Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma

Hepatolithiasis(HL)poses a significant risk for cholangiocarcinoma(CCA)development,with reported incidences ranging from 5%-13%.Risk factors include older age,smoking,hepatitis B infection,and prolonged HL duration.Chronic inflammation and mechanical stress on the biliary epithelium contribute to CCA pathogenesis.Hepatectomy reduces CCA risk by removing stones and atrophic liver segments.However,residual stones and incomplete removal increase CCA risk.Kim et al identified carbohydrate antigen 19-9,carcinoembryonic antigen,and stone laterality as CCA risk factors,reaffirming the importance of complete stone removal.Nonetheless,challenges remain in preventing CCA recurrence post-surgery.Longer-term studies are needed to elucidate CCA risk factors further.

Rare primary squamous cell carcinoma of the intrahepatic bile duct: A case report and review of literature

BACKGROUND Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis.Adenocarcinoma is the most common pathological type of cho-langiocarcinomas,but rare squamous,adenosquamous,and mucinous variants have been reported without adequate clinical data.CASE SUMMARY This report describes a rare case of primary squamous cell carcinoma(SCC)of the intrahepatic bile duct.The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms.Examination revealed hepatitis B surface antigen positivity,a slight increase in alfa-fetoprotein to 16.34 ng/mL,and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe,which was initially thought to be hepatocellular carcinoma.Laparoscopic re-section was performed,and the final pathology suggested a rare primary SCC of the intrahepatic bile duct.Immunohistochemistry indicated positivity for villin,partial positivity for p63,and negativity for hepatocyte,CK7,CK8,CK19,and CK20.The Ki-67 index was approximately 60%.The patient received six cycles of Tegio chemotherapy.A new lesion was detected in the liver after 15 months.The surgery was performed,and the patient was followed-up at a local hospital.To date,no new lesions have been observed.CONCLUSION Surgery is the first choice for resectable lesions,and combined chemotherapy based on pathology is essential for increasing overall survival.

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma:A systematic review and meta-analysis

BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy.Its incidence and mortality rates have been increasing in recent years.Hepatitis C virus(HCV)infection is a risk factor for development of cirrhosis and cholan-giocarcinoma.Currently,surgical resection remains the only curative treatment option for cholangiocarcinoma.We aim to study the impact of HCV infection on outcomes of liver resection(LR)in intrahepatic cholangiocarcinoma(ICC).AIM To study the outcomes of curative resection of ICC in patients with HCV(i.e.,HCV+)compared to patients without HCV(i.e.,HCV-).METHODS We conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)and observational studies to assess the outcomes of LR in ICC in HCV+patients compared to HCV-patients in tertiary care hospitals.PubMed,EMBASE,The Cochrane Library and Scopus were systematically searched from inception till August 2023.Included studies were RCTs and non-RCTs on patients≥18 years old with a diagnosis of ICC who underwent LR,and compared outcomes between patients with HCV+vs HCV-.The primary outcomes were overall survival(OS)and recurrence-free survival.Secondary outcomes include perioperative mortality,operation duration,blood loss,intrahepatic and extrahepatic recurrence.RESULTS Seven articles,published between 2004 and 2021,fulfilled the selection criteria.All of the studies were retrospective studies.Age,incidence of male patients,albumin,bilirubin,platelets,tumor size,incidence of multiple tumors,vascular invasion,bile duct invasion,lymph node metastases,and stage 4 disease were comparable between HCV+and HCV-group.Alanine transaminase[MD 22.20,95%confidence interval(CI):13.75,30.65,P<0.00001]and aspartate transaminase levels(MD 27.27,95%CI:20.20,34.34,P<0.00001)were significantly higher in HCV+group compared to HCV-group.Incidence of cirrhosis was significantly higher in HCV+group[odds ratio(OR)5.78,95%CI:1.38,24.14,P=0.02]compared to HCV-group.Incidence of poorly differentiated disease was significantly higher in HCV+group(OR 2.55,95%CI:1.34,4.82,P=0.004)compared to HCV-group.Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+group(OR 8.31,95%CI:2.36,29.26,P=0.001)compared to HCV-group.OS was significantly worse in the HCV+group(hazard ratio 2.05,95%CI:1.46,2.88,P<0.0001)compared to HCV-group.CONCLUSION This meta-analysis demonstrated significantly worse OS in HCV+patients with ICC who underwent curative resection compared to HCV-patients.

Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor α mRNA in isolated rat intrahepatic bile duct epithelial cells *

AIM To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor α mRNA (TNF α mRNA) with cultured rat intrahepatic bile duct epithelial cells.

Congenital left intrahepatic bile duct draining into gastric wall mimicking biliary reflux gastritis

Abnormalities and variations of the biliary ducts are not rare.Most aberrant bile ducts eventually drain into the descending part of duodenum through the papilla of vater.However,drainage of the left hepatic bile duct into the stomach is extremely rare.A 29-year old man was admitted to the hospital with the diagnosis of biliary reflux gastritis.Comprehensive imaging modalities were performed including electronic endoscopy,endoscopic ultrasonography,endoscopic retrograde cholangiopancreatography and magnetic resonance cholangio-pancreatography.Finally,congenital ectopic left intrahepatic bile duct draining into the stomach was found,which caused biliary reflux gastritis.The patient did not receive any surgery.Good recovery was achieved by medical treatment.

A case of very large intrahepatic bile duct adenoma followed for 7 years

A 70-year-old man was referred to our hospital due to abnormal liver function. A tumor of 92 mm × 61 mm was detected on ultrasound screening of the left liver lobe. Although the tumor was suspected to be intrahepatic bile duct carcinoma, he had chronic heart disease and was unable to undergo surgery. Therefore, he was followed without further testing. No increase in tumor serum markers or tumor size was observed for the subsequent 7 years. We continued to suspect intrahepatic bile duct carcinoma, and we decided to perform a tumor biopsy. Tumor biopsy findings indicated intrahepatic bile duct adenoma(BDA), which is a rare benign epithelial liver tumor typically ranging from 1 mm to20 mm. We herein report a case of very large BDA followed for 7 years.

Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD catheter in ERCP

The rendezvous procedure combines an endoscopic technique with percutaneous transhepatic biliary drainage(PTBD).When a selective common bile duct cannulation fails,PTBD allows successful drainage and retrograde access for subsequent rendezvous techniques.Traditionally,rendezvous procedures such as the PTBDassisted over-the-wire cannulation method,or the parallel cannulation technique,may be available when a bile duct cannot be selectively cannulated.When selective intrahepatic bile duct(IHD) cannulation fails,this modified rendezvous technique may be a feasible alternative.We report the case of a modified rendezvous technique,in which the guidewire was retrogradely passed into the IHD through the C2 catheter after end-to-end contact between the tips of the sphincterotome and the C2 catheter at the ampulla's orifice,in a 39-year-old man who had been diagnosed with gallbladder carcinoma with a metastatic right IHD obstruction.Clinically this procedure may be a feasible and timesaving technique.

Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy

Aims: The abnormal increase of bile acid is found in intrahepatic cholestasis of pregnancy (ICP). It also can be observed the damage of placental tissue in ICP. The aim of this study was to find the associations of the bile acid in umbilical vein and the damage of placental tissue. Methods: Thirty women diagnosed with ICP and fifty normal pregnant women between September 2015 and September 2017 at Nanshan District Maternity & Child Healthcare Hospital of Shenzhen were included in this study. The glycocholic acid (GA), total bile acids (TBA), total bilirubin (TB), direct bilirubin (DB) and albumin level in umbilical vein were measured by cycle enzyme method in ICP and control group. The placental damage was analyzed by morphologic study using hematoxylin dyes in two groups. The correlation between the level of the bile acid in the umbilical vein and the damage of the placenta was assessed using SPSS software. Results: The GA, TBA, TB, DB and albumin level in umbilical vein were significantly higher in ICP than those of pregnant women, respectively. The placental villis were expanded and the structure was destroyed in ICP. The vessel was damaged and the cell trophoblast hyperplasia in ICP. It also can be seen that there was obvious nodules and a typical fibrous necrotic substance in ICP but not in control group. There is a positive correlation between the level of the TBA in the umbilical vein and the damage of the placenta in ICP. Conclusion: The TBAs were significantly higher in umbilical vein and were related to the placental damage in ICP.

Clinical Studies on Ultrasound Lithotripsy in Intrahepatic Bile－duct via Abdomen

patients with left/right intrahepatic bile-duct calculi received ultrasonic lithotresis via abdomen by using the percutaneous cholecystoscopeand ultrasonic lithotresis apparatus. The results indicated that all the surgical manipulations were successful with a residual rate of 6. 7 %, compared with a residual rate of 78. 2 % in 23 cases of left/right intrahepatic bile-duct lithiasis treated simultaneously by lithotomy apparatus. The differences between them were statistically significant (μ= 4. 29, P<0. 01). Among 12 cases undergoing follow-up observation , no side effect due to ultrasonic lithotresis and no residual calculus after 2- 4 check-ups with B-mode ultrasound diagnostic set were found and all of their symptoms disappeared except for 1 case.

Liver stiffness in pregnant women with intrahepatic cholestasis of pregnancy:A case control study

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a rare but severe complication for both the mother and the unborn child.The diagnosis is primarily based on elevated serum levels of bile acids.In a large ICP cohort,we here study in detail liver stiffness(LS)using transient elastography(TE),now widely used to noninvasively screen for liver cirrhosis within minutes.AIM To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated pregnancy.METHODS LS and hepatic steatosis marker controlled attenuation parameter(CAP)were measured in 100 pregnant women with ICP using TE(Fibroscan,Echosens,Paris,France)between 2010 and 2020.In 17 cases,LS could be measured postpartum.450 women before and 38 women after delivery with uncomplicated pregnancy served as control group.Routine laboratory,levels of bile acids and apoptosis marker caspase-cleaved cytokeratin 18 fragment(M30)were also measured.RESULTS Women with ICP had significantly elevated transaminases but normal gammaglutamyl transferase(GGT).Mean LS was significantly increased at 7.3±3.0 kPa compared to the control group at 6.2±2.3 kPa(P<0.0001).Postpartum LS decreased significantly in both groups but was still higher in ICP(5.8±1.7 kPa vs 4.2±0.9 kPa,P<0.0001),respectively.In ICP,LS was highly significantly correlated with levels of bile acids and M30 but not transaminases.No correlation was seen with GGT that even increased significantly after delivery in the ICP group.Bile acids were mostly correlated with the liver apoptosis marker M30,LS and levels of alanine aminotransferase,aspartate aminotransferase,and bilirubin.In multivariate analysis,LS remained the sole parameter that was independently associated with elevated bile acids.CONCLUSION In conclusion,LS is significantly elevated in ICP which is most likely due to toxic bile acid accumulation and hepatocyte apoptosis.In association with conventional laboratory markers,LS provides additional non-invasive information to rapidly identify women at risk for ICP.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and elevated levels of liver enzymes and bile acids.The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate,but the efficacy of this approach remains less than optimal.Recently,polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects.AIM To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate on bile acid levels,liver enzyme indices,and pregnancy outcomes in patients with ICP.METHODS From June 2020 to June 2021,600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via randomnumber table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(control group,n=300)or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(combined group,n=300).Outcome measures included bile acids levels,liver enzyme indices,and pregnancy outcomes.RESULTS Prior to treatment,no significant differences were observed between the two groups(P>0.05).Post-treatment,patients in both groups had significantly lower pruritus scores,but the triple-drug combination group had lower scores than the dual-drug combination group(P<0.05).The bile acid levels decreased significantly in both groups,but the decrease was more significant in the triple-drug group(P<0.05).The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group(P<0.05).CONCLUSION Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP,providing a positive impact on pregnancy outcome and a high safety profile.Further clinical trials are required prior to clinical application.

The abnormal expression of E-cadherin in intrahepatic bile duct epithelia cells in biliary atresia and its relationship with apoptosis

To explore the relationship between the expression of E-cadherin and the apoptosis in intrahepatic bile duct epithelial cells in biliary atresia (BA).Methods The E-cadherin expression was demonstrated by immunohistochemical staining for the liver specimens from 38 children with BA and 16 normal children.The apoptotic intrahepatic bile duct epithelial cells in these specimens were visualized by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay,and the apoptotic index (AI) was calculated from the percentage of apoptotic cells in total cells.Results The intensity of E-cadherin expression in bile duct epithelial cells in BA group was lower than that in the normal control group (0.33±0.12 vs 0.62±0.20,P<0.01).On the other hand,the AI in BA group was significant higher than that in control group (51.74±19.93 vs 12.34±19.32,P<0.01).An inverse correlation was detected between the intensity of E-cadherin and the AI in the liver from children with BA.Conclusion The abnormal decrease of E-cadherin may lead to an increase of the apoptosis of intrahepatic bile epithelial cells in BA,resulting in developmental disorder of intrahepatic bile duct and ductal plate malformation in the liver.12 refs,4 figs,1 tab.

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass

AIM:To study the diagnosis of hepatocellular carcinoma(HCC)presenting as bile duct tumor thrombus with no detectable intrahepatic mass.METHODS:Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration,were collected.Their clinical and imaging data were retrospectively analyzed.The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings.RESULTS:Jaundice was the major clinical symptom of the patients.The elevated serum total bilirubin,direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease.Of the 6 patients showing evidence of viral hepatitis,5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9,and 1 was positive for serum carcinoembryonic antigen.No patient was correctly diagnosed by ultrasound.The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct,with large filling defects presenting as casting moulds in the expanded bile duct,hypervascular intraluminal nodules,debris or blood clots in the bile duct.No obvious circular thickening of the bile duct walls was observed.CONCLUSION:Even with no detectable intrahepatic tumor,bile duct HCC thrombus should be considered in patients predisposed to HCC,and some imaging signs are indicative of its diagnosis.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Extrahepatic bile duct reconstruction in pigs with heterogenous animal-derived artificial bile ducts:A preliminary experience

BACKGROUND Extrahepatic biliary duct injury(BDI)remains a complicated issue for surgeons.Although several approaches have been explored to address this problem,the high incidence of complications affects postoperative recovery.As a nonimmunogenic scaffold,an animal-derived artificial bile duct(ada-BD)could replace the defect,providing good physiological conditions for the regeneration of autologous bile duct structures without changing the original anatomical and physiologic conditions.AIM To evaluate the long-term feasibility of a novel heterogenous ada-BD for treating extrahepatic BDI in pigs.METHODS Eight pigs were randomly divided into two groups in the study.The animal injury model was developed with an approximately 2 cm segmental defect of various parts of the common bile duct(CBD)for all pigs.A 2 cm long novel heterogenous animal-derived bile duct was used to repair this segmental defect(group A,ada-BD-to-duodenum anastomosis to repair the distal CBD defect;group B,ada-BD-to-CBD anastomosis to repair the intermedial CBD defect).The endpoint for observation was 6 mo(group A)and 12 mo(group B)after the operation.Liver function was regularly tested.Animals were euthanized at the above endpoints.Histological analysis was carried out to assess the efficacy of the repair.RESULTS The median operative time was 2.45 h(2-3 h),with a median anastomosis time of 60.5 min(55-73 min).All experimental animals survived until the endpoints for observation.The liver function was almost regular.Histologic analysis indicated a marked biliary epithelial layer covering the neo-bile duct and regeneration of the submucosal connective tissue and smooth muscle without significant signs of immune rejection.In comparison,the submucosal connective tissue was more regular and thicker in group B than in group A,and there was superior integrity of the regeneration of the biliary epithelial layer.Despite the advantages of the regeneration of the bile duct smooth muscle observed in group A,the effect on the patency of the ada-BD grafts in group B was not confirmed by macroscopic assessment and cholangiography.CONCLUSION This approach appears to be feasible for repairing a CBD defect with an ada-BD.A large sample study is needed to confirm the durability and safety of these preliminary results.

Mechanism of Dynamic Near-infrared Fluorescence Cholangiography of Extrahepatic Bile Ducts and Applications in Detecting Bile Duct Injuries Using Indocyanine Green in Animal Models

Fluorescence intraoperative cholangiography（IOC） is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green（ICG）. However, the dynamic process and mechanism of fluorescence IOC have not been elucidated in previous publications. Herein, the optical properties of the complex of ICG and bile, dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated. The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration. Extrahepatic bile ducts could fluoresce 2 min after intravenous injection, and the fluorescence intensity reached a peak at 8 min. In addition, biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum. Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein. Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells, excretion of ICG into the bile and then its interaction with protein molecules in the bile. Moreover, fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models. All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.

Pediatric intrahepatic bile duct adenoma-rare liver tumor: A case report

BACKGROUND Intrahepatic bile duct adenoma(BDA)is one of the rarest of the rare benign tumors of the liver in the pediatric age group.It arises from the epithelial lining of intrahepatic bile ducts.The overall incidence of BDA is 1.3%of all primary benign liver tumors.Few case reports of this rare tumor occurring in adult population are present in the literature and to date,only one pediatric case has been reported worldwide.CASE SUMMARY An 18-month-old male child presented with chief complaints of mass per abdomen for 8 mo.Computerized tomography abdomen revealed a well-defined exophytic solid tumor arising from the posteroinferior margin of the right lobe of the liver with heterogenous enhancement and cystic changes,suggesting a suspicion of hepatoblastoma.Non-anatomical liver resection was done and a tumor of 10 cm×9.5 cm was excised.Histopathology of the specimen was conclusive with the diagnosis of intrahepatic bile duct adenoma,which was further supported by immunohistochemistry panel testing.The post-operative period was uneventful.On follow-up,the child was doing well and had no postoperative complication.CONCLUSION Intrahepatic bile duct adenoma in children is very rare and to date only one case has been reported.This is the second pediatric case of intrahepatic bile duct adenoma in the world.Additionally this is the first ever case of such a large tumor presenting in a child.

Molecular overview of progressive familial intrahepatic cholestasis

Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.

A Novel Preparation of Artificial Bile Ducts for Clinical Application of Biliary Diseases

The aim of this paper was to prepare an artificial bile duct using polytetrafluoroethylene（PTFE） for the development of a new treatment for biliary diseases. The basic properties of the PTFE material, such as crystallization properties, were characterized; the surface structures of the sample tubes were observed by scanning electron microscope（SEM） and water permeability test of different tubes was evaluated by osmosis device. Six Shanghai white pigs were selected to do the implantation surgery of the artificial biIe ducts. After 90 days, the artifidai bile ducts were removed from the pigs and characterized by electron microscope in order to study the tissue compatibility. The results of animal test indicated that the artificial bile duct had good tissue compatibility. This new artificial bile duct shows great potential for the treatment of biliary diseases.