Browsing by Author "Masand, Prakash"

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    Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis
    (Wolters Kluwer, 2021-05-13) Ye, Wen; Leung, Daniel H.; Molleston, Jean P.; Ling, Simon C.; Murray, Karen F.; Nicholas, Jennifer L.; Huang, Suiyuan; Karmazyn, Boaz W.; Harned, Roger K.; Masand, Prakash; Alazraki, Adina L.; Navarro, Oscar M.; Otto, Randolph K.; Palermo, Joseph J.; Towbin, Alexander J.; Alonso, Estella M.; Karnsakul, Wikrom W.; Schwarzenberg, Sarah Jane; Seidel, Glenn F.; Siegel, Marilyn; Magee, John C.; Narkewicz, Michael R.; Freeman, A. Jay; Pediatrics, School of Medicine
    Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (rs = − 0.28, P = 0.0071) and positive correlation with aspartate aminotransferase-to-platelet ratio index (rs = 0.38, P = 0.0002), Fibrosis-4 index (rs = 0.36, P = 0.0007), gamma-glutamyltransferase (GGT; rs = 0.35, P = 0.0017), GGT-to-platelet ratio (rs = 0.35, P = 0.003), and US spleen size z-score (rs = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF.
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    Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children
    (Wiley, 2022) Schwarzenberg, Sarah Jane; Palermo, Joseph J.; Ye, Wen; Huang, Suiyuan; Magee, John C.; Alazraki, Adina; Freeman, A. Jay; Harned, Roger; Karmazyn, Boaz; Karnsakul, Wikrom; Leung, Daniel H.; Ling, Simon C.; Masand, Prakash; Molleston, Jean P.; Murray, Karen F.; Navarro, Oscar M.; Nicholas, Jennifer L.; Otto, Randolph K.; Paranjape, Shruti M.; Siegel, Marilyn J.; Stoll, Janis; Towbin, Alexander J.; Narkewicz, Michael R.; Alonso, Estella M.; CFLD NET; Pediatrics, School of Medicine
    Objectives: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. Methods: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. Results: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. Conclusions: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
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    Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children
    (Wiley, 2022-09-06) Schwarzenberg, Sarah Jane; Palermo, Joseph J.; Ye, Wen; Huang, Suiyuan; Magee, John C.; Alazraki, Adina; Freeman, A. Jay; Harned, Roger; Karmazyn, Boaz; Karnsakul, Wikrom; Leung, Daniel H.; Ling, Simon C.; Masand, Prakash; Molleston, Jean P.; Murray, Karen F.; Navarro, Oscar M.; Nicholas, Jennifer L.; Otto, Randolph K.; Paranjape, Shruti M.; Siegel , Marilyn J.; Stoll, Janis; Towbin, Alexander J.; Narkewicz, Michael R.; Alonso, Estella M.; Pediatrics, School of Medicine
    Background: Cystic fibrosis-related liver disease (CFLD) begins early in life. Symptoms may be vague, mild or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of cystic fibrosis-related liver disease (CFLD) to determine the impact of early CFLD on general and disease-specific QOL. Methods: US patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age≥5 y) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1-year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. Results: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. Conclusions: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
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    Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease
    (Elsevier, 2023) Siegel, Marilyn J.; Leung, Daniel H.; Molleston, Jean P.; Ye, Wen; Paranjape, Shruti M.; Freeman, A. Jay; Palermo, Joseph J.; Stoll, Janis; Masand, Prakash; Karmazyn, Boaz; Harned, Roger; Ling, Simon C.; Navarro, Oscar M.; Karnsakul, Wikrom; Alazraki, Adina; Schwarzenberg, Sarah Jane; Towbin, Alex J.; Alonso, Estella M.; Nicholas, Jennifer L.; Green, Nicole; Otto, Randolph K.; Magee, John C.; Narkewicz, Michael R.; CFLD Network; Pediatrics, School of Medicine
    Background: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). Methods: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. Results: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. Conclusions: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD.
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    Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study
    (Elsevier, 2020-04) Siegel, Marilyn J.; Freeman, A. Jay; Ye, Wen; Palermo, Joseph J.; Molleston, Jean P.; Paranjape, Shruti M.; Stoll, Janis; Leung, Daniel; Masand, Prakash; Karmazyn, Boaz; Harned, Roger; Ling, Simon C.; Navarro, Oscar M.; Karnsakul, Wikrom; Alazraki, Adina; Schwarzenberg, Sarah Jane; Seidel, F. Glen; Towbin, Alex; Alonso, Estella M.; Nicholas, Jennifer L.; Murray, Karen F.; Otto, Randolph K.; Sherker, Averell H.; Magee, John C.; Narkewicz, Michael R.; Pediatrics, School of Medicine
    Objective: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. Study design: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. Results: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). Conclusions: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.