Reviews in Basic and Clinical GastroenterologyRisk Factors for Idiosyncratic Drug-Induced Liver Injury
Section snippets
Age
Age is a risk factor for DILI, but only from specific medications.1, 2 Younger age is a risk factor for certain medications such as valproic acid and for Reye syndrome, associated with aspirin use.1, 2 As age increases, so does the risk of liver injury from compounds such as erythromycin, halothane, isoniazid, nitrofurantoin, and flucloxacillin.1, 2, 12 The risk of hepatotoxicity from isoniazid increases significantly with age.1, 8 In a large study of patients in a US tuberculosis clinic, the
Genetic Risk Factors
Because of their rarity and unpredictability, idiosyncratic DILI events are considered to have a strong genetic basis,12, 15, 16, 17, 18, 19 but significant association between certain genetic traits and DILI has been shown for only a few compounds.15, 16, 17, 18, 100 Even when such an association has been observed, generally the odds ratio (OR) of a given haplotype to increase the risk of DILI has been rather low (with the exception of flucloxacillin).100 DILI is likely a complex genetic
Future Directions
DILI is a problem that is important not only to patients, but also to physicians, regulatory agencies, and drug developers. Although we have gained insight into its pathogenic mechanisms, we have much to learn about its clinical manifestations and factors that might be used in the diagnosis and determination of prognosis. Prospective registries are an important source of data, but firm and systematically established postmarketing surveillance methods urgently are required. Pharmaceutical
References (156)
- et al.
Incidence of drug-induced hepatic injuries: a French population-based study
Hepatology
(2002) - et al.
Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period
Gastroenterology
(2005) - et al.
Drug-induced liver injury following positive drug rechallenge
Regul Toxicol Pharmacol
(2009) - et al.
Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic
Chest
(2005) - et al.
Drug metabolism and drug interactions in the elderly
Best Pract Res Clin Gastroenterol
(2001) - et al.
Causality assessment of drug-induced hepatotoxicity: promises and pitfalls
Clin Liver Dis
(2007) - et al.
Jaundice secondary to promazine and an analysis of possible cross sensitivities between phenothiazines derivatives
Gastroenterology
(1960) - et al.
Idiosyncratic drug reactions: the reactive metabolite syndromes
Lancet
(2000) Role of reactive metabolites in drug-induced hepatitis
J Hepatol
(1995)- et al.
Toxic hepatitis with isoniazid and rifampinA meta-analysis
Chest
(1991)
Isoniazid-rifampin fulminant hepatitisA possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction
Gastroenterology
Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid
Hepatology
Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity
Hepatology
Methotrexate and histologic hepatic abnormalities: a meta-analysis
Am J Med
Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment
J Hepatol
Liver injury during antituberculosis treatment: an 11-year study
Tuber Lung Dis
Are patients with elevated liver tests at increased risk of drug-induced liver injury?
Gastroenterology
Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity
Gastroenterology
Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study
J Hepatol
Incidence of statin hepatotoxicity in patients with hepatitis C
Clin Gastroenterol Hepatol
Clinical characteristics and prognostic markers in disulfiram-induced liver injury
J Hepatol
Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy
Chest
Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States
Am J Gastroenterol
Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study
J Hepatol
Hepatitis C coinfection increases the risk of fulminant hepatic failure in patients with HIV in the HAART era
J Hepatol
Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections
Hepatology
The fluctuations of viral load and serum alanine aminotransferase levels in chronic hepatitis C
Hepatol Res
Effects of long-term rifampicin administration in primary biliary cirrhosis
Gastroenterology
Epidemiology of idiosyncratic drug-induced liver injury
Semin Liver Dis
Epidemiology and individual susceptibility to adverse drug reactions affecting the liver
Semin Liver Dis
A review of epidemiologic research on drug-induced acute liver injury using the general practice research data base in the United Kingdom
Pharmacotherapy
Acute and clinically relevant drug-induced liver injury: a population based case-control study
Br J Clin Pharmacol
Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States
Ann Intern Med
Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the United States?
Am J Gastroenterol
Searching for a needle in a haystack: use of ICD-9-CM codes in drug-induced liver injury
Am J Gastroenterol
Outcome and prognostic markers in severe drug-induced liver disease
Hepatology
Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States
Gastroenterology
Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver
Drug induced liver injury: premarketing clinical evaluation
Current concepts of mechanisms in drug-induced hepatotoxicity
Curr Med Chem
Drug-induced liver injury: insights from genetic studies
Pharmacogenomics
Genetic association studies in drug-induced liver injury
Semin Liver Dis
Identifying genetic risk factors for serious adverse reactions; current progress and challenges
Nat Rev Drug Discov
Idiosyncratic drug reactions: current understanding
Annu Rev Pharmacol Toxicol
New concepts in immunology relevant to idiosyncratic drug reactions: the “danger hypothesis” and innate immune system
Chem Res Toxicol
Idiosyncratic drug hepatotoxicity
Nat Rev Drug Discov
Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain
Hepatology
Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and gender
Hepatology
The influence of age and sex on the clearance of cytochrome P450 3A substrates
Clin Pharmacokinet
The effect of age upon liver volume and apparent liver blood flow in healthy man
Hepatology
Cited by (0)
Conflicts of interest Dr Chalasani has served as a paid consultant within the preceding 12 months to Teva, Eli Lilly, Karobio, Salix, Debiovision, Amylin, Genentech, Abbott, and Gilead on issues related to drug safety, and has research support from Eli Lilly and Monarch LifeSciences; and Dr Björnsson has served as a paid consultant for Astellas Pharma Europe, AstraZeneca, and Karobio.