IU Indianapolis ScholarWorks :: Browsing by Author "Molleston, Jean P."

Browsing by Author "Molleston, Jean P."

Now showing 1 - 10 of 24

Baseline ultrasound and clinical correlates in children with cystic fibrosis.
(Elsevier, 2015-10) Leung, Daniel H.; Ye, Wen; Molleston, Jean P.; Weymann, Alexander; Ling, Simon; Paranjape, Shruti M.; Romero, Rene; Schwarzenberg, Sara Jane; Palermo, Joseph; Alonso, Estella M.; Murray, Karen F.; Marshall, Bruce C.; Sherker, Averell H.; Siegel, Marilyn J.; Krishnamurthy, Rajesh; Harned, Roger; Karmazyn, Boaz; Magee, John C.; Narkewicz, Michael R.; Department of Pediatrics, IU School of Medicine
Objective: To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design: Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results: Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) had
Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease
(Elsevier, 2018-07) Harlow, Kathryn E.; Africa, Jonathan A.; Wells, Alan; Belt, Patricia H.; Behling, Cynthia A.; Jain, Ajay K.; Molleston, Jean P.; Newton, Kimberly P.; Rosenthal, Philip; Vos, Miriam B.; Xanthakos, Stavra A.; Lavine, Joel E.; Schwimmer, Jeffrey B.; Pediatrics, School of Medicine
OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.
Diagnosis and Follow-up of Incidental Liver Lesions in Children
(Wolters Kluwer, 2022-03) Karmazyn, Boaz; Rao, Girish S.; Johnstone, Lindsey S.; Severance, Tyler S.; Ferguson, Michael J.; Marshalleck, Francis E.; Molleston, Jean P.; Radiology and Imaging Sciences, School of Medicine
ABSTRACT: Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH) and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was FDA-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and AFP should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and when biopsy is not feasible.
Drug-Induced Liver Injury Module for Medical Students
(Association of American Medical Colleges, 2020-07-15) Dilly, Christen K.; Craven, Hannah J.; Molleston, Jean P.; Medicine, School of Medicine
Introduction No published curricula exist to introduce medical students to drug-induced liver injury (DILI). However, DILI is the most common cause of acute liver failure in the US, and drug-drug interactions are tested on the USMLE Step 1. Methods We developed an independent study module to introduce students to DILI. This module consisted of a narrated PowerPoint introduction, a journal article, and four example cases. Students completed the module independently. To evaluate the effectiveness of the activity, exam data and responses to the cases were reviewed, and end-of-course survey data were used. These responses were used to modify questions for clarity and to develop a feedback rubric. Results Mean scores on case-related questions in the module ranged from 44% to 73%. However, mean scores on test questions related to DILI ranged from 61% to 98%. It is possible that students learned from receiving feedback in the form of correct answers to the cases. On course evaluations, 52.4% of students agreed or strongly agreed that the online modules as a group (which included the DILI module) were an effective teaching method. Discussion This module introduces students to DILI and enables them to interact with valuable resources. We hope that modifications will improve the learning experience and effectiveness of the module. Going forward, we plan to collect validity evidence for the feedback rubric and develop an advanced version of the module for gastroenterology fellows.
Durability of Response in Children Treated with Pegylated Interferon alfa-2a +/- Ribavirin for Chronic Hepatitis C
(Lippincott Williams & Wilkins, 2016-01) Schwarz, Kathleen B.; Molleston, Jean P.; Jonas, Maureen M.; Wen, Jessica; Murray, Karen F.; Rosenthal, Philip; Gonzalez-Peralta, Regino P.; Lobritto, Steven J.; Mogul, Douglas; Pavlovic, Vedran; Warne, Charles; Wat, Cynthia; Thompson, Bruce; Department of Pediatrics, IU School of Medicine
Objectives: No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a ± ribavirin (RBV) in the PEDS-C trial. Methods: A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1–6.6) and 6 (6.6, 5.1–7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. Results: The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4–7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non-CC, P = 0.028). Conclusion: Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC.
Extrahepatic anomalies in infants with biliary atresia: results of a large prospective North American multicenter study
(Wiley, 2013-11) Schwarz, Kathleen B.; Haber, Barbara H.; Rosenthal, Philip; Mack, Cara L; Moore, Jeffrey; Bove, Kevin E.; Bezerra, Jorge A.; Karpen, Saul J.; Kerkar, Nanda; Shneider, Benjamin L.; Turmelle, Yumirle P.; Whitington, Peter F.; Molleston, Jean P.; Murray, Karen F.; Ng, Vicky L.; Romero, René; Wang, Kasper S.; Sokol, Ronald J.; Magee, John C.; Pediatrics, School of Medicine
Background and aims The etiology of biliary atresia (BA) is unknown. Given that patterns of anomalies might provide etiopathogenetic clues, we utilized data from the North American Childhood Liver Disease Research and Education Network to analyze patterns of anomalies in infants with BA. Methods Two hundred eighty-nine infants who were enrolled into the prospective database prior to surgery at any of 15 centers participating were evaluated. Results Group 1 was non-syndromic, isolated BA (without major malformations) (n = 242, 84 %), Group 2 was BA and at least one malformation considered major as defined by the National Birth Defects Prevention Study but without laterality defects (n = 17, 6%). Group 3 was syndromic, with laterality defects (n = 30, 10%). In the population as a whole, anomalies (either major or minor) were most prevalent in the cardiovascular (16%) and gastrointestinal (14%) systems. Group 3 patients accounted for the majority of subjects with cardiac, gastrointestinal and splenic anomalies. Group 2 subjects also frequently displayed cardiovascular (71%) and gastrointestinal (24 %) anomalies; interestingly this group had genitourinary anomalies more frequently (47%) compared to Group 3 subjects (10%). Conclusions This study identified a group of BA (Group 2) that differed from the classical syndromic and non-syndromic groups and that was defined by multiple malformations without laterality defects. Careful phenotyping of the patterns of anomalies may be critical to the interpretation of both genetic and environmental risk factors associated with BA, allowing new insight into pathogenesis and/or outcome.
Genetic Testing and Counseling in Metabolic Liver Disease: An Interactive Lecture for Medical Students
(Association of American Medical Colleges, 2020-10-19) McPheron, Molly A.; Craven, Hannah J.; Molleston, Jean P.; Dilly, Christen K.; Medical and Molecular Genetics, School of Medicine
Introduction Medical students have limited opportunities to learn about current genetic testing. This session provided exposure to different types of testing and the complex issues that physicians may encounter when counseling patients on proper testing and interpreting results. Methods We designed a 1-hour interactive lecture for second-year medical students. We presented an overview of the topic, then applied the concepts to specific disorders and cases. Students were asked to answer questions regarding cases using an audience response system, and we used their responses as the basis for our in-class discussion. This session has been held twice, with 25 students attending in 2018 and 31 students in 2019. The session was also recorded so that additional students not in attendance could watch, and was available to 151 students in 2018 and 333 students in 2019. Results Students answered questions via audience response system. There was a range of 47%–100% of students giving the correct answers in 2018, and 55%–93% in 2019. Exam questions covering genetic counseling issues were answered correctly by 66% and 77% of students in 2018, and 70% and 68% of students in 2019. Discussion This session provided an opportunity for medical students to be exposed to some of the complex ethical and psychosocial issues that may arise with genetic testing for liver disease and to consider how to navigate them. Using an audience response system during the lecture made the session more interactive and allowed the teacher to correct errors and teach based on the responses.
Hepatic lipid peroxidation and cytochrome P-450 2E1 in pediatric nonalcoholic fatty liver disease and its subtypes
(Wolters Kluwer, 2011-10) Bell, Lauren N.; Molleston, Jean P.; Morton, Michael J.; Klipsch, Ann; Saxena, Romil; Vuppalanchi, Raj; Chalasani, Naga; Department of Medicine, IU School of Medicine
GOAL: To compare hepatic lipid peroxidation and cytochrome P-450 2E1 (CYP2E1) protein content in liver biopsies from children with nonalcoholic fatty liver disease (NAFLD) and 2 control groups. BACKGROUND: Elevated hepatic lipid peroxidation resulting from increased hepatic CYP2E1 enzyme activity is involved in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) in adults, but studies in children are lacking. STUDY: Liver biopsies from 59 children with NAFLD (49 with NASH), 10 children with normal liver histology, and 9 children with mild chronic hepatitis C (HCV) infection were examined. Hepatic malondialdehyde (a measure of lipid peroxidation) levels and CYP2E1 protein content were quantitated, as a percentage of the total area, by immunohistochemical staining of liver biopsy material followed by digital image quantitation. RESULTS: Lipid peroxidation was significantly greater in NAFLD liver biopsies (46.7 ± 20.8%) compared with biopsies from children with normal liver histology (7.6 ± 9.4%; P<0.001) or HCV infection (7.7 ± 7.6%; P<0.001). However, hepatic CYP2E1 expression was not different across the NAFLD, normal liver histology, and HCV groups (60.7 ± 8.7%, 53.5 ± 10.7%, and 60.0 ± 11.9%, respectively; P=0.116). Among children with NAFLD, lipid peroxidation and CYP2E1 protein content did not differ between biopsies with and without NASH. Body mass index was independently associated with hepatic lipid peroxidation levels (r=0.549; P<0.001). CONCLUSIONS: Hepatic lipid peroxidation is increased in children with NAFLD but this is not related to hepatic CYP2E1 expression. No difference in lipid peroxidation in pediatric NAFLD versus NASH argues against a role in disease progression.
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.
Histologic Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels.
(Elsevier, 2014-04) Molleston, Jean P.; Schwimmer, Jeffrey B.; Yates, Katherine P.; Murray, Karen F.; Cummings, Oscar W.; Lavine, Joel E.; Brunt, Elizabeth M.; Scheimann, Ann O.; Unalp-Arida, Aynur; Department of Pediatrics, IU School of Medicine
Objectives: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26–50 U/L boys, 23–44 U/L girls), or elevated (> 50 boys, > 44 girls) serum alanine aminotransferase (ALT) levels. Study design: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) enrolls children 5–18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy within 180 days of ALT, and compared them with 392 children with elevated ALT. Results: Of 91 children, 17 (19%) had normal and 74 (81%) had mildly elevated ALT levels. Overall, 45% of biopsies had ≥ 33% steatosis, lobular inflammation grade was ≥ 2 in 22%, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, and 8% had definite NASH, 34% had NAFLD activity score (NAS) ≥ 4. Overall, 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in mildly elevated vs normal, with no difference in ballooning, inflammation, or NAS ≥ 4. Fibrosis stage 3/4 was seen in none of the children with normal ALT, and in 9% of the mildly elevated and 15% of the elevated. Conclusions: Liver biopsies of children with NAFLD with normal or mildly elevated ALT levels show significant histologic abnormalities, including advanced fibrosis in children with mildly elevated ALT. ALT thus may underestimate liver injury in NAFLD. Appropriate ALT cut-off levels can help identify children at risk for more severe disease.

Browsing by Author "Molleston, Jean P."

Results Per Page

Sort Options