目的:在评估肝功能时,必须区分结构性吲哚菁绿(ICG)排泄缺陷。最近有报道称,由于SLCO1B3基因的同源改变而导致的OATP1B3表达缺失可诱导ICG排泄缺陷;然而,其与临床检查的相关性以及异质性SLCO1B3基因改变的临床意义尚不清楚.
方法:在评估15分钟ICG保留率(ICGR15)和tech-99m-半乳糖基血清白蛋白(99mTc-GSA)肝闪烁显像后,在49例接受肝切除术的患者中评估了OATP1B3的表达。此外,在无OATP1B3表达的患者中分析了SLCO1B3的改变.随后,对59例接受肝切除术治疗的结直肠癌肝转移(CRLM)患者进行分析。
结果:在49例患者中,6(12%)的OATP1B3表达缺失。他们的ICGR15值明显更高(74.7%vs.23.5%;p<0.0001),更好的修饰白蛋白-胆红素(ALBI)等级(≤2A级,100%vs.42%;p=0.010),更正常的99mTc-GSA肝闪烁显像(100%vs.28%;p=0.0003),和更好的病理性肝纤维化(F0-1,100%vs.49%;p=0.027)与具有OATP1B3表达的那些相比。三个可用的无OATP1B3表达的病例冷冻块显示SLCO1B3纯合改变。在59例正常肝脏背景的CRLM患者中,5例(8.5%)在SLCO1B3中有杂合插入,但与其他患者相比,他们的ICGR15值或其他临床表现没有差异.
结论:结构性ICG排泄缺陷可能由OATP1B3表达的完全缺失定义。改良的ALBI等级和99mTc-GSA肝闪烁显像可用于检测结构性ICG排泄缺陷。
OBJECTIVE: Constitutional indocyanine green (ICG) excretory defects must be distinguished when assessing liver function. The absence of OATP1B3 expression due to homogenous alterations in the
SLCO1B3 gene has been recently reported to induce ICG excretory defects; however, its association with the clinical examinations and the clinical implications of heterogeneous
SLCO1B3 gene alteration remain unclear.
METHODS: OATP1B3 expression was evaluated in 49 patients who underwent hepatectomy after evaluation of the ICG retention rate at 15 min (ICGR15) and technetium-99 m-galactosyl serum albumin (99mTc-GSA) hepatic scintigraphy. Additionally, alterations in
SLCO1B3 were analyzed in patients without OATP1B3 expression. Subsequently, 59 patients who underwent hepatectomy for colorectal liver metastasis (CRLM) were analyzed.
RESULTS: Of 49 patients, 6 (12%) had absent OATP1B3 expression. They had significantly higher ICGR15 value (74.7% vs. 23.5%; p < 0.0001), better modified albumin-bilirubin (ALBI) grade (≤grade 2A, 100% vs. 42%; p = 0.010), more normal 99mTc-GSA hepatic scintigraphy (100% vs. 28%; p = 0.0003), and better pathological liver fibrosis (F0-1, 100% vs. 49%; p = 0.027) compared to those with OATP1B3 expression. Three available frozen blocks of cases without OATP1B3 expression showed homozygous alterations in
SLCO1B3. Of 59 patients with CRLM in normal liver background, five (8.5%) had heterozygous insertion in
SLCO1B3, however they had no difference in ICGR15 values or other clinical findings compared to the other patients.
CONCLUSIONS: Constitutional ICG excretory defects may be defined by the complete absence of OATP1B3 expression. The modified ALBI grade and 99mTc-GSA hepatic scintigraphy were useful for detecting constitutional ICG excretory defects.