| 摘要: | 研究目的
慢性病毒性肝炎在治療結核病病患的過程中是否會影響病人肝功能異常出現的機會和肝功能異常出現的時間目前仍有爭論。本研究的目的在探討在治療前肝功能正常的急性結核病病人在接受抗結核藥物治療時，慢性病毒性肝炎是否會影響肝功能異常的比率和出現的時間。
研究方法
所有在2002 到 2009 年間在這個中臺灣三級轉診醫學中心新診斷的結核病人資料會經由電腦資訊系統收集病人一系列的肝功能資料，包括轉胺?和黃膽指數。暫時性肝臟生化指數異常的定義如以下，需合乎以下兩個條件 (1)假如轉胺?上昇高於正常值，但是在持續用抗結核藥物的情?下，肝臟生化指數又回復到正常的範圍 (2)假如藥物一開始因為肝?生化指數異常而停用，但在肝臟生化指數回復到正常後，重新使用抗結核藥物後並未再出現肝臟生化指數異常。藥物引起的肝炎定義為服用抗結核藥物後肝臟生化檢查中的轉胺?超過120 IU/L 合併急性肝炎的症狀，或是轉胺?超過了200 IU/L 合併或未合併急性肝炎症狀。當肝功能回復正常後，在重新使用抗結核藥物後轉胺?又超過了120IU/L。肝臟生化檢查異常出現的比率和出現的時間會在有B型肝炎、C型肝炎及無慢性病毒性肝炎（對照組）間比較。
研究結果
共有 533 病人進入此研究。藥物引起的肝炎的比率，在治療前肝功能正常者，在有慢性病毒性肝炎和無慢性病毒性肝炎的對照組比較並無顯著差異 [8% (32/392) 比上7% (11/161), P > 0.05]，暫時肝臟生化檢查異常出現的比率在無慢性病毒性肝炎者的比率較低且有統計上的明顯差異 [2% (9/392) 比上12% (20/161), P < 0.001]。平均肝臟生化檢查異常出現的時間，在藥物引起的肝炎者在對照組是40 天，在慢性病毒性B型肝炎者是39 天， 在慢性病毒性C型肝炎者是 67 天 （所有 P > 0.05)。 暫時性肝臟生化檢查異常出現的時間，在對照組是23 天，在慢性病毒性B型肝炎者是48 天，在慢性病毒性C型肝炎者是 68 天( 和對照組比較，所有 P < 0.05)。在慢性病毒性肝炎的病人，發生暫時性肝臟生化檢查的比率是藥物引起的肝炎發生的兩倍，不論異常是否發生在服藥開始的兩個月內。而在無病毒性肝炎的病人，在前兩個月發生肝功能異常者，有76%是藥物引起的肝炎，而在兩個月後發生的肝功能異常者，完全是藥物引起的肝炎。
研究結論
在有慢性病毒性肝炎的病人，肝臟生化功能檢查異常的原因以暫時性肝臟生化檢查異常的比率較高，暫時性肝臟生化檢查異常發生的時間也較晚，而藥物引起的肝炎發生的時間則無明顯差異。醫師需要將肝功能異常發生時間列入考量，以決定是否要停藥。
Objective: Whether chronic viral hepatitis affects the incidence and onset time of elevation of liver biochemistry test during anti-tuberculosis (TB) treatment in patients with chronic hepatitis is still controversial. The aim of this retrospective study was to answer whether chronic viral hepatitis would influence the incidence and onset time of liver biochemistry test in patients with normal baseline liver function.
Methods: All patients diagnosed with active TB and being treated at a tertiary referral hospital in central Taiwan between 2002 and 2009 were identified from medical records, among which 533 patients enrolled in the study. Serial liver function tests at baseline and during anti-TB treatment were collected including levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and direct bilirubin. Transient liver function impairment (TLI) was defined under 2 sets of conditions: (1) if AST or ALT levels increased at any level, but resolved spontaneously despite continued anti-TB medications; (2) if the drug was first discontinued and the patient was successfully re-challenged with the drug after the liver function test results were normal. Drug induced hepatitis (DIH) was confirmed in a patient if the liver transaminase level exceeded 120 IU/L with symptoms of acute hepatitis or exceeded 200 IU/L with or without symptoms while the anti-TB drug treatment was stopped, and the liver transaminase level increased to >120 IU/L when the patient was re-challenged with the culprit drug. The incidence and onset time of DIH and TLI in patients with and without chronic viral hepatitis (controls) were compared.
Results: The incidence of DIH was similar in patients with and without chronic hepatitis (8% [32/392] vs. 7% [11/161], P > 0.05). The incidence of transient liver function impairment (TLI) was significantly lower in controls than in chronic hepatitis patients (2% [9/392] vs. 12% [20/161], P < 0.001. The mean onset of DIH in the control, hepatitis B virus (HBV), and hepatitis C virus (HCV) groups were not significantly different (40 days, 39 days, and 67 days, respectively, all P > 0.05). The mean onset times of TLI in the control, HBV, and HCV groups were significantly different (23 days, 48 days, and 68 days, respectively, all P < 0.05). In patients with chronic viral hepatitis, liver function impairment during anti-TB therapy may be caused by TLI or DIH, and the chance of TLI is approximately twice of DIH regardless of whether the onset time is within the first 2 months after initiation of anti-TB therapy. Whereas in patients without chronic hepatitis who experienced liver function impairment within 2 months of treatment, the likelihood of DIH is 76%, TLI is 24% and liver function impairment occurred after 2 months were all caused by DIH.
Conclusions: Liver function impairment during anti-TB therapy in patients with chronic viral hepatitis was mostly because of TLI, with TLI occurring later than in controls. Chronic viral hepatitis had no significant effect on the incidence of DIH. Physicians should take the onset time of liver function impairment into consideration to decide whether the potential hepatotoxic drug should be stopped. |
