Publications by authors named "Jeffrey H Teckman"

Background And Aims: Children with alpha-1-antitrypsin deficiency (AATD) exhibit a wide range of liver disease outcomes from portal hypertension and transplant to asymptomatic without fibrosis. Individual outcomes cannot be predicted. Liver injury in AATD is caused by the accumulation in hepatocytes of the mutant Z alpha-1-antitrypsin (AAT) protein, especially the toxic, intracellular polymerized conformation.

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Article Synopsis
  • High serum levels of matrix metalloproteinase-7 (MMP-7) have been identified as a potential diagnostic biomarker for biliary atresia (BA) in infants with cholestasis, showing strong accuracy in a large North American study.
  • MMP-7 demonstrated a high area under the receiver operating characteristic (AUROC) score of 0.90, with a sensitivity of 94.03% and a specificity of 77.78% at a cutoff of 52.8 ng/mL, outperforming other clinical markers such as gamma-glutamyl transferase.
  • Results support using MMP-7 in clinical settings to improve diagnostic efficiency for BA, as cutoff values vary with different
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Background: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

Methods: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS).

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Liver disease in homozygous ZZ alpha-1 antitrypsin (AAT) deficiency occurs due to the accumulation of large quantities of AAT mutant Z protein polymers in the liver. The mutant Z protein folds improperly during biogenesis and is retained within the hepatocytes rather than appropriately secreted. These intracellular polymers trigger an injury cascade, which leads to liver injury.

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The clinical presentation of liver disease is highly variable in homozygous ZZ alpha-1 antitrypsin (AAT) deficiency, and not all patients with the homozygous ZZ genotype develop liver disease. Although not fully identified, there is likely a strong influence of genetic and environmental modifiers of the intracellular injury cascade and fibrotic response. Most ZZ children are well and remain undiagnosed.

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α1-Antitrypsin (AAT) deficiency is a common genetic disease presenting with lung and liver diseases. AAT deficiency results from pathogenic variants in the gene encoding AAT and the common mutant Z allele of encodes for Z α1-antitrypsin (ATZ), a protein forming hepatotoxic polymers retained in the endoplasmic reticulum of hepatocytes. PiZ mice express the human ATZ and are a valuable model to investigate the human liver disease of AAT deficiency.

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Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well-characterized multi-institutional cohort.

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The autosomal codominant genetic disorder alpha-1 antitrypsin (AAT) deficiency (AATD) causes pulmonary and liver disease. Individuals homozygous for the mutant Z allele accumulate polymers of Z-AAT protein in hepatocytes, where AAT is primarily produced. This accumulation causes endoplasmic reticulum (ER) stress, oxidative stress, damage to mitochondria, and inflammation, leading to fibrosis, cirrhosis, and hepatocellular carcinoma.

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Objectives: Chronic hepatitis B virus infection is a major cause of morbidity and mortality. The aim of the study is to describe the hepatic histology in children chronically infected with hepatitis B virus living in the United States and Canada.

Methods: Liver biopsies of 134 treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation, fibrosis, and other histological features, and correlated with clinical and laboratory data.

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Background: While liver biopsy remains the gold standard, given the procedure risks and sampling errors, there is a need for reliable noninvasive biomarkers of hepatic fibrosis.

Objective: Determine the accuracy of two-dimensional shear wave elastography (2-D SWE) in predicting the histological severity of liver fibrosis in pediatric patients with known or suspected liver disease.

Materials And Methods: Subjects 0-18 years old with known or suspected liver disease and liver biopsy within 30 days (n=70) were included.

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Article Synopsis
  • HBeAg is a key marker indicating hepatitis B virus infection, linking to higher infectiousness and increased risk of liver cancer.
  • In a study with 2241 participants, 37% tested positive for HBeAg, with prevalence decreasing from 85% in children under 10 to 12% in adults over 50.
  • Factors like age, race, and HBV genotype influenced HBeAg positivity, with unique patterns noted among different racial groups, highlighting potential strategies for HBV infection prevention and treatment options.
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Background: Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime.

Objective: To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD.

Materials And Methods: We conducted a retrospective study of 77 patients (7-18 years; 68.

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In homozygous ZZ alpha-1-antitrypsin (AAT) deficiency, the liver synthesizes large quantities of AAT mutant Z, which folds improperly during biogenesis and is retained within the hepatocytes and directed into intracellular proteolysis pathways. These intracellular polymers trigger an injury cascade, which can lead to liver injury. This is highly variable and not all patients develop liver disease.

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Alpha-1 Antitrypsin (α1AT) Deficiency is a genetic disease in which accumulation of α1AT mutant Z (α1ATZ) protein in the ER of hepatocytes causes chronic liver injury, liver fibrosis, and hepatocellular carcinoma. No effective medical therapy is currently available for the disease. We previously found that norUDCA improves the α1AT deficiency associated liver disease by promoting autophagic degradation of α1ATZ protein in liver in a mouse model of the disease.

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Cystic fibrosis (CF) is a severe, progressive, multisystemic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Optimizing nutrition is critical, as higher growth parameters are associated with better pulmonary function and outcomes, but unfortunately patients with this disease are prone to malnutrition, growth failure, and vitamin deficiencies. The purpose of this review is to provide a timely highlight of the physiologic processes and outcome data to support today's management strategies, as well as review these principles themselves.

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Alpha-1 antitrypsin deficiency (AATD) is a hereditary liver disease caused by mutations in the SERPINA1 serine protease inhibitor gene. Most severe patients are homozygous for PiZ alleles (PiZZ; amino acid E324K), which lead to protein aggregates in hepatocytes and reduced circulating levels of AAT. The liver aggregates typically lead to fibrosis, cirrhosis, and hepatocellular carcinoma, and the reduced circulating AAT levels can lead to emphysema and chronic obstructive pulmonary diseases.

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Alpha-1 antitrypsin (a1AT) deficiency, in its classical form, is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults. The vast majority of liver disease is associated with homozygosity for the Z mutant allele, also called PiZZ. This homozygous allele synthesizes large quantities of a1AT mutant Z protein in the liver, but the mutant protein also folds improperly during biogenesis.

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Classical alpha-1 antitrypsin (a1AT) deficiency is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults (Teckman and Jain, Curr Gastroenterol Rep 16(1):367, 2014). The vast majority of the liver disease is associated with homozygosity for the Z mutant allele, the so-called PIZZ. These homozygous individuals synthesize large quantities of a1AT mutant Z protein in the liver, but the mutant protein folds improperly during biogenesis and approximately 85% of the molecules are retained within the hepatocytes rather than appropriately secreted.

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Unlabelled: Alpha-1-antitrypsin (AAT) deficiency (AATD) is a genetic disease, caused by mutation of the AAT gene. Accumulation of mutated AAT protein aggregates in hepatocytes leads to endoplasmic reticulum stress, resulting in impairment of liver functions and, in some cases, hepatocellular carcinoma, whereas decline of AAT levels in sera is responsible for pulmonary emphysema. In advanced liver disease, the only option for treatment is liver transplantation, whereas AAT replacement therapy is therapeutic for emphysema.

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α1-Proteinase inhibitor (antitrypsin) is a canonical example of the serpin family member that binds and inhibits serine proteases. The natural metastability of serpins is crucial to carry out structural rearrangements necessary for biological activity. However, the enhanced metastability of the mutant Z variant of antitrypsin, in addition to folding defect, may substantially contribute to its polymerization, a process leading to incurable serpinopathy.

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Objectives: To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS.

Study Design: Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory (PedsQL) questionnaires were administered to 70 children with ALGS, 95 children with alpha-1-antitrypsin deficiency (A1ATD), and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent proxy PedsQL scores were recorded for children aged 2-18 years (98 ALGS, 123 A1ATD, and 68 IHC).

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Objectives: α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers.

Methods: Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ.

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α-1-Antitrypsin (α1AT) is a serum glycoprotein synthesized in the liver. The majority of patients with α1AT deficiency liver disease are homozygous for the Z mutant of α1AT (called ZZ or 'PIZZ'). This mutant gene directs the synthesis of an abnormal protein which folds improperly during biogenesis.

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