Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated.
BACKGROUND
Lamivudine is a treatment option for the therapy of chronic hepatitis B with an excellent safety profile. Unfortunately, viral resistance to lamivudine is common in the course of therapy. The lamivudine resistant mutants are usually less pathogenic than the wild type, but development of viral resistance can also lead to acute exacerbation of the underlying hepatitis. The recently FDA approved nucleoside analogue adefovir dipivoxil has potent antiviral activity against lamivudine-resistant mutants and can prevent viral replication effectively.


METHODS
A 31-year-old man with pre-existing compensated liver cirrhosis developed resistance to lamivudine therapy leading to subacute liver failure. After referral adefovir dipivoxil 10 mg daily was initiated within an early access protocol. Since initiating therapy with adefovir dipivoxil progression of the subacute liver failure was delayed accompanied by a rapid decrease of ALT and decline of HBV viral load. Even so, the clinical course was not reverted but showed slower deterioration. This enabled the patient to undergo living-related liver transplantation. Adefovir dipivoxil was well tolerated in the acute phase of the disease and did not cause nephrotoxicity or favour the development of hepatorenal syndrome.


CONCLUSIONS
Adefovir dipivoxil resulted in a delay of hepatic decompensation and enabled liver transplantation as final treatment option for this patient. Earlier initiation might even have prevented the need of liver transplantation. Thus, in patients with pre-existing liver cirrhosis an early switch to adefovir dipivoxil appears indicated after emergence of lamivudine resistance.
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
J
J
Wiegand
J J
JJ
Tischendorf
B
B
Nashan
J
J
Klempnauer
P
P
Flemming
P
P
Niemann
P
P
Rohde
M P
MP
Manns
C
C
Trautwein
H L
HL
Tillmann
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications*; D017093:Liver Failure / Q000209:etiology / Q000517:prevention & control; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D009154:Mutation; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil