Evaluation of Possible Risk Factors of Lamivudine Resistance in Chronic Hepatitis B patients: A Retrospective Study in Iran

Background and Aims: Clinical resistance to lamivudine (LAM) can lead to exacerbation and high-level cross-resistance to all L-nucleotides in chronic hepatitis B patients, but the underlying reasons for this remain unclear. This study aimed to compare the clinicopathological features of LAM-resistant and LAM-responsive patients and tried to detect the tissue levels of Glutathione S-transferas pi (GSTpi) in the naive biopsies of both groups to find possible risk factors of LAM resistance.

Methods: Patients with naive biopsies and successful LAM therapy for one year were included as controls (n = 25), and patients who interrupted their LAM regimen during clinical relapse (n = 16) were considered cases. Clinicopathological characteristics of patients and GSTpi levels were compared between the two groups by an immunohistochemical analysis.

Results: Although no significant difference was detected between tissue levels of GSTpi in cases and controls, statistical tests showed a significant role of prior interferon-alpha (IFN-a) (P = 0.024, odds ratio [OR] = 5.25) therapy and higher HAI scores (P = 0.05, OR = 4.08) of naive biopsy samples and emphasized their roles as two relative risk factors for LAM resistance. Half of the cases showed higher HAI scores (> 6) whereas only 19% of controls showed the same pattern. A higher rate of LAM withdrawal was detected in patients with a history of IFN therapy (P = 0.024), and a history of IFN therapy was considered to be a possible risk factor of LAM withdrawal (OR = 5.21). Higher HAI scores were also detected in patients with a history of INF therapy (P = 0.041, OR = 4.8), and a history of INF therapy was considered to be a possible risk factor of tyrosine-methionine-aspartate-aspartate (YMDD) mutation (OR = 3.83).

Conclusions: This study has introduced two possible new predictive markers of LAM resistance in chronic hepatitis patients, which should be confirmed in future studies with larger groups to optimize the best pharmacotherapy regimens in chronic hepatitis B patients and may help physicians reduce the risk of adverse drug reactions.