Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu Clinical and Molecular Hepatology.2024; 30(2): 276. CrossRef
Han Ah Lee, Yeon Seok Seo, Seung Woon Park, Sang Jung Park, Tae Hyung Kim, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um
Clin Mol Hepatol 2016;22(3):382-389. Published online September 25, 2016
Background/Aims Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response.
Methods This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal.
Result s: After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10 IU/mL (n=11) and >3 log10 IU/mL (n=28), respectively.
Conclusions The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log10 IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.
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Background/Aims Lamivudine, an oral nucleoside analogue, effectively suppresses HBV replication and improves liver enzymes as well as liver histology. Long-term lamivudine therapy can induce the emergence of drug resistant HBV strains in some patients. The aim of this study was to evaluate the effects of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after HBeAg loss. Methods: A total of 190 patients with HBeAg and HBV DNA positive showing abnormal serum levels of aminotransferases for at least 6 months received 100 mg of lamivudine once daily. The duration of lamivudine therapy was from 6-36 months (mean 14 months). Responder was defined as the ALT normalization with sustained suppression of HBV DNA and HBeAg loss. Therapy was to be stopped after HBeAg loss. Post-treatment monitoring continued for 1-21 months (mean 6 months). Results: The cumulative HBeAg loss rates at 12 months and 18 months were 35% and 43%, respectively. Pretreatment serum HBeAg quantitation, and the duration of lamivudine therapy were independent predictive factors for HBeAg loss. The cumulative breakthrough rates at 18 and 24 months were 38% and 57%, respectively. Pretreatment HBV DNA level was the only predictable factor for breakthrough. Therapy was discontinued after HBeAg loss in 52 patients. Most episodes of relapse (15/16) occurred within 6 months after cessation of lamivudine. The cumulative relapse rates at 3 months and 6 months were 21% and 50%, respectively. A predictive factor for post-treatment relapse after HBeAg loss was the duration of lamivudine therapy. Conclusions: These results suggested the pretreatment quantitative HBeAg in serum and duration of lamivudine therapy are independent predictive factors for HBeAg loss. The HBeAg response of lamivudine-induced HBeAg loss was not durable after discontinuing therapy.(Korean J Hepatol 2001;7:77-89)
Background/Aims Lamivudine therapy is effective in inhibiting HBV replications in patients with HBeAg-negative chronic liver disease. However, the sustained response rate appears to be particularly poor, because the vast majority of patients relapse soon after cessation of therapy. The aim of this study was to evaluate the efficacy of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after response in patients with HBeAg-negative chronic liver disease. Methods: Fifty-nine patients with HBeAg-negative chronic liver disease who have received lamivudine for at least 6 months, were studied. The mean duration of treatment was 14 months. Complete response was defined as undetectable serum HBV DNA by bDNA and normalization of ALT levels. Once HBV DNA disappearance and ALT normalization were observed, lamivudine therapy was continued for at least two additional months. The mean follow-up after cessation of treatment was 6 (1-22) months. Results: Fifty-six patients were undetectable HBV DNA. The cumulative HBV DNA loss rates at 3 months and 5 months were 90% and 95%, respectively. The ALT normalization was observed in 52 patients. The cumulative ALT normalization rates at 6 months and 10 months were 78% and 86%, respectively. The complete response was observed in 52 patients. The cumulative rates of complete response at 10 months and 18 months were 80% and 88%, respectively. A predictive factor for complete response was only the duration of lamivudine treatment. Virological breakthrough was observed in 5 (8.5%). Thirty-four patients stopped taking lamivudine after 7.7 (2-15) months of the additional therapy. Seventeen of those patients (50%) experienced relapse. The cumulative relapse rates at 3 months, 6 months and 10 months were 24%, 47%, and 66%, respectively. The only predictive factor for relapse was the duration of additional lamivudine treatment after response. Conclusions: Lamivudine was an effective treatment of HBeAg negative chronic liver disease. Relapse, however, was usually observed after cessation of lamivudine. Our results showed that long-term lamivudine therapy is required in order to decrease the high relapse rates in patients with HBeAg-negative chronic liver disease.(Korean J Hepatol 2003;9:69-78)
Background/Aims The post-treatment relapse patterns and efficacy of lamivudine re-treatment for relapsed patients have not been clarified. The aims of this study were to evaluate the relapse patterns after discontinuing therapy and the effects of lamivudine re-treatment for relapsed patients after HBeAg seroconversion. Methods: Therapy was discontinued after HBeAg seroconversion in 121 patients. Sixty-six patients were relapsed and included in this study. The duration of lamivudine re-treatment therapy was from 6-35 (mean: 16) months. Post-retreatment monitoring continued for 1-40 (mean: 8,9) months. Results: Among the relapsed 66 patients, 50 (75.8%) had HBeAg reappearance while 16 (24.2%) remained HBeAg negative and anti-HBe positive, The cumulative relapse rates at 3, 6, 12 and 24 months were 27%, 47%, 60% and 66%, respectively, Forty-two relapsers received lamivudine re-treatment, Among them, 33 were HBeAg positive and 9 were HBeAg negative and anti-HBe positive, Response was achieved in 31 of the 42 patients (73.8%). The cumulative response rates at 6, 9 and 12 months were 62%, 69% and 72%, respectively. Six patients (14.3%) developed viral breakthrough, All patients were HBeAg positive chronic hepatitis B. The duration of lamivudine re-treatment was the only predictable factor for response of lamivudine re-treatment. Therapy was discontinued after response in 21 patients, Eleven patients were relapsed, including 6 who were HBeAg positive and 5 who were HBeAg negative. Predictive factors for post-retreatment relapse were age and the duration of additional lamivudine therapy after response, Conclusions: The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The breakthrough and relapse rates, however, were similar in both initial and retreated lamivudine therapy.(Korean J Hepatol 2003;9:188-197)
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