Environmental toxicants modulate disease severity in pediatric metabolic dysfunction-associated steatohepatitis.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH.

Methods: Environmental chemicals, common in household items, perfluoroalkyl substances (PFAS), polybrominated flame retardants (polybrominated diphenyl ethers [PBDEs]), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2.

MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown.

Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD-PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level.

The nonalcoholic steatohepatitis extended hepatocyte ballooning score: histologic classification and clinical significance.

Background And Aims: The NAFLD activity score was developed to measure histologic changes in NAFLD during therapeutic trials. Hepatocyte ballooning (HB) is the most specific feature in steatohepatitis diagnosis, yet the impact of variations in HB has not been incorporated.

Approach And Results: Liver biopsies from patients enrolled in the NASH Clinical Research Network with an initial diagnosis of NASH or NAFL (n=1688) were evaluated to distinguish classic hepatocyte ballooning (cHB) from smaller, nonclassic hepatocyte ballooning (nHB), and also to designate severe ballooning and assign an extended hepatocyte ballooning (eB) score [0 points, no ballooning (NB); 1 point, few or many nHB; 2 points, few cHB; 3 points, many cHB; 4 points, severe cHB] to the biopsy assessment.

The Nimble Stage 1 Study Validates Diagnostic Circulating Biomarkers for Nonalcoholic Steatohepatitis.

Background There are no approved noninvasive tests (NIT) for the diagnosis of nonalcoholic steatohepatitis (NASH) and its histological phenotypes. Methods The FNIH-NIMBLE consortium tested 5 serum-based NIT panels for the following intended uses: NIS4: At-risk NASH, a composite of NASH with NAFLD activity score (NAS) ≥ 4 and fibrosis stage ≥ 2, OWLiver: NASH and NAS ≥ 4, enhanced liver fibrosis (ELF), PROC3 and Fibrometer VCTE: fibrosis stages ≥ 2, ≥ 3 or 4. Aliquots from a single blood sample obtained within 90 days of histological confirmation of NAFLD were tested.

Nonalcoholic fatty liver disease risk and histologic severity are associated with genetic polymorphisms in children.

Background And Aims: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity.

Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial.

Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.

Glycogenosis is common in nonalcoholic fatty liver disease and is independently associated with ballooning, but lower steatosis and lower fibrosis.

Background/aims: Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD).

Methods: Glycogenosis in NAFLD liver biopsies was graded as "none", "focal" (in <50% of hepatocytes), or "diffuse" (in ≥50% of hepatocytes).

Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth.

Methods: We compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8-17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015.

Digital Whole Slide Imaging Compared With Light Microscopy for Primary Diagnosis in Surgical Pathology.

Context.—: The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility.

Objective.

Standardising the interpretation of liver biopsies in non-alcoholic fatty liver disease clinical trials.

Background: There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised.

Aim: To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD.

Methods: An expert panel of 14 liver pathologists and three hepatologists was assembled.

Haptoglobin 2 Allele is Associated With Histologic Response to Vitamin E in Subjects With Nonalcoholic Steatohepatitis.

Background: Haptoglobin (Hp) genotype has been linked to oxidative stress and cardiovascular outcomes in response to vitamin E (VitE) among patients with diabetes mellitus. Its effect on histologic response to VitE in nonalcoholic steatohepatitis (NASH) is unknown.

Goals: Our objective was to determine if Hp genotype associates with response to VitE in patients with NASH.

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease.

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.

In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.

Background & Aims: Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD.

Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models.

Objectives: The aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy.

Methods: Galactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, (68)Ga, and injected (i.

Association between metabolic syndrome and liver histology among children with nonalcoholic Fatty liver disease.

Objectives: Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome (MetS) among adults. Emerging data suggest that MetS may be associated with nonalcoholic fatty liver disease (NAFLD) in children as well. We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD.

Impact of abdominal helical computed tomography on the rate of negative appendicitis.

Helical abdominal computed tomography (HCT) is a common test in the evaluation of patients with presumed appendicitis. Studies have demonstrated HCT to have high sensitivity, specificity, and positive and negative predictive value. Despite this, there has not been consistent demonstration that HCT has had beneficial effect on patient outcome.

Age and time as factors in the left-to-right shift of the subsite of colorectal adenocarcinoma: a study of 213,383 cases from the California Cancer Registry.

Goals: Using a data set of more than 200,000 cases, we can measure the effects of age, time, sex, and race/ethnicity on the shift of the site of origin of colorectal adenocarcinoma from the left to the right side.

Background: As people become older, there is a shift of the site of origin of adenocarcinoma of the colorectum from the left to the right side. Although some studies do show some relationship of this shift, in addition to age, to race/ethnicity and to sex, there are no large, total population-based data studying the effects of these factors and time trends in this shift.

Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR imaging.

Purpose: To retrospectively evaluate the accuracy of double contrast material-enhanced (hereafter double-enhanced) magnetic resonance (MR) imaging depiction of hepatic fibrosis, with histopathologic analysis findings as the reference standard.

Materials And Methods: The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. One hundred one patients (58 men, 43 women; mean age +/- standard deviation, 52 years +/- 10) who underwent double-enhanced MR imaging with superparamagnetic iron oxide (SPIO)-enhanced and double-enhanced spoiled gradient-echo (SPGR) sequences between 2001 and 2004 and had a reliable reference standard for the diagnosis of liver fibrosis were included.

Impact of helical computed tomography on the rate of negative appendicitis.

Objective: To assess the impact of helical computed tomography (HCT) on the rate of negative appendicitis (NA).

Methods: A before-and-after comparison study comparing data from a prospective consecutive case series to data from a retrospective chart review. The prospective series included all patients presenting to the ED during a 19-month period, during which patients with suspected appendicitis were managed in accordance with a guideline that stipulated HCT in selected cases.

Cytomegalovirus ischemic colitis: a near-fatal presentation of HIV infection.

Cytomegalovirus infection occurs in immunocompromised patients. We present a 45-year-old male with no prior medical history who presented to the hospital with weight loss and non-bloody diarrhea. During hospitalization, he developed severe hematochezia and hypotension.

Utility of immediate evaluation of endoscopic ultrasound-guided transesophageal fine needle aspiration of mediastinal lymph nodes.

Objective: To assess the value of immediate cytologic evaluation (ICE) in mediastinal endoscopic ultrasound-guided transesophageal fine needle aspiration (EUS-FNA).

Study Design: Fifty eight patients with mediastinal lymphadenopathy underwent transesophageal EUS-FNA. Cellularity, number of needle passes and number of slides prepared were reviewed retrospectively.

Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer.

Background & Aims: 5-Fluorouracil improves mortality in stage III colorectal cancer patients. In vitro studies suggest that microsatellite instability influences cell survival after 5-fluorouracil treatment. We investigated the survival influence of 5-fluorouracil in patients with microsatellite instability-high tumors.

Increased expression of endoarterial vascular cell adhesion molecule-1 mRNA in an experimental model of lung transplant rejection: diagnosis by pulmonary arterial biopsy.

Background: Early detection of rejection after lung transplantation may prevent allograft failure. This study determines if mRNA from the cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in pulmonary endovascular tissue samples could be markers of early rejection.

Methods: Single left lung transplants were performed in five dogs.