The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Einar Bjornsson - One of the best experts on this subject based on the ideXlab platform.
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drug induced Liver Injury types and phenotypes
The New England Journal of Medicine, 2019Co-Authors: Jay H Hoofnagle, Einar BjornssonAbstract:Drug-Induced Liver Injury The Liver has a range of responses to drug-induced Injury, with a number of phenotypes. In addition, idiosyncratic reactions may occur as a consequence of both direct drug...
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easl clinical practice guidelines drug induced Liver Injury
Journal of Hepatology, 2019Co-Authors: Raul J Andrade, Neil Kaplowitz, Einar Bjornsson, Guruprasad P Aithal, Gerd A Kullakublick, Dominique Larrey, Tom H KarlsenAbstract:Idiosyncratic (unpredictable) drug-induced Liver Injury is one of the most challenging Liver disorders faced by hepatologists, because of the myriad of drugs used in clinical practice, available herbs and dietary supplements with hepatotoxic potential, the ability of the condition to present with a variety of clinical and pathological phenotypes and the current absence of specific biomarkers. This makes the diagnosis of drug-induced Liver Injury an uncertain process, requiring a high degree of awareness of the condition and the careful exclusion of alternative aetiologies of Liver disease. Idiosyncratic hepatotoxicity can be severe, leading to a particularly serious variety of acute Liver failure for which no effective therapy has yet been developed. These Clinical Practice Guidelines summarize the available evidence on risk factors, diagnosis, management and risk minimization strategies for drug-induced Liver jury.
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Liver Injury from herbal and dietary supplements
Hepatology, 2017Co-Authors: Victor J Navarro, Ikhlas A Khan, Einar Bjornsson, Leonard B Seeff, Jose Serrano, Jay H HoofnagleAbstract:Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced Liver Injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced Liver Injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced Liver Injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting Liver Injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like Injury. Currently, however, the majority of cases of HDS-associated Liver Injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced Liver Injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373).
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hepatotoxicity associated with statins reports of idiosyncratic Liver Injury post marketing
Journal of Hepatology, 2012Co-Authors: Einar Bjornsson, Elin I Jacobsen, Evangelos KalaitzakisAbstract:Background & Aims: Limited data exist on drug-induced Liver Injury (DILI) associated with statins. Methods: Reports on adverse reactions suspected to be due to statins received by the Swedish Adverse Drug Reactions Advisory Committe 1988–2010 were analyzed. Only cases with >5 � upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2 � ULN were included. Results: The most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had at least possible relationship, median age 64 years (57–73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations of Liver tests and 26 due to unlikely relationship and/or lack of data. A statin-related DILI episode was reported in 1.2/100,000 users. Atorvastatin was implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and others. Two patients died of acute Liver failure, one underwent Liver transplantation and 25 (34%) had jaundice. Three patients were rechallenged with the same statin producing similar patterns of Liver Injury. The median duration of therapy was 90 days (30–120), 120 (39–248) for atorvastatin, and 75 (30–150) for simvastatin (NS). Cholestatic/mixed Injury was more common with atorvastatin, 17/30 (56%) than with simvastatin, 7/28 (24%) (p = 0.018). Conclusions: Idiosyncratic Liver Injury associated with statins is rare but can be severe. After recovery, a similar pattern of Liver Injury can be reproduced on re-exposure. Most patients experience Liver Injury 3–4 months after start of therapy. Atorvastatin is mostly associated with cholestatic Liver Injury whereas hepatocellular Injury is more common with simvastatin. 2011 European Association for the Study of the Liver. Published
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drug induced Liver Injury in a swedish university hospital out patient hepatology clinic
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: M B De Valle, Av V Klinteberg, N Alem, R Olsson, Einar BjornssonAbstract:Summary Background Limited data exist on the proportion of drug-induced Liver Injury among out-patients seen in a hepatology clinic. Aim To determine the proportion of drug-induced Liver Injury cases, and identify the most important agents and the nature of the Liver Injury. Methods A computerized diagnoses database in an out-patient hepatology clinic in a Swedish University hospital was analysed during the period 1995–2005. All suspected drug-induced Liver Injury cases were causality assessed with the International Consensus Criteria. Results A total of 1164 cases were seen for the first time during this period. Drug-induced Liver Injury with at least a possible causal relationship was found in 77 cases (6.6%), 38 (3.3%) of whom were referred for evaluation to the out-patient clinic whereas 3% had a follow-up after hospitalization of drug-induced Liver Injury. The median age was 58 years, 43 (56%) were females, a hepatocellular pattern was observed in 37 cases (48%), cholestatic in 31 (40%) and mixed in 12%. Antibiotics were the most common agents causing drug-induced Liver Injury followed by non-steroidal anti-inflammatory drugs, with diclofenac most often responsible for the drug-induced Liver Injury. Conclusions Drug-induced Liver Injury cases constituted 6% of all out-patients and 3% of referrals and occurred more often in women. Antibiotics and diclofenac were the most common causes of drug-induced Liver Injury among out-patients.
Jay H Hoofnagle - One of the best experts on this subject based on the ideXlab platform.
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drug induced Liver Injury types and phenotypes
The New England Journal of Medicine, 2019Co-Authors: Jay H Hoofnagle, Einar BjornssonAbstract:Drug-Induced Liver Injury The Liver has a range of responses to drug-induced Injury, with a number of phenotypes. In addition, idiosyncratic reactions may occur as a consequence of both direct drug...
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Liver Injury from herbal and dietary supplements
Hepatology, 2017Co-Authors: Victor J Navarro, Ikhlas A Khan, Einar Bjornsson, Leonard B Seeff, Jose Serrano, Jay H HoofnagleAbstract:Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced Liver Injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced Liver Injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced Liver Injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting Liver Injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like Injury. Currently, however, the majority of cases of HDS-associated Liver Injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced Liver Injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373).
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identification and characterization of cefazolin induced Liver Injury
Clinical Gastroenterology and Hepatology, 2015Co-Authors: Saleh A Alqahtani, Jay H Hoofnagle, David E Kleiner, Marwan Ghabril, Don C RockeyAbstract:Background & Aims Cephalosporin antibiotics are popular because they have a broad spectrum of activity and are generally well tolerated; however, cephalosporin-induced Liver Injury is considered rare. We describe a new syndrome associated with a single intravenous dose of cefazolin and the clinical features of cephalosporin-induced Liver Injury. Methods The Drug-Induced Liver Injury (DILI) Network collected detailed clinical data on 1212 patients with DILI between 2004 and 2012. We analyzed data from 41 patients in whom cephalosporins were implicated as primary agents of Liver disease; 33 formally were adjudicated as having cephalosporin-induced DILI. Results Nineteen patients developed clinically apparent DILI after a single intravenous dose of cefazolin. All patients developed self-limited Liver Injury 3 to 23 days after receiving cefazolin during surgery—often during a minor outpatient procedure. The latency period was 20 days. Clinical features included itching, jaundice, nausea, fever, and rash. Laboratory abnormalities included a mixed or cholestatic pattern of serum enzyme increases. We identified 14 more patients with DILI attributed to other cephalosporins (5 first-generation, 2 second-generation, 6 third-generation, and 1 fourth-generation agent). Although latency and Injury patterns were similar for cefazolin and other cephalosporins, the other cephalosporins were associated with more severe courses of Injury, including 2 deaths from Liver failure. Conclusions DILI can develop after a single dose of cefazolin. It is characterized by a latency period of 1 to 3 weeks after exposure, a cholestatic biochemical pattern, and a self-limited moderate to severe clinical course. Other cephalosporins can cause a similar but more severe Injury.
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clinical and histologic features of azithromycin induced Liver Injury
Clinical Gastroenterology and Hepatology, 2015Co-Authors: Melissa Martinez, Jay H Hoofnagle, Robert J Fontana, David E Kleiner, Raj Vuppalanchi, Andrew Stolz, Paul H Hayashi, Naga ChalasaniAbstract:Background & Aims Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced Liver Injury. Methods We identified patients with azithromycin-induced Liver Injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. Results Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from Liver tests were first detected 14 days after azithromycin cessation (range, 9–20 d). The median duration of azithromycin treatment was 4 days (range, 2–7 d). The pattern of Injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic Injury, 1 patient died, and 1 patient underwent Liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent Liver transplantation had underlying chronic Liver disease. Conclusions Azithromycin-induced Liver Injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic Injury, and serious complications leading to death or Liver transplantation can occur (ClinicalTrials.gov identifier, NCT00345930).
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spectrum of statin hepatotoxicity experience of the drug induced Liver Injury network
Hepatology, 2014Co-Authors: Mark W Russo, Jay H Hoofnagle, Huiman X Barnhart, Robert J Fontana, David E Kleiner, Naga Chalasani, Herbert L BonkovskyAbstract:The HMG-CoA reductase inhibitors (statins) are widely prescribed for patients with hyperlipidemia and are generally well tolerated. Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced Liver Injury is rare. The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent Liver Injury due to statins. Among 1,188 cases of drug-induced Liver Injury enrolled between 2004 and 2012 in a prospective registry by the U.S. Drug Induced Liver Injury Network, 22 were attributed to a statin. All patients were evaluated in a standard fashion and followed for at least 6 months after onset. The median age was 60 years (range 41-80), and 15 (68%) were female. The latency to onset of Liver Injury ranged from 34 days to 10 years (median = 155 days). Median peak levels were alanine aminotransferase 892 U/L, alkaline phosphatase 358 U/L, and total bilirubin 6.1 mg/dL. Nine patients presented with cholestatic hepatitis and 12 patients presented with hepatocellular Injury, of which six had an autoimmune phenotype. Nine patients were hospitalized, four developed evidence of hepatic failure, and one died. All commonly used statins were implicated. Four patients developed chronic Liver Injury, of which three had an autoimmune phenotype of Liver Injury. Conclusion: Drug-induced Liver Injury from statins is rare and characterized by variable patterns of Injury, a range of latencies to onset, autoimmune features in some cases, and persistent or chronic Injury in 18% of patients, most of whom have an autoimmune phenotype. (Hepatology 2014;60:679–686)
Arthur I. Cederbaum - One of the best experts on this subject based on the ideXlab platform.
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CYP2E1 and oxidative Liver Injury by alcohol.
Free radical biology & medicine, 2007Co-Authors: Arthur I. CederbaumAbstract:Ethanol-induced oxidative stress seems to play a major role in mechanisms by which ethanol causes Liver Injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway seems to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide and, in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This review article summarizes some of the biochemical and toxicological properties of CYP2E1 and briefly describes the use of cell lines developed to constitutively express CYP2E1 and CYP2E1 knockout mice in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic Liver Injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help us to understand the actions of CYP2E1 and its role in alcoholic Liver Injury.
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alcohol and oxidative Liver Injury
Hepatology, 2006Co-Authors: Aparajita Dey, Arthur I. CederbaumAbstract:Acute and chronic ethanol treatment has been shown to increase the production of reactive oxygen species, lower cellular antioxidant levels, and enhance oxidative stress in many tissues, especially the Liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces Liver Injury. Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced Liver Injury. Many of the seminal reports in this topic have been published in Hepatology , and it is fitting to review this research area for the 25th Anniversary Issue of the Journal. (Hepatology 2006;43:S63–S74.)
Gary C Chen - One of the best experts on this subject based on the ideXlab platform.
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acute Liver Injury induced by weight loss herbal supplements
World Journal of Hepatology, 2010Co-Authors: Gary C Chen, Vivek S Ramanathan, David Law, Pauline Funchain, Samuel W French, Boris Shlopov, Viktor E Eysselein, Daniel C Chung, Sonya ReicherAbstract:We report three cases of patients with acute Liver Injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute Liver Injury. To our knowledge, we are the first institute to report acute Liver Injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.
Sonya Reicher - One of the best experts on this subject based on the ideXlab platform.
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acute Liver Injury induced by weight loss herbal supplements
World Journal of Hepatology, 2010Co-Authors: Gary C Chen, Vivek S Ramanathan, David Law, Pauline Funchain, Samuel W French, Boris Shlopov, Viktor E Eysselein, Daniel C Chung, Sonya ReicherAbstract:We report three cases of patients with acute Liver Injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute Liver Injury. To our knowledge, we are the first institute to report acute Liver Injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.
