The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: a case control study.
OBJECTIVE
Nodular regenerative hyperplasia (NRH) leading to non-cirrhotic portal hypertension has been described in HIV-infected patients and has been linked to didanosine. The relation between NRH and other antiretrovirals remains unclear.


METHODS
A case-control study was performed in 13 patients with NRH and 78 controls matched for time of inclusion, baseline CD4, and duration of follow-up. Univariate and multivariate conditional logistic regression analyses were performed.


RESULTS
Control patients and patients with NRH were similar at baseline regarding demographics and biological data with the exception of older age for patients with NRH (43.9 vs. 33.5 years, p=0.044). At the time of NRH diagnosis, cases had a lower CD4 count (327 vs. 468/mm(3), p=0.013), a similar CD4 percentage (24 vs. 26.2%, p=0.7), a lower platelet count (169 vs. 228 giga/L, p=0.003) and a higher AST level (33 vs. 26 IU/L, p=0.001) than controls. Univariate analysis demonstrated that patients with NRH had been exposed longer than controls to didanosine, stavudine, tenofovir, didanosine+stavudine, and didanosine+tenofovir. The age at baseline [OR 2.2 (1.0-5.0) per 10 years, p=0.053] and didanosine+stavudine cumulative exposure [OR 3.7 (1.4-10.2) per year, p=0.011] were independently associated with NRH. The age at baseline [OR 2.3 (1.0-5.3) per 10 years, p=0.045], cumulative exposure to didanosine [OR 1.4 (1.1-1.9) per year, p=0.023] and to tenofovir [OR 1.7 (1.0-2.8) per year, p=0.04] were independently associated with NRH when didanosine+stavudine exposure was excluded from the model.


CONCLUSIONS
NRH in HIV-infected patients seems strongly related to age and the cumulative exposure to didanosine+stavudine, didanosine, and stavudine.
Hospices Civils de Lyon, Lyon, France. laurent.cotte@chu-lyon.fr
Laurent
L
Cotte
Thomas
T
Bénet
Claire
C
Billioud
Patrick
P
Miailhes
Jean-Yves
JY
Scoazec
Tristan
T
Ferry
Corinne
C
Brochier
André
A
Boibieux
Philippe
P
Vanhems
Michèle
M
Chevallier
Fabien
F
Zoulim
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D016022:Case-Control Studies; D016049:Didanosine / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D006975:Hypertension, Portal / Q000209:etiology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D018119:Stavudine / Q000009:adverse effects*; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine; D016049:Didanosine