RSS Feeds
Hepatotoxicity Associated with Ritonavir
- Odile Picard, MD;
- Olivier Rosmorduc, MD, PhD; and
- Jean Cabane, MD
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 Unpublished letters cannot be returned.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.
TO THE EDITOR:
Liver injuries associated with protease inhibitors have been poorly characterized. Three cases of severe hepatitis were recently reported in patients receiving indinavir [1]. We report the first case of acute liver failure after exposure to the protease inhibitor ritonavir.
A 28-year-old woman with AIDS who was seronegative for hepatitis B and C had been sequentially treated with zidovudine, didanosine, zalcitabine, and lamivudine between 1994 and 1996. Liver enzyme levels have remained normal. Ritonavir (1200 mg/d) and stavudine were added to lamivudine in 1996, when the CD4 cell count was 3 cells/µL and the HIV level was 433 000 RNA copies/mL.
After 5 weeks of triple therapy, serum aspartate aminotransferase and alanine aminotransferase levels increased to 167 IU/mL (normal, <30) and 133 IU/mL (normal, <35), respectively. Ritonavir therapy was stopped, and liver enzyme levels rapidly returned to normal. Ritonavir therapy was then reintroduced. Five weeks later, the patient was hospitalized with abdominal pain, nausea, vomiting, and jaundice. Her body weight was 38 kg, and she had tender hepatomegaly and ascites. Hepatic failure with encephalopathy and lactic acidosis developed. Serum aspartate aminotransferase and alanine aminotransferase levels increased to 327 IU/mL and 254 IU/mL, respectively; prothrombin time and factor V level decreased to 22% and 37% of values in the normal range, respectively; and total and conjugated bilirubin levels gradually increased to 308 µmol/L (normal, <25) and 215 µmol/L, respectively. Alcohol-related, viral, and other toxic causes were ruled out. Histologic analysis of the liver revealed moderate microvesicular steatosis with marked hepatocellular cholestasis, extensive fibrosis, and minimal inflammation. Liver test results returned to normal 8 weeks after discontinuation of antiviral treatment. Lamivudine and stavudine therapy was reintroduced at the beginning of 1997. No clinical or biological hepatotoxicity was observed during 9 months of follow-up.
Clinical, biological, and histologic findings were consistent with the occurrence of acute mitochondrial toxicity, as previously observed after treatment with fialuridine and other nucleoside analogues [2, 3]. Thus, our observation strongly suggests that ritonavir may have a direct hepatotoxic effect or may hasten liver toxicity induced by reverse transcriptase inhibitors in some patients with AIDS, especially those with underlying liver disease. In conclusion, we recommend that patients be closely monitored for liver function after initiation of ritonavir therapy. Further evaluation of ritonavir-related liver toxicity is required in large populations because of the wide use of the drug at early stages of HIV infection.
Odile Picard, MD
Olivier Rosmorduc, MD, PhD
Jean Cabane, MD
Hopital Saint-Antoine; Paris, France
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
