Posted by Phillipa on July 25, 2009, at 0:25:16
Liver Damage from meds includes antibiotics, and other meds tylenol as well. Phillipa
From MedScape News
July 15, 2009 Although drug-induced acute liver failure (DIALF) is very rare, it can be fatal, according to the results of a retrospective cohort study reported in the July issue of Liver Transplantation."Acute liver failure (ALF) is an uncommon but potentially lethal drug-related adverse effect that often leads to liver transplantation (LT) or death," write Ayse L. Mindikoglu, from the University of Maryland School of Medicine in Baltimore, and colleagues. "It is also the leading cause of regulatory action, including withdrawal of drugs from the market, restrictions in indications, and warnings to healthcare providers and patients, in the United States over the past 5 decades."
Using the United Network for Organ Sharing Standard Transplant Analysis and Research files, the investigators identified and analyzed data from 661 patients (567 adults and 94 children < age 18 years) who underwent liver transplantation for DIALF from October 1, 1987, through December 31, 2006. Data were analyzed for 20 recipient and 6 donor demographic and clinical variables.
The 4 drug groups most often responsible for DIALF were acetaminophen (n = 265; 40%), antituberculosis drugs (n = 50; 8%), antiepileptics (n = 46; 7%), and antibiotics (n = 39; 6%). Estimated 1-year survival rates were 76% for acetaminophen, 82% for antituberculosis drugs, 52% for antiepileptics, 82% for antibiotics, and 79% for DIALF caused by other drugs.
For antiepileptic-induced ALF, the lower survival rate was attributed mostly to deaths in children, with a mortality rate of 73% within the first year among the 22 patients younger than 18 years who had ALF caused by antiepileptics, These patients were also least likely to be listed as status 1, spent the most time waiting on the transplant list, and had the longest warm and cold ischemia times. However, controlling for these variables in multivariate analysis did not change the relatively low survival probability in this patient subgroup.
Although overall survival rate was statistically similar for acetaminophen-related and nonacetaminophen-related ALF, the former group required dialysis before liver transplantation at a significantly higher rate than all other drug groups (27% vs 3% - 10%; P < .0001).
The need for life support, DIALF caused by antiepileptic drugs at age younger than 18 years, and elevated serum creatinine levels were independent pretransplant predictors of death after liver transplantation, based on Cox proportional hazards regression analysis. The investigators derived a mathematical prognostic model that showed strong predictive ability in the entire study population.
"The leading drug groups causing LT due to DIALF in the United States were acetaminophen, antituberculosis drugs, antiepileptics, and antibiotics," the study authors write. "Children who had ALF due to antiepileptics had a substantially higher risk of death after LT in comparison with other drugs. Patients transplanted for acetaminophen-related ALF required dialysis at a significantly higher rate."
Limitations of this study include inability to determine causality and small pediatric sample.
In an accompanying editorial, Paul H. Hayashi, from the University of North Carolina at Chapel Hill, and Paul B. Watkins, from the Institute for Drug Safety at the Hamner Institutes of Health Sciences, Research Triangle Park, North Carolina, recommend more focused research on drug-induced liver injury in pediatric populations. They also note that the clinical usefulness of the predictive model, if validated, may be limited.
"Large registries such as the UNOS [United Network for Organ Sharing] database provide valuable population-based data to form hypotheses, but they lack all desired phenotypic information about the patients," the editorialists conclude. "Multicenter studies such as the Acute Liver Failure Study Group and Drug Induced Liver Injury Network can provide detailed individual patient data, sera, and genomic DNA, which can be used to investigate these new hypotheses. The combined efforts will hopefully shed better light on preventive factors, including genetic predisposition, and move us beyond simply reporting cases and case series."
The Health Resources and Services Administration supported this study. The content does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. One of the study authors is employed by Eli Lilly.
poster:Phillipa
thread:908426
URL: http://www.dr-bob.org/babble/20090721/msgs/908426.html