Adefovir Dipivoxil for Chemotherapy-Induced Activation of Hepatitis B Virus Infection
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《新英格兰医药杂志》
To the Editor: Adefovir dipivoxil is an oral prodrug of adefovir, an analogue of AMP. Adefovir has recently been used for treatment of chronic infection with hepatitis B virus (HBV), resulting in an improvement in liver histology and a reduction in serum HBV DNA.1 We describe a case of subfulminant HBV infection that was successfully treated with adefovir.
A 69-year-old man with prostate adenocarcinoma (stage D2) and bone metastasis had had intermittent cholestasis of unknown origin years earlier. The patient had completed a course of chemotherapy with mitoxantrone and prednisone 30 days before he was admitted to the hospital for asthenia, anorexia, and jaundice. Laboratory tests revealed an international normalized ratio of 1.61, an alanine aminotransferase level of 990 IU per liter, and a total bilirubin level of 10.7 mg per deciliter (183.0 μmol per liter). The serum was positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), IgM antibodies against the HBV core antigen (anti-HBc), and HBV DNA. Other liver diseases were ruled out, including infiltrative disease. The results of liver-function tests and the evolution of the serologic profile can be seen in Figure 1.
Figure 1. Serologic Profile of a Patient with Acute Subfulminant Hepatitis B Treated with Adefovir.
Day 0 represents the end of chemotherapy. Question marks denote the absence of serologic data, plus signs positive on serologic testing, minus signs negative, anti-HBs antibodies against HBsAg, and anti-HBe antibodies against HBeAg. To convert total bilirubin to micromoles per liter, multiply by 17.1.
The serologic pattern and a transjugular liver biopsy suggested acute subfulminant hepatitis (probably due to previously undetected chronic hepatitis). Treatment with adefovir was begun at 10 mg per day and reduced the alanine aminotransferase and total bilirubin levels from day 5 and stabilized the levels by 48 days after the beginning of treatment. At that time, the serum was negative for HBeAg and HBV DNA. Once viral inactivation was achieved, and given that the prostate-specific antigen level was four times as great as its previous value, the cycles of chemotherapy (with docetaxel) were restarted and given along with adefovir, with no complications.
Although lamivudine is recommended for acute HBV infection in immunosuppressed patients,2,3 the development of resistance to this drug must not be overlooked. Lamivudine resistance may predispose patients to acute or subacute liver failure, which may lead to death.4,5
Wiegand et al.5 described the efficacy of adefovir in a patient with hepatic cirrhosis and subacute hepatitis B, probably due to lamivudine resistance. Adefovir was our first choice for treatment in our patient since its use reduced the possibility of resistance and allowed chemotherapy to begin as soon as possible for rapid control of the disease. The choice of the drug was supported by limited but effective use of adefovir in cases of severe hepatitis.4,5
Francisco Pérez-Roldán, M.D.
Pedro González-Carro, M.D.
María Concepción Villafá?ez-García, M.D.
Hospital General La Mancha-Centro
13600 Alcázar de San Juan, Spain
References
Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003;348:808-816.
Ahmed A, Keeffe EB. Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection. Am J Gastroenterol 1999;94:249-251.
Reshef R, Sbeit W, Tur-Kaspa R. Lamivudine in the treatment of acute hepatitis B. N Engl J Med 2000;343:1123-1124.
Bruno R, Sacchi P, Filice C, Filice G. Acute liver failure during lamivudine treatment in a hepatitis B cirrhotic patient. Am J Gastroenterol 2001;96:265-265.
Wiegand J, Tischendorf JJ, Nashan B, et al. Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated. Z Gastroenterol 2004;42:15-18.
A 69-year-old man with prostate adenocarcinoma (stage D2) and bone metastasis had had intermittent cholestasis of unknown origin years earlier. The patient had completed a course of chemotherapy with mitoxantrone and prednisone 30 days before he was admitted to the hospital for asthenia, anorexia, and jaundice. Laboratory tests revealed an international normalized ratio of 1.61, an alanine aminotransferase level of 990 IU per liter, and a total bilirubin level of 10.7 mg per deciliter (183.0 μmol per liter). The serum was positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), IgM antibodies against the HBV core antigen (anti-HBc), and HBV DNA. Other liver diseases were ruled out, including infiltrative disease. The results of liver-function tests and the evolution of the serologic profile can be seen in Figure 1.
Figure 1. Serologic Profile of a Patient with Acute Subfulminant Hepatitis B Treated with Adefovir.
Day 0 represents the end of chemotherapy. Question marks denote the absence of serologic data, plus signs positive on serologic testing, minus signs negative, anti-HBs antibodies against HBsAg, and anti-HBe antibodies against HBeAg. To convert total bilirubin to micromoles per liter, multiply by 17.1.
The serologic pattern and a transjugular liver biopsy suggested acute subfulminant hepatitis (probably due to previously undetected chronic hepatitis). Treatment with adefovir was begun at 10 mg per day and reduced the alanine aminotransferase and total bilirubin levels from day 5 and stabilized the levels by 48 days after the beginning of treatment. At that time, the serum was negative for HBeAg and HBV DNA. Once viral inactivation was achieved, and given that the prostate-specific antigen level was four times as great as its previous value, the cycles of chemotherapy (with docetaxel) were restarted and given along with adefovir, with no complications.
Although lamivudine is recommended for acute HBV infection in immunosuppressed patients,2,3 the development of resistance to this drug must not be overlooked. Lamivudine resistance may predispose patients to acute or subacute liver failure, which may lead to death.4,5
Wiegand et al.5 described the efficacy of adefovir in a patient with hepatic cirrhosis and subacute hepatitis B, probably due to lamivudine resistance. Adefovir was our first choice for treatment in our patient since its use reduced the possibility of resistance and allowed chemotherapy to begin as soon as possible for rapid control of the disease. The choice of the drug was supported by limited but effective use of adefovir in cases of severe hepatitis.4,5
Francisco Pérez-Roldán, M.D.
Pedro González-Carro, M.D.
María Concepción Villafá?ez-García, M.D.
Hospital General La Mancha-Centro
13600 Alcázar de San Juan, Spain
References
Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003;348:808-816.
Ahmed A, Keeffe EB. Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection. Am J Gastroenterol 1999;94:249-251.
Reshef R, Sbeit W, Tur-Kaspa R. Lamivudine in the treatment of acute hepatitis B. N Engl J Med 2000;343:1123-1124.
Bruno R, Sacchi P, Filice C, Filice G. Acute liver failure during lamivudine treatment in a hepatitis B cirrhotic patient. Am J Gastroenterol 2001;96:265-265.
Wiegand J, Tischendorf JJ, Nashan B, et al. Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated. Z Gastroenterol 2004;42:15-18.