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Liu JF, Bai YT, Leng YE, Chang E, Wei YX, Wei W. Post-marketing safety concerns with luspatercept: a disproportionality analysis of the FDA adverse event reporting system. Expert Opin Drug Saf 2025:1-8. [PMID: 39912511 DOI: 10.1080/14740338.2025.2464071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 12/04/2024] [Accepted: 12/17/2024] [Indexed: 02/07/2025]
Abstract
BACKGROUND Luspatercept, approved for treating beta thalassemia, myelodysplastic syndromes (MDS) associated anemia, and MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis associated anemia, has uncertain long-term safety in large populations. This study analyzed adverse events (AEs) linked to luspatercept using data from the FDA Adverse Event Reporting System (FAERS) with data mining techniques. RESEARCH DESIGN AND METHODS We collected and analyzed luspatercept-related reports from the FAERS database from the first quarter of 2022 through the first quarter of 2024. Disproportionality analysis was used in data mining to quantify luspatercept-related AE signals. RESULTS A total of 46 AE signals were detected in 13 SOCs (system organ classes). In addition to the AEs identified during the clinical trial stage, this study also identified some unexpected and important AEs, such as product preparation error, prescribed overdose, product preparation issue, prescribed underdose, and acute hepatitis. CONCLUSIONS Our study provides a comprehensive description of the post-marketing safety of luspatercept and identifies new potential AEs. Healthcare workers must be vigilant in avoiding product preparation errors, an adverse event that highlights the need for enhanced training and the participation of pharmacists in assessing medication utilization scenarios.
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Affiliation(s)
- Jin-Feng Liu
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
| | - Ying-Tao Bai
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
| | - Yan-En Leng
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
| | - En Chang
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
| | - Yu-Xun Wei
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
| | - Wei Wei
- Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, Sichuan, China
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Ahmed T, Ahmad J. Recent advances in the diagnosis of drug-induced liver injury. World J Hepatol 2024; 16:186-192. [PMID: 38495272 PMCID: PMC10941738 DOI: 10.4254/wjh.v16.i2.186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/03/2024] [Accepted: 02/03/2024] [Indexed: 02/27/2024] Open
Abstract
Drug-induced liver injury (DILI) is a major problem in the United States, commonly leading to hospital admission. Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes. In addition, DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease. Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems. This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.
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Affiliation(s)
- Taqwa Ahmed
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Jawad Ahmad
- Department of Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
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Barritt AS, Barnhart H, Gu J, Dellinger A, Rudnick S, Bonkovsky HL. When Is Suspected Drug-Induced Liver Injury (DILI) Not DILI? An Analysis of Unlikely Cases From the Drug-Induced Liver Injury Network. Am J Gastroenterol 2023; 118:2301-2304. [PMID: 37311048 PMCID: PMC10898250 DOI: 10.14309/ajg.0000000000002370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 06/08/2023] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Diagnosis of drug-induced liver injury (DILI) is difficult. We reviewed cases in the DILI Network prospective study that were adjudicated to have liver injury due to other causes to discover pearls for improved diagnostic accuracy. METHODS Cases were adjudicated by expert opinion and scored from 1 (definite DILI) to 5 (unlikely DILI). Confirmed cases (1-3) were compared with unlikely cases (5). RESULTS One hundred thirty-four of the 1,916 cases (7%) were unlikely DILI. Alternative diagnoses were autoimmune hepatitis (20%), hepatitis C (20%), bile duct pathology (13%), and hepatitis E (8%). DISCUSSION Thorough evaluation, including follow-up, is essential to minimize incorrect diagnosis of idiosyncratic DILI.
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Affiliation(s)
- A Sidney Barritt
- UNC Liver Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | | | - Jiezhun Gu
- Duke University, Durham, North Carolina, USA
| | | | - Sean Rudnick
- Wake Forest University School of Medicine & Atrium Wake Forest Baptist Health, Winston-Salem, North Carolina, USA
| | - Herbert L Bonkovsky
- Wake Forest University School of Medicine & Atrium Wake Forest Baptist Health, Winston-Salem, North Carolina, USA
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de Oliveira GC, Kumar A, Szempruch KR, Barritt AS, Zendel A, Desai CS. Hydralazine-Induced Fulminant Liver Failure Requiring Urgent Liver Transplant: Common Drug With Rare Complication. EXP CLIN TRANSPLANT 2023; 21:55-58. [PMID: 35297336 DOI: 10.6002/ect.2021.0446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.
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Affiliation(s)
- Guilherme C de Oliveira
- From the Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA
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RECAM: A New and Improved, Computerized Causality Assessment Tool for DILI Diagnosis. Am J Gastroenterol 2022; 117:1387-1389. [PMID: 35973138 DOI: 10.14309/ajg.0000000000001836] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/06/2022] [Indexed: 12/11/2022]
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Wang JB, Zhu Y, Bai ZF, Wang FS, Li XH, Xiao XH. Guidelines for the Diagnosis and Management of Herb-Induced Liver Injury. Chin J Integr Med 2018. [PMID: 29542018 DOI: 10.1007/s11655-018-3000-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Herb-induced liver injury (HILI) is a type of adverse drug reactions related to using Chinese medicine (CM) or herbal medicine (HM), and is now a growing segment of drug-induced liver injury (DILI) worldwide. Owing to the complicated compositions and miscellaneous risk factors associated with the clinical usage of CM or HM, it is more challenging to diagnose and manage HILI than DILI. In the present guideline issued by the China Association of Chinese Medicine (CACM), the authors present an evidence chain-based workflow with 9 structured judgment criteria for diagnosing HILI. The 3 diagnostic ending points-suspected diagnosis, clinical diagnosis, and confirmed diagnosis-could be reached according to the length of the evidence chain acquired in the structured diagnostic workflow. Either identifying the species of CM or HM or excluding adulterations and toxin contaminants was strongly recommended to improve the level of evidence for a clinical diagnosis of HILI. In addition, the authors report that the improper use of CM, which violates the general law of CM theory, is one of the most important factors that contributes to HILI and should be avoided. By contrast, based on syndrome differentiation, some CM can also be used to treat HILI if used in accordance with the general law of CM theory. Therefore, 9 recommendations are put forward in this guideline.
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Affiliation(s)
- Jia-Bo Wang
- Integrative Medical Center, 302 Military Hospital of China, Beijing, 100039, China
| | - Yun Zhu
- Integrative Medical Center, 302 Military Hospital of China, Beijing, 100039, China
| | - Zhao-Fang Bai
- Integrative Medical Center, 302 Military Hospital of China, Beijing, 100039, China
| | - Fu-Sheng Wang
- Research Center for Biological Therapy, 302 Military Hospital of China, Beijing, 100039, China
| | - Xiu-Hui Li
- Integrative Medical Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
| | - Xiao-He Xiao
- Integrative Medical Center, 302 Military Hospital of China, Beijing, 100039, China.
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Research Advances on Hepatotoxicity of Herbal Medicines in China. BIOMED RESEARCH INTERNATIONAL 2016; 2016:7150391. [PMID: 28078299 PMCID: PMC5203888 DOI: 10.1155/2016/7150391] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 07/31/2016] [Indexed: 02/07/2023]
Abstract
In general, herbal medicines have been considered as safe by the general public, since they are naturally occurring and have been applied in treatment for over thousands of years. As the use of herbal medicine is rapidly increasing globally, the potential toxicity of herbal drugs, in particular drug-induced liver injury (DILI), has now become a serious medical issue. According to the literature, the authors analyzed and discussed the hepatotoxicity problem of Chinese herbal medicines (CHM), including global overview on herbal-induced liver injury (HILI), current research progress on toxic CHM, diagnosis and treatment of HILI, and modern approaches and technologies of study of hepatotoxicity. As to promote the recognition of HILI and tackle the issue, a guideline for the diagnosis and treatment of HILI has recently been drafted by Chinese scientists. As suggested by the guideline, the hepatotoxicity issue of CHM, as a matter of fact, is overestimated. Up to date, the investigation of hepatotoxicity of CHM is now booming with worldwide application of CHM. This review therefore provides useful information for investigating hepatotoxicity of herbal medicine and characterizing DILI caused by CHM. In addition, authors describe in which way further efforts should be made to study the rationale of CHM and liver injury.
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Hasin Y, Shteingart S, Dahari H, Gafanovich I, Floru S, Braun M, Shlomai A, Verstandig A, Dery I, Uprichard SL, Cotler SJ, Lurie Y. Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report. World J Hepatol 2016; 8:858-862. [PMID: 27458506 PMCID: PMC4945506 DOI: 10.4254/wjh.v8.i20.858] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Revised: 04/28/2016] [Accepted: 06/29/2016] [Indexed: 02/06/2023] Open
Abstract
The United States Food and Drug Administration recently warned that the direct acting antiviral (DAA) combination hepatitis C virus (HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin (PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis (compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment with PODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.
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Tziatzios G, Gkolfakis P, Papanikolaou IS, Dimitriadis G, Triantafyllou K. An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice. Hepatobiliary Pancreat Dis Int 2016; 15:220-222. [PMID: 27020640 DOI: 10.1016/s1499-3872(15)60402-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.
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Affiliation(s)
- Georgios Tziatzios
- Hepatogastroenterology Unit, 2nd Department of Internal Medicine and Research Institute, "Attikon" University General Hospital, Medical School, University of Athens, Athens, Greece.
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Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum. Front Med 2015; 9:457-67. [PMID: 26459430 DOI: 10.1007/s11684-015-0417-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 07/07/2015] [Indexed: 12/12/2022]
Abstract
Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.
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Nayudu SK, Badipatla S, Niazi M, Balar B. Cholestatic hepatitis with small duct injury associated with celecoxib. Case Rep Med 2013; 2013:315479. [PMID: 23861685 PMCID: PMC3687603 DOI: 10.1155/2013/315479] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 05/21/2013] [Indexed: 12/13/2022] Open
Abstract
Drug-induced liver injury (DILI) is a common clinical entity but is underreported due to various reasons. Cyclooxygenase-2 inhibitors like Celecoxib have been proven to be associated with lesser incidence of adverse drug reactions compared to other nonsteroidal anti-inflammatory drugs (NSAID). However, Celecoxib has been rarely reported to be associated with cholestasis and hepatitis. We present a young Hispanic female presented with cholestatic liver chemistries who has been taking Celecoxib for 3 weeks. Extensive workup did not support diagnosis of viral, autoimmune, or metabolic liver diseases. Liver biopsy revealed findings suggestive of secondary sclerosing cholangitis. Imaging studies were negative for large duct involvement, and endoscopy ruled out inflammatory bowel disease. Liver chemistries normalized after cessation of medication. We recommend that physician should be aware of this rare complication when prescribing Celecoxib.
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Affiliation(s)
- Suresh Kumar Nayudu
- Division of Gastroenterology and Hepatology, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
- Department of Medicine, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
| | - Shanti Badipatla
- Department of Medicine, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
| | - Masooma Niazi
- Department of Pathology, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
| | - Bhavna Balar
- Division of Gastroenterology and Hepatology, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
- Department of Medicine, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, USA
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Drug-Induced Liver Injury Throughout the Drug Development Life Cycle: Where We Have Been, Where We are Now, and Where We are Headed. Perspectives of a Clinical Hepatologist. Pharmaceut Med 2013. [DOI: 10.1007/s40290-013-0015-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Stine JG, Lewis JH. Drug-induced liver injury: a summary of recent advances. Expert Opin Drug Metab Toxicol 2011; 7:875-90. [PMID: 21510822 DOI: 10.1517/17425255.2011.577415] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The knowledge base of drug-induced liver injury (DILI) continues to grow each year as additional drugs are identified as hepatotoxins. There is still a need to improve our ability to predict and diagnose DILI in the preclinical and post-approval settings. AREAS COVERED This article presents the new and updated DILI registries for 2010, including the latest information on the causes and outcomes of non-acetaminophen DILI cases in the US Acute Liver Failure Study Group database. As DILI is still largely a diagnosis of exclusion, it is appropriate that causality assessment instruments are again the subject of considerable discussion. EXPERT OPINION DILI research remains extremely active including studies aimed at being better able to identify causative agents, utilize potential biomarkers, predict who is at greatest risk of injury and manage outcomes. With respect to identifying DILI risk factors at the genetic level, the field is rapidly approaching the day where 'personalized medicine' (based on pharmacogenomics) will become a reality. A large single-center series from India reminds us that geography can influence the drugs responsible for liver injury; however, Hy's law remains universal. As our DILI knowledge continues to grow, it remains essential to keep abreast of the important changes reported each year.
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Affiliation(s)
- Jonathan G Stine
- Department of Medicine, Georgetown University Hospital, Washington DC 20007, USA
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