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Acute Liver Failure in the United States
- William M. Lee, MD;
- Anne Larson, MD;
- Robert Fontana, MD; and
- George Ostapowicz, MD
- From University of Texas Southwestern Medical Center, Dallas, TX 75390-9151; University of Washington, Seattle, WA 98195-6174; University of Michigan, Ann Arbor, MI 48109-0362; and Gold Coast Hospital, Southport, QLD 4215, Australia.
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IN RESPONSE:
Space did not permit us to expand on cases in which therapeutic doses of acetaminophen caused acute liver failure or to describe their particular features. The diagnosis for each case reported in our prospective trial was made by the site investigator, an experienced hepatologist, on the basis of standard criteria, including history of ingestion, plasma acetaminophen levels, and alanine aminotransferase levels exceeding 3500 U/L, as well as exclusion of other etiologies. History of ingestion may be inaccurate and difficult to obtain in patients whose mental status is altered, but ancillary information is usually available from family and from the referring hospital, where the patient may have been able to give a more detailed history.
We are more concerned with those patients who ingested large amounts of acetaminophen without any awareness of possible toxicity. The median overall dose per day was 13.2 g, more than 3 times the package recommendation, and 56% of overdoses were considered unintentional on the basis of a history of ingestion over several days, a specific cause of pain identified, and denial of suicidal ideation. The low-dose toxicity issue is important, however. A manuscript detailing these cases and answering many of the questions posed by Dr. Carey is under way.
More important questions than those posed might be: Why has package labeling not been improved to state clearly that there are substantial risks if more than accepted doses are taken and to list acetaminophen in large letters on combination medications? And why has the U.S. Food and Drug Administration not considered limiting package size or using blister packs, as Great Britain has done, to curb impulsive or suicidal behavior that can have tragic results (1, 2)?
Regarding Dr. Schears's letter, we disagree with the statement that our selection criteria were “highly subjective.” Since the 1970s, these criteria have been standard for determining that patients are developing very severe liver failure (3). Assessment of mental change by the investigator, using standard criteria and the prothrombin time (INR), is certainly not a subjective test. Virtually all patients with acute liver failure in fact have jaundice (although occasionally not if the disease is very acute). Patients with acute liver failure may demonstrate agitation and disruptive behavior. Only in stage II encephalopathy will they demonstrate asterixis. It is understood that patients receiving anticoagulants or sedatives would be excluded from study entry.
William M. Lee, MD
University of Texas Southwestern Medical Center; Dallas, TX 75390-9151
George Ostapowicz, MD
Gold Coast Hospital; Southport, QLD 4215, Australia
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
