. Our paper has several limitations. First, it is retrospective and observational which did not allow us to control for which patients underwent biopsy, restricts the amount of available data regarding the decision to perform selective biopsy, and limits the standardization with which preoperative imaging was obtained. In some respects, this limitation is also a strength in that it provides real-world data regarding provider practice. Second, because histology was evaluated at two centers, and over a long time period, there is a possibility for inconsistency in grading steatosis and fibrosis. However, any inconsistency should have affected patients at random and so should not introduce bias into the study. Conclusion AYA patients undergoing MBS are a high-risk population for a diagnosis of MASLD, with a prevalence of MASLD of 80% in our cohort. Currently, there are no standard recommendations for intraoperative liver biopsy. Our results suggest that over half of patients with histologic MASLD had normal LFTs and total bilirubin and would therefore potentially remain undiagnosed if laboratory markers or were used to guide biopsy. While further investigation is needed to standardize a biopsy protocol, given the low risks associated with intraoperative biopsy and the imperfect correlation between biologic markers and the presence of MASLD, it may be reasonable to consider routine liver biopsy among AYA patients undergoing MBS. Declarations CONFLICT OF INTEREST / DISCLOSURE STATEMENT None of the authors have anything to disclose and none of the authors have any conflicts of interest. Funding / Support statement: No authors received extramural support or funding. Author Contribution AS wrote the main manuscript and performed data analyss. RH, MK, IN, JR performed data analysis and reviewed the manuscript. CB, FB acquired data and reviewe the manuscript. JP and CG designed and interpreted the study and reviewed the manuscript. References Wirth, K.M., et al., Bariatric Surgery is Associated With Decreased Progression of Nonalcoholic Fatty Liver Disease to Cirrhosis: A Retrospective Cohort Analysis . 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Gastroenterology, 2015. 149(3): p. 623 – 34.e8. Jeong, S., et al., Development of a simple nonalcoholic fatty liver disease scoring system indicative of metabolic risks and insulin resistance . Ann Transl Med, 2020. 8(21): p. 1414. Blanco-Grau, A., et al., Assessing Liver Fibrosis Using the FIB4 Index in the Community Setting . Diagnostics (Basel), 2021. 11(12). Vali, Y., et al., FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis . J Clin Med, 2021. 10(11). Bernstein, D. and A.J. Kovalic, Noninvasive assessment of fibrosis among patients with nonalcoholic fatty liver disease [NAFLD] . Metabol Open, 2022. 13: p. 100158. Poynard, T., et al., Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease . BMC Gastroenterol, 2006. 6: p. 34. Concon, M.M., et al., SHOULD ROUTINE LIVER BIOPSY BE CONSIDERED IN BARIATRIC SURGICAL PRACTICE? AN ANALYSIS OF THE LIMITATIONS OF NON-INVASIVE NAFLD MARKERS . Arq Gastroenterol, 2022. 59(1): p. 110–116. Ryan, P.M., et al., Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis . J Pediatr, 2021. 236: p. 137–147.e13. Agosta, M., et al., Efficacy of liraglutide in pediatric obesity: A review of clinical trial data . Obesity Medicine, 2024. 48. Tables Table 1 Demographics of patients by biopsy type. IQR: Interquartile range; BMI: body mass index Total Routine biopsy Selective biopsy, performed Selective biopsy, not performed p-value N 240 63 56 121 Sex Male 82 (34.2%) 20 (31.7%) 26 (46.4%) 36 (29.8%) 0.084 Female 158 (65.8%) 43 (68.3%) 30 (53.6%) 85 (70.2%) Site Site #1 112 (46.7%) 55 (87.3%) 12 (21.4%) 45 (37.2%) < 0.001 Site #2 128 (53.3%) 8 (12.7%) 44 (78.6%) 76 (62.8%) Race White 114 (47.5%) 45 (71.4%) 20 (35.7%) 49 (40.5%) < 0.001 Black 29 (12.1%) 5 (7.9%) 4 (7.1%) 20 (16.5%) Other 23 (9.6%) 2 (3.2%) 4 (7.1%) 17 (14.0%) Unknown 74 (30.8%) 11 (17.5%) 28 (50.0%) 35 (28.9%) Ethnicity Non-Hispanic 139 (57.9%) 43 (68.3%) 26 (46.4%) 70 (57.9%) < 0.001 Hispanic 94 (39.2%) 14 (22.2%) 29 (51.8%) 51 (42.1%) Unknown 7 (2.9%) 6 (9.5%) 1 (1.8%) 0 (0.0%) Age at surgery (median, IQR) 17.6 (16.4, 18.6) 18.1 (17.1, 19.8) 17.3 (16.1, 18.1) 17.5 (16.2, 18.5) 0.001 Pre-op BMI (median, IQR) 48.1 (43.3, 53.0) 51.1 (45.2, 55.7) 48.78 (42.3, 55.6) 46.4 (42.2, 50.8) 0.001 Table 2 Patients who underwent MBS during a period of selective biopsy. BMI: body mass index; ALT: alanine aminotransferase; AST: aspartate aminotransferase; HDL: high-density lipoprotein; LDL: low-density lipoprotein Selective biopsy, performed Selective biopsy, not performed p-value N = 56 N = 121 Sex Male 26 (46.4%) 36 (29.8%) Female 30 (53.6%) 85 (70.2%) 0.031 Site Site #1 12 (21.4%) 45 (37.2%) 0.037 Site #2 44 (78.6%) 76 (62.8%) Race White 20 (35.7%) 49 (40.5%) 0.029 Black 4 (7.1%) 20 (16.5%) Other 4 (7.1%) 17 (14.0%) Unknown 28 (50.0%) 35 (28.9%) Ethnicity Non-Hispanic 26 (46.4%) 70 (57.9%) 0.14 Hispanic 29 (51.8%) 51 (42.1%) Age 17.0 (2.0) 17.3 (1.6) 0.25 BMI 48.8 (7.4) 47.6 (8.1) 0.36 Laboratory markers Elevated ALT 41 (73.2%) 67 (55.4%) 0.038 Elevated AST 24 (42.9%) 11 (9.6%) < 0.001 Elevated Total bilirubin 3 (5.4%) 0 (0.0%) 0.013 Elevated Cholesterol 17 (32.7%) 37 (33.3%) 0.95 Elevated Triglycerides 38 (73.1%) 69 (63.9%) 0.25 Low HDL 38 (74.5%) 70 (64.8%) 0.22 Elevated LDL 13 (28.3%) 35 (33.0%) 0.56 Insulin resistance 20 (35.7%) 30 (24.8%) 0.32 Table 3 Diagnosis of MASLD in patients who had a biopsy performed during MBS. ALT: alanine aminotransferase; AST: aspartate aminotransferase; HDL: high-density lipoprotein; LDL: low-density lipoprotein Level No Diagnosis of MASLD Diagnosis of MASLD p-value 28 91 Sex Male 6 (26%) 40 (42%) 0.17 Female 17 (74%) 56 (58%) Ethnicity Non-Hispanic 17 (74%) 52 (54%) 0.22 Hispanic 5 (22%) 38 (40%) Unknown 1 (4%) 6 (6%) Laboratory markers Elevated ALT 7 (30%) 68 (71%) < 0.001 Elevated AST 2 (9%) 30 (31%) 0.035 Elevated Total bilirubin 0 (0%) 3 (3%) 0.40 Elevated Cholesterol 5 (24%) 32 (35%) 0.30 Elevated Triglycerides 10 (48%) 60 (67%) 0.10 Low HDL 12 (57%) 66 (74%) 0.12 Elevated LDL 7 (33%) 29 (35%) 0.89 Insulin resistance 3 (13%) 36 (38%) 0.029 Additional Declarations No competing interests reported. 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Oliveira","lastName":"Filho","suffix":""},{"id":453972295,"identity":"d52715ce-fe6c-42bb-84ba-1ef3e5b3bc97","order_by":8,"name":"Janey Pratt","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Janey","middleName":"","lastName":"Pratt","suffix":""},{"id":453972296,"identity":"7b7cba7e-f60f-42d9-8100-ce2b6ff7632c","order_by":9,"name":"Cornelia Griggs","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cornelia","middleName":"","lastName":"Griggs","suffix":""}],"badges":[],"createdAt":"2025-04-18 17:38:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6480681/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6480681/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82713312,"identity":"96d25411-0fdf-43fb-8487-60fc351d4f5c","added_by":"auto","created_at":"2025-05-14 11:50:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22105,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnosis of MASLD in patients who underwent a biopsy.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6480681/v1/47a5ce69afa2449322d259ef.png"},{"id":84797020,"identity":"4a51bf7b-c11d-4add-a930-5628a59f5103","added_by":"auto","created_at":"2025-06-17 12:32:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":844216,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6480681/v1/2ee96187-4024-4ef9-8780-4047f09e0473.pdf"},{"id":82713315,"identity":"ab3bb111-cb74-482d-b51a-114fed082eb9","added_by":"auto","created_at":"2025-05-14 11:50:38","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":62492,"visible":true,"origin":"","legend":"","description":"","filename":"MASLDsupplementobesitysurgery.docx","url":"https://assets-eu.researchsquare.com/files/rs-6480681/v1/44a5db60113aa94157b0b7aa.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Metabolic Dysfunction-associated Steatotic Liver Disease in Adolescent and Young Adult Patients Undergoing Bariatric Surgery: When to Biopsy?","fulltext":[{"header":"Key points","content":"\u003cul\u003e\n \u003cli\u003ePreoperative findings do not identify which patients should undergo liver biopsy during MBS.\u003c/li\u003e\n \u003cli\u003eA policy of selective liver biopsy fails to diagnose AYA patients with MASLD.\u003c/li\u003e\n \u003cli\u003eRoutine intraoperative liver biopsy could capture additional patients with MASLD, ensuring they undergo appropriate management and surveillance\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eMetabolic and bariatric surgery (MBS) is now recognized as the most effective treatment for severe obesity and obesity-related medical problems in adolescent and young adult (AYA) patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, metabolic dysfunction-associated steatotic liver disease (MASLD) is comparatively challenging to follow as there is no simple method of diagnosis [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Previously known as non-alcoholic fatty liver disease, MASLD is defined as hepatic steatosis\u0026thinsp;\u0026gt;\u0026thinsp;5% by imaging or biopsy and the presence of a cardiometabolic risk factor [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. While most patients with MASLD are asymptomatic, MASLD contributes to the population with chronic liver disease and patients with fibrosis secondary to MASLD are at increased risk of liver-related mortality [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMASLD is the most common liver disease in AYA patients with an estimated prevalence of approximately 30% among those with obesity. The spectrum of disease can range from isolated steatosis to fibrosis or cirrhosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. While studies have identified factors predictive of MASLD, including elevated liver function tests (LFTs), waist-hip ratio, waist circumference, diabetes, insulin resistance, and elevated triglycerides, the results of these studies are heterogeneous and fail to demonstrate a laboratory or anthropometric test that can adequately differentiate which patients undergoing MBS should have an intraoperative liver biopsy performed [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Improvements have been made in the use of imaging for diagnosis, but the role of these tests remains limited given a need for insurance approval, varied diagnostic accuracy, and risks of repeat radiation exposure [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Ultrasound is low-cost and non-invasive, and increased echogenicity can support a diagnosis of MASLD, but lacks sensitivity and specificity, especially at lower grades of steatosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Controlled attenuation parameter (CAP) may be a simple and more accurate alternative, although this also has limitations with sensitivity and specificity, especially in the setting of severe obesity [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Magnetic resonance imaging (MRI) proton density fat fraction is a validated approach to diagnosing and staging hepatic steatosis but is expensive and not widely available [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Therefore, while serum transaminases are currently used as a surrogate for diagnosis and monitoring, many patients require diagnosis through liver biopsy.\u003c/p\u003e \u003cp\u003eBiopsy practices in AYA patients undergoing MBS are not standardized. While the American Association for Study of Liver Disease (AASLD) has recommendations for appropriate timing of liver biopsy in adults, these may not apply to younger populations and do not specifically address when to perform a biopsy during MBS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. An argument against biopsy is that tissue diagnosis would not necessarily affect management of MASLD, since patients undergoing MBS are already receiving the most effective treatment possible [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, given the prevalence of MASLD in patients with obesity, the long-term negative ramifications of untreated MASLD, the possibility that patients with severe fibrosis are less likely to achieve resolution even after MBS, and the fact that patients are already under anesthesia, some centers choose to perform routine biopsy for AYA patients undergoing MBS [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In this study, we investigate the preoperative factors associated with a diagnosis of MASLD and the biopsy protocols of two centers. We hypothesized that liver biopsy would identify patients with MASLD who otherwise would be undiagnosed.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eWe performed a retrospective chart review of AYA patients (age\u0026thinsp;\u0026lt;\u0026thinsp;22) who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at two tertiary centers between 01/01/2014\u0026ndash;12/31/2023. Site #1 is integrated within adult hospitals but has a dedicated pediatric weight loss center, while Site #2 is a standalone children\u0026rsquo;s hospital. Institutional Review Board approval was granted at both sites.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLiver Biopsy\u003c/h3\u003e\n\u003cp\u003eAt Site #1, liver biopsy was routinely performed during MBS through 6/2018, then was selectively performed. At Site #2, liver biopsy was selectively performed except between 5/1/2018\u0026ndash;9/30/2018 when it was routine (Supplementary Fig.\u0026nbsp;1). Liver biopsy is performed via laparoscopic wedge of the peripheral left lobe of the liver. Sites stopped routinely performing liver biopsies based on guidelines from the adult population. At both centers, the decision to pursue a selective biopsy was made at the discretion of the care team based on preoperative risk factors in consultation with the patient and family. Both institutions had variable indications for the threshold at which to perform biopsy. For the purpose of analysis, patients were grouped into three cohorts: underwent routine liver biopsy, underwent selective liver biopsy, and did not undergo liver biopsy. When evaluating biopsy protocols, we compared patients who underwent selective liver biopsy to those that did not. When evaluating characteristics predictive of a histologic diagnosis of MASLD, we combined all patients who had undergone liver biopsy (both selective and routine).\u003c/p\u003e \u003cp\u003ePreoperative laboratory values included in the analysis of factors associated with a histologic diagnosis of MASLD were alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, cholesterol, triglycerides, low density lipoprotein (LDL), high-density lipoprotein (HDL), and glycated hemoglobin (HbA1C).\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eData were independently collected at each site, de-identified, and compiled. Laboratory markers were classified as elevated based on the following cutoffs: ALT\u0026thinsp;\u0026gt;\u0026thinsp;26 U/L for males and 22 U/L for females, AST\u0026thinsp;\u0026ge;\u0026thinsp;40 U/L, cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;120 mg/dL, LDL\u0026thinsp;\u0026ge;\u0026thinsp;110 mg/dL, HDL\u0026thinsp;\u0026lt;\u0026thinsp;40 mg/dL, or triglycerides\u0026thinsp;\u0026ge;\u0026thinsp;130 mg/dL. Insulin resistance was defined as HbA1c\u0026thinsp;\u0026gt;\u0026thinsp;5.7%. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. An imaging diagnosis of MASLD was made if steatosis with or without the presence of fibrosis or cirrhosis, was noted on CT, ultrasound, or MRI. On histology, samples were labeled with an internalized scoring system based on elements of the NAFLD activity score (NAS) involving steatosis, hepatocyte ballooning, and lobular inflammation where Grade I is mild (5\u0026ndash;33%), Grade II is moderate (34\u0026ndash;66%), and Grade III is severe (67\u0026ndash;100%). Histologic MASLD was defined as the presence of steatosis, fibrosis, or steatohepatitis on histology.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were compared using an independent sample, 2-tailed t-test. Discrete variables were analyzed with a chi-squared test. We used multiple regression to assess for relationships between preoperative variables and whether a biopsy was performed as well as a diagnosis of MASLD. Patients missing preoperative laboratory values were excluded from univariate analyses. Statistical analysis was performed using STATA (Version. 17.0; StataCorp, College Station, TX). Significance was defined as a p value of \u0026lt;\u0026thinsp;.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGroup Demographics\u003c/h2\u003e \u003cp\u003eOur cohort included 241 patients. One patient was excluded due to incomplete information in the medical chart, so analysis was performed on 240 patients. Site #1 contributed 112 patients (46.7%), and the remainder by Site #2. Two-thirds (65.8%) of the patients were female and the majority of patients were white (47.5%) and not Hispanic (57.9%). Median preoperative lab values are displayed in Supplementary Table\u0026nbsp;1. Median age at surgery was 17.6 years, and median BMI was 48.1 kg/m\u003csup\u003e2\u003c/sup\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no complications within thirty days related to liver biopsy for any patient.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCharacteristics associated with a diagnosis of MASLD\u003c/h3\u003e\n\u003cp\u003eA total of 119 patients had a biopsy performed (routine or selective) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Within this cohort, 81% had a diagnosis of MASLD based on either histology or imaging: 63.9% had a histologic diagnosis without imaging findings, 12.6% had both a radiographic and histologic diagnosis, and 4.2% had only imaging findings without histologic changes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients underwent imaging due to concerns for the presence of MASLD. There were 28 patients (23.5%) with steatohepatitis and 13 patients (10.9%) with \u0026ge;\u0026thinsp;Grade 2 fibrosis. Among patients who underwent routine biopsy, 74.6% of had a diagnosis of MASLD. We performed a subset analysis of the 75 patients with a diagnosis of MASLD on biopsy but who had negative imaging. Patients who were older at time of surgery were more likely to have MASLD detected on imaging (p\u0026thinsp;=\u0026thinsp;0.044) but other demographic characteristics (sex, race, ethnicity) and risk factors for MASLD (BMI and laboratory values) did not differ significantly between those with imaging findings of MASLD and those without (Supplementary Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eOf the 104 patients included in univariable analysis, 88 (80%) had a histologic or imaging diagnosis of MASLD. Preoperative elevated ALT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), elevated AST (p\u0026thinsp;=\u0026thinsp;.009), and insulin resistance (p\u0026thinsp;=\u0026thinsp;.008) were associated with a diagnosis of MASLD. On multivariable analysis, only elevated preoperative ALT (p\u0026thinsp;=\u0026thinsp;.01) remained significant. The sensitivity and specificity of ALT for diagnosing MASLD was 90.7% and 46.5% respectively, with an area under the curve of 0.77 (95% confidence interval 0.65, 0.88).\u003c/p\u003e \u003cp\u003eIn our cohort, among the 75 patients with an elevated ALT, 7 patients (9.3%) did not have a diagnosis of MASLD and among the 32 patients with elevated AST, 2 (6.3%) did not have a diagnosis of MASLD. The biopsy reports for these patients noted either no abnormalities (4/9) or mild non-specific changes (5/9).\u003c/p\u003e \u003cp\u003eThere were 78 patients who underwent some form of preoperative imaging, with 72 (92%) patients undergoing abdominal ultrasound and 4 patients undergoing cross-sectional imaging. Twenty-six patients (33%) had negative imaging but were diagnosed with MASLD on histology, one of which had undergone computed tomography (CT). Of these 26 patients, 3 (11.5%) had grade 3 steatosis and 10 (38%) had fibrosis.\u003c/p\u003e\n\u003ch3\u003eRelationship between choice to perform biopsy and diagnosis of MASLD\u003c/h3\u003e\n\u003cp\u003eOf 240 patients, 177 underwent surgery when selective biopsies were being performed. Of these patients, 56 (31.6%) had a biopsy performed with a diagnosis rate of MASLD of 78.6% (44/56). Patients who were male, had surgery at Site #2, or had elevated ALT, AST, or total bilirubin had a greater likelihood of undergoing a biopsy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the 54 patients included in univariable analysis, elevated preoperative AST (p\u0026thinsp;\u0026lt;\u0026thinsp;.001), ALT (p\u0026thinsp;=\u0026thinsp;.05) and total bilirubin (p\u0026thinsp;=\u0026thinsp;0.01) were associated with biopsy. On multivariable analysis, only elevated AST was associated with selective biopsy being performed (p\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e \u003cp\u003eThere was no significant difference in the likelihood of a positive biopsy between the routine group (47/63, 75%) and selective group (44/56, 79%) (Chi-square\u0026thinsp;=\u0026thinsp;.25, p\u0026thinsp;=\u0026thinsp;0.61). Among patients who underwent a routine biopsy, and had a normal ALT, AST, and total bilirubin, 16/28 (57.1%) had a diagnosis of MASLD on biopsy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn adults, MASLD has become the most frequent indication for liver transplant, and emerging data suggest that a diagnosis of MASLD in adolescence increases risk of hepatic morbidity in adulthood [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Confirming a diagnosis of MASLD through liver biopsy can inform patients and providers of the presence of end-organ damage and ensure that patients are referred to a hepatologist for surveillance.\u003c/p\u003e \u003cp\u003eIn our cohort, rates of diagnosis of MASLD were not significantly different between the group who underwent routine biopsy and underwent selective biopsy. Furthermore, no concerning laboratory markers were identified among patients who were found to have MASLD on routine biopsy. This demonstrates how challenging it is for care teams to accurately predict which patients should be biopsied. Presuming a similar overall prevalence of MASLD between patients who underwent surgery during routine and selective biopsy periods, our calculations suggest that of the 121 patients who were not chosen for biopsy, 75\u0026ndash;80% of them would be expected to have undiagnosed pathology. This raises the question of whether a diagnosis was missed in 90\u0026ndash;95 children among the cohort of 121 patients. Notably, biopsy was obtained after patients had undergone a two-week liquid diet fast in preparation for MBS, which has been shown to significantly decrease the protein-density fat fraction [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Therefore, their baseline degree of steatosis was likely higher than what was captured during biopsy at time of surgery.\u003c/p\u003e \u003cp\u003eConsistent with our finding that elevated ALT and AST were associated with the decision to perform a biopsy, elevated ALT is considered the most highly predictive laboratory value for a diagnosis of MASLD and is commonly incorporated into NAFLD scoring systems[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, it is an imperfect measure, with one study finding an ALT as high as 231 U/L is necessary to create an area under the curve\u0026thinsp;\u0026gt;\u0026thinsp;90 [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] \u0026ndash; for comparison, the interquartile range in our cohort was 19\u0026ndash;45 with only two patients having an ALT\u0026thinsp;\u0026ge;\u0026thinsp;231. The heterogeneity of proposed cut-offs reported in the literature (ranging from 26\u0026ndash;39 in males and 17\u0026ndash;31 in females) and the false negative rate of around 25% also demonstrate that ALT is insufficient as a standalone marker [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, elevated LFTs in a patient with obesity can lead to the false assumption of an underlying diagnosis of MASLD. While no patients with elevated LFTs in our cohort were found to have another form of hepatic disease, six patients had mild non-specific changes that could later be diagnosed as an etiology distinct from MASLD.\u003c/p\u003e \u003cp\u003eObesity, MASLD, and insulin resistance are intrinsically linked, comprising the diagnosis of metabolic syndrome, with liver dysfunction likely both contributing to and resulting from insulin resistance [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Given this, the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines recommend screening overweight children ages 9\u0026ndash;11 with insulin resistance for hepatic steatosis [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. However, while insulin resistance in the setting of obesity is associated with increased risk of MASLD, an elevated Hb1Ac is not sufficiently sensitive or specific to be used to make a diagnosis of MASLD.\u003c/p\u003e \u003cp\u003eImaging has been used to diagnose steatosis, but like elevated ALT, has limitations. Conventional imaging modalities of ultrasound, CT, and CAP have overall sensitivities and specificities ranging from 60\u0026ndash;100% and are less equipped to diagnose moderate steatosis or discern mild steatosis from no steatosis [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Elastography has an AUC of of 0.78\u0026ndash;0.96 but is also more predictive with severe fibrosis [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. MRI can reliably be used for detection and grading of steatosis but is limited by availability and cost [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our cohort, imaging failed to detect MASLD in approximately one-third of patients, including those with severe steatosis or some degree of fibrosis, highlighting its limited sensitivity. Older age at the time of surgery was associated with increased likelihood of detection (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.044), which underscores that imaging alone should not be relied upon as a diagnostic tool for MASLD in AYA patients.\u003c/p\u003e \u003cp\u003eCurrently, the International Society for Pediatrics recommends that adolescents with diabetes be screened using ALT (\u0026ge;\u0026thinsp;22 for females, \u0026ge; 26 for males), with referral to a gastroenterologist if liver enzymes remain elevated despite weight loss and glycemic control [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. However, AYA patients undergoing MBS represent a unique population in that they have a high pretest probability for MASLD and will already be under general anesthesia and in a position to easily undergo surgical biopsy. The additional risk of bleeding with biopsy is very low, estimated at under 0.3% [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. The risk of bile leak is also exceedingly rare, with only case reports in the literature, and the risk of causing adhesions secondary to liver biopsy is minimal compared to the risk of adhesions secondary to the bariatric procedure [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChoice to perform liver biopsy is not standardized in AYA patients [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. We found that only elevated AST was associated with selective biopsy. Other studies in adults have proposed algorithms to predict for MASLD and/or to indicate a biopsy is warranted; these scoring systems include the BMI, age, ALT, triglycerides (BAAT) score, Fibrosis-4 (FIB4) index, Korea-NAFLD (K-NAFLD) score, Fatty Liver Index (FLI), FibroTest, FibroMeter, NashTest, and NAFLD Fibrosis Score (NFS) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] [\u003cspan additionalcitationids=\"CR48 CR49 CR50 CR51\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. If centers wish to pursue a practice of selective biopsy, the development of similar scoring systems in pediatrics could help ensure a higher capture rate of a diagnosis of MASLD.\u003c/p\u003e \u003cp\u003eManagement of pediatric obesity is a rapidly evolving field, and the implications of MASLD on the long-term health of children are still not fully understood. However, accurate identification of children who are most at risk and subsequent staging of this disease is critical as we work to bridge that knowledge gap [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. First, it will allow for tailored surveillance of this population, just as the screening schedule for many other conditions depends on disease severity. Second, accurate staging of MASLD can provide guidance on when to take additional steps to ensure weight-loss and to reduce or prevent further end-organ damage, including with additional surgery or the use of medications [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Lastly, improved knowledge of the natural history of this disease will help us understand the relationship between obesity, MASLD, and future health outcomes.\u003c/p\u003e \u003cp\u003eOur paper has several limitations. First, it is retrospective and observational which did not allow us to control for which patients underwent biopsy, restricts the amount of available data regarding the decision to perform selective biopsy, and limits the standardization with which preoperative imaging was obtained. In some respects, this limitation is also a strength in that it provides real-world data regarding provider practice. Second, because histology was evaluated at two centers, and over a long time period, there is a possibility for inconsistency in grading steatosis and fibrosis. However, any inconsistency should have affected patients at random and so should not introduce bias into the study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAYA patients undergoing MBS are a high-risk population for a diagnosis of MASLD, with a prevalence of MASLD of 80% in our cohort. Currently, there are no standard recommendations for intraoperative liver biopsy. Our results suggest that over half of patients with histologic MASLD had normal LFTs and total bilirubin and would therefore potentially remain undiagnosed if laboratory markers or were used to guide biopsy. While further investigation is needed to standardize a biopsy protocol, given the low risks associated with intraoperative biopsy and the imperfect correlation between biologic markers and the presence of MASLD, it may be reasonable to consider routine liver biopsy among AYA patients undergoing MBS.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e CONFLICT OF INTEREST\u003c/strong\u003e / DISCLOSURE STATEMENT\u003c/p\u003e \u003cp\u003eNone of the authors have anything to disclose and none of the authors have any conflicts of interest.\u003c/p\u003e \u003cp\u003eFunding / Support statement: No authors received extramural support or funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAS wrote the main manuscript and performed data analyss. RH, MK, IN, JR performed data analysis and reviewed the manuscript. CB, FB acquired data and reviewe the manuscript. JP and CG designed and interpreted the study and reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWirth, K.M., et al., \u003cem\u003eBariatric Surgery is Associated With Decreased Progression of Nonalcoholic Fatty Liver Disease to Cirrhosis: A Retrospective Cohort Analysis\u003c/em\u003e. Ann Surg, 2020. 272(1): p. 32\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiester, T.L., N. Jagtap, and R. Kalapala, \u003cem\u003eReview of paediatric obesity and non-alcoholic fatty liver disease-A focus on emerging non-pharmacologic treatment strategies\u003c/em\u003e. Pediatr Obes, 2023. 18(10): p. e13067.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlbers, T., et al., \u003cem\u003eLaparoscopic Roux-en-Y gastric bypass in adolescents with severe obesity (AMOS): a prospective, 5-year, Swedish nationwide study\u003c/em\u003e. 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J Pediatr Gastroenterol Nutr, 2017. 64(2): p. 319\u0026ndash;334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang, W. and J.S. Song, \u003cem\u003eNon-Invasive Imaging Methods to Evaluate Non-Alcoholic Fatty Liver Disease with Fat Quantification: A Review\u003c/em\u003e. Diagnostics (Basel), 2023. 13(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiao, Y.Y., et al., \u003cem\u003eMultifeature analysis of an ultrasound quantitative diagnostic index for classifying nonalcoholic fatty liver disease\u003c/em\u003e. Sci Rep, 2016. 6: p. 35083.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWells, M.M., et al., \u003cem\u003eComputed Tomography Measurement of Hepatic Steatosis: Prevalence of Hepatic Steatosis in a Canadian Population.\u003c/em\u003e Can J Gastroenterol Hepatol, 2016. 2016: p. 4930987.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFitzpatrick, E., et al., \u003cem\u003eTransient elastography is a useful noninvasive tool for the evaluation of fibrosis in paediatric chronic liver disease\u003c/em\u003e. J Pediatr Gastroenterol Nutr, 2013. 56(1): p. 72\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRam\u0026iacute;rez-Mej\u0026iacute;a, M.M., et al., \u003cem\u003eA Review of the Increasing Prevalence of Metabolic-Associated Fatty Liver Disease (MAFLD) in Children and Adolescents Worldwide and in Mexico and the Implications for Public Health\u003c/em\u003e. Med Sci Monit, 2021. 27: p. e934134.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrenzel, C., et al., \u003cem\u003eComplications and risk factors in 2731 diagnostic mini-laparoscopies in patients with liver disease\u003c/em\u003e. Liver Int, 2012. 32(6): p. 970\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClapp, B., et al., \u003cem\u003eSafety of liver biopsy at the time of bariatric surgery: an analysis of the MBSAQIP database\u003c/em\u003e. Surg Endosc, 2022. 36(1): p. 413\u0026ndash;421.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAranda, M., et al., \u003cem\u003eBiloma Secondary to Percutaneous Liver Biopsy Case Report.\u003c/em\u003e Case Rep Surg, 2020. 2020: p. 9605370.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXanthakos, S.A., et al., \u003cem\u003eHigh Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery\u003c/em\u003e. Gastroenterology, 2015. 149(3): p. 623\u0026thinsp;\u0026ndash;\u0026thinsp;34.e8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeong, S., et al., \u003cem\u003eDevelopment of a simple nonalcoholic fatty liver disease scoring system indicative of metabolic risks and insulin resistance\u003c/em\u003e. Ann Transl Med, 2020. 8(21): p. 1414.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlanco-Grau, A., et al., \u003cem\u003eAssessing Liver Fibrosis Using the FIB4 Index in the Community Setting\u003c/em\u003e. Diagnostics (Basel), 2021. 11(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVali, Y., et al., \u003cem\u003eFibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis\u003c/em\u003e. J Clin Med, 2021. 10(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBernstein, D. and A.J. Kovalic, \u003cem\u003eNoninvasive assessment of fibrosis among patients with nonalcoholic fatty liver disease [NAFLD]\u003c/em\u003e. Metabol Open, 2022. 13: p. 100158.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoynard, T., et al., \u003cem\u003eDiagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease\u003c/em\u003e. BMC Gastroenterol, 2006. 6: p. 34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConcon, M.M., et al., \u003cem\u003eSHOULD ROUTINE LIVER BIOPSY BE CONSIDERED IN BARIATRIC SURGICAL PRACTICE? AN ANALYSIS OF THE LIMITATIONS OF NON-INVASIVE NAFLD MARKERS\u003c/em\u003e. Arq Gastroenterol, 2022. 59(1): p. 110\u0026ndash;116.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan, P.M., et al., \u003cem\u003eSafety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis\u003c/em\u003e. J Pediatr, 2021. 236: p. 137\u0026ndash;147.e13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgosta, M., et al., \u003cem\u003eEfficacy of liraglutide in pediatric obesity: A review of clinical trial data\u003c/em\u003e. Obesity Medicine, 2024. 48.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":" \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\u003eDemographics of patients by biopsy type. IQR: Interquartile range; BMI: body mass index\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRoutine biopsy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelective biopsy, performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSelective biopsy, not performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSex\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (31.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e158 (65.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (68.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85 (70.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSite\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite #1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112 (46.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (87.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45 (37.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite #2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (78.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76 (62.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRace\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49 (40.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (16.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEthnicity\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (68.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (51.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery (median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.6 (16.4, 18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.1 (17.1, 19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.3 (16.1, 18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.5 (16.2, 18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-op BMI (median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.1 (43.3, 53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.1 (45.2, 55.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.78 (42.3, 55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.4 (42.2, 50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\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\u003ePatients who underwent MBS during a period of selective biopsy. BMI: body mass index; ALT: alanine aminotransferase; AST: aspartate aminotransferase; HDL: high-density lipoprotein; LDL: low-density lipoprotein\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSelective biopsy, performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSelective biopsy, not performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSex\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (70.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSite\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite #1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (37.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite #2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (78.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (62.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRace\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (40.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (16.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEthnicity\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (51.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.0 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.3 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.8 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.6 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLaboratory markers\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated ALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (73.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (55.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated AST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Total bilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Triglycerides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (73.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (63.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow HDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (74.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (64.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated LDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (28.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (33.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (24.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eDiagnosis of MASLD in patients who had a biopsy performed during MBS. ALT: alanine aminotransferase; AST: aspartate aminotransferase; HDL: high-density lipoprotein; LDL: low-density lipoprotein\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Diagnosis of MASLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDiagnosis of MASLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSex\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEthnicity\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLaboratory markers\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated ALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated AST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Total bilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Triglycerides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow HDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated LDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"metabolic and bariatric surgery (MBS), liver biopsy, metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), adolescent and young adult (AYA)","lastPublishedDoi":"10.21203/rs.3.rs-6480681/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6480681/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction:\u003c/p\u003e\n\u003cp\u003eMetabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in adolescent and young adults (AYA) with obesity. However, the role of liver biopsy during metabolic bariatric surgery (MBS) is debated.\u003c/p\u003e\n\u003cp\u003eMethods:\u003c/p\u003e\n\u003cp\u003eThis is a retrospective chart review of AYA patients \u0026lt; 22 years old who underwent MBS between 2014-2023 at two institutions. A policy of selective liver biopsy was used for the majority of the study, but both sites had periods of routine biopsy. Selective biopsy was based on preoperative factors associated with MASLD. Patients with steatosis, fibrosis, or steatohepatitis on histology were considered to have a diagnosis of MASLD. Preoperative laboratory markers were evaluated for association with MASLD using multivariate regression.\u003c/p\u003e\n\u003cp\u003eResults:\u003c/p\u003e\n\u003cp\u003eAmong 240 patients, 121 (50%) underwent biopsy, with 63 (53%) performed during routine biopsy periods. The remaining 56 biopsies (32%) were in the 177 patients who underwent MBS during a selective period. There was no difference in rate of positive biopsy between routine (47, 75%) and selective (44, 79%) groups (p=0.61). \u0026nbsp;Steatohepatitis was present in 28 (23.5%) of patients and ≥ Stage 2 fibrosis in 13 (10.9%) of patients. Elevated BMI, ALT, and HbA1c were associated with a diagnosis of MASLD. Among 28 routine-biopsy patients with normal preoperative laboratory markers, 16 (57.1%) had MASLD on biopsy.\u003c/p\u003e\n\u003cp\u003eConclusion:\u003c/p\u003e\n\u003cp\u003eIn our cohort, selective biopsy was no more effective than chance at identifying patients with MASLD, suggesting a high rate of missed diagnoses. This presents an opportunity to standardize biopsy protocols including consideration of routine liver biopsy in AYA patients undergoing MBS.\u003c/p\u003e","manuscriptTitle":"Metabolic Dysfunction-associated Steatotic Liver Disease in Adolescent and Young Adult Patients Undergoing Bariatric Surgery: When to Biopsy?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-14 11:50:33","doi":"10.21203/rs.3.rs-6480681/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14b0c164-a817-462c-8fcb-c1c433d42765","owner":[],"postedDate":"May 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-17T12:24:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-14 11:50:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6480681","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6480681","identity":"rs-6480681","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}