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Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis
Qin Yang1, Yong Zhou, Fu-Yu Li
1Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, China. lfy_74@vip.163.com.
Background:
There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis (PC), which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.
Methods:
After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.
Results:
The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and beta-glucuronidase activity.
Conclusion:
Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.
Insights
Gefitinib effectively inhibits biliary hyperplasia and stone formation in patients with hepatolithiasis. This targeted therapy shows promise for preventing biliary restenosis and recurrent stones after surgery.
Area of Science:
- Gastroenterology
- Hepatology
- Oncology
Background:
- Hepatolithiasis, characterized by proliferative cholangitis (PC), lacks effective treatments for preventing stone recurrence post-surgery.
- Current therapeutic options for PC and associated lithogenesis are limited.
Purpose of the Study:
- To investigate the efficacy of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, in mitigating cholangio hyperplasia and lithogenesis in PC.
- To evaluate gefitinib's potential as a novel therapeutic strategy for hepatolithiasis.
Main Methods:
- A cohort of 94 hepatolithiasis patients underwent choledochoscopic lithotomy with indwelling catheters.
- 49 patients received gefitinib treatment (250 mg weekly) via catheter, while 45 served as controls.
- Choledochoscopic biopsies were performed at 6 and 12 weeks to assess treatment effects.
Main Results:
- Gefitinib treatment significantly reduced EGFR, PCNA, and procollagen I expression.
- Patients receiving gefitinib exhibited decreased biliary epithelial and submucosal gland hyperplasia, and reduced collagen fiber deposition.
- Gefitinib also lowered mucin 3 expression and beta-glucuronidase activity.
Conclusions:
- Postoperative gefitinib administration effectively inhibits PC-mediated hyperplasia and lithogenesis.
- Gefitinib presents a potential novel strategy for preventing biliary restenosis and stone recurrence in hepatolithiasis patients.
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