| 摘要: | 背景：C型肝炎病毒感染導致腎臟功能衰退，包括直接性引發慢性發炎或腎絲球腎炎、間接性的造成肝硬化演變成肝腎症候群，C肝病毒治療的重要性不言而喻，新型的抗病毒藥物(direct acting agent, DAA)的病毒清除率以及藥物頻率治療方便性無疑是感染C型肝炎合併慢性腎臟疾病患者的一線曙光，然而以Sofosbuvir為主的藥物組合在C型肝炎完治與Sofosbuvir對腎功能影響的利弊得失，目前仍是主要的考量。
方法：在PubMed、Embase、Cochrane Library及Web of science數據庫中搜索了隨機對照試驗或前瞻性或回溯性世代研究，研究文獻以感染C型肝炎合併慢性腎臟疾病族群接受Sofosbuvir為主的藥物治療組合，並提供藥物治療過程中不同時間點的腎功能的數值，便將予以納入，進而分析藥物療程結束、達到SVR12以及追蹤後一年三個不同時間點的腎功能與藥物治療前的腎功能變化量。洗腎病患、肝腎移植後、有明確腎絲球腎炎診斷，以及同時有HBV或HIV感染者會予以排除。
結果：
本篇研究一共納入了12篇文獻，包含8篇回溯性研究及4篇前瞻性研究，包含20877位C型肝炎感染合併慢性腎臟疾病尚未進入透析病患，50.6% (N=10560) 為男性，45.2% (N=9446) 有肝硬化，12.6% (N=2632) 為中重度腎功能不全；其中共11463位C型肝炎感染合併慢性腎臟疾患者接受Sofosbuvir為主的藥物治療納入治療前後腎功能變化統合分析。
統合分析主要結果顯示，在藥物療程結束、達到SVR12以及追蹤後一年三個時間點的腎功能相較於藥物治療前的腎絲球過濾率改善的情形分別為3.877±.1432, P=0.007；3.419±2.220, P=0.124 及4.796±4.005, p=0.231，中重度腎功能不全族群在三個時間點的腎絲球過濾率改善的情形分別為9.228±4.812, P=0.055；7.616±3.816, P=0.046及8.570±5.186, p=0.098。
在次族群的分析中顯示，納入研究的族群中，年齡小於60歲及男性比例越高的研究顯示在三個時間點的腎功能都相較於治療前改善較為穩定；肝硬化比例越高的研究在治療完一年的追蹤時間點有較明顯的腎功能改善；藥物合併上，併用RBV並無使腎臟功能惡化，而當藥物組合上當合併NS3/4A比例越低或是合併NS5A比例越高的研究，在三個時間點的腎功能都相較於治療前穩定。
結論：在慢性腎臟疾病合併C型肝炎患者接受Sofosbuvir為主的藥物治療對於維持腎臟功能是有益的；臨床上C型肝炎合併慢性腎臟功能不全患者，尤以男性、年紀輕、合併肝硬化的族群，以及合併NS5A類組合藥物族群可能預期有較穩定改善的腎功能。
Background: hepatitis C virus infection can result in kidney function deterioration including causing glomerulonephritis or chronic inflammation disorder directly and hepato-renal syndrome owing to decompensated liver cirrhosis indirectly. Due to direct-acting agent with promising efficacy and safety, the vicious cycle between these two vital organs might have the chance to overcome under complete DAA treatment. The metabolism of sofosbuvir is through kidney, therefore, it has been a concerned greatly issue that weighting the benefit of treating hepatitis C and the risk of medications related kidney injury.
Methods: Four database including PubMed, Embase, Cochrane Library and Web of science were searched. Articles focus on hepatitis C infected chronic kidney disease patients receiving sofosbuvir-based regimen treatment and reports pre-and post-treatment renal function value were collected. Renal function comparison between baseline, end of treatment, serology viral response 12 and end of follow up were analyzed. Exclusion criteria included dialysis groups, post transplanted groups, known glomerulonephritis or HBV/HIV co-infection. Subgroup with different chronic kidney disease severity, age, gender, cirrhosis and drug combination regimen were also performed.
Results: Twelve studies (eight retrospective and four prospective) containing 11463 patients including 73 (6%) advanced chronic kidney disease (G3b-G5, eGFR less than 45) were included. The meta-analysis results illustrated that renal function (eGFR value) got improvement while comparing three time point including at end of treatment, SVR12 and end of follow up to pre-medications baseline status with value 3.877±1.432, P=0.007；3.419±2.220, P=0.124 and 4.796±4.005, P=0.231 respectively. Also, moderate to advanced chronic kidney disease groups with improvement of eGFR with values 9.228±4.812, P=0.055; 7.616±3.816, P=0.046 and 8.570±5.816, P=0.098. In subgroup analysis, renal function keeps relatively stable while studies groups with age younger than 60 years old and male. Studies containing higher liver cirrhosis ratio showed significant renal function improvement at end of follow up. Besides, lower NS3/4 A and higher NS5A combination regimen also seems to have better renal outcome.
Conclusion: Sofosbuvir-based regimen might have effect in renal function stabilization in hepatis C infected chronic kidney diseases groups including in more severity groups. In clinical practice, renal prognosis may be expected in groups with male, younger groups, liver cirrhosis or combination with SOF and NS5A regimen. |
