Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B: Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial.
Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B: Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial.
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DOI：
10.14309/ajg.0000000000002176
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发表时间：
2023-07-01
期刊：
影响因子：
--
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在慢性B型肝炎感染中，越来越多的人评估撤回核苷（酸）类似物治疗作为诱导B型肝炎表面抗原（HBsAg）丢失的策略。B型肝炎研究网络免疫活性试验评价了用替诺福韦（TDF）治疗4年±最初6个月的聚乙二醇干扰素-α（PegIFN）（NCT 01369212），之后停止治疗。停止TDF的合格参与者（B肝炎e抗原[HBeAg]-/抗-HBe+，B肝炎病毒[HBV] DNA <103 IU/mL，无肝硬化）至少随访1年，此后可选择随访。重新治疗是基于预先确定的标准。在接受4年治疗的201例受试者中，97例受试者（TDF组45例，TDF + PegIFN组52例，亚洲人79例）停用TDF。5名参与者发生HBsAg丢失，2名在退出后25周内，3名在退出后89-119周内（2年累积率为4.3%）。36例（37.1%）受试者在TDF停药后发生丙氨酸氨基转移酶（ALT）突变（>5倍正常值上限），与治疗开始时HBeAg+相比，HBeAg-受试者发生频率更高，发生时间更早。ALT发作与年龄较大、治疗前和发作前访视时HBV DNA水平较高相关。ALT发作与HBsAg下降或丢失无显著相关性，但与停药后1年（70.6% vs 11.9%，P < 0.0001）和2年（66.7% vs 25.9%，P = 0.03）的免疫活性疾病相关。13名（13.4%）参与者需要重新开始治疗，另外13名参与者在研究随访结束时仍处于持续的非活动携带状态。没有可靠的标准预测安全的治疗退出。本试验的结果不支持TDF停药作为治疗策略。在停止长期TDF后2年内HBsAg丢失的情况很少。如果考虑停药，应仔细监测HBV DNA，如果水平升高超过4 log 10 IU/mL，应重新开始治疗，以降低ALT发作的风险，因为它们与随后的HBsAg下降或丢失无关。
Withdrawal of nucleos(t)ide analog therapy is increasingly being evaluated in chronic hepatitis B infection as a strategy to induce hepatitis B surface antigen (HBsAg) loss. The Hepatitis B Research Network Immune-Active Trial evaluated treatment with tenofovir (TDF) for 4 years ± an initial 6 months of peginterferon-α (PegIFN) (NCT01369212) after which treatment was withdrawn. Eligible participants (hepatitis B e antigen [HBeAg]−/anti-HBe+, hepatitis B virus [HBV] DNA <103 IU/mL, no cirrhosis) who discontinued TDF were followed for at least 1 year with optional follow-up thereafter. Retreatment was based on predefined criteria. Among 201 participants who received 4 years of treatment, 97 participants (45 TDF and 52 TDF + PegIFN arm, 79 Asian) discontinued TDF. HBsAg loss occurred in 5 participants, 2 within 25 weeks and 3 within 89–119 weeks postwithdrawal (cumulative rate 4.3% by 2 years). Alanine aminotransferase (ALT) flares (>5× upper limit of normal) after TDF withdrawal occurred in 36 (37.1%) participants and occurred more frequently and earlier in those HBeAg− compared with HBeAg+ at treatment initiation. ALT flares were associated with older age and higher HBV DNA pretreatment and at the visit before the flare. ALT flares were not significantly associated with HBsAg decline or loss but were associated with immune active disease at 1 year (70.6% vs 11.9%, P < 0.0001) and 2 years (66.7% vs 25.9%, P = 0.03) postwithdrawal. Treatment reinitiation was required in 13 (13.4%) participants, and 13 others remained in a sustained inactive carrier state by the end of the study follow-up. No criteria reliably predicted safe treatment withdrawal. Results from this trial do not support TDF withdrawal as a therapeutic strategy. HBsAg loss was infrequent within 2 years of stopping long-term TDF. If withdrawal is considered, HBV DNA should be carefully monitored with reinitiation of therapy if levels rise above 4 log10IU/mL to reduce the risk of ALT flares, as they were not associated with subsequent HBsAg decline or loss.
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影响因子：
3.7
作者：
Sohn HR;Min BY;Song JC;Seong MH;Lee SS;Jang ES;Shin CM;Park YS;Hwang JH;Jeong SH;Kim N;Lee DH;Kim JW
通讯作者：
Kim JW
影响因子：
25.7
作者：
García-López M;Lens S;Pallett LJ;Testoni B;Rodríguez-Tajes S;Mariño Z;Bartres C;García-Pras E;Leonel T;Perpiñán E;Lozano JJ;Rodríguez-Frías F;Koutsoudakis G;Zoulim F;Maini MK;Forns X;Pérez-Del-Pulgar S
通讯作者：
Pérez-Del-Pulgar S
影响因子：
29.4
作者：
Hadziyannis, Stephanos J.;Sevastianos, Vassilios;Hadziyannis, Emilia
通讯作者：
Hadziyannis, Emilia
影响因子：
3
作者：
Su, Chien-Wei;Wu, Chun-Ying;Wu, Jaw-Ching
通讯作者：
Wu, Jaw-Ching
DOI：
10.1002/hep.31506
发表时间：
2021-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Lau DTY;Ganova-Raeva L;Wang J;Mogul D;Chung RT;Lisker-Melman M;Chang KM;Shaikh OS;Janssen HLA;Wahed AS;Lok AS;Hepatitis B Research Network
通讯作者：
Hepatitis B Research Network