Intrahepatic cholestasis, or primary intrahepatic cholestasis, refers specifically to stones that originate in the intrahepatic bile duct system, excluding stones that drain from the gallbladder and migrate up the intrahepatic bile duct, or stones that form secondary to biliary stasis and biliary inflammation caused by other biliary diseases such as injurious biliary strictures, biliary cysts, and biliary anatomical variations.
Intrahepatic bile duct stones are a common benign biliary disease in the Asia-Pacific region, and the incidence can be as high as 30.0% to 50.0% in endemic regions. They are particularly common in the vast regions of South China, Southwest China, Yangtze River basin and Southeast coast of China. The causes of intrahepatic bile duct stones are not fully understood, and gender, diet, and environmental factors are involved in the development of the disease, and malnutrition and poverty are significantly associated with the development of intrahepatic bile duct stones. Because of the complexity of the lesions, the high recurrence rate and the frequent serious complications, this disease is an important cause of death from benign biliary diseases in China.
Intrahepatic bile duct stones are mainly divided into two types: bile pigment stones and cholesterol stones, the majority of which are bile pigment stones. Most of the bile pigment stones are secondary to bile duct strictures and bacterial infections. The proportion of cholesterol stones is relatively small, accounting for only 5.8% to 13.1% of all intrahepatic bile duct stones, but there has been an increasing trend of cholesterol stones in recent years. Congenital or acquired metabolic abnormalities are involved in the development of cholesterol stones. Because of the acute angle of the confluence of the left hepatic duct with the common bile duct, the left liver is more likely to form and retain stones when biliary stenosis is present here.
Asymptomatic intrahepatic bile duct stones may be found incidentally during an abdominal examination. When epigastric or right upper abdominal pain, jaundice and fever are present, it suggests that the patient has developed acute cholangitis. In severe cases, patients may develop purulent cholangitis or liver abscess or even biliary sepsis. Very few patients can develop thrombocytopenia and enhanced platelet function, leading to abnormalities in coagulation and fibrinolysis. Long-standing bile duct stones and biliary strictures can lead to distal bile duct dilatation and atrophy of the liver parenchyma. In some patients, intrahepatic bile duct stones can fall into the common bile duct causing obstructive jaundice, acute cholangitis or biliary pancreatitis. The incidence of bile duct cell carcinoma in patients with intrahepatic bile duct stones is 2.4%-10.0%, and the proportion of patients with bile duct cell carcinoma combined with intrahepatic bile duct stones is as high as 17.0%-27.0%.
Depending on the distribution of stones in the liver, the degree of lesions in the corresponding hepatic ducts and liver, and the combination of extrahepatic bile duct stones, intrahepatic bile duct stones are divided into 2 main types and 1 additional type.
Type I: Regional type, where stones are confined along the intrahepatic biliary tree in 1 or several liver segments, often combined with stenosis of the hepatic ducts in the lesioned segment and atrophy of the affected liver segments. The clinical presentation can be static, obstructive or cholangitis.
Type II: Diffuse type, with stones spread throughout the bile ducts of both hepatic lobes, is subdivided into three subtypes according to the parenchymal lesions of the liver.
Type IIa: diffuse type, without significant parenchymal fibrosis and atrophy.
Type IIb: diffuse type with regional parenchymal fibrosis and atrophy, usually combined with stenosis of the main hepatic duct in the atrophic liver region.
Type IIc: Diffuse type with extensive fibrosis of the liver parenchyma leading to secondary biliary cirrhosis and portal hypertension, usually combined with severe stenosis of the right and left hepatic ducts or bile ducts below the confluence.
Type E: Additional type, referring to the combination of extrahepatic bile duct stones. It is subdivided into 3 subtypes according to the functional status of the sphincter of Oddi.
Ea: Normal sphincter of Oddi.
Eb: Sphincter of Oddi is relaxed.
Ec: narrowed sphincter of Oddi.
The treatment of bile duct stones in the liver has always been a difficult problem for hepatobiliary surgeons. The common clinical treatment modalities include: partial hepatectomy, transhepatic parenchymal bile duct dissection and stone extraction, transhepatic common duct fiberoptic choledochoscopy and T-tube drainage, hilar choledochoplasty and bile-intestinal anastomosis, and liver transplantation. As for the choice of the procedure, an individualized treatment plan should be developed according to the site and extent of the patient’s stones. Regardless of the treatment modality, the treatment principle of “removing stones, relieving obstruction, clearing drainage, and preventing recurrence” should be followed.
I. Hepatectomy for intrahepatic bile duct stones
Hepatectomy is the most thorough and effective treatment for intrahepatic bile duct stones. According to the location of bile duct stricture and the extent of stones, regular resection of liver segments or lobes is the key to avoid residual lesions and reduce the recurrence rate after surgery. The indications for surgery include: intrahepatic bile duct stones limited to one liver lobe or one liver segment; combined with liver tissue atrophy, fibrosis or liver abscess formation; combined with intrahepatic bile duct cell carcinoma; multiple intrahepatic bile duct stones with bile duct strictures where endoscopic or access treatment is not effective. Complications after hepatectomy mainly include subdiaphragmatic infection and bile leak, etc. Most of them can be improved by conservative treatment, while severe cases require puncture and drainage or surgical treatment. Figures 1 and 2 show cases of multiple bile duct stones with hepatic tissue atrophy combined with lower bile duct stones confined to the left outer lobe of the liver, which were cured by laparoscopic resection of the left outer lobe of the liver and laparoscopic extraction of the stones in combination with choledochoscopy.
Otani et al. reported that among 54 patients with intrahepatic bile duct stones, those who underwent hepatic resection had significantly better rates of bile duct stricture (18.2% vs. 58.3%), stone recurrence (16.0% vs. 54.3%), and long-term survival (77.0% vs. 50.0%) than those treated with percutaneous percutaneous biliary lithotripsy and stone extraction. Liang Lijian et al. reported that the proportion of 504 patients with intrahepatic bile duct stones treated with hepatic resection was 55.8%, and the stone residual rate was 21.7%, compared with 32.0% in non-hepatic resected patients. He Zhenping et al. reported that the surgical complication rate of 644 patients with intrahepatic bile duct stones treated by hepatic resection was 18.9%, and the perioperative mortality rate was 1.5%, with a mean follow-up of 15.5 years and an excellent rate of 88.0%.
Hepatoportal choledochotomy and angioplasty
Hepatoportal choledochotomy is mainly applied to patients with stenosis of the left and right hepatic duct openings or stenosis of the common hepatic duct. According to the scope and degree of the lesion, we can choose the methods of stenosis ring dissection and stenosis segment excision to release the bile duct obstruction, remove the stones distal to the obstruction and restore the bile flow. In order to avoid local restenosis after surgery, a T-tube should be left in the bile duct for support, and Cheng et al. treated 190 patients with postoperative residual stones close to the bile duct stenosis with stenotomy and T-tube support. 88.4% of the patients had complete stone removal. Figures 3 and 4 show a case of multiple stones in the right intrahepatic bile duct. Since the patient involved both the anterior and posterior lobe of the right liver bile ducts, treatment with hepatic resection would result in too little residual liver tissue, so the right hepatic duct stenosis was treated with a combination of stenotomy and reconstruction via parenchymal bile duct.
Transhepatic parenchymal choledochotomy
Transhepatic parenchymal choledochotomy is mainly used for emergency or serious patients, aiming at temporary drainage of bile, control of biliary infection, improvement of liver function, and gaining a chance for patients to be treated by surgery again. This procedure may be considered for patients with limited lesions close to the liver surface. Based on the removal of the stone, it is important to treat the bile duct stricture and restore the bile flow. However, due to the extensive nature of most intrahepatic bile duct stones, a simple transhepatic parenchymal bile duct extraction is often not sufficient. Most of them need to be treated in combination with transhepatic common duct lithotripsy.
Biliary-intestinal anastomosis
Bile-intestinal anastomosis is mostly used in combination with hilar choledochotomy, and it is suitable for patients with long stenosis of the near hilar bile duct, and the original bile duct tissue cannot be reconstructed after excision or resection of the stenosis. The bile duct-jejunum anastomosis can be used to obtain a sufficiently spacious anastomosis to avoid obstruction and ensure unobstructed bile drainage. When the hepatic duct is incised to a high level and multiple bile duct openings are present, a hepatoportal-jejunal pelvic anastomosis can be applied for reconstruction. Reflux cholangitis is a common complication of bile-intestinal anastomosis surgery. To reduce the incidence of reflux cholangitis, bile-intestinal anastomosis should be performed with Roux-en-Y anastomosis using the upper jejunal segment, and the intestinal loop between the bile-intestinal anastomosis and jejunal anastomosis should be no shorter than 40 cm; before performing bile-intestinal anastomosis, it should be ensured that stones have been removed and obstruction has been released. Xie Chuping and others reported 74 patients with intrahepatic bile duct stones who underwent single ductoplasty followed by Roux-en-Y anastomosis, and only 2 cases developed reflux cholangitis and 3 cases had residual stones in the distal intrahepatic bile duct after surgery, which achieved very good treatment results.
V. Liver transplantation
For patients with extensive bile duct stones causing liver destruction and liver function loss, liver transplantation should be considered. Zhang Jianjun and Yang Yong have reported the successful treatment of refractory intrahepatic bile duct stones by liver transplantation. However, in view of the shortage of donor livers and the need for long-term immunosuppression after liver transplantation, effective treatment should be taken at the early stage of the lesion to avoid serious destruction of the liver.
Application of fiberoptic cholangioscopy
Fiberoptic choledochoscope can observe the bile duct under direct vision to see whether there are strictures and stones, and can be used with a lithotripsy basket to extract stones under direct vision, which has unique advantages for the treatment of deep stones that cannot be reached by conventional instruments. In recent years, the development and application of choledochoscopic laser lithotripsy and hydraulic shock wave lithotripsy techniques and equipment have enriched the treatment of refractory intrahepatic bile duct stones. The routine application of intraoperative and postoperative choledochoscopy can evaluate the stone extraction effect and reduce the stone residual rate. Marilyn et al. reported that the application of intraoperative cholangioscopy reduced the residual rate of surgical stones from 78.0% to 24.4%, and the final residual rate of stones was reduced to 2.4% after postoperative treatment by cholangioscopic stone extraction.
VII. Treatment of residual stones
The residual stone rate after intrahepatic bile duct stone surgery reported in domestic literature is around 30.0%. And residual stones often mean treatment failure, and most patients will have recurrence of cholangitis. Therefore, it is necessary to enhance the perioperative management to reduce the residual stone rate.
Preoperative application of CT, MRCP, ERCP, PTC and other means for careful disease assessment can help to accurately determine the site of bile duct stricture and the extent of lesion involvement, and provide help for reasonable selection of surgical plan. Intraoperative choledochoscopic exploration, ultrasound or cholangiography are routinely applied to help detect residual stones and reduce the proportion of residual stones after surgery.
Postoperative fiberoptic choledochoscopy via the T-tube sinus tract is the treatment of choice, and the combined application of liquid electroshock wave lithotripsy and laser lithotripsy can significantly improve the success rate of stone extraction. Reoperation is also a common method to treat residual stones, especially for patients with recurrent postoperative cholangitis, combined liver abscess, liver tissue atrophy, and suspected combined bile duct cancer. Among the 644 patients observed by He Zhenping and others, the percentage of those who had undergone more than two surgeries was as high as 93.3%.
In conclusion, intrahepatic bile duct stones are complex and intractable benign diseases, and one or a combination of multiple surgical procedures should be selected for treatment according to the location and extent of the patient’s lesions. The exact removal of biliary obstruction and restoration of bile flow is the key to successful treatment. For patients with relatively limited lesions, regular hepatectomy is the most ideal treatment modality. Intraoperative and postoperative choledochoscopic exploration and stone extraction help to improve the stone retrieval rate. For patients with postoperative residual stones causing recurrent cholangitis, liver abscess, liver atrophy, or suspected cancer, reoperative treatment should be aggressively performed based on accurate evaluation.