The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials
Abstract
Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum markers of fibrosis in 475 patients with NASH with bridging fibrosis (F3) or compensated cirrhosis (F4) enrolled in two phase 2b, placebo-controlled trials of simtuzumab. The trials were terminated after 96 weeks because of lack of efficacy, so data from treatment groups were combined. Liver biopsies and HVPG measurements (only for patients with F4 fibrosis) were collected at screening and at weeks 48 and 96. Patients were assessed for Ishak fibrosis stage, hepatic collagen content and alpha-smooth muscle actin (by morphometry), NAFLD Activity Score (NAS), and serum markers of fibrosis. Associations with progression to cirrhosis (in patients with F3 fibrosis) and liver-related clinical events (in patients with F4 fibrosis) were determined. Progression to cirrhosis occurred in 22% (48/217) of F3 patients, and liver-related clinical events occurred in 19% (50/258) of patients with cirrhosis. Factors significantly associated with progression to cirrhosis included higher baseline values of and greater increases in hepatic collagen content, level of alpha-smooth muscle actin, and Enhanced Liver Fibrosis score. Similar factors, plus lack of fibrosis stage improvement (hazard ratio, 9.30; 95% confidence interval, 1.28-67.37), higher HVPG at baseline, and greater increase in HVPG over time, were associated with an increased risk of liver-related clinical events in patients with cirrhosis. Disease progression was not associated with the NAS at baseline or changes in NAS during treatment after adjustment for fibrosis stage. Conclusion: In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.
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“The metabolic heterogeneity of study populations, particularly regarding T2D comorbidity, remains an unexplored source of the inconsistent outcomes with omega-3 PUFA therapy.13,14”
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“Direct antifibrotic therapeutic actions may become more critical when liver disease is already too advanced to allow sufficient time for primarily causal therapeutics to act, since clinical progression of advanced fibrosis may occur more rapidly than previously anticipated.24”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [24]
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“However, despite being ‘negative’ the biomaterial and data obtained during these clinical trials have provided important pathogenetic and clinical insights into these diseases.24 229”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [24]
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Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781
Self-citationSterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., S. Sulkowski, M., Torriani, F. J., Dieterich, D. T., Thomas, D. L., et al. (2006) · Hepatology · doi:10.1002/hep.21178 · Cited by 5,021 · cited 1×
“Serum fibrosis markers including the Enhanced Liver Fibrosis (ELF) test score (Siemens Healthcare, Erlangen, Germany), FibroSure (LabCorp, Burlington, NC)/FibroTest (Biopredictive, Paris, France), NAFLD fibrosis score, fibrosis-4 (FIB-4) index,(18) and aspartate aminotransferase-to-platelet ratio index (APRI)(19) were…”
MethodWai, C.-T., Greenson, J. K., Fontana, R. J., Kalbfleisch, J. D., Marrero, J. A., Conjeevaram, H. S., & Lok, A. S.-F. (2003) · Hepatology · doi:10.1053/jhep.2003.50346 · Cited by 4,406
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Hepatology · doi:10.1002/hep.25762 · Cited by 3,854
Self-citationAngulo, P., Kleiner, D. E., Dam-Larsen, S., Adams, L. A., Bjornsson, E. S., Charatcharoenwitthaya, P., Mills, P. R., Keach, J. C., Lafferty, H. D., Stahler, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.043 · Cited by 2,987
D'Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2005.10.013 · Cited by 2,687
Estes, C., Razavi, H. A., Loomba, R. S., Younossi, Z. M., & Sanyal, A. J. (2017) · Hepatology · doi:10.1002/hep.29466 · Cited by 2,496
Self-citationEkstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S., & Hultcrantz, R. (2015) · Hepatology · doi:10.1002/hep.27368 · Cited by 2,287
Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., Sebastiani, G., Ekstedt, M., Hagstrom, H., Nasr, P., et al. (2017) · Hepatology · doi:10.1002/hep.29085 · Cited by 1,965
Self-citationPrevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis
García–Tsao, G., Sanyal, A. J., Grace, N. D., & Carey, W. (2007) · Hepatology · doi:10.1002/hep.21907 · Cited by 1,714
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Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667
Self-citationTacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
Self-citationMechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Berzigotti, A., Tsochatzis, E., Boursier, J., Castera, L., Cazzagon, N., Friedrich-Rust, M., Petta, S., & Thiele, M. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.05.025 · Cited by 1,925
Nonalcoholic Fatty Liver Disease 2020: The State of the Disease
Cotter, T. G., & Rinella, M. E. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.052 · Cited by 1,251
Metadata
- Authors
- Sanyal, A. J., Harrison, S. A., Ratziu, V., Abdelmalek, M. F., Diehl, A. M., Caldwell, S., Shiffman, M. L., Aguilar Schall, R., Jia, C., McColgan, B., Djedjos, C. S., McHutchison, J. G., Subramanian, G. M., Myers, R. P., Younossi, Z., Muir, A. J., Afdhal, N. H., Bosch, J., & Goodman, Z.
- Affiliations
- Virginia Commonwealth University (US)
- Pinnacle Clinical Research (US)
- Pitié-Salpêtrière Hospital (FR)
- Duke Clinical Research Institute (US)
- University of Virginia (US)
- Liver Institute of Virginia,Richmond,VA
- Gilead Sciences, Inc,Foster City,CA
- Gilead Sciences (United States) (US)
- Inova Fairfax Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- University of Bern (CH)
- Corresponding author
- Sanyal, Arun J.
- ORCID
- Venue
- Hepatology
- Published
- 2019-05-28
- Volume
- 70
- Issue
- 6
- Pages
- 1913-1927
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2938096756
- Cited by
- 390
- References
- 27
- Citations by year
- 2026: 32 · 2025: 53 · 2024: 57 · 2023: 83 · 2022: 55 · 2021: 54 · 2020: 49 · 2019: 6
- FWCI
- 31.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- nonalcoholic steatohepatitis, liver fibrosis, disease progression, liver cirrhosis, hepatic venous pressure gradient, alpha-smooth muscle actin, enhanced liver fibrosis test, NAFLD activity score, compensated cirrhosis, bridging fibrosis
- MeSH terms
- Actins, Female, Hepatic Veins, Humans, Liver Cirrhosis, Male, Middle Aged, Prognosis, Venous Pressure, Randomized Controlled Trials as Topic, Disease Progression, Antibodies, Monoclonal, Humanized, Non-alcoholic Fatty Liver Disease
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