利用 Tenofovir 來治療慢性 B 型肝炎病人對其他口 服抗病毒使用後反應不佳之療效與安全性評估

Efficacy and Safety of Tenofovir for Chronic Hepatitis B Patients After Suboptimal Virological Response to Other Nucleos(t)ide Analogues Treatment

陳奎閔(Kwei-Ming Chen)

指導教授 ： 張浤榮 ； 林俊哲

中山醫學大學/醫學院/醫學研究所/碩士(2016年)

摘要

簡介:慢性B型肝炎的病人在接受干安能(Lamivudine),干適 能(Adefovir),喜必福(Telbivudine)或貝樂克(Entecavir)後, 不論是單一療法或是組合療法,常常都會遇到病毒反應不佳的情 況。本研究就是要探討這些接受其他口服抗病毒藥物之後反應不 佳的情況下改用惠立妥來評估它的療效與安全性。
方法: 從2011年9月至2015年12月,我們回溯性的去分析慢 性B型肝炎病人在接受非惠立妥(non-Tenofovir)的口服抗病毒 藥物後產生反應不佳的情況後,之後接受惠立妥單一治療大於24 週的病人才納入分析。B型肝炎病毒量(HBV DNA),表面抗原 (HbsAg),以及其他的生化檢查每3-6月都會定期追蹤。我們的主 要endpoint是病人的病毒量在惠立妥治療當中檢驗不到(又稱之 完全病毒反應)。次要endpoint是e抗原(HbeAg)的陰轉率以及腎 臟功能安全性的評估。
結果: 總共22個病人被納入最終分析。12個病人(54.5%)在 平均127週的治療當中達到完全病毒反應。有7個病人(31.8%)甚 至在惠立妥治療24周後就達到完全病毒反應。那些沒有達到完全 病毒反應的患者他們的病毒量也都大幅度的下降。14個病人當中 有3個病人(21.4%)達到e抗原的陰轉。沒有病人的腎臟功能受到 損害。先前口服核甘酸藥物治療的時間的長短對於病人後續接受
惠立妥治療的完全病毒反應有影響(p=0.048) 。
結論: 惠立妥單一療法對於慢性B型肝炎病人接受口服抗
病毒藥物後反應不佳的情況下是一種強力的救援療法。先前口服 核甘酸藥物治療的時間越長的話可以預測病人後續接受惠立妥 的療效。

關鍵字

惠立妥 ； 慢性B型肝炎 ； 病毒反應不佳 ； 核甘酸類似物

並列摘要

Introductions: A suboptimal response is common in chronic hepatitis B (CHB) patients treated with Lamivudine (LAM), Adefovir (ADV), Telbivudine (LdT) or Entecavir (ETV); either by monotherapy or combination therapy. This study is aimed to evaluate the efficacy and safety of Tenofovir (TDF) monotherapy for CHB patients after suboptimal virological response (SOR) to
other nucleos(t)ide analogues (NUC) treatment.
Methods: From September 2011 to December 2015, we retrospectively analyzed CHB patients with SOR to other NUCs treatment. Patients subsequently received TDF monotherapy at least 24 weeks were included. Hepatitis B virus (HBV) DNA, HbsAg and other biochemistries were monitored every 3-6 months. The primary endpoint was defined as an undetectable HBV DNA level during TDF treatment. Secondary endpoints were hepatitis B envelop antigen (HBeAg) seroclearance and safety of renal function.
Results: A total of 22 patients were included in the study. Twelve (54.5 %) patients achieved CVR after median 127 weeks treatment. Seven patients (31.8%) achieved CVR early at 24 weeks of TDF treatment. Patients did not achieved CVR also had marked HBV DNA suppression after TDF treatment. Three of fourteen patients (21.4%) developed HbeAg seroclearance. No patient developed renal impairment during TDF treatment. The prior Nucs treatment duration had impact on CVR rate (p = 0.048).
Conclusions: TDF monotherapy is a potent rescue therapy for CHB patients with SOR to other Nucs. Longer prior Nucs treatment had marginal effect on CVR rate. Patient’s renal function remained stable after TDF treatment, even in those with baseline eGFR< 80 ml/min 1.73 m2.

並列關鍵字

Tenofovir ； Chronic hepatitis B ； suboptimal virological response ； nucleos(t)ide analogues

參考文獻

Lamivudine for patients with chronic hepatitis B and advanced liver

disease. N Engl J Med ; 351:1521–31.

AC et al.,2014. Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population. Clin Gastroenterol Hepatol ;12:885–93.

[4] Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H et al.,2013. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology;58:98–107.

[5] Wu CY, Lin JT, Ho HJ, Su CW, Lee TY, Wang SY et al.,2014. Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide