Hepatic Bile Duct Research Articles

Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases.

Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA. Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p=0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm2, p=0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.

Hilar Anatomy in 3035 Living Liver Donors: A Novel Classification for Donor Surgery and Suitability, Hepatic Surgeries, and Hepatobiliary Interventions.

This study examines the vascular and biliary variations in 3035 liver donors. We propose a novel classification of hepatic arteries, portal veins, and bile ducts and clinically relevant donor classification. Preoperative imaging and operative details of 3035 donors from 2005 to 2020 were reviewed. Hilar anatomical variations were identified and grouped on the basis of incidence and clinical relevance. Hilar structures are classified according to the numbers supplying or draining the graft: for the hepatic artery, right (R) and left (L), RA1/LA1 (1 artery), RA2/LA2 (2 arteries), and RA3/LA3 (3 arteries), respectively, further defined on the basis of the inflow trunk into C (for common hepatic artery), S (for superior mesenteric artery), and L (for left gastric artery); for the portal vein, RP1 (1 vein) and RP2 (2 veins) for the right lobe; and for the hepatic duct, RB1/LB1 (1 duct), RB2/LB2 (2 ducts), RB3 (3 right ducts), and RB4 (4 right ducts). Donors were classified on the basis of anatomical variations into 3 groups: class 1 and class 2 donors, who can donate liver with acceptable risks, and class 3 donors, who are high-risk donors because they are anatomically unacceptable ( Figures S1 to S4, SDC , http://links.lww.com/TP/C918 ). Defining hilar anatomical variations and donor grouping into anatomy-based clinical classes helps in operative planning of donors, hepatobiliary surgeries, and interventional procedures.

Hirsutella sinensis mycelium polysaccharides attenuate the TGF-β1-induced epithelial-mesenchymal transition in human intrahepatic bile duct epithelial cells

Hirsutella sinensis is the anamorph of Ophiocordyceps sinensis, and its mycelia has been used to effectively treat a variety of hepatobiliary diseases in clinical practice. In the present study, we performed a systematic study on the composition and structure of its polysaccharides, and then employed a TGF-β1-induced human intrahepatic bile duct epithelial cell-epithelial-mesenchymal transition (HIBEC-EMT) model to investigate their effects on treating primary biliary cholangitis (PBC) based on hepatic bile duct fibrosis. Four polysaccharide fractions were obtained from H. sinensis mycelia by hot-water extraction, DEAE-cellulose column and gradient ethanol precipitation separation. HSWP-1a was an α-(1,4)-D-glucan; HSWP-1b and HSWP-1d mainly consisted of mannoglucans with a backbone composed of 1,4-linked α-D-Glcp and 1,4,6-linked α-D-Manp residues branched at O-6 of the 1,4-linked α-D-Glcp with a 1-linked α-D-Glcp as a side chain; and HSWP-1c mainly contained galactomannoglucans. These polysaccharide fractions protected HIBECs from a TGF-β1-induced EMT, according to HIBEC morphological changes, cell viability, decreased E-cadherin and ZO-1 expression, and increased vimentin and collagen I expression. Furthermore, the effects of the polysaccharides might be mediated by inhibiting the activation of the TGF-β/Smad signaling pathway, which attenuated hepatic bile duct fibrosis and potential PBC effects.

Papillary neoplasms of biliary tract-a histopathological surprise

Papillary neoplasms of the biliary tract is a relatively new entity which most often comes as a histological surprise. They are often diagnosed as malignancies and are treated like that. But the prognosis is better when compared to malignancy itself. Here we reported two cases of papillary neoplasms of the biliary tract. First case was a 50 year old male who was evaluated for obstructive jaundice and on evaluation found to be type 3b hilar cholangiocarcinoma and underwent left hepatectomy with extra hepatic bile duct resection and portal lymphadenectomy. Histo-pathological report was intra-ductal papillary neoplasm - biliary type (IPN B). Second case was an incidental finding of arterial enhancing lesion in the gallbladder wall on CT scan, which was done for the evaluation of bicytopenia. This also was reported as malignancybin pre-operative imaging and hence underwent anticipated extended cholecystectomy with wedge resection of 2 cm adjacent hepatic parenchyma. Again histopathology revealed it as intra-cholecystic papillary neoplasm with focal dysplasia. Both cases were followed up for more than one and half years and showed no evidence of recurrence, hence pointing towards better prognosis. Papillary neoplasms are difficult to diagnose preoperatively and are often treated with oncological resections but they carry a better prognosis when compared with their malignancy counterparts.

Variations of the hepatic artery and bile duct in patients with pancreaticobiliary maljunction: Impact on postoperative outcomes.

Preoperative comprehension of the anatomical variations of the hepatic artery and bile duct is essential for safe laparoscopic surgery for pancreaticobiliary maljunction (PBM). This study aimed to investigate the impact of anatomical variations of the hepatic artery and bile duct on surgical technique and postoperative complications. We conducted a retrospective review of patients with PBM who underwent laparoscopic surgery at our institution between January 2014 and December 2022 to investigate anatomical variations in the hepatic artery and bile duct, surgical technique, and postoperative complications. We included 112 patients with PBM, with a median age of 4 years (interquartile range, 0-55). Overall, 29 of 112 patients had an aberrant right hepatic artery (ARHA) running ventral to the common hepatic duct (CHD), and they underwent hepaticojejunostomy on the ventral side of the ARHA. Additionally, eight of 112 patients had an aberrant posterior hepatic duct (APHD), which was joined to the CHD in all but one case. The presence of APHD was associated with postoperative bile leak occurrence. Performing hepaticojejunostomy ventral to the ARHA is important to prevent complications. Furthermore, APHD may be a risk factor for postoperative bile leak and requires careful bile duct plasty.

Early onset Caroli’s disease with associated renal cystic disease presented with recurrent fever and epigastric pain: a case report

BackgroundCaroli’s disease is characterized by non-obstructive dilatation of intrahepatic biliary radicals with formation of calculi followed by recurrent episodes of cholangitis. It is a rare congenital malformation and often remains silent, diagnosed accidentally. But if kept unattended, and without any early intervention, it may lead to fatal residual complications. Hence, its early recognition is of utmost importance to prevent recurrent cholangitis, hepatic abscess, liver cirrhosis and cholangiocarcinoma. Hence, we feel that this case must be reported so as to increase awareness among physicians regarding this entity.Case presentationWe hereby report a case of 10-year-old boy who reported with complaints of recurrent episodes of fever, breathing difficulty and multiple episodes of epigastric abdominal pain with apparently healthy siblings. His routine investigation, laboratory parameters were within normal limits. Ultrasonography abdomen showed liver with normal echo-texture with varying sized multiple thin walled cysts involving both the lobes, right more than left with saccular dilatation of 2nd and 3rd order intra-hepatic biliary radicals without calcification without any colour flow on Doppler evaluation. The common hepatic and common bile ducts were normal in calibre and lumen. Magnetic resonance imaging abdomen had similar findings and upper GI endoscopy was also normal. He was finally diagnosed to be a case of Caroli’s disease and was managed with broad spectrum antibiotics, ursodeoxycholic acid, multivitamins, and calcium supplements. He made an uneventful recovery thereafter. Parents were counselled about the risk of cholangitis and cholangiocarcinoma and was referred to tertiary care centre for genetic counselling and for future need of liver transplantation.ConclusionAge presentation of Caroli’s disease varies. Majority present during adolescence and early adulthood. This often poses a diagnostic challenge owing its rare entity and silent presentation. A strong index of suspicion and prompt diagnosis is warranted to prevent its fatal residual complications.

Description and development of Auerbachia ignobili n. sp. (Cnidaria: Myxosporea: Bivalvulida) from the giant trevally, Caranx ignobilis (Forsskål, 1775) from Indian waters.

The present study describes a new species of myxosporean, Auerbachia ignobili n. sp., infecting the hepatic bile ducts of Caranx ignobilis (Forsskål, 1775). Myxospores are club-shaped with a broad anterior region and a narrow, slightly curved and blunt caudal extension, measuring 17.4 ± 1.5 μm in length and 7.5 ± 7.4 μm in width. Shell valves asymmetrical, with a faint suture line, and enclosed a single, elongate-elliptical polar capsule with a ribbon-like polar filament, arranged in 5-6 coils. Developmental stages included early and late presporogonic stages, pansporoblast, and sporogonic stages with monosporic and disporic plasmodia. A. ignobili n. sp. differs from the other described species of Auerbachia in the shape and dimensions of the myxospores and polar capsules. The molecular analysis generated ~1400 bp long SSU rDNA sequences and the present species exhibited a maximum similarity 94.04-94.91% with A. chakravartyi. Genetic distance analysis indicated the lowest interspecies divergence of 4.4% with A. chakravartyi. In phylogenetic analysis, A. ignobili n. sp. was positioned independently with a high bootstrap value (1/100) and appeared as sister to A. maamouni and A. chakravartyi. Fluorescent in situ hybridization and histology indicates that the parasite develops within the hepatic bile ducts. Histological studies did not reveal any pathological changes. Considering the morphological, morphometric, molecular, and phylogenetic differences coupled with the differences in host and geographic locations, the present myxosporean is treated as a new species and named A. ignobili n. sp.

Multifocal biliary carcinoma; whether synchronous or metastatic: A need to conquer

Multiple synchronous primary carcinoma involving gall bladder, liver and common bile duct are rare and difficult to differentiate with hepatic and extrahepatic bile duct metastasis from single primary. Radiological features, molecular landscape, and even integrated mutational profiling are not of much help. We describe a case of 48-year-old male who presented with jaundice and follow up CT scan raised the suspicion of gall bladder carcinoma with hepatic metastasis. Peroperative frozen section examination revealed adenocarcinoma with involvement of cystic duct margin; however revised common duct margin was free from tumor invasion. Final histopathology on resected gall bladder revealed multifocal adenocarcinoma, while histomorphology of hepatic nodule was consistent with cholangiocarcinoma. Common bile duct a one focus had also revealed adenocarcinoma while cut margins were negative form malignancy. In view of different morphology of gall bladder and hepatic tumor, no continuity of three tumors and single large, firm, non umblicated hepatic nodule, diagnosis of multiple synchronous carcinoma was suggested.

Aflatoxin B1 induces liver injury by disturbing gut microbiota-bile acid-FXR axis in mice.

Aflatoxin B1 (AFB1) is one of major pollutant in food and feed worldwide. The purpose of this study is to investigate the mechanism of AFB1-induced liver injury. Our results showed that AFB1 caused hepatic bile duct proliferation, oxidative stress, inflammation and liver injury in mice. AFB1 exposure induced gut microbiota dysbiosis and reduced fecal bile salt hydrolase (BSH) activity. AFB1 exposure promoted hepatic bile acid (BA) synthesis and changed intestinal BA metabolism, especially increased intestinal conjugated bile acids levels. AFB1 exposure inhibited intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) signaling. Furthermore, the mice received fecal microbiota transplantation from AFB1-treated mice induced liver injury, reduced intestinal FXR signaling and increased hepatic BA synthesis. Finally, the intestine-restricted FXR agonist treatment decreased hepatic BA synthesis, ROS level, inflammation and liver injury in AFB1-treated mice. This study suggests that modifying the gut microbiota, altering intestinal BA metabolism and/or activating intestinal FXR/FGF-15 signaling may be of value for the treatment of AFB1-induced liver disease.

OPTION TO FINISH SURGICAL OPERATION IN PATIENT WITH MIRIZZI SYNDROME

Mirizzi syndrome is a rare condition caused by the obstruction of the common bile duct or common hepatic duct by external compression from multiple impacted gallstones or a single large impacted gallstone in Hartman's pouch.
 Mirizzi syndrome is one of the most severe complications of cholelithiasis and the most complex pathological process in biliary surgery in general. Mirizzi syndrome is a compression of the common hepatic bile duct by a gallstone, which is usually located in Hartmann's pouch, and the subsequent formation of a cholecysto-choledochial fistula. This syndrome is named after the Argentinean surgeon, who described the obstruction of the common bile duct or common hepatic duct by external compression from multiple impacted gallstones or a single large impacted gallstone; the phenomenon was observed during the intraoperative cholangiography. Mirizzi syndrome is conventionally classified into four types: type I is described as the compression of the common hepatic duct by a stone from the gallbladder side; type II is characterized by the presence of a cholecysto-choledochial fistula that involves one-third of the choledochus diameter; type III is similar to type II but involves two-thirds of the choledochus diameter; type IV represents complete destruction of the wall of the common hepatic duct, resulting in the formation of a complete biliobiliary fistula. Mirizzi syndrome does not have its own specific clinical manifestations, and screening methods like abdominal ultrasonography may not always provide a clear indication of this pathology. In such cases, diagnostic procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance imaging (MRI) of the biliary tract can help establish an accurate diagnosis and determine the appropriate surgical approach prior to the operation. The article presents the clinical case of a 29-year-old patient M., who was admitted to the surgical department. Although there was a discrepancy between the findings of magnetic resonance imaging of the biliary tract and the identified anatomical changes during diagnostic laparoscopy of the hepatobiliary tract, the surgeons' expertise and adherence to safe cholecystectomy guidelines enabled the successful completion of the operation using a minimally invasive approach.

Alagille-like syndrome with surprising karyotype: a case report

BackgroundChromosome 5p partial monosomy (5p-syndrome) and chromosome 6p partial trisomy are chromosomal abnormalities that result in a variety of symptoms, but liver dysfunction is not normally one of them. Alagille syndrome (OMIM #118450) is a multisystem disorder that is defined clinically by hepatic bile duct paucity and cholestasis, in association with cardiac, skeletal, and ophthalmologic manifestations, and characteristic facial features. Alagille syndrome is caused by mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1. Here, we report a preterm infant with karyotype 46,XX,der(5)t(5,6)(p15.2;p22.3) and hepatic dysfunction, who was diagnosed as having incomplete Alagille syndrome.Case presentationThe Japanese infant was diagnosed based on the cardiac abnormalities, ocular abnormalities, characteristic facial features, and liver pathological findings. Analysis of the JAG1 and NOTCH sequences failed to detect any mutations in these genes.ConclusionsThese results suggest that, besides the genes that are known to be responsible for Alagille syndrome, other genetic mutations also may cause Alagille syndrome.

Features of the Peribiliary Glands of the Extrahepatic Biliary Tract in the Elderly and Long-Living Individuals

The aim of the study was to analyse histologically and morphometrically the peribiliary glands of the extrahepatic biliary tract in the elderly and long-living people.Material and methods. The study included wholemounts of the gallbladder, the cystic, hepatic and common bile ducts obtained from the corpses of both sexes aged 22 to 35 years (n=16) and older than 76 years (n=39). Macro-microscopy was used to evaluate the number, localization, sizes and shape of the glands, the area of the lumen of the excretory duct orifices, the area of the initial section of the glands, the number of initial (terminal) parts and the proportion of epithelial parenchyma in their composition.Results. With age, there is a decreased proportion of "complexly branched" glands with a significant number of initial sections and excretory ducts of the 1st order. The proportion of "simple" glands, with one initial section increases to 70.2–78.3% in the senile age, while it is 41.0–52.1% in people of mature age. In long-living people, there is an increased number (up to 70–85%) of glands with ampullar extensions of the common excretory duct. The total number, density of gland localization, the length and width of the initial section of the peribiliary glands tend to decrease from the period of mature age to longevity. In senile age, the size and quantitative parameters of the glands stabilize, and do not modify in long-living people.Conclusion. The results of the morphological analysis demonstrate that there is no progression of involutive changes in the peribiliary glands of the extrahepatic biliary tract from senile age to the period of longevity. In some cases, long-living individuals manifest compensatory-adaptive reactions, such as an increased severity of the epithelial parenchymal component in the composition of the glands and an increased proportion of glands with an ampullar expansion of the common excretory duct.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Primary sclerosing cholangitis revealed by pregnancy

Introduction: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of poorly understood, probably dysimmune, mechanism. It is a slow-growing disease, with a tendency to worsen. We are reporting a rare case of primary sclerosing cholangitis revealed during pregnancy. Case presentation: A 30-year-old woman who had pruritus during 12 weeks of gestation with a disturbance of the liver biologic tests. Imaging investigations found a chronic liver with areas of stenosis and dilation of VBIH and right and left hepatic bile ducts suggestive of primary sclerosing cholangitis with evidence of portal hypertension. She was put under treatment by ursodeoxycholic acid and the pregnancy proceeded without maternal-fetal complications giving birth to a healthy newborn with uneventful postpartum follow-up. Conclusion: This case highlights the importance of considering pathologies other than benign intrahepatic cholestasis of pregnancy as the cause of cholestasis during pregnancy.

CORRELATION OF PRE OPERATIVE AND INTRA OPERATIVE FINDINGS IN GALL STONE DISEASE

Background: Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct or gallbladder. GD is one of the most prevalent gastrointestinal diseases with a substantial burden to health care systems. GD can result in serious outcomes such as acute gallstone pancreatitis and gallbladder cancer. The epidemiology, correlation with USG ndings and anatomical variants encountered during cholecystectomy are discussed in this study. To compare preoperative and intraope Aims and objectives: rative ndings of gall stone disease in patients who underwent cholecystectomy. 104 patients who underwent cholecystect Materials and methods: omy in Kanyakumari Government Medical College from January 2019 to December 2022. Majority of the patients were Results: in age group between 19 to 78 years of age with a mean age of 42.5. Female predominance was reported in our study comprising 65% of total study participants. The study identied a sensitivity of 0.84 and a specicity of 1 for ultrasound in the identication of gallstones.10 % of the study population had different anatomical variants which were encountered during cholecystectomy. <4% of study population was intraoperatively converted from laparoscopic to open cholecystectomy. 78% of stones are pigment stones based on dry weight analysis. Reproductive Age and fe Summary: male sex are profoundly associated with the incidence of gallstone disease. This study suggests that despite an evolution in the resolution of ultrasound imaging, there has not been a corresponding improvement in sensitivity. Knowledge of Variation in cystic duct anatomy is important to avoid inadvertent injury to the biliary tree during Cholecystectomy. The study population have a predominance of pigment stones based on dry weight analysis

Cholangioscopy-Assisted Laser Lithotripsy for Treatment of Postcholecystectomy Mirizzi Syndrome: Case Series

Introduction. Mirizzi syndrome (MS) represents a rare clinical entity caused by impaction of one or multiple stones in the infundibulum of the gall bladder or the cystic duct resulting in partial or complete obstruction of the common hepatic or common bile duct (CBD). Though described more than a century ago, MS is still one of the most challenging diseases in the spectrum of biliary pathology. In recent years, endoscopic treatment has become an increasingly popular treatment modality. Patients and methods. Three consecutive patients subjected to cholangioscopy-assisted laser lithotripsy (CA-LL) for postocholecystectomy MS (pMS) were retrospectively evaluated. Case reports. Successful clearance of the cystic duct was achieved in all patients in one or two sessions. One complication in the form of mild cholangitis was observed. Clinical success was 100%. Discussion. According to current research, CA-LL achieves a high rate of ductal clearance and acceptable complication rate in patients with pMS. A 250 µm laser fiber seems to be the optimal choice for CA-LL. Our results suggest that procedure duration is closely associated to the stone size and possibly to the operator experience. In our opinion, upon obtainment of successful ductal clearance and drainage, prophylactic stenting does not improve clinical outcome. Conclusions. Our results demonstrate that CA-LL is a safe and effective treatment for pMS.

Improving the Safety of Laparoscopic Cholecystectomy with Indocyanine Green Dye Using Critical View of Safety Plus.

During a laparoscopic cholecystectomy, the critical view of safety is obtained through dissection of the gallbladder from the liver until there is anterior and posterior visualization of the cystic duct and cystic artery. This view is used to allow for proper identification of the cystic duct and artery that will be clipped and incised during the operation. Indocyanine green (ICG) can be used during the operation to directly visualize the biliary tract because of its excretion through the biliary system and elimination via the GI tract. Using a laparoscope capable of visualizing ICG allows for identification of bile duct anatomy to include: common hepatic bile duct, cystic duct, and aberrant, or accessory bile ducts. Additionally, visualization of the biliary structures using ICG prior to clipping and incision will allow for identification and prevention of missed biliary anatomy which could reduce incidence of bile leak, a known complication of cholecystectomies. We propose that visualization of the critical view of safety with ICG fluoroscopy be termed the critical view of safety plus. We hypothesized that using the critical view of safety plus method for laparoscopic cholecystectomy will yield better scores and increase the decision of the control surgeon to choose to cut and proceed with the operation when compared with the traditional critical view of safety. Comparision of operative photos of critical view of safety and critical view of safety plus which were randomized, double blinded, and graded by a single control surgeon. Our study consisted of fifty patients of which 72% female (n = 36) and 28% male (n = 14). The ethnic background included 76% non-Hispanic (n = 38) and 24% Hispanic or of Latino/a origin (n = 12). The average age of our patient was 49 years old (range 20 to 93 years old). Inclusion criteria consisted of patients undergoing laparoscopic cholecystectomy greater than or equal to 18 years old. Exclusion criteria included allergy to indocyanine dye or iodine and pregnancy. The scores were evaluated using Chi-squared and paired T-test analysis using MedCalc, MedCalc Sofware Ltd, Belgium. The decision to cut and proceed with the operation was chosen 29 times (58%) when viewing the critical view of safety plus vs 22 times (44%) with the critical view of safety (χ2 = 65.822, p < 0.0001). The decision to proceed with further dissection to isolate the cystic duct viewing the critical view of safety plus was chosen 8 times (16%) vs 11 times (22%) with critical view of safety (χ2 = 65.822, p < 0.0001) as shown in Fig. 2. The comparison of total scores with critical view of safety plus vs critical view of safety showed an average of 4.36 vs 4.04, p = 0.0733. The critical view of safety plus and critical view of safety individual criteria scores are: "two structures connected to the gallbladder" (average 1.54 vs 1.50, p = 0.598), "cystic plate clearance" (average 1.42 vs 1.28, p = 0.018), and "hepatocystic triangle clearance" (average 1.4 vs 1.26, p =0.0334). We recommend routine use of ICG fluoroscopy to obtain the critical view of safety plus to allow for improved visualization of the biliary tree, identification of aberrant biliary anatomy, and the potential to reduce risk of bile duct injury.

Dietary Fat Exacerbates Liver Disease in Bile Duct-Ligated Rats

Previous studies have suggested that the mortality of bile duct-ligated (BDL) rats is related to the amount of dietary fat consumed. We investigated the influence of dietary fat concentration on liver disease in BDL rats. Groups of rats were fed for 4 wk either a low fat diet (LF, 0.92 kJ/g; 3% of total energy from fat), a high fat diet (HF, 1.07 kJ/g; 30% fat), a high fat diet with energy density equivalent to that of the LF diet (HFIB, 0.92 kJ/g; 30% fat) or a diet based on the composition of commercial nonpurified diets (COMP, 0.90 kJ/g; 10% fat). Energy intake, body weight gain, plasma biochemical indices and hepatic histology were compared in BDL and sham-operated control rats. Bile duct-ligated animals consuming the LF diet showed a faster recovery of energy intake and greater body weight gain following surgery than did BDL animals fed the other three diets. Plasma alkaline phosphatase activity was significantly greater in BDL animals fed either of the high fat diets than in those fed the LF or COMP diet starting 1 and 2 wk, respectively, after surgery. Hepatic fibrosis and bile duct proliferation at d 28 post-ligation were greater in rats fed a 30% fat (HF) diet than in rats fed the 3% fat (LF) diet. These results suggest that dietary fat concentration can influence the severity of liver dysfunction in extrahepatic biliary obstruction.

Association of Early Bifurcation of Hepatic Artery With Arterial Injury in Right-Sided Living-Donor Hepatectomy: Retrospective Analysis of 500 Cases.

The aim of this study was to explore the incidence of early bifurcation of the right hepatic artery (RHA) and the right posterior hepatic artery (RPHA), which is crucial in right lobe graft (RLG) and right posterior sector graft (RPSG) procurement for living-donor liver transplantation. Early bifurcation of the hepatic artery tends to induce oversight of one of the bifurcated arteries and its injury in RLG/RPSG procurement. Unrecognizable on conventional 3-dimensional (3-D) images, its significance is underestimated. We enrolled 500 patients who underwent preoperative imaging for scheduled surgeries at two major transplant centers. All-in-one 3-D images consisting of the hepatic artery, portal vein, and bile duct were constructed. Early bifurcation of the RHA and the RPHA was defined as the arteries bifurcating proximal to the cutting line of the right hepatic duct and the right posterior duct, respectively. Early bifurcation of the RHA was seen in 11.3% of cases of an infra-portal RPHA and in 46.0% of cases of a supraportal RPHA ( P < 0.001). Early bifurcation of the RPHA was encountered in 35.3% of cases of an infra-portal RPHA, in no cases of a supra-portal RPHA, and in 100% of cases in which the arteries to segment 6/7 arose individually from the RHA. The overall incidence of early bifurcation was 19.9% for RHA and 43.6% for RPHA. Early bifurcation of the RHA and the RPHA is frequently encountered and requires caution for RLG/RPSG procurement. Special attention should be paid to supraportal RPHA for RLG procurement.

Hepatocyte-to-cholangiocyte conversion occurs through transdifferentiation independently of proliferation in zebrafish.

Injury to biliary epithelial cells (BECs) lining the hepatic bile ducts leads to cholestatic liver diseases. Upon severe biliary damage, hepatocytes can convert to BECs, thereby contributing to liver recovery. Given a potential of augmenting this hepatocyte-to-BEC conversion as a therapeutic option for cholestatic liver diseases, it will be important to thoroughly understand the cellular and molecular mechanisms of the conversion process. Towards this aim, we have established a zebrafish model for hepatocyte-to-BEC conversion by employing Tg(fabp10a:CFP-NTR) zebrafish with a temporal inhibition of Notch signaling during regeneration. Cre/loxP-mediated permanent and H2B-mCherry-mediated short-term lineage tracing revealed that in the model, all BECs originate from hepatocytes. During the conversion, BEC markers are sequentially induced in the order of Sox9b, Yap/Taz, Notch activity/ epcam , and Alcama/ krt18 ; the expression of the hepatocyte marker Bhmt disappears between the Sox9b and Yap/Taz induction. Importantly, live time-lapse imaging unambiguously revealed transdifferentiation of hepatocytes into BECs: hepatocytes convert to BECs without transitioning through a proliferative intermediate state. In addition, using compounds and transgenic and mutant lines that modulate Notch and Yap signaling, we found that both Notch and Yap signaling are required for the conversion even in Notch- and Yap-overactivating settings. Hepatocyte-to-BEC conversion occurs through transdifferentiation independently of proliferation, and Notch and Yap signaling control the process in parallel with a mutually positive interaction. The new zebrafish model will further contribute to a thorough understanding of the mechanisms of the conversion process.