台湾超过 6% 停止 HBV 治疗导致严重肝炎爆发

StephenW

AASLD，肝脏会议，2021 年 11 月 12-15 日马克·马斯科利尼在恩替卡韦 (ETV) 或富马酸替诺福韦酯 (TDF) 停止后，台湾一项 10,000 人的全国性研究显示，严重肝炎发作的四年累积发生率为 6.58% [1]。严重发作后 6 个月内的四年死亡发生率为 0.79%。义大医疗集团和台湾义守大学的研究人员指出，核苷（酸）类似物（Nucs）不能治愈乙肝病毒感染。一个 4769 人的国际研究小组中，只有 2% 的人在 10 年内从血清中清除了乙型肝炎表面抗原 (HBsAg) [2]。停用 NRTIs 可能会促进 HBsAg 消失，但停用 NRTIs 通常会导致病毒重新激活——有时还会导致严重的危及生命的爆发。但是，NRTI 停用后出现严重发作的风险仍不清楚。为了更多地了解耀斑发生率和风险因素，台湾的研究人员开展了一项全国性的基于人群的队列研究。在台湾，慢性 HBV 感染者经常停止 ETV 或 TDF，因为国民健康保险通常只支付固定期限的药物。研究人员从国家健康保险实验室数据库中收集了之前未经治疗的开始 ETV 或 TDF 的人的数据，这些人继续治疗至少 1 年然后停止。该分析排除了患有严重合并症的人，包括任何恶性肿瘤、其他病毒感染或酒精相关疾病。研究小组将严重肝炎突发定义为血清丙氨酸氨基转移酶（ALT）高于正常上限（即 200 U/L）的 5 倍，加上血清胆红素高于 2 mg/dL。他们列出了严重发作后 6 个月内的死亡或肝移植。随访持续至死亡、肝移植、再治疗后 6 个月或 2018 年 12 月 31 日。10,192 名队列成员的中位年龄为 50.9 岁，其中 28.3% 是女性。肝硬化的显着并发症或合并症的发生率为 10.7%，肝失代偿率为 4.6%，糖尿病为 27%，高血压为 34.6%，血脂异常为 44.9%。有可用数据的 7413 人的中位 ALT 为 24 U/L。三分之二的人参加了 ETV 和三分之一的 TDF。中位治疗持续时间为 3 年。在中位 2.15 年的随访期间，3360 人（35.9%）恢复了抗病毒治疗。停止治疗后 4 年，459 人出现严重肝炎发作，4 年累积发病率为 6.58%（95% 置信区间 [CI] 5.91 至 7.30）。 43 人在严重发作后 6 个月内死亡，13 人需要肝移植，4 年死亡加移植的发生率为 0.79%（95% CI 0.58 至 1.05）。不计算移植，4 年死亡率达到 0.63%。当 Nucs 在以下风险比 (HR) 和 95% CI 下停止时，四个因素预测了严重的耀斑：— 每增加 10 岁：HR 1.19，95% CI 1.09 至 1.29，P < 0.0001— 男性：HR 1.76，95% CI 1.41 至 2.22，P < 0.0001— 肝硬化的诊断：HR 1.84，95% CI 1.45 至 2.33，P < 0.0001— 肝功能失代偿病史：HR 1.45，95% CI 1.01 至 2.09，P = 0.044在该分析中与爆发无关的因素是 TDF 与 ETV、异常血脂、糖尿病和高血压。三个变量预测严重耀斑后的死亡率：— 每增加 10 岁：HR 1.70，95% CI 1.32 至 2.19，P < 0.0001— 肝硬化诊断：HR 6.12，95% CI 3.17 至 11.8，P < 0.0001— 高血压：HR 2.29，95% CI 1.09 至 4.82，P < 0.029研究人员敦促将慢性乙型肝炎患者停止 ETV 或 TDF 时严重爆发和死亡的风险因素告知政策制定者和个体患者。来自 Jules：演讲者在口头中说“很难直接确认偶然的关系，但强有力的证据表明，亚洲慢性乙型肝炎患者的大多数严重发作是 HBV 复制的结果”。

StephenW

Severe Hepatitis Flare in Over 6% Stopping HBV Therapy in Taiwan

AASLD, The Liver Meeting, November 12-15, 2021

Mark Mascolini

Four-year cumulative incidence of severe hepatitis flare stood at 6.58% in a 10,000-person nationwide study in Taiwan after entecavir (ETV) or tenofovir disoproxil fumarate (TDF) stopped [1]. Four-year incidence of death within 6 months of a severe flare measured 0.79%.

Nucleos(t)ide analogs (Nucs) can’t cure HBV infection, noted researchers from E-Da Healthcare Group and I-Shou University in Taiwan. Only 2% of a 4769-person international study group taking first-line ETV or TDF for chronic hepatitis B infection cleared hepatitis B surface antigen (HBsAg) from serum in 10 years [2]. Withdrawing NRTIs may promote HBsAg loss, but stopping NRTIs usually leads to viral reactivation—and sometimes in severe life-threatening flares. But the risk of severe flares following NRTI withdrawal remains unclear.

To learn more about flare incidence and risk factors, researchers in Taiwan mounted a nationwide population-based cohort study. In Taiwan people with chronic HBV infection often stop ETV or TDF because national health insurance usually pays for the drugs only for a fixed period. The investigators gathered data from the National Health Insurance Laboratory Databases for previously untreated people starting ETV or TDF who continued treatment for at least 1 year then stopped. The analysis excluded people with severe comorbidities including any malignancy, other viral infections, or alcohol-related disease.

The research team defined severe hepatitis flare as serum alanine aminotransferase (ALT) above 5 times the upper limit of normal (that is, 200 U/L) plus serum bilirubin above 2 mg/dL. They tabulated deaths or liver transplantations within 6 months of severe flare. Follow-up continued until death, liver transplantation, 6 months after retreatment, or December 31, 2018.

Median age stood at 50.9 years in the 10,192 cohort members, 28.3% of whom were women. Rates of notable complications or comorbidities were 10.7% for cirrhosis, 4.6% for hepatic decompensation, 27% for diabetes, 34.6% for hypertension, and 44.9% for abnormal lipids. Median ALT stood at 24 U/L in 7413 people with available data. Two thirds of the group took ETV and one third TDF. Median treatment duration measured 3 years.

During a median 2.15 years of follow-up, 3360 people (35.9%) resumed antiviral therapy. Through 4 years after stopping therapy, 459 people had a severe hepatitis flare for a 4 year cumulative incidence of 6.58% (95% confidence interval [CI] 5.91 to 7.30). Forty-three people died within 6 months of a severe flare and 13 needed a liver transplant for a 4-year death-plus-transplant incidence of 0.79% (95% CI 0.58 to 1.05). Not counting transplants, 4-year mortality came to 0.63%.

Four factors predicted severe flares when Nucs stopped at the following hazard ratios (HR) and 95% CIs:

— Every additional 10 years of age: HR 1.19, 95% CI 1.09 to 1.29, P < 0.0001
— Male sex: HR 1.76, 95% CI 1.41 to 2.22, P < 0.0001
— Diagnosis of cirrhosis: HR 1.84, 95% CI 1.45 to 2.33, P < 0.0001
— History of hepatic decompensation: HR 1.45, 95% CI 1.01 to 2.09, P = 0.044

Factors not associated with flares in this analysis were TDF vs ETV, abnormal lipids, diabetes, and hypertension.

Three variables predicted mortality after a severe flare:

— Every additional 10 years of age: HR 1.70, 95% CI 1.32 to 2.19, P < 0.0001
— Cirrhosis diagnosis: HR 6.12, 95% CI 3.17 to 11.8, P < 0.0001
— Hypertension: HR 2.29, 95% CI 1.09 to 4.82, P < 0.029

The researchers urged informing policymakers—and individuals patients—about risk factors for severe flares and death when people with chronic hepatitis B stop ETV or TDF.

from Jules: in the oral the presenter said “it’s difficult to directly confirm casual relationship but robust evidence showed that the majority of severe flares in Asian patients with CHB were the result f HBV replication”.

小牡丹

94％的停药成功率很好了。停药后坚持化验，定时评价身体状况，可以尝试。

乙肝人1949

让别人试验？要不自实验下？

小牡丹

做人要有尊严。嗑药超过5年的，副作用严重的，应该尝试。看看王震宇的亿人化验结果，有很多战友尝试过了，问题不大

Newbegin

小牡丹 发表于 2021-11-14 13:18
94％的停药成功率很好了。停药后坚持化验，定时评价身体状况，可以尝试。 ...

该工作做得很扎实，赞

乙肝人1949

不知道你们有勇气不。可以自己问问自己

乙肝人1949

己所不欲，勿施于人

afug

停药加上严密监视才可以， 上面的没有提及后期的监视情况

StephenW

回复 afug 的帖子

同意  我实际上对 6% 的相对较低的数字感到惊讶.

"台湾慢性HBV感染者经常停止ETV或TDF，因为国民健康保险通常只支付固定期限的药物。" -
未说明停止时患者的状态 , 例如，血清 HBsAg 水平 . 它提到 35% 恢复抗病毒治疗. 研究似乎表明 :肝硬化、失代偿病史、高龄、男性患者 停止治疗时应非常小心 .