Author
David E. Kleiner
Other affiliations: University of Virginia, Tufts University, University of Texas MD Anderson Cancer Center ...read more
Bio: David E. Kleiner is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Liver biopsy & Nonalcoholic fatty liver disease. The author has an hindex of 104, co-authored 495 publications receiving 50296 citations. Previous affiliations of David E. Kleiner include University of Virginia & Tufts University.
Papers published on a yearly basis
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TL;DR: A strong scoring system and NAS for NAFLD and NASH with reasonable inter‐rater reproducibility that should be useful for studies of both adults and children with any degree ofNAFLD are presented.
8,253 citations
Virginia Commonwealth University1, Indiana University – Purdue University Indianapolis2, Virginia Mason Medical Center3, Case Western Reserve University4, Duke University5, University of California, San Francisco6, Saint Louis University7, University of California, San Diego8, Johns Hopkins University9, Washington University in St. Louis10, National Institutes of Health11
TL;DR: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes, and significant benefits of pioglitazone were observed for some of the secondary outcomes.
Abstract: Background Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrho sis. Currently, there is no established treatment for this disease. Methods We randomly assigned 247 adults with nonalcoholic steatohepatitis and without dia betes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The pri mary outcome was an improvement in histologic features of nonalcoholic steato hepatitis, as assessed with the use of a composite of standardized scores for steato sis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indi cate statistical significance. Results Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0. 001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P = 0. 04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pio glitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P = 0. 005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P = 0. 02 for vitamin E and P = 0. 004 for pioglitazone) but not with improvement in fibrosis scores (P = 0. 24 for vitamin E and P = 0. 12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. Conclusions Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT000 63622.)
2,632 citations
TL;DR: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.
2,061 citations
Saint Louis University1, University of California, San Diego2, Virginia Commonwealth University3, Columbia University4, Johns Hopkins University5, Duke University6, Indiana University – Purdue University Indianapolis7, Case Western Reserve University8, University of California, San Francisco9, Virginia Mason Medical Center10, Cleveland Clinic11, Washington University in St. Louis12, National Institutes of Health13
TL;DR: Obeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification.
1,798 citations
TL;DR: Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts and development of a p53 target gene expression signature correlating with poor survival was enabled.
1,623 citations
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Harvard University1, Vanderbilt University2, Netherlands Cancer Institute3, University of Colorado Denver4, Institut Gustave Roussy5, University of Duisburg-Essen6, University of Mannheim7, University of Utah8, VU University Amsterdam9, Mount Sinai Hospital10, Washington University in St. Louis11, University Hospital Southampton NHS Foundation Trust12, University of Paris13, Technische Universität München14, Loyola University Chicago15, Memorial Sloan Kettering Cancer Center16, University of South Florida17, Medarex18, Bristol-Myers Squibb19
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Abstract: Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
13,081 citations
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Abstract: Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.
10,602 citations
TL;DR: A strong scoring system and NAS for NAFLD and NASH with reasonable inter‐rater reproducibility that should be useful for studies of both adults and children with any degree ofNAFLD are presented.
8,253 citations
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Abstract: Background Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. Methods In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. Results As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The media...
6,812 citations
TL;DR: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.
6,746 citations