Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients

Abstract

The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61-122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<10(6) copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.

When can we stop nucleoside analogues in patients with chronic hepatitis B?

“…Moreover, the follow‐up in these studies was relatively short, usually 6‐12 months after stopping therapy, and more patients may relapse with longer follow‐up. In a small 10 year study of patients who stopped NAs, 76.7%, of HBeAg negative patients relapsed, mostly within the first 48 months . The main benefit of stopping therapy for the APASL guidelines is cost‐savings since there did not seem to be any clinical benefit except to convert a patient who requires therapy into one who does not fulfil the criteria for therapy.…”

Clinical characteristics and outcomes of patients with recurrent chronic hepatitis B after nucleos(t)ide analog withdrawal with stringent cessation criteria: A prospective cohort study

“…Thus far, no consensus on the definition of “relapse” is available, and the different definitions may be one of the main causes for the disparity in relapse rates and clinical features reported in recent studies . As patients with serum HBV DNA <2000 IU/mL are at a lower risk for development of long‐term complications such as liver cirrhosis and HCC, 2000 IU/mL or 10 4 copies/mL were the preferred cut‐off values for defining virologic relapse, which is also in accordance with the APASL guidelines.…”

“…Thus, at least 4 years and 3 years of close follow‐up are necessary for HBeAg‐positve and HBeAg‐negative patients who cannot continue long‐term treatment and need to discontinue therapy before HBsAg seroclearance, which is in accordance with Pan et al . 's study with Chinese patients. Of note, among the patients who relapsed 4 years later, one case was due to pregnancy, and another was due to the use of glucocorticoids, suggesting caution is needed in women of childbearing age and patients with immunosuppression agents.…”

Long‐term outcome of telbivudine versus entecavir in treating higher viral load chronic hepatitis B patients without cirrhosis

“…Adverse events, such as myalgia and tiredness, an increase in creatinine‐kinase (CK, >150 U/L), CK‐M (>25 U/L), lactic acid dehydrogenase (LDH, >280 U/L), occurred in 7 LdT‐treated patients for a mean of 9 months . None of these effects occurred in the ETV‐treated patients.…”