Improvements in parameters of end-stage liver disease in patients with HIV/HBV-related cirrhosis treated with tenofovir.
BACKGROUND
Mortality related to end-stage liver disease is increasing in HIV/hepatitis B virus (HBV)-coinfected patients and effective treatment options are limited. Tenofovir is now widely used in HIV/HBV coinfection and results in significant HBV suppression, in both patients with and patients without lamivudine resistance. The safety and efficacy of tenofovir in HIV/HBV cirrhosis has not been previously described.


METHODS
Seven cirrhotic HIV/HBV patients treated with tenofovir were identified within the HIV clinic. Parameters of hepatic function, CD4+ T-cell counts, HBV DNA levels and Child-Pugh Class (C-P-C) were determined before and after addition of tenofovir. All patients had prior lamivudine experience with a median baseline HBV DNA of 6.23 x 10(7) copies/ml.


RESULTS
Four of seven patients were C-P-C -A and hepatitis 'e' antigen (HBeAG) was positive in 4/7 patients. After a median duration of tenofovir of 28 months, all laboratory parameters improved, with significant changes in albumin and prothrombin (PT) (median pre/post-tenofovir: alanine aminotransferase 63/39; bilirubin 26/18; albumin 39/44, P = 0.028; PT 17.5/15, P = 0.018). All three patients with C-P-C -B or -C improved to C-P-C -A, which for one patient enabled removal from the liver transplant waiting list. Three patients lost HBeAG with two anti-HBe seroconversions. Median HBV DNA was suppressed to <35 copies/mi.


CONCLUSIONS
This study demonstrates that tenofovir can produce HBV viral suppression, HBeAg seroconversion and improvement in markers of hepatic function in HIV/HBV-coinfected patients with cirrhosis. The potential reversal of end-stage liver disease may provide an important survival benefit in this population.
Matthews
Gail V
GV
HIV/Immunology/Infectious Diseases Unit, St. Vincent's Hospital, Sydney, Australia. gmatthews@nchecr.unsw.edu.au
Cooper
David A
DA
Dore
Gregory J
GJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006509:Hepatitis B / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D017093:Liver Failure / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine