Clinical and virological effects of long-term (over 5 years) lamivudine therapy.

Ideally, long-term lamivudine therapy should not induce tyrosine-methionine-aspartate-aspartate (YMDD) mutants (reverse transcription [rt]; rt M204I/V) in patients with chronic hepatitis B. There is little or no information on the clinical features of patients who do not develop such mutants. We analyzed 368 patients who received lamivudine therapy for more than 6 months between 1995 and 2003. Among them, 98 patients were negative for YMDD mutants during 5-year lamivudine therapy. Multivariate analysis identified hepatitis B e antigen (HBeAg) negativity, lack of cirrhosis, and high gamma glutamyltranspeptidase (GGTP) level as independent factors associated with lack of emergence of YMDD mutants during 5-year treatment. In these 98 patients, 21 patients developed YMDD mutants in the 5-year posttreatment follow-up. Old age was identified as the only factor associated with the emergence of YMDD mutants during that period. For all patients, 53 showed no elevation of alanine aminotransferase (ALT) or viral load after emergence of YMDD mutants during 5 years. Short latency to emergence of YMDD mutants, mixed (tyrosine-isoleucine-aspartate-aspartate (YIDD) [rtM204I] + tyrosine-valine-aspartate-aspartate (YVDD) [rtM204V]) type, and low ALT level were identified as independent factors associated with elevation ALT or viral load. HBeAg negativity, lack of cirrhosis, and high GGTP level were associated with lack of emergence of YMDD mutants during 5-year period. Young age protected against emergence of YMDD mutants over the 5-year period. Moreover, after the emergence of YMDD mutants, short latency to the emergence of YMDD mutant, mixed type mutants, and low baseline ALT level were associated with elevation of ALT or viral load.

Effectiveness of combination therapy of splenectomy and long-term interferon in patients with hepatitis C virus-related cirrhosis and thrombocytopenia.

AIM: To elucidate the effectiveness of combination therapy of splenectomy and long-term interferon (IFN) on survival and hepatocarcinogenesis, we retrospectively analyzed 180 patients with hepatitis C virus (HCV)-related cirrhosis and thrombocytopenia. METHODS: Group A consisted of 121 patients who received neither splenectomy nor IFN therapy. Group B consisted of 11 patients who underwent splenectomy only. Group C consisted of 32 patients who underwent IFN therapy only. Group D consisted of 16 patients who received the combination therapy splenectomy followed by IFN therapy. RESULTS: The viral response in group D estimated at least 6 months after IFN therapy showed sustained viral response in four patients, biochemical response in one and no response in six. Multivariate analysis using time-dependent variables showed significant improvement of survival rate in patients on the combination therapy,but no effect on the appearance rate of hepatocarcinogenesis relative to the findings in group A. CONCLUSIONS: In this study, the splenectomy did not directly improve the prognosis, but increased the ability for patients to undergo IFN. As a result, we considered that the combination therapy of splenectomy and long-term IFN significantly improved survival rate in patients with advanced HCV-related cirrhosis and thrombocytopenia.