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目的了解长期口服四硫化四砷(As_4S_4)对急性早幼粒细胞白血病(APL)患者肝脏的慢性毒性。方法对长期服用 As_4S_4的 APL 患者各时期生化指标、超声检查结果(包括肝、脾大小形态,实质回声及门脉宽度的检查)及肝纤维化指标(PⅢNP 及Ⅳ型胶原)进行跟踪分析。结果 106例服用 As_4S_4的 APL 患者,中位随访时间为36(6～72)个月,丙肝阴性组84例,初始服用时,丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)高于2倍正常值的发生率分别为16.7%和15.5%.ALT、AST、γ-谷氨酰转移酶(GGT)水平比服药前有明显升高(P 值均<0.05),连续用药0.5,1.0,2.0,3.0年及3.0年以上 ALT、AST、GGT 水平与用药前相比差异无统计学意义(P 值均>0.05),其他生化指标:碱性磷酸酶(ALP)、乳酸脱氧酶(LDH)、总胆红素(TBIL)、直接胆红素(DBIL)、总蛋白(TP)、白蛋白(ALB)、白蛋白与球蛋白比值(A/G)、尿素氮(BUN)、肌酐(CRE)与用药前相比差异均无统计学意义(P 值均>0.05);丙肝阳性组22例,初始服用时 ALT、AST 高于2倍正常值的发生率分别为63.6%和59.1%,连续用药2年后肝功能恢复至接近正常水平。连续用药3年以上的 APL 患者42例,丙肝阴性组33例患者中,2例睥肿大、1例门脉增宽,21例(63.6%)被诊断为脂肪肝,16例进行肝纤维化指标检测均为正常;丙肝阳性组9例患者中,4例脾肿大,2例门脉增宽,6例(66.7%)被诊断为脂肪肝,6例进行肝纤维化指标检测,2例高于正常值。结论 APL 患者长期服用 As_4S_4对肝功能无显著影响,未引起明显的肝纤维化和门脉高压症状,但脂肪肝发病率较高,应长期随访。
Objective To investigate chronic toxicity of As 4 S 4 in the liver of acute promyelocytic leukemia (APL) patients. Methods The biochemical parameters, ultrasonographic results (including liver and spleen size, echogenicity and portal vein width) and hepatic fibrosis indexes (PⅢNP and type Ⅳ collagen) of APL patients taking As_4S_4 long-term were followed up. Results A total of 106 APL patients treated with As_4S_4 had a median follow-up of 36 (6 ~ 72) months and 84 patients with hepatitis C-negative. After initial administration, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 16.7% and 15.5% respectively higher than those of 2 times normal.The levels of ALT, AST and γ-glutamyl transferase (GGT) were significantly higher than those before treatment (P <0.05) The levels of ALT, AST and GGT were not significantly different from those before treatment (P> 0.05). Other biochemical indexes such as alkaline phosphatase (ALP), creatine kinase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin and albumen ratio (A / G) BUN and creatinine were not significantly different from those before treatment (P> 0.05). The positive rates of ALT and AST in initial group were 22.6 % And 59.1% respectively. After 2 years of continuous medication, liver function recovered to near normal level. Of the 42 patients with APL who were treated for more than 3 years in a row, 2 of 33 patients with hepatitis C negative were swollen, 1 had portal vein widened, 21 (63.6%) were diagnosed as fatty liver and 16 had liver fibrosis Of the 9 patients with hepatitis C positive, 4 had splenomegaly, 2 had portal vein widened, 6 (66.7%) were diagnosed as fatty liver, 6 had liver fibrosis detection, and 2 Higher than normal. Conclusion Long-term administration of As_4S_4 in APL patients has no significant effect on liver function, and does not cause obvious symptoms of liver fibrosis and portal hypertension. However, the incidence of fatty liver is high and should be followed up for a long time.