Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach
Open accessAbstract
Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity is the only histological predictor of liver-related morbidity and mortality in NASH identified to date. Moreover, fibrosis regression is associated with improved clinical outcomes. However, despite numerous clinical trials of plausible drug candidates, an approved antifibrotic therapy remains elusive. Increased understanding of NASH susceptibility and pathogenesis, emerging human multiomics profiling, integration of electronic health record data and modern pharmacology techniques hold enormous promise in delivering a paradigm shift in antifibrotic drug development in NASH. There is a strong rationale for drug combinations to boost efficacy, and precision medicine strategies targeting key genetic modifiers of NASH are emerging. In this Perspective, we discuss why antifibrotic effects observed in NASH pharmacotherapy trials have been underwhelming and outline potential approaches to improve the likelihood of future clinical success.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets.
“Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets.”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [10]
Fibrosis and even cirrhosis can regress following successful antiviral therapy in chronic viral hepatitis, immunosuppression in autoimmune hepatitis, or lifestyle modifications and bariatric surgery in metabolic dysfunction-associated steatohepatitis.
“Fibrosis and even cirrhosis can regress, as described following successful antiviral therapy in patients with chronic viral hepatitis, immunosuppression in autoimmune hepatitis, or lifestyle modifications and bariatric surgery in patients with metabolic dysfunction-associated steatohepatitis (MASH) (8–10).”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791 · see citing works
Younossi, Z. M., Golabi, P., Paik, J. M., Henry, A., Van Dongen, C., & Henry, L. (2023) · Hepatology · doi:10.1097/hep.0000000000000004 · Cited by 3,383 · see citing works
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286 · see citing works
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 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., Gonzalez-Fabian, L., Friedman, S. L., Diago, M., & Romero-Gomez, M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.005 · Cited by 2,492 · see citing works
The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis
Riazi, K., Azhari, H., Charette, J. H., Underwood, F. E., King, J. A., Afshar, E. E., Swain, M. G., Congly, S. E., Kaplan, G. G., & Shaheen, A.-A. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00165-0 · Cited by 2,246 · see citing works
Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease
Ratziu, V., Charlotte, F., Heurtier, A., Gombert, S., Giral, P., Bruckert, E., Grimaldi, A., Capron, F., & Poynard, T. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.084 · Cited by 2,106 · see citing works
Mechanisms 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 · see citing works
Self-citationGlobal epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention
Huang, D. Q., El-Serag, H. B., & Loomba, R. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00381-6 · Cited by 1,855 · see citing works
Self-citationSingh, S., Allen, A. M., Wang, Z., Prokop, L. J., Murad, M. H., & Loomba, R. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.04.014 · Cited by 1,748 · see citing works
Self-citationCAR T cells produced in vivo to treat cardiac injury
Rurik, J. G., Tombácz, I., Yadegari, A., Méndez Fernández, P. O., Shewale, S. V., Li, L., Kimura, T., Soliman, O. Y., Papp, T. E., Tam, Y. K., et al. (2022) · Science · doi:10.1126/science.abm0594 · Cited by 1,400 · see citing works
Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.069 · Cited by 1,383 · cited 1× · see citing works
“An early-phase trial (NCT05506488) evaluating the combination of the tyrosine kinase inhibitor dasatinib and the antioxidant quercetin, which decreases senescent cells in diabetic kidney disease 59 , will provide important proof-of-principle for their use in fibrotic NASH 60–62 .”
BackgroundRandomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis
Promrat, K., Kleiner, D. E., Niemeier, H. M., Jackvony, E., Kearns, M., Wands, J. R., Fava, J. L., & Wing, R. R. (2010) · Hepatology · doi:10.1002/hep.23276 · Cited by 1,330 · see citing works
Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)33041-7 · Cited by 1,277 · see citing works
Self-citationProspective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease
Sanyal, A. J., Van Natta, M. L., Clark, J., Neuschwander-Tetri, B. A., Diehl, A., Dasarathy, S., Loomba, R., Chalasani, N., Kowdley, K., Hameed, B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2029349 · Cited by 1,146 · see citing works
Self-citationSenolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098 · see citing works
Iredale, J. P., Benyon, R. C., Pickering, J., McCullen, M., Northrop, M., Pawley, S., Hovell, C., & Arthur, M. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1018 · Cited by 1,075 · see citing works
Cross-tissue organization of the fibroblast lineage
Buechler, M. B., Pradhan, R., Krishnamurty, A. T., Cox, C. B., Calviello, A. K., Wang, A. W., Yang, Y. A., Tam, L., Caothien, R. H., Roose‐Girma, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03549-5 · Cited by 1,073 · see citing works
Cellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044 · see citing works
Self-citationDinu, M., Pagliai, G., Casini, A., & Sofi, F. (2018) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2017.58 · Cited by 1,016 · see citing works
Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.
Friedman, S. L., Roll, F. J., Boyles, J., & Bissell, D. M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8681 · Cited by 859 · see citing works
A Protein-Truncating <i>HSD17B13</i> Variant and Protection from Chronic Liver Disease
Abul-Husn, N. S., Cheng, X., Li, A. H., Xin, Y., Schurmann, C., Stevis, P., Liu, Y., Kozlitina, J., Stender, S., Wood, G. C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1712191 · Cited by 827 · see citing works
Vilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quiñones Sanz, M., Conde-Martin, A. F., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.034 · Cited by 806 · see citing works
Advancing the global public health agenda for NAFLD: a consensus statement
Lazarus, J. V., Mark, H. E., Anstee, Q. M., Arab, J. P., Batterham, R. L., Castera, L., Cortez-Pinto, H., Crespo, J., Cusi, K., Dirac, M. A., et al. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00523-4 · Cited by 757 · see citing works
Self-citationMechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis
Schwabe, R. F., Tabas, I., & Pajvani, U. B. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.311 · Cited by 671 · see citing works
Lassailly, G., Caiazzo, R., Ntandja-Wandji, L.-C., Gnemmi, V., Baud, G., Verkindt, H., Ningarhari, M., Louvet, A., Leteurtre, E., Raverdy, V., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.06.006 · Cited by 622 · see citing works
Sato, Y., Murase, K., Kato, J., Kobune, M., Sato, T., Kawano, Y., Takimoto, R., Takada, K., Miyanishi, K., Matsunaga, T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1396 · Cited by 610 · see citing works
Laboratory mice born to wild mice have natural microbiota and model human immune responses
Rosshart, S. P., Herz, J., Vassallo, B. G., Hunter, A., Wall, M. K., Badger, J. H., McCulloch, J. A., Anastasakis, D. G., Sarshad, A. A., Leonardi, I., et al. (2019) · Science · doi:10.1126/science.aaw4361 · Cited by 572 · see citing works
Tsurusaki, S., Tsuchiya, Y., Koumura, T., Nakasone, M., Sakamoto, T., Matsuoka, M., Imai, H., Yuet-Yin Kok, C., Okochi, H., Nakano, H., et al. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1678-y · Cited by 529 · see citing works
A multi-organ chip with matured tissue niches linked by vascular flow
Ronaldson-Bouchard, K., Teles, D., Yeager, K., Tavakol, D. N., Zhao, Y., Chramiec, A., Tagore, S., Summers, M., Stylianos, S., Tamargo, M., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00882-6 · Cited by 512 · see citing works
Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes
Wang, T., Johmura, Y., Suzuki, N., Omori, S., Migita, T., Yamaguchi, K., Hatakeyama, S., Yamazaki, S., Shimizu, E., Imoto, S., et al. (2022) · Nature · doi:10.1038/s41586-022-05388-4 · Cited by 481 · see citing works
Govaere, O., Cockell, S., Tiniakos, D., Queen, R., Younes, R., Vacca, M., Alexander, L., Ravaioli, F., Palmer, J., Petta, S., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aba4448 · Cited by 479 · see citing works
Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials
Davison, B. A., Harrison, S. A., Cotter, G., Alkhouri, N., Sanyal, A., Edwards, C., Colca, J. R., Iwashita, J., Koch, G. G., & Dittrich, H. C. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.06.025 · Cited by 448 · see citing works
Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis
Dobie, R., Wilson-Kanamori, J. R., Henderson, B. E. P., Smith, J. R., Matchett, K. P., Portman, J. R., Wallenborg, K., Picelli, S., Zagorska, A., Pendem, S. V., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.024 · Cited by 420 · see citing works
Harrison, S. A., Abdelmalek, M. F., Caldwell, S., Shiffman, M. L., Diehl, A. M., Ghalib, R., Lawitz, E. J., Rockey, D. C., Schall, R. A., Jia, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.006 · Cited by 384 · see citing works
Aminian, A., Al-Kurd, A., Wilson, R., Bena, J., Fayazzadeh, H., Singh, T., Albaugh, V. L., Shariff, F. U., Rodriguez, N. A., Jin, J., et al. (2021) · JAMA · doi:10.1001/jama.2021.19569 · Cited by 375 · see citing works
Association of histologic disease activity with progression of nonalcoholic fatty liver disease
Kleiner, D. E., Brunt, E. M., Wilson, L. A., Behling, C., Guy, C., Contos, M., Cummings, O., Yeh, M., Gill, R., Chalasani, N., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.12565 · Cited by 372 · see citing works
Self-citationGeneration of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids
Mun, S. J., Ryu, J., Lee, M., Son, Y. S., Oh, S. J., Cho, H., Son, M., Kim, S. J., Kim, S. J., Yoo, H. J., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.06.030 · Cited by 369 · see citing works
Chalasani, N., Abdelmalek, M. F., Garcia-Tsao, G., Vuppalanchi, R., Alkhouri, N., Rinella, M., Noureddin, M., Pyko, M., Shiffman, M., Sanyal, A., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.296 · Cited by 358 · see citing works
Self-citationWright, M. C., Issa, R., Smart, D. E., Trim, N., Murray, G. I., Primrose, J. M., Arthur, M. J. P., Iredale, J. P., & Mann, D. A. (2001) · Gastroenterology · doi:10.1053/gast.2001.27188 · Cited by 356 · see citing works
Self-citationChallenges and opportunities in NASH drug development
Harrison, S. A., Allen, A. M., Dubourg, J., Noureddin, M., & Alkhouri, N. (2023) · Nature Medicine · doi:10.1038/s41591-023-02242-6 · Cited by 353 · see citing works
Berzigotti, A., Albillos, A., Villanueva, C., Genescá, J., Ardevol, A., Augustín, S., Calleja, J. L., Bañares, R., García‐Pagán, J. C., Mesonero, F., et al. (2017) · Hepatology · doi:10.1002/hep.28992 · Cited by 334 · see citing works
Ajmera, V., Cepin, S., Tesfai, K., Hofflich, H., Cadman, K., Lopez, S., Madamba, E., Bettencourt, R., Richards, L., Behling, C., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2022.11.010 · Cited by 327 · see citing works
Self-citationIssa, R., Williams, E., Trim, N., Kendall, T. J., Arthur, M. J. P., Reichen, J., Benyon, R. C., & Iredale, J. P. (2001) · Gut · doi:10.1136/gut.48.4.548 · Cited by 321 · see citing works
Self-citationLoomba, R., Noureddin, M., Kowdley, K. V., Kohli, A., Sheikh, A., Neff, G., Bhandari, B. R., Gunn, N., Caldwell, S. H., Goodman, Z., et al. (2021) · Hepatology · doi:10.1002/hep.31622 · Cited by 296 · see citing works
Self-citationZelber‐Sagi, S., Salomone, F., & Mlynarsky, L. (2017) · Liver International · doi:10.1111/liv.13435 · Cited by 273 · see citing works
Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat
Maher, T. M., & Strek, M. E. (2019) · Respiratory Research · doi:10.1186/s12931-019-1161-4 · Cited by 266 · see citing works
Viel, G., Rafael Boscolo-berto, A., Cecchetto, G., Fais, P., Nalesso, A., & Ferrara, S. D. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131114788 · Cited by 253 · see citing works
Cirrhosis reversal: a duel between dogma and myth
Desmet, V. J., & Roskams, T. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.03.007 · Cited by 247 · see citing works
Alkhouri, N., Herring, R., Kabler, H., Kayali, Z., Hassanein, T., Kohli, A., Huss, R. S., Zhu, Y., Billin, A. N., Damgaard, L. H., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.003 · Cited by 230 · see citing works
Self-citationTeufel, A., Itzel, T., Erhart, W., Brosch, M., Wang, X. Y., Kim, Y. O., von Schönfels, W., Herrmann, A., Brückner, S., Stickel, F., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.05.051 · Cited by 229 · see citing works
Lindén, D., Ahnmark, A., Pingitore, P., Ciociola, E., Ahlstedt, I., Andréasson, A., Sasidharan, K., Madeyski-Bengtson, K., Zurek, M., Mancina, R. M., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.01.013 · Cited by 211 · see citing works
Harrison, S. A., Bashir, M., Moussa, S. E., McCarty, K., Pablo Frias, J., Taub, R., & Alkhouri, N. (2021) · Hepatology Communications · doi:10.1002/hep4.1657 · Cited by 197 · see citing works
Im, Y. R., Hunter, H., de Gracia Hahn, D., Duret, A., Cheah, Q., Dong, J., Fairey, M., Hjalmarsson, C., Li, A., Lim, H. K., et al. (2021) · Hepatology · doi:10.1002/hep.31897 · Cited by 195 · see citing works
Staufer, K., Huber-Schönauer, U., Strebinger, G., Pimingstorfer, P., Suesse, S., Scherzer, T. M., Paulweber, B., Ferenci, P., Stimpfl, T., Yegles, M., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.040 · Cited by 190 · see citing works
Non-alcoholic fatty liver disease in lean individuals
Albhaisi, S. A. M., Chowdhury, A., & Sanyal, A. J. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.08.002 · Cited by 179 · see citing works
Principles of Cell Circuits for Tissue Repair and Fibrosis
Adler, M., Mayo, A., Zhou, X., Franklin, R. A., Meizlish, M. L., Medzhitov, R., Kallenberger, S. M., & Alon, U. (2020) · iScience · doi:10.1016/j.isci.2020.100841 · Cited by 177 · see citing works
Wang, S., Li, K., Pickholz, E., Dobie, R., Matchett, K. P., Henderson, N. C., Carrico, C., Driver, I., Borch Jensen, M., Chen, L., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add3949 · Cited by 176 · see citing works
Sanyal, A. J., Anstee, Q. M., Trauner, M., Lawitz, E. J., Abdelmalek, M. F., Ding, D., Han, L., Jia, C., Huss, R. S., Chung, C., et al. (2022) · Hepatology · doi:10.1002/hep.32204 · Cited by 171 · see citing works
Emdin, C. A., Haas, M. E., Khera, A. V., Aragam, K. G., Chaffin, M. D., Klarin, D. M., Hindy, G., Jiang, L., Wei, W., Feng, Q., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008629 · Cited by 162 · see citing works
Pockros, P. J., Fuchs, M. A., Freilich, B. L., Schiff, E. R., Kohli, A., Lawitz, E., Hellstern, P. A., Owens-Grillo, J. K., Biene, C. V., Shringarpure, R., et al. (2019) · Liver International · doi:10.1111/liv.14209 · Cited by 161 · see citing works
García–Tsao, G., Bosch, J., Kayali, Z., Harrison, S. A., Abdelmalek, M. F., Lawitz, E., Satapathy, S. K., Ghabril, M., Shiffman, M. L., Younes, Z. H., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.12.010 · Cited by 158 · see citing works
Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis
Feaver, R. E., Cole, B. K., Lawson, M. J., Hoang, S. A., Marukian, S., Blackman, B. R., Figler, R. A., Sanyal, A. J., Wamhoff, B. R., & Dash, A. (2016) · JCI Insight · doi:10.1172/jci.insight.90954 · Cited by 153 · see citing works
Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH
Loomba, R. S., Neuschwander‐Tetri, B. A., Sanyal, A. J., Chalasani, N., Diehl, A. M., Terrault, N. A., Kowdley, K. V., Dasarathy, S., Kleiner, D. E., Behling, C. A., et al. (2020) · Hepatology · doi:10.1002/hep.31121 · Cited by 151 · see citing works
Self-citationA human multi-lineage hepatic organoid model for liver fibrosis
Guan, Y., Enejder, A., Wang, M., Fang, Z., Cui, L., Chen, S.-Y., Wang, J., Tan, Y., Wu, M., Chen, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26410-9 · Cited by 149 · see citing works
Parisinos, C. A., Wilman, H. R., Thomas, E. L., Kelly, M., Nicholls, R. C., McGonigle, J., Neubauer, S., Hingorani, A. D., Patel, R. S., Hemingway, H., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.032 · Cited by 148 · see citing works
Kizawa, H., Nagao, E., Shimamura, M., Zhang, G., & Torii, H. (2017) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2017.04.004 · Cited by 143 · see citing works
Maher, J. J., Friedman, S. L., Roll, F. J., & Bissell, D. M. (1988) · Gastroenterology · doi:10.1016/0016-5085(88)90566-5 · Cited by 140 · see citing works
Kim, D., Konyn, P., Cholankeril, G. T., & Ahmed, A. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.06.029 · Cited by 133 · see citing works
Breakthroughs in therapies for NASH and remaining challenges
Ratziu, V., Francque, S., & Sanyal, A. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.002 · Cited by 132 · see citing works
Loomba, R., Ratziu, V., Harrison, S. A., Loomba, R., McFarlane, S. C., Tamaki, N., Ratziu, V., Abdelmalek, M. F., Rinella, M. E., Anstee, Q. M., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2021.10.051 · Cited by 127 · see citing works
Self-citationRustgi, V. K., Li, Y., Gupta, K., Minacapelli, C. D., Bhurwal, A., Catalano, C., & Elsaid, M. I. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.03.021 · Cited by 125 · see citing works
Turco, L., Villanueva, C., Mura, V. L., García‐Pagán, J. C., Reiberger, T., Genescà, J., Groszmann, R. J., Sharma, B. C., Merkel, C., Bureau, C., et al. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.05.050 · Cited by 125 · see citing works
Bazerbachi, F., Vargas, E. J., Rizk, M., Maselli, D. B., Mounajjed, T., Venkatesh, S. K., Watt, K. D. S., Port, J. D., Basu, R., Acosta, A. J., et al. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.04.068 · Cited by 124 · see citing works
Formation of extracellular matrix in normal rat liver: Lipocytes as a major source of proteoglycan
Arenson, D. M., Friedman, S. L., & Bissell, D. M. (1988) · Gastroenterology · doi:10.1016/0016-5085(88)90502-1 · Cited by 123 · see citing works
Understanding the cellular interactome of non-alcoholic fatty liver disease
Wallace, S. J., Tacke, F., Schwabe, R. F., & Henderson, N. C. (2022) · JHEP Reports · doi:10.1016/j.jhepr.2022.100524 · Cited by 116 · see citing works
Naoumov, N. V., Brees, D., Loeffler, J., Chng, E., Ren, Y., Lopez, P., Tai, D., Lamle, S., & Sanyal, A. J. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.018 · Cited by 115 · see citing works
Liver transplantation for nonalcoholic fatty liver disease: New challenges and new opportunities
Shaker, M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i18.5320 · Cited by 112 · see citing works
Lawitz, E. J., Shevell, D. E., Tirucherai, G. S., Du, S., Chen, W., Kavita, U., Coste, A., Poordad, F., Karsdal, M., Nielsen, M., et al. (2022) · Hepatology · doi:10.1002/hep.32181 · Cited by 107 · see citing works
A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision‐Cut Liver Slices
Paish, H. L., Reed, L. H., Brown, H., Bryan, M. C., Govaere, O., Leslie, J., Barksby, B. S., Garcia Macia, M., Watson, A., Xu, X., et al. (2019) · Hepatology · doi:10.1002/hep.30651 · Cited by 106 · see citing works
Self-citationLei, Y., Tang, L., Chen, Q., Wu, L., He, W., Tu, D., Wang, S., Chen, Y., Liu, S., Xie, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34671-1 · Cited by 104 · see citing works
Human Nonalcoholic Steatohepatitis on a Chip
Freag, M. S., Namgung, B., Reyna Fernandez, M. E., Gherardi, E., Sengupta, S., & Jang, H. L. (2021) · Hepatology Communications · doi:10.1002/hep4.1647 · Cited by 102 · see citing works
Glass, O., Filozof, C., Noureddin, M., Berner-Hansen, M., Schabel, E., Omokaro, S. O., Schattenberg, J. M., Barradas, K., Miller, V., Francque, S., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.030 · Cited by 89 · see citing works
Precision-cut human liver slice cultures as an immunological platform
Wu, X., Roberto, J. B., Knupp, A., Kenerson, H. L., Truong, C. D., Yuen, S. Y., Brempelis, K. J., Tuefferd, M., Chen, A., Horton, H., et al. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.01.012 · Cited by 81 · see citing works
Evaluating causality of cellular senescence in non-alcoholic fatty liver disease
Meijnikman, A. S., Herrema, H., Scheithauer, T. P. M., Kroon, J., Nieuwdorp, M., & Groen, A. K. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100301 · Cited by 77 · see citing works
Drenth, J. P. H., & Schattenberg, J. M. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1839888 · Cited by 72 · see citing works
SynToxProfiler: An interactive analysis of drug combination synergy, toxicity and efficacy
Ianevski, A., Kononov, A., Timonen, S. H., Aittokallio, T. A., & Giri, A. K. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007604 · Cited by 70 · see citing works
Modeling nonalcoholic fatty liver disease on a liver lobule chip with dual blood supply
Du, K., Li, S., Li, C., Li, P., Miao, C., Luo, T., Qiu, B., & Ding, W. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.07.013 · Cited by 69 · see citing works
In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations
Kaur, S., Kidambi, S., Ortega‐Ribera, M., Thủy, L. T. T., Nieto, N., Cogger, V. C., Xie, W., Tacke, F., & Gracia‐Sancho, J. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.11.008 · Cited by 67 · see citing works
Lawitz, E., Bhandari, B. R., Ruane, P. J., Kohli, A., Harting, E., Ding, D., Chuang, J.-C., Huss, R. S., Chung, C., Myers, R. P., et al. (2022) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.12.044 · Cited by 56 · see citing works
Self-citationState-of-the-art liver disease research using liver-on-a-chip
Deguchi, S., & Takayama, K. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00248-0 · Cited by 50 · see citing works
A human liver chimeric mouse model for non-alcoholic fatty liver disease
Bissig-Choisat, B., Alves-Bezerra, M., Zorman, B., Ochsner, S. A., Barzi, M., Legras, X., Yang, D., Borowiak, M., Dean, A. M., York, R. B., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100281 · Cited by 49 · see citing works
Huang, D. Q., Sharpton, S. R., Amangurbanova, M., Tamaki, N., Sirlin, C. B., Loomba, R. S., Bettencourt, R., Madamba, E. V., Jung, J., Siddiqi, H., et al. (2022) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2022.08.036 · Cited by 49 · see citing works
Self-citationTamargo, J. A., Sherman, K. E., Campa, A. L., Martínez, S. S., Li, T., Hernández, J., Teeman, C. S., Mandler, R. N., Chen, J., Ehman, R. L., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa362 · Cited by 47 · see citing works
Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis
Bianchi, A., Marchetti, L., Hall, Z., Lemos, H., Vacca, M., Paish, H., Green, K., Elliott, B., Tiniakos, D., Passos, J. F., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001022 · Cited by 45 · see citing works
Self-citationShared Mechanisms between Cardiovascular Disease and NAFLD
Huang, D. Q., Downes, M., Evans, R. M., Witztum, J. L., Glass, C. K., & Loomba, R. S. (2022) · Seminars in Liver Disease · doi:10.1055/a-1930-6658 · Cited by 45 · see citing works
Self-citationYan, Z., Liu, Y., Li, W., Zhao, X., Lin, W., Zhang, J., Yu, S., Ma, J., Wang, J., Yu, P., et al. (2022) · European Journal of Clinical Investigation · doi:10.1111/eci.13855 · Cited by 40 · see citing works
Case Reports of Pre-clinical Replication Studies in Metabolism and Diabetes
von Herrath, M., Pagni, P. P., Grove, K. L., Christoffersson, G., Tang‐Christensen, M., Karlsen, A. E., & Petersen, J. S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.004 · Cited by 39 · see citing works
Bai, W., Al‐Karaghouli, M., Stach, J., Sung, S., Matheson, G. J., & Abraldeṣ, J. G. (2021) · Hepatology · doi:10.1002/hep.32033 · Cited by 39 · see citing works
Emerging synthetic drugs for the treatment of liver cirrhosis
Fallowfield, J. A., Ramos, M. J., & Robertson, A. (2021) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2021.1918099 · Cited by 38 · see citing works
Self-citationBaratta, F., D’Erasmo, L., Bini, S., Pastori, D., Angelico, F., Ben, M. D., Arca, M., & Costanzo, A. D. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.08.011 · Cited by 34 · see citing works
Alvarado‐Tápias, E., Aguado, D. M., Kennedy, K. F., Fernández‐Carrillo, C., Cots, M. V., Morales-Arráez, D. E., Atkinson, S. R., Clemente, A. P. G., Argemí, J., & Bataller, R. A. (2023) · Obesity Surgery · doi:10.1007/s11695-023-06490-w · Cited by 32 · see citing works
Chhatwal, J., Dalgic, O. O., Chen, W., Samur, S., Bethea, E. D., Xiao, J., Hur, C., Corey, K. E., & Loomba, R. S. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.30426 · Cited by 28 · see citing works
Self-citationThe Placebo Response in Randomized Trials in Nonalcoholic Steatohepatitis Simply Explained
Rowe, I. A. C., & Parker, R. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.05.059 · Cited by 28 · see citing works
Fibrosis progression rate in a systematic review of placebo‐treated nonalcoholic steatohepatitis
Roskilly, A., Hicks, A., Taylor, E., Jones, R. L., Parker, R., & Rowe, I. A. C. (2020) · Liver International · doi:10.1111/liv.14749 · Cited by 27 · see citing works
Astbury, S., Grove, J. I., Dorward, D. A., Guha, I. N., Fallowfield, J. A., & Kendall, T. J. (2021) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.227 · Cited by 24 · see citing works
Self-citationPericàs, J. M., Tacke, F., Anstee, Q. M., Prospero, N. A. D., Kjær, M. S., Mesenbrink, P. G., König, F., Genescà, J., & Ratziu, V. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.09.021 · Cited by 23 · see citing works
Advancements in MAFLD Modeling with Human Cell and Organoid Models
Wang, S.-X., Yan, J.-S., & Chan, Y.-S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911850 · Cited by 22 · see citing works
Sherry, A. P., Willis, S. A., Yates, T. E., Johnson, W., Razieh, C., Sargeant, J. A., Malaikah, S., Stensel, D. J., Aithal, G. P., & King, J. A. (2022) · JHEP Reports · doi:10.1016/j.jhepr.2022.100622 · Cited by 22 · see citing works
The Effect of the Intra-gastric Balloon on Gastric Emptying and the DeMeester Score
Barrichello, S. A., Badurdeen, D., Hedjoudje, A., et al. (2019) · Obesity Surgery · doi:10.1007/s11695-019-04039-4 · Cited by 22 · see citing works
Bhattacharya, D., Becker, C., Readhead, B. P., Goossens, N., Buros, J. L., Fiel, M. I., Cousens, L. P., Magnusson, B., Backmark, A., Hicks, R., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99008-2 · Cited by 20 · see citing works
Heimbach, J. K. (2014) · Liver Transplantation · doi:10.1002/lt.23980 · Cited by 17 · see citing works
Assmus, F., Driouich, J., Abdelnabi, R., Vangeel, L., Touret, F., Adehin, A., Chotsiri, P., Cochin, M., Foo, C. S.-Y., Jochmans, D., et al. (2022) · Microorganisms · doi:10.3390/microorganisms10081639 · Cited by 10 · see citing works
Regression of human cirrhosis.
Chedid, A. (2000) · PubMed · doi:10.5858/2000-124-1591-rohc · Cited by 9 · see citing works
Oldham, S. N., Rivera, C., Boland, M. L., et al. (2019) · Journal of Visualized Experiments · doi:10.3791/59130 · Cited by 5 · see citing works
Herring, W. L., Gould, I. G., Wittrup-Jensen, V., Ertle, J., Kuti, E. L., & Wolowacz, S. E. (2022) · Journal of Comparative Effectiveness Research · doi:10.2217/cer-2021-0194 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [20]Ostovaneh MR Association of liver fibrosis with cardiovascular diseases in the general population: the Multi-Ethnic Study of Atherosclerosis (MESA) Circ. Cardiovasc. Imaging 2018 11 e007241 10.1161/CIRCIMAGING.117.007241 29523555 PMC5846116 · DOI
- [79]Ratziu V Friedman SL Why do so many NASH trials fail? Gastroenterology 2020 10.1053/J.GASTRO.2020.05.046 32439497 · DOI · Paper page
Cited by
Sorted by citations
Akkız, H., Gieseler, R. K., & Canbay, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147873 · Cited by 191 · see citing works
Yanagisawa, H., Maeda, H., Noguchi, I., Tanaka, M., Wada, N., Nagasaki, T., Kobayashi, K., Kanazawa, G., Taguchi, K., Chuang, V. T. G., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103314 · Cited by 10 · see citing works
- Authors
- Brennan, P. N., Elsharkawy, A. M., Kendall, T. J., Loomba, R., Mann, D. A., & Fallowfield, J. A.
- Affiliations
- University of Dundee (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- University of Edinburgh (GB)
- University of California San Diego (US)
- Koç University (TR)
- Corresponding author
- Mann, Derek A.
- Fallowfield, Jonathan A.
- ORCID
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2023-06-02
- Volume
- 20
- Issue
- 10
- Pages
- 679-688
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC10236408
- OpenAlex
- W4379142260
- Cited by
- 68
- References
- 117
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 26 · 2023: 10
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Cancer Research UK (DRCRPG‐Nov22/100007, 23390)
- National Institutes of Health (UL1TR001442)
- Medical Research Council (MR/R023026/1)
- National Heart, Lung, and Blood Institute (P01HL147835)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124318, R01DK121378, R01DK106419, P30DK120515, U01DK061734, U01DK130190)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- nonalcoholic steatohepatitis, antifibrotic therapy, liver fibrosis, fibrosis regression, drug development, precision medicine, genetic modifiers, multi-omics profiling, electronic health records, combination therapy, end-stage liver disease, liver cirrhosis
- MeSH terms
- Humans, Liver, Liver Cirrhosis, Liver Transplantation, End Stage Liver Disease, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
