David E. Kleiner
A5019378601- Liver Disease Diagnosis and Treatment
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver Disease and Transplantation
- Drug-Induced Hepatotoxicity and Protection
- Cancer Genomics and Diagnostics
- Liver Diseases and Immunity
- Lung Cancer Research Studies
- Cancer Immunotherapy and Biomarkers
- Hepatocellular Carcinoma Treatment and Prognosis
- Lung Cancer Treatments and Mutations
- Diet, Metabolism, and Disease
- Pancreatic and Hepatic Oncology Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Drug Transport and Resistance Mechanisms
- Immune Cell Function and Interaction
- Lipid metabolism and disorders
- Immunotherapy and Immune Responses
- Pancreatitis Pathology and Treatment
- Gut microbiota and health
- Peptidase Inhibition and Analysis
- Pharmacogenetics and Drug Metabolism
- Immunodeficiency and Autoimmune Disorders
- Alcohol Consumption and Health Effects
National Cancer Institute
2016-2025
Center for Cancer Research
2016-2025
National Cancer Institute
2003-2025
National Institutes of Health
2016-2025
National Institute of Diabetes and Digestive and Kidney Diseases
1997-2024
Hepatitis B Foundation
2023
Research Network (United States)
2023
Klein Buendel (United States)
2023
National Institute of Allergy and Infectious Diseases
1991-2022
National Human Genome Research Institute
1999-2022
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history significant alcohol use or other known disease. steatohepatitis (NASH) progressive form NAFLD. The Pathology Committee NASH Clinical Research Network designed and validated histological feature scoring system that addresses full spectrum lesions NAFLD proposed activity score (NAS) for clinical trials. comprised 14 features, 4 which were evaluated semi-quantitatively: (0-3), lobular...
Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there no established treatment for this disease.
Liver cancer has the second highest worldwide mortality rate and limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing DNA copy number analyses, we 196 HCC methylation, RNA, miRNA, proteomic expression also. mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, SMARCA4. Significant alterations or downregulation hypermethylation in genes likely to result metabolic reprogramming (ALB, APOB, CPS1) were...
Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that strongly associated with obesity. Currently, there no approved therapy for NASH. Weight reduction typically recommended, but efficacy data are lacking. We performed randomized controlled trial to examine the effects of lifestyle intervention using combination diet, exercise, and behavior modification, goal 7% 10% weight reduction, on clinical parameters The primary outcome measure was change in NASH histological...
PREAMBLE The study of NAFLD has intensified significantly, with more than 1400 publications since 2018, when the last American Association for Study Liver Diseases (AASLD) Guidance document was published.1 This new AASLD reflects many advances in field pertinent to any practitioner caring patients and emphasizes noninvasive risk stratification therapeutics. A separate guideline focused on management context diabetes been written jointly by Clinical Endocrinology AASLD.2 Given significant...
Abstract The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern specific histological abnormalities on liver biopsy. A separate system scoring features fatty disease (NAFLD) called NAFLD Activity Score (NAS) was developed as a tool to measure changes in during therapeutic trials. However, some studies have used threshold values NAS, specifically NAS ≥5, surrogate for histologic NASH. To evaluate whether this unintended use valid, biopsy clinical data from...
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms human are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted durable cancer regression immune-mediated toxicities. A report diagnosis, pathology, treatment, clinical outcome, significance enterocolitis seen presented.We treated 198 patients metastatic melanoma (MM) or...
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 humans are unknown. We identified germline heterozygous subjects with severe dysregulation from four unrelated families. Whereas Ctla4 mice have no obvious phenotype, human haploinsufficiency caused FoxP3(+) regulatory (Treg) cells, hyperactivation effector and lymphocytic infiltration target organs. Patients also exhibited progressive loss circulating B...
We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, systemic vasculopathy in three unrelated patients. suspected genetic cause because the disorder presented early childhood.We performed whole-exome sequencing initial patients their unaffected parents candidate-gene with similar phenotype, as well two young siblings polyarteritis nodosa one patient small-vessel vasculitis. Enzyme assays,...
Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. considered one the clinical features metabolic syndrome in insulin resistance plays central role. This prospective study evaluates role insulin-sensitizing agent treatment NASH. Eighteen nondiabetic biopsy-proven were treated pioglitazone (30 mg daily) 48 weeks. Tests sensitivity body composition as...
The prognoses with respect to mortality and hepatic nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.
Abstract: Nonalcoholic fatty liver disease is a common cause of chronic in the general population. steatohepatitis (NASH), aggressive form nonalcoholic disease, associated with an increased risk liver-related mortality and cardiovascular disease. At present, biopsy only generally acceptable method for diagnosis NASH assessment its progression toward cirrhosis. Although several treatments have shown evidence efficacy clinical trials varying design, there are no approved NASH, published often...
Despite signs of infection—including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema macules—the involvement the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated analyzed two single-cell RNA sequencing datasets human minor salivary glands gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated normalization annotation, classified 34 unique subpopulations between gingiva. Severe acute...
Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape liver cancer biospecimens from 19 patients. We found varying degrees heterogeneity malignant cells within between diverse landscapes tumor microenvironment (TME). Strikingly, with higher were associated patient's worse overall survival. link hypoxia-dependent vascular endothelial growth expression TME polarization....
We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection.
Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe integrated analysis somatic mutations, RNA expression, copy number, DNA methylation by The Cancer Genome Atlas a set predominantly intrahepatic CCA cases propose molecular classification scheme. We identified IDH mutant-enriched subtype distinct features including low expression chromatin modifiers, elevated mitochondrial genes, increased number....