Trial reportHepatology (Baltimore, Md.)2015
Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity.
Trial report in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00063622 (Clinical Research Network in Nonalcoholic Steatohepatitis), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical Research Network in Nonalcoholic Steatohepatitis: Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Efficacy of selected dietary supplements and pharmacological agents on metabolic and oxidative stress outcomes in metabolic dysfunction-associated fatty liver disease (MAFLD): a Bayesian network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD): an attempted network meta-analysis.The Cochrane database of systematic reviews · 2017Pooled it
- Envisioning how to advance the MASH field.Nature reviews. Gastroenterology & hepatology · 2024Review
- Pharmacotherapies in Dupuytren Disease: Current and Novel Strategies.The Journal of hand surgery · 2023Review
- Non-alcoholic fatty liver disease: the pathologist's perspective.Clinical and molecular hepatology · 2023Review
- The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Understanding the cellular interactome of non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2022Review
- Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation.Biomedicines · 2021Review
- Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis.Nature reviews. Gastroenterology & hepatology · 2021Review
- Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis.Gastroenterology · 2020Review
- FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases.Frontiers in endocrinology · 2020Review
- Pathogenesis of NASH: The Impact of Multiple Pathways.Current hepatology reports · 2018Article
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
- Lipometabolism and Glycometabolism in Liver Diseases.BioMed research international · 2018Review
- Role of canonical Hedgehog signaling pathway in liver.International journal of biological sciences · 2018Review
- Developmental origins of NAFLD: a womb with a clue.Nature reviews. Gastroenterology & hepatology · 2017Review
- Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.PloS one · 2017Article
- Molecular Pathogenesis of NASH.International journal of molecular sciences · 2016Review
- c-Jun N-terminal kinase-mediated Rubicon expression enhances hepatocyte lipoapoptosis and promotes hepatocyte ballooning.World journal of gastroenterology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledHedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK-sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE treatment and improvement in NASH were associated with changes in Hh pathway activity. Immunohistochemistry (IHC) was performed on both pre- and posttreatment liver biopsies of 59 PIVENS patients randomized to VitE (n = 30) or placebo (n = 29). Sonic Hh (Shh) ligand-producing cells and Shh-responsive cells were quantified. The latter was accomplished by triple IHC for gli2+ (marker of Hh signaling), sox-9 (progenitor marker), and α-smooth muscle actin (α-SMA; myofibroblast marker). Ballooned hepatocytes were quantified by keratin 8/18 and ubiquitin (K8/18/Ub) staining. IHC results were correlated with primary clinical and histologic PIVENS data. Pretreatment clinical, histologic, and IHC parameters did not differ significantly in the two treatment groups. Regardless of treatment arm, the number of Shh+ hepatocytes correlated with K8/18/Ub foci (r(2) = 0.47, P < 0.001) and aspartate aminotransferase (AST) (r(2) = 0.15, P = 0.002). Treatment-related changes in the numbers of Shh+ hepatocytes correlated with changes in serum AST (partial r(2) = 0.75, P < 0.0001), hepatocyte ballooning (P = 0.004), the ductular reaction (i.e., numbers of gli2+/sox9+ cells; P = 0.03 and α-SMA+ cells; P = 0.10), and fibrosis stage (P = 0.02). Treatment response was associated with a greater decrease in Shh+ hepatocytes than nonresponse (P = 0.007). The VitE group demonstrated a greater reduction in K8/18/Ub+ foci (P < 0.08) and Shh+ hepatocytes (P < 0.05) than the placebo group, effects that became more significant after correction for baseline differences and multiple linear regression analysis.
conclusionDuring PIVENS, treatment response correlated with loss of Shh+ hepatocytes and improvement in Hh-regulated processes that promote NASH progression.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.