The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: A case control study

Background & Aims: 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.