Histological improvements after a three-year lamivudine therapy in patients with chronic hepatitis B in whom YMDD mutants did not or did develop

OBJECTIVE: The long-term effects of lamivudine and the influence of YMDD mutants on the histology of chronic hepatitis B are not known. METHODS: 3-year lamivudine therapy was given to 16 patients with chronic hepatitis B. YMDD mutants did not develop in 9 patients (group A), while they appeared in the remaining 7 patients (group B). RESULTS: Biochemical and virological responses were invariably achieved in the 9 patients without YMDD mutants, while virological breakthroughs with or without biochemical relapses occurred in all 7 patients with such mutants. All 16 patients accomplished histological improvement, with the total histology activity index (HAI) score decreasing from 11.3 +/- 3.0 to 4.1 +/- 1.7 (p < 0.001). The total HAI score decreased from 11.6 +/- 3.8 to 3.4 +/- 1.3 in the 9 patients in group A (p < 0.001). Although to a significantly lesser extent (p < 0.02), the total HAI score also decreased in the 7 patients in group B from 10.9 +/- 1.0 to 5.0 +/- 1.7 (p < 0.001). CONCLUSION: The results obtained indicate that 3-year lamivudine therapy can induce histological improvements, regardless of the appearance of YMDD mutants accompanied by virological breakthroughs and biochemical relapses.