研究使用抗腫瘤壞死因子治僵直性脊椎炎或類風濕關節炎合併慢性B型肝炎的病人的肝癌預估風險

Estimated risk of hepatocellular carcinoma in chronic hepatitis B patients with rheumatic diseases treated with tumor necrosis factor blockers

目的：藉由B型肝炎病毒引起肝細胞癌的計算圖表來研究使用抗腫瘤壞死因子治療僵直性脊椎炎及類風濕關節炎合併B型肝炎慢的感染的病人的肝炎發生風險。方法：回溯性研究，回顧自西元2007年1月至2012年5月間中山醫學大學附設醫院所使用抗腫瘤壞死因子的病人，並檢驗病患之血清中的aminotransferase（ALT）及肝炎病毒標記：B型肝炎表面抗原（HBsAg）、B型肝炎表面抗體（HBsAb）、B型肝炎核心抗體（HBV core IgG antibody）及B型肝炎病毒DNA（HBVDNA）。利用台灣的B型肝炎病毒有關的肝細胞癌風險計算圖表評估病人使用抗腫瘤壞死因子前後的肝細胞癌風險變化。結果：合共150個病人在這段期間曾使用抗腫瘤壞死因子治療，其中94人為僵直性脊椎炎病患，56人為類風濕關節炎病患。病人中有18人的血清發現含B型肝炎表面抗原，使用抗腫瘤壞死因子前，所有病患從未使用過抗病毒藥物治療。兩位病患因資料不足而被排除。在16位病患中，其中12位病患合乎B型肝炎病毒再活化的定義，兩位病患曾使用抗病毒藥物治療，其中7（44%）名病患在停止抗腫瘤壞死因子後病毒量下降。並沒有病患因使用抗腫瘤壞死因子而使肝功能持續異常。當中9名病患因使用抗腫瘤壞死因子治療後，其5年及10年內得到肝細胞癌之風險有上升。其他人則因使用抗病毒藥物或停止使用抗腫瘤壞死因子而使得肝細胞癌之風險持平或下降。結論：使用生物製劑前必須評估病患的B型肝炎感染狀態及有適當的風險管理措施，B型肝炎的病人除了要小心監控病人的HBV DNA病毒量之外，也要評估病患肝細胞癌的危險因子。使用肝細胞癌的計算圖表為一個簡單的協助評估肝癌風險、幫助治療決策及與病人溝通的良好工具。

Objective: To study the associations of the risk of hepatocellular carcinoma (HCC) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients with chronic hepatitis B (CHB) who have been treated with anti-TNF antagonists by nomograms for the risk of HCC in patients with chronic hepatitis B virus (HBV) infection in Taiwan. Methods: We carried out a retrospective study and reviewed all of the patients of RA and AS treated with etanercept or adalimumab from January 2007 to May 2012 in Chung Shan Medical University Hospital. A series of serum aminotransferase (ALT) levels and hepatitis serologic status, including: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV core IgG antibody (HBcAb) and HBV-DNA was reviewed. We calculated the risk scores of HCC of those patients with CHB infections and investigated the fluctuations of risk scores in nomograms developed by Yang et al. for risk of HCC in patients with chronic HBV infection in Taiwan. Results: A total of 150 patients with RA or AS were documented to be treated with entanercept and adalimumab. Eighteen (12%) of the 150 patients were positive for HbsAg. None of them had received antiviral treatment for hepatitis B before starting on anti-TNF agents. Two patients were excluded due to missing data. Fifty-six percent (9/16) of patients had increased risk scores for HCC during the anti-TNF treatment; 7 (44%) patients’ risk scores remained unchanged or were lowered by interventions such as antiviral treatment or interruption of anti-TNF therapy. Conclusion: Fifty-six percent (9/16) of patients had increased risk scores for HCC during the anti-TNF treatment. Nomograms for risk of HCC in patients with chronic HBV infection are an easy-touse tool based on independent clinical risk factors for rheumatologists to employ in the communication of risk management and decision making concerning CHB patients treated with anti-TNF therapy. Further investigation and observation of the association of the biological agent with HCC in CHB patients are needed.