The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Hepatic Failure and Lactic Acidosis Due to Fialuridine (FIAU), an Investigational Nucleoside Analogue for Chronic Hepatitis B
Open accessAbstract
BACKGROUND: We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. METHODS: Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. RESULTS: During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. CONCLUSIONS: In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Fialuridine (Section 7.1) and troglitazone (Section 7.4) are intrinsic toxicodynamic failures, driven by human-relevant mitochondrial injury and reactive-metabolite formation, respectively.”
From Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions (2026) · cites this paper as [69]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Fialuridine, an antiviral nucleoside analogue, caused catastrophic hepatic failure and lactic acidosis in a 1993 clinical trial, resulting in five deaths and two liver transplantations.”
From Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions (2026) · cites this paper as [69]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Preclinical studies across multiple species showed no indication of the severe mitochondrial toxicity observed in humans, because fialuridine’s incorporation into mitochondrial DNA is mediated by a human-specific mitochondrial transporter [69,70].”
From Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions (2026) · cites this paper as [69]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Fourth, idiosyncratic toxicities, such as those underlying the fialuridine and troglitazone failures, are by definition not captured by any pharmacokinetic scaling framework, and even sophisticated PBPK or PBPK–PD models cannot reliably anticipate them without orthogonal mechanistic assays [69,70,75,76].”
From Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions (2026) · cites this paper as [69]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“even sophisticated PBPK or PBPK–PD models cannot reliably anticipate them without orthogonal mechanistic assays [69,70,75,76]”
From Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions (2026) · cites this paper as [69]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Even a pilot study on 43 patients treated for 2 and 4 weeks duration with Fialuridine did not reveal any signs of hepatic toxicity on initial examination.[17]”
From TGN1412: From Discovery to Disaster (2010) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“During 13th week of phase II studies, one of the patients suddenly developed hepatic toxicity and lactic acidosis. At this point, trial was stopped for all other patients.”
From TGN1412: From Discovery to Disaster (2010) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Even after discontinuation of Fialuridine administration, seven other patients showed signs of severe hepatic toxicity five of which could not survive and other two could survive only after liver transplantation.[17]”
From TGN1412: From Discovery to Disaster (2010) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wong, D., Cheung, A. M., O'Rourke, K., Naylor, C. D., Detsky, A. S., & Heathcote, J. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-119-4-199308150-00011 · Cited by 974
Perrillo, R. P., Schiff, E. R., Davis, G. L., Bodenheimer, H. C., Lindsay, K. L., Payne, J., Dienstag, J. L., O'Brien, C., Tamburro, C. H., Jacobson, I. M., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199008023230503 · Cited by 838
Mitochondrial Myopathy Caused by Long-Term Zidovudine Therapy
Dalakas, M. C., Illa, I., Pezeshkpour, G. H., Laukaitis, J. P., Cohen, B. H., & Griffin, J. L. (1990) · New England Journal of Medicine · doi:10.1056/nejm199004193221602 · Cited by 837
Doong, S.-L., Tsai, C. H., Schinazi, R. F., Liotta, D. C., & Cheng, Y. C. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.19.8495 · Cited by 513
Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy
Arnaudo, E., Shanske, S., DiMauro, S., Schon, E. A., Moraes, C. T., Schon, E. A., & Dalakas, M. C. (1991) · The Lancet · doi:10.1016/0140-6736(91)91294-5 · Cited by 504
Randomized, controlled trial of recombinant human α-interferon in patients with chronic hepatitis B
Hoofnagle, J. H., Peters, M. G., Mullen, K. D., Jones, D. B., Rustgi, V. K., Bisceglie, A. M. D., Hallahan, C. W., Park, Y., Meschievitz, C., & Jones, E. A. (1988) · Gastroenterology · doi:10.1016/0016-5085(88)90367-8 · Cited by 420
Self-citationReversal of Fulminant Hepatic Failure Using An Extracorporeal Liver Assist Device
Sussman, N., Chong, M. G., Koussayer, T., He, D.-E., Shang, T. A., Whisennand, H. H., & Kelly, J. H. (1992) · Hepatology · doi:10.1002/hep.1840160112 · Cited by 341
Chen, C., Vazquez-Padua, M. A., & Cheng, Y. C. (1991) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)11067-5 · Cited by 296
A controlled trial of interferon with or without prednisone priming for chronic hepatitis B
Lok, A. S.-F., Wu, P., Lai, C., Lau, J. Y. N., Leung, E. K. Y., Wong, L. S. K., Ma, O. C. K., Lauder, I. J., Ng, C. P. L., & Chung, H.-T. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)90337-x · Cited by 239
Hodge, R. A. V., Sutton, D., Boyd, M. R., Harnden, M. R., & Jarvest, R. L. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.10.1765 · Cited by 207
Research works printed but not linked: 7
- Dusheiko G, Hoofnagle JH. Hepatitis B. In: McIntyre N, Benhamou JP, Bircher J, Rizzetto M, Rodes J, eds. Oxford textbook of clinical hepatology. New York: Oxford University Press, 1991:571-92.
- Paar DP, Hooten TM, Smiles KA, et al. The effect of FIAU on chronic hepatitis B virus (HBV) infection in HIV-infected subjects (ACTG 122b). In: Program and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif., October 10–14, 1992. Washington, D.C.: American Society for Microbiology, 1992:264. abstract.
- 10.1002/hep.1840160402 · DOI
- Stevenson W, 1995, Transplant Proc, 27, 1219
- Chen CH, 1991, Mol Pharmacol, 39, 625
- Klecker RW, 1994, Mol Pharmacol, 46, 1204
- Maxson CJ, 1992, Am J Gastroenterol, 87, 708
Cited by
Sorted by citations
Items 101–200 of 614
Lee, E., Lai, Y., Zhang, H., & Unadkat, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513825200 · Cited by 108
Toxicity of Antiretroviral Nucleoside and Nucleotide Analogues
Moyle, G. J. (2000) · Drug Safety · doi:10.2165/00002018-200023060-00001 · Cited by 104
Ramesh, D., Vijayakumar, B. G., & Kannan, T. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112801 · Cited by 103
Antiviral activity and toxicity of fialuridine in the woodchuck model of hepatitis B virus infection
Tennant, B. C., Baldwin, B. H., Graham, L. A., Ascenzi, M., Hornbuckle, W. E., Rowland, P. H., Tochkov, I. A., Yeager, A. E., Erb, H. N., Colacino, J. M., et al. (1998) · Hepatology · doi:10.1002/hep.510280124 · Cited by 103
MitochondriaPreprint
Chandel, N. S. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040543 · Cited by 109
Imaging of Musculoskeletal Bacterial Infections by [124I]FIAU-PET/CT
Diaz, L. A., Foss, C. A., Thornton, K. A., Nimmagadda, S., Endres, C. J., Uzuner, Ö., Seyler, T. M., Ulrich, S. D., Conway, J. D., Bettegowda, C., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001007 · Cited by 100
Mitochondrial dysfunction and antiretroviral nucleoside analog toxicities: what is the evidence?
Dagan, T., Sable, C., Bray, J., & Gerschenson, M. (2002) · Mitochondrion · doi:10.1016/s1567-7249(02)00003-x · Cited by 100
Mutimer, D., Naoumov, N., Honkoop, P., Marinos, G., Ahmed, M., de Man, R., McPhillips, P., Johnson, M., Williams, R. L., Elias, E., et al. (1998) · Journal of Hepatology · doi:10.1016/s0168-8278(98)80338-3 · Cited by 99
Seok, J. I., Lee, D. K., Lee, C. H., Park, M. S., Kim, S., Kim, H., Jo, H., Lee, C. H., & Kim, D. (2009) · Hepatology · doi:10.1002/hep.22959 · Cited by 98
Zoulim, F., & TREPO, C. G. (1998) · Journal of Hepatology · doi:10.1016/s0168-8278(98)80191-8 · Cited by 98
Humanized Mice as Unique Tools for Human-Specific Studies
Yong, K. S. M., Her, Z., & Chen, Q. (2018) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-018-0506-x · Cited by 103
Liu, Z., Shi, Q., Ding, D., Kelly, R. J., Fang, H., & Tong, W. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002310 · Cited by 96
Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA
Koczor, C. A., & Lewis, W. (2010) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2010.526602 · Cited by 97
Aging and HIV/AIDS: pathogenetic role of therapeutic side effects
Torres, R. A., & Lewis, W. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.142 · Cited by 99
Walker, P., Ryder, S., Lavado, A., Dilworth, C., & Riley, R. J. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02763-w · Cited by 95
Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors
Fu, D.-X., Tanhehco, Y. C., Chen, J., Foss, C. A., Fox, J. J., Chong, J. M., Hobbs, R. F., Fukayama, M., Sgouros, G., Kowalski, J., et al. (2008) · Nature Medicine · doi:10.1038/nm.1864 · Cited by 92
Hepatitis B virus: old, new and future approaches to antiviral treatment
Karayiannis, P. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg163 · Cited by 92
Famciclovir treatment of hepatitis B virus recurrence after liver transplantation: A pilot study
Krüger, M., Tillmann, H. L., Trautwein, C., Bode, U., Oldhafer, K. J., Maschek, H., Böker, K. H. W., Broelsch, C. E., Pichlmayr, R., & Manns, M. P. (1996) · Liver Transplantation and Surgery · doi:10.1002/lt.500020402 · Cited by 92
Emtricitabine, a New Antiretroviral Agent with Activity against HIV and Hepatitis B Virus
Saravolatz, L. D., & Saag, M. S. (2005) · Clinical Infectious Diseases · doi:10.1086/498348 · Cited by 91
EFFICACY OF LAMIVUDINE IN CONTROLLING HEPATITIS B VIRUS RECURRENCE AFTER LIVER TRANSPLANTATION
Nery, J., Weppler, D., Rodriguez, M. J., Ruiz, P., Schiff, E. R., & Tzakis, A. G. (1998) · Transplantation · doi:10.1097/00007890-199806270-00013 · Cited by 91
The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity
Lauschke, V. M., & Ingelman‐Sundberg, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101714 · Cited by 92
Hyperlactataemia syndromes associated with HIV therapy
Ogedegbe, A., Thomas, D. L., & Diehl, A. M. (2003) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(03)00654-6 · Cited by 90
Brown, J. J., Parashar, B., Moshage, H. J., Tanaka, K. E., Engelhardt, D., Rabbani, E., Roy‐Chowdhury, N., & Roy‐Chowdhury, J. (2000) · Hepatology · doi:10.1002/hep.510310126 · Cited by 89
The Acinar Cell and Early Pancreatitis Responses
Gorelick, F. S., & Thrower, E. C. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.07.036 · Cited by 88
Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents
Cavaliere, A., Probst, K. C., Westwell, A. D., & Ślusarczyk, M. (2017) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0095 · Cited by 88
Hilleman, M. R. (2003) · Vaccine · doi:10.1016/s0264-410x(03)00529-2 · Cited by 88
Cell death in drug-induced liver injury
Iorga, A., & Dara, L. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2019.01.006 · Cited by 89
Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance
Young, M. J. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00074 · Cited by 87
Xu, D., Nishimura, T., Nishimura, S., Zhang, H., Zheng, M., Guo, Y., Masek, M., Michie, S. A., Glenn, J. S., & Peltz, G. (2014) · PLoS Medicine · doi:10.1371/journal.pmed.1001628 · Cited by 87
Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment
Fung, J., Seto, W., Lai, C., & Yuen, M. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12499 · Cited by 86
Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus
Feng, J. Y., Xu, Y., Barauskas, O., Perry, J. K., Ahmadyar, S., Stepan, G. J., Yu, H., Babusis, D. M., Park, Y., McCutcheon, K. M., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01922-15 · Cited by 85
Self-citationProgress in the Discovery of Compounds Inhibiting Orthopoxviruses in Animal Models
Smee, D. F. (2008) · Antiviral Chemistry and Chemotherapy · doi:10.1177/095632020801900302 · Cited by 84
Review article: long‐term safety of oral anti‐viral treatment for chronic hepatitis B
Wong, G. L., Seto, W., Wong, V. W., Yuen, M., & Chan, H. L. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14497 · Cited by 84
Humanized mice: A brief overview on their diverse applications in biomedical research
Fujiwara, S. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26022 · Cited by 86
Cytometric analysis for drug-induced steatosis in HepG2 cells
Donato, M. T., Martínez‐Romero, A., Jiménez, N., Negro, A., Herrera, G., Castell, J. V., O’Connor, J., & Gómez‐Lechón, M. J. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.07.019 · Cited by 85
Safety evaluation of 2′-deoxy-2′-fluoro nucleotides in GalNAc-siRNA conjugates
Janas, M. M., Zlatev, I., Liu, J., Jiang, Y., Barros, S. A., Sutherland, J. E., Davis, W. P., Liu, J., Brown, C. R., Liu, X., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz140 · Cited by 83
Bengel, F. M., Anton, M., Richter, T., Simões, M. V., Haubner, R., Henke, J., Erhardt, W. D., Reder, S., Lehner, T., Brandau, W., et al. (2003) · Circulation · doi:10.1161/01.cir.0000091401.26280.a0 · Cited by 82
Corrigan, O. (2002) · Social Science & Medicine · doi:10.1016/s0277-9536(01)00183-6 · Cited by 81
Mitochondrial toxicity–new adverse drug effects
Swartz, M. N. (1995) · New England Journal of Medicine · doi:10.1056/nejm199510263331710 · Cited by 80
Mitochondrial Injury Lessons from the Fialuridine Trial
Honkoop, P., Scholte, H. R., de Man, R. A., & Schalm, S. W. (1997) · Drug Safety · doi:10.2165/00002018-199717010-00001 · Cited by 80
Animal models of idiosyncratic drug-induced liver injury—Current status
Roth, R. A., & Ganey, P. E. (2011) · Critical Reviews in Toxicology · doi:10.3109/10408444.2011.575765 · Cited by 79
Tang, W., & Lu, A. Y. H. (2009) · Drug Metabolism Reviews · doi:10.3109/03602530903401658 · Cited by 78
Predicting human safety: screening and computational approaches
Johnson, D. E., & Wolfgang, G. H. I. (2000) · Drug Discovery Today · doi:10.1016/s1359-6446(00)01559-2 · Cited by 77
Quantitative kinetics of [124I]FIAU in cat and man.
Jacobs, A., Bräunlich, I., Graf, R., Lercher, M., Sakaki, T., Voges, J., Heßelmann, V., Brandau, W., Wienhard, K., & Heiss, W. (2001) · PubMed · Cited by 77
Myopathy and neuropathy associated with nucleos(t)ide analog therapy for hepatitis B
Fleischer, R. D., & Lok, A. S.-F. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.06.011 · Cited by 74
Lewis, W., Haase, C. P., Raidel, S. M., Russ, R. B., Sutliff, R. L., Hoit, B. D., & Samarel, A. M. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780366 · Cited by 74
Neuschwander‐Tetri, B. A., & Bacon, B. R. (1996) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70483-1 · Cited by 74
The rational use of potentially hepatotoxic medications in patients with underlying liver disease
Lewis, J. H. (2002) · Expert Opinion on Drug Safety · doi:10.1517/14740338.1.2.159 · Cited by 73
Kim, J., Lee, H., Woo, G. H., Yoon, J., Jang, J., Je, G., & Kim, C. Y. (2001) · Clinical Infectious Diseases · doi:10.1086/321879 · Cited by 73
Treatment of chronic hepatitis B: Case selection and duration of therapy
Leung, N. W. Y. (2002) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2002.02767.x · Cited by 72
Govindarajan, R., Endres, C. J., Whittington, D., LeCluyse, E. L., Pastor‐Anglada, M., Tse, C., & Unadkat, J. D. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00542.2007 · Cited by 71
Infectious Diseases Society of America (2009) · Clinical Infectious Diseases · doi:10.1086/605454 · Cited by 71
Stravitz, R. T., & Sanyal, A. J. (2003) · Clinics in Liver Disease · doi:10.1016/s1089-3261(03)00027-8 · Cited by 71
Mitochondrial respiratory chain disorders and the liver
Morris, A. A. M. (1999) · Liver International · doi:10.1111/j.1478-3231.1999.tb00063.x · Cited by 72
Lewis, W. (2003) · Antiviral Research · doi:10.1016/s0166-3542(03)00069-x · Cited by 70
2′F-Arabinonucleic acids (2′F-ANA) — History, properties, and new frontiers
Watts, J. K., & Damha, M. J. (2008) · Canadian Journal of Chemistry · doi:10.1139/v08-049 · Cited by 69
Acosta, E. P., & Fletcher, C. V. (1997) · Annals of Pharmacotherapy · doi:10.1177/106002809703100211 · Cited by 69
LOCARNINI, S. A., & Birch, C. J. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80118-4 · Cited by 69
Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase
Szymański, M. R., Kuznetsov, V. B., Shumate, C. K., Meng, Q., Lee, Y., Patel, G., Patel, S. S., & Yin, Y. W. (2015) · The EMBO Journal · doi:10.15252/embj.201591520 · Cited by 69
Montaner, J. S. G., Côté, H. C. F., Harris, M., Hogg, R. S., Yip, B., Chan, J. W. H., Harrigan, P. R., & O’Shaughnessy, M. V. (2003) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200309011-00013 · Cited by 66
Characterization of Hepatic Mitochondrial Injury Induced by Fatty Acid Oxidation Inhibitors
Vickers, A. E. M. (2009) · Toxicologic Pathology · doi:10.1177/0192623308329285 · Cited by 65
Addressing the selectivity and toxicity of antiviral nucleosides
Feng, J. Y. (2018) · Antiviral chemistry & chemotherapy · doi:10.1177/2040206618758524 · Cited by 64
Tutty, M. A., Movia, D., & Prina‐Mello, A. (2022) · Drug Delivery and Translational Research · doi:10.1007/s13346-022-01147-0 · Cited by 67
Welker, M., Luhne, S., Lange, C. M., Vermehren, J., Farnik, H., Herrmann, E. M., Welzel, T. M., Zeuzem, S., & Sarrazin, C. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.034 · Cited by 63
Simpson, D. M. (2002) · Journal of NeuroVirology · doi:10.1080/13550280290167939 · Cited by 63
Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury
Lin, C., & Khetani, S. R. (2016) · BioMed Research International · doi:10.1155/2016/1829148 · Cited by 66
Cancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 65
Vanwolleghem, T., Meuleman, P., Libbrecht, L. J., Roskams, T., Vos, R. D., & Leroux-Roels, G. G. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.07.007 · Cited by 62
Drug-induced cholestasis risk assessment in sandwich-cultured human hepatocytes
Oorts, M., Baze, A., Bachellier, P., Heyd, B., Zacharias, T., Annaert, P., & Richert, L. (2016) · Toxicology in Vitro · doi:10.1016/j.tiv.2016.03.008 · Cited by 63
HIV-associated neuromuscular weakness syndrome
Simpson, D. M., Estanislao, L., Evans, S. R., McArthur, J. C., Marcus, K. A., Truffa, M. M., Lucey, B. P., Naismith, R. T., Lonergan, J. T., & Clifford, D. B. (2004) · AIDS · doi:10.1097/01.aids.0000131309.70451.fe · Cited by 61
The histopathological evaluation of drug‐induced liver injury
Kleiner, D. E. (2016) · Histopathology · doi:10.1111/his.13082 · Cited by 62
Self-citationP450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity
Bissig, K., Han, W., Barzi, M., Kovalchuk, N., Ding, L., Fan, X., Pankowicz, F. P., Zhang, Q.-Y., & Ding, X. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.083303 · Cited by 60
Atienzar, F., Blomme, E. A. G., Chen, M., Hewitt, P. G., Kenna, J. G., Labbe, G., Moulin, F., Pognan, F., Roth, A. B., Suter‐Dick, L., et al. (2016) · BioMed Research International · doi:10.1155/2016/9737920 · Cited by 60
Alteration of mitochondrial DNA homeostasis in drug-induced liver injury
Fromenty, B. (2019) · Food and Chemical Toxicology · doi:10.1016/j.fct.2019.110916 · Cited by 59
Entecavir: a potent new antiviral drug for hepatitis B
Honkoop, P., & de Man, R. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.4.683 · Cited by 59
Mechanisms for the anti-hepatitis B virus activity and mitochondrial toxicity of fialuridine (FIAU)
Colacino, J. M. (1996) · Antiviral Research · doi:10.1016/0166-3542(95)00836-5 · Cited by 59
Aguesse-Germon, S., Liu, S.-H., Chevallier, M., Pichoud, C., Jamard, C., Borel, C., Chu, C. K., TREPO, C. G., Cheng, Y., & Zoulim, F. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.2.369 · Cited by 58
Clevudine myopathy in patients with chronic hepatitis B
Kim, B. K., Oh, J., Kwon, S. Y., Choe, W. H., Ko, S. Y., Rhee, K. H., Seo, T. H., Lim, S. D., & Lee, C. H. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.04.019 · Cited by 57
Dragović, S., Vermeulen, N. P. E., Gerets, H. H. J., Hewitt, P. G., Ingelman‐Sundberg, M., Park, B. K., Juhila, S., Snoeys, J., & Weaver, R. J. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1845-1 · Cited by 57
Mitochondria and Childhood Liver Diseases
Sokol, R. J., & Treem, W. R. (1999) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1002/j.1536-4801.1999.tb01995.x · Cited by 57
Reverse transcription of the HIV‐1 pandemic
Basavapathruni, A., & Anderson, K. S. (2007) · The FASEB Journal · doi:10.1096/fj.07-8697rev · Cited by 61
Zhang, X. M., Zhang, H. H., McLeroth, P., Berkowitz, R. D., Mont, M. A., Stabin, M. G., Siegel, B. A., Alavi, A. A., Barnett, T. M., Gelb, J., et al. (2016) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2016.01.004 · Cited by 56
Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints
Kim, E., & Nam, H. (2017) · BMC Bioinformatics · doi:10.1186/s12859-017-1638-4 · Cited by 57
Mitochondria: important target for drug toxicity?
Krähenbühl, S. (2001) · Journal of Hepatology · doi:10.1016/s0168-8278(00)00106-9 · Cited by 56
Can ‘humanized’ mice improve drug development in the 21st century?
Peltz, G. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.03.005 · Cited by 55
Iasella, C. J., Johnson, H. J., & Dunn, M. A. (2016) · Clinics in Liver Disease · doi:10.1016/j.cld.2016.08.005 · Cited by 55
Mitochondrial Dysfunction: Patient Monitoring and Toxicity Management
McComsey, G. A., & Lonergan, J. T. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000137004.63376.27 · Cited by 55
Pessayre, D., & Larrey, D. G. (2007) · Wiley eBooks · doi:10.1002/9780470691861.ch14a · Cited by 54
Hiemstra, S. W., Ramaiahgari, S., Wink, S., Callegaro, G., Coonen, M. L. J., Meerman, J. H. N., Jennen, D. G. J., van den Nieuwendijk, K., Dankers, A. C. A., Snoeys, J., et al. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02552-0 · Cited by 55
Cheng, L., Zhang, Z., Li, G., Li, F., Wang, L., Zhang, L., Zurawski, S., Zurawski, G., Lévy, Y., & Su, L. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.09.052 · Cited by 54
John, A. P. (2001) · Medical Hypotheses · doi:10.1054/mehy.2001.1335 · Cited by 53
Involvement of the Immune System in Idiosyncratic Drug Reactions
Zhang, X., Liu, F., Chen, X., Zhu, X., & Uetrecht, J. (2010) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-10-rv-085 · Cited by 53
Mazzucco, C. E., Hamatake, R. K., Colonno, R. J., & Tenney, D. J. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01122-07 · Cited by 52
Combination Gemcitabine and Docetaxel Therapy in Advanced Adenocarcinoma of the Pancreas
Sherman, W. H., & Fine, R. L. (2001) · Oncology · doi:10.1159/000058527 · Cited by 52
Cullen, J. M., Smith, S., Davis, M. G., Dunn, S. E., Botteron, C., Cecchi, A., Linsey, D., Linzey, D. W., Frick, L., Paff, M. T., et al. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.10.2076 · Cited by 52
Bailey, J., & Balls, M. (2019) · BMC Medical Ethics · doi:10.1186/s12910-019-0352-3 · Cited by 51
Gasmi, B., & Kleiner, D. E. (2019) · Clinics in Liver Disease · doi:10.1016/j.cld.2019.09.004 · Cited by 53
Self-citationPridgeon, C. S., Schlott, C., Wong, M. W., Heringa, M. B., Heckel, T., Leedale, J., Launay, L., Gryshkova, V., Przyborski, S. A., Bearon, R. N., et al. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2152-9 · Cited by 52
Hepatocyte transplantation and drug-induced perturbations in liver cell compartments
Wu, Y., Joseph, B., Berishvili, E., Kumaran, V., & Gupta, S. K. (2007) · Hepatology · doi:10.1002/hep.21937 · Cited by 50
Mechanisms of idiosyncratic drug-induced liver injury
Uetrecht, J. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2018.12.001 · Cited by 49
Metadata
- Authors
- McKenzie, R., Fried, M. W., Sallie, R., Conjeevaram, H., Di Bisceglie, A. M., Park, Y., Savarese, B., Kleiner, D., Tsokos, M., Luciano, C., Pruett, T., Stotka, J. L., Straus, S. E., & Hoofnagle, J. H.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Institute of Allergy and Infectious Diseases (US)
- National Cancer Institute (UA)
- University of Virginia Hospital (US)
- Eli Lilly (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1995-10-26
- Volume
- 333
- Issue
- 17
- Pages
- 1099-1105
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2327070670
- Cited by
- 616
- References
- 39
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 17 · 2023: 13 · 2022: 11 · 2021: 19 · 2020: 13 · 2019: 26 · 2018: 32 · 2017: 23 · 2016: 27 · 2015: 16 · 2014: 12 · 2013: 16 · 2012: 10
- FWCI
- 28.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- NIH Clinical Center
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Keywords
- FIAU, lactic acidosis, liver failure, hepatotoxicity, chronic hepatitis B, nucleoside analogues, drug toxicity, mitochondrial damage, pancreatitis, neuropathy, myopathy, liver transplantation, drug-induced liver injury
- MeSH terms
- Acidosis, Lactic, Adult, Alanine Transaminase, Antiviral Agents, Arabinofuranosyluracil, Chronic Disease, DNA, Mitochondrial, DNA, Viral, Female, Hepatitis B, Humans, Jaundice, Liver, Male, Middle Aged, Pancreatitis, Peripheral Nervous System Diseases, Drugs, Investigational, Liver Transplantation, Liver Failure
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
