HBV DNA，表面抗原预示停止核苷（t）治疗后的复发

StephenW

HBV DNA, surface antigen predict relapse after ceasing nucleos(t)ide therapy

Kuo MT, et al. J Gastroenterol Hepatol. 2018;doi:10.1111/jgh.14142.
March 12, 2018

Baseline hepatitis B DNA and end-of-treatment HBV surface antigen levels predicted virological relapse among patients with chronic HBV who ceased Baraclude or Viread therapy during chemotherapy, according to a recently published study.

“HBV reactivation can be spontaneous but is most commonly triggered by cancer chemotherapy, immune suppression, or alteration in immune function,” Ming-Te Kuo, MD, from the Chang Gung University College of Medicine, Taiwan, and colleagues wrote. “Multiple clinical guidelines and studies have shown that antiviral prophylaxis before the initiation of immunosuppressive treatment or chemotherapy can markedly decrease the risk of HBV reactivation.”

Between January 2010 and November 2015, Kuo and colleagues enrolled 122 patients with chronic HBV and cancer. At baseline, 78 patients had HBV DNA less than 2,000 IU/mL and 44 patients were active carriers with HBV DNA of 2,000 IU/mL or higher. Mean duration of antiviral prophylactic for chemotherapy was 62.2 weeks.

Median follow-up after patients ceased Baraclude (entecavir, Bristol-Myers Squibb) or Viread (tenofovir disoproxil fumarate, Gilead) was 106.5 weeks (range, 24-288 weeks). Fifty-two patients experienced virological relapse during follow-up.

Multivariate analysis showed that baseline HBV DNA of 2,000 IU/mL or higher (HR = 3.014; 95% CI, 1.662-5.465) and end-of-treatment HBsAg levels (HR = 1.657; 95% CI, 1.145-2.398) independently predicted virologic relapse.

Among patients with baseline HBV DNA less than 2,000 IU/mL, rituximab (HR = 5.416; 95% CI, 1.875-15.642) and end-of-treatment HBsAg levels (HR = 1.846; 95% CI, 1.154-2.953) independently predicted virological relapse.

The researchers found that an HBsAg level of 501.2 IU/mL was the best cut-off value to predict virological relapse within 3 years (AUROC = 0.773). HBsAg of 500 IU/mL was significant for those with a baseline HBV DNA less than 2,000 IU/mL, but not for those with higher HBV DNA.

Additionally, the researchers observed 18 patients who experienced clinical relapse. Multivariate analysis showed that old age, use of rituximab, Fibrosis-4 index higher than 3.25, combination of baseline alanine aminotransferase of 40 U/L and HBV DNA of 2,000 IU/mL or higher, and end-of-treatment HBsAg were independent risk factors for clinical relapse.

“The consolidation duration of antiviral prophylaxis for 6 to 12 months after cessation of the immunosuppressive treatment might be not enough for these patients. We suggested that the stopping rules of antiviral prophylaxis treatment in these cancer patients should be the same with the immunocompetent [chronic hepatitis B (CHB) patients],” the researchers wrote. “Close monitoring is needed for timely retreatment in cancer patients after the withdrawal of antiviral prophylaxis.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

StephenW

HBV DNA，表面抗原预示停止核苷（t）治疗后的复发

Kuo MT等人。 J Gastroenterol Hepatol。 2018; DOI：10.1111 / jgh.14142。
2018年3月12日

根据最近发表的一项研究，基线乙型肝炎DNA和治疗结束时HBV表面抗原水平预测了在化疗期间停止Baraclude或Viread治疗的慢性HBV患者的病毒学复发。

“HBV再激活可以是自发的，但最常见的是由癌症化疗，免疫抑制或免疫功能改变引发，”台湾长庚大学医学院的Ming-Te Kuo博士及其同事写道。 “多项临床指南和研究表明，免疫抑制治疗或化疗开始前的抗病毒预防可显着降低HBV再激活的风险。”

在2010年1月至2015年11月期间，Kuo和同事招收了122名慢性HBV和癌症患者。在基线时，78名患者的HBV DNA低于2,000 IU / mL，44名患者是HBV DNA为2,000 IU / mL或更高的活性载体。抗病毒药物预防化疗的平均持续时间为62.2周。

患者停用Baraclude（恩替卡韦，Bristol-Myers Squibb）或Viread（替诺福韦酯替诺福韦富马酸盐，Gilead）后的平均随访时间为106.5周（范围24-288周）。随访期间有52名患者出现病毒学复发。

多变量分析显示，2,000 IU / mL或更高（HR = 3.014; 95％CI，1.662-5.465）和治疗结束时HBsAg水平（HR = 1.657; 95％CI，1.145-2.398）的基线HBV DNA独立预测病毒学复发。

在基线HBV DNA低于2,000 IU / mL的患者中，利妥昔单抗（HR = 5.416; 95％CI，1.875-15.642）和治疗结束时HBsAg水平（HR = 1.846; 95％CI，1.154-2.953）独立预测病毒学复发。

研究人员发现，501.2 IU / mL的HBsAg水平是预测3年内病毒学复发的最佳截止值（AUROC = 0.773）。对于基线HBV DNA低于2,000 IU / mL的患者，500 IU / mL的HBsAg显着，但对于那些HBV DNA较高的患者则无显着差异。

此外，研究人员观察到18名经历临床复发的患者。多因素分析显示，年龄较大，使用利妥昔单抗，纤维化-4指数高于3.25，基线丙氨酸转氨酶40 U / L与HBV DNA 2,000 IU / mL或更高以及治疗结束时HBsAg的组合是独立风险临床复发因素。

“停止免疫抑制治疗后6〜12个月的抗病毒预防巩固治疗时间可能不足以满足这些患者的需求。我们建议这些癌症患者的抗病毒预防治疗的停止规则应该与免疫功能正常的[慢性乙型肝炎（CHB）患者]相同，“研究人员写道。 “在撤销抗病毒药物预防后，需要密切监测癌症患者的及时复治。” - Talitha Bennett

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