Developmental anatomy of the liver from computerized three-dimensional reconstructions of four human embryos (from Carnegie stage 14 to 23).

BACKGROUND & AIM: Some aspects of human embryogenesis and organogenesis remain unclear, especially concerning the development of the liver and its vasculature. The purpose of this study was to investigate, from a descriptive standpoint, the evolutionary morphogenesis of the human liver and its vasculature by computerized three-dimensional reconstructions of human embryos. MATERIAL & METHODS: Serial histological sections of four human embryos at successive stages of development belonging to three prestigious French historical collections were digitized and reconstructed in 3D using software commonly used in medical radiology. Manual segmentation of the hepatic anatomical regions of interest was performed section by section. RESULTS: In this study, human liver organogenesis was examined at Carnegie stages 14, 18, 21 and 23. Using a descriptive and an analytical method, we showed that these stages correspond to the implementation of the large hepatic vascular patterns (the portal system, the hepatic artery and the hepatic venous system) and the biliary system. CONCLUSION: To our knowledge, our work is the first descriptive morphological study using 3D computerized reconstructions from serial histological sections of the embryonic development of the human liver between Carnegie stages 14 and 23.

Is there a role for fetal ductus venosus and hepatic artery Doppler in screening for fetal aneuploidy in the first trimester?

OBJECTIVE: The aim of the present study was to evaluate the utility of ductus venosus (DV) and hepatic artery (HA) doppler in pregnant women who have high risk for aneuploidy in first trimester combined screening. METHODS: This prospective study was performed between February 2011 and February-2012, at a tertiary referral hospital. Singleton pregnancies with high risk for aneuploidy in combined screening test and normal nuchal translucency (NT) measurements were included in the study group. Measurements of DV Pulsatility Index of Veins (PIV) and HA Pulsatility Index (PI) were compared between the study group and controls. RESULTS: Within the study period, 104 women with singleton pregnancies were evaluated for DV and HA measurements and among these, 64 women met the inclusion criteria. A control group that comprised 40 women with similar gestational age, normal NT measurements and low-risk in first trimester combined tests was generated. DV-PIV measurements were significantly higher (p = 0.03), whereas HA-PI measurements were similar (p > 0.05) in women who had high-risk for aneuploidy in first trimester combined test. CONCLUSION: We concluded that the addition of DV-PIV and HA-PI measurements to the first trimester combined screening might increase the accuracy for Down syndrome detection.

[Fetal hepatic artery flow assessment in prenatal diagnostics--a review of the literature]. / Ocena przeplywów w tetnicy watrobowej plodu w diagnostyce prenatalnej. Przeglad literatury.

Standards of screening tests for the most frequent fetal chromosomal defects in modern non-invasive prenatal diagnostics provide sensitivity of about 93-96%, with the false positive rate of 2.5%. During the first trimester scan, routinely performed between 11 and 13+6 week of pregnancy the calculation of the risk for chromosomal aberrations is based on maternal age (MA), nuchal translucency (NT), levels of free beta human chorionic gonadotropin (free beta-hCG), pregnancy associated plasma protein A (PAPP-A) in maternal blood, as well as the parameters from extended ultrasound examination like evaluation of the nasal bone (NB), blood flow in ductus venosus (DV), visualization of the tricuspid valve with potential regurgitation (TR) or measurement of the frontomaxillary facial angle (FMFA). The 100% detection rate remains unachievable at present, despite constantly improving guidelines for specialists, quality of imaging, and advancement in ultrasound technology Therefore, several studies have been undertaken to establish the group of 'additional markers' of chromosomal defects which, when combined with basic markers of routine screening tests, might increase the detection rate and approach it to 100%. Results of recent studies imply that evaluation of blood flow in fetal hepatic artery performed during the first trimester scan may become a new additional marker for chromosomal defects.

[Anatomy of the liver. What does the radiologist need to know?]. / Anatomie der Leber. Was muss der Radiologe wissen?

The liver is the largest unpaired parenchymatous organ in the human body and takes part in almost all important metabolic processes. Many patients show alterations of the whole organ due to vascular/cardiac disorders, metabolic or infectious diseases (congestion, fatty liver disease, fibrosis and cirrhosis). However the liver is also a common site for metastatic lesions of malignant tumors. Additionally, benign focal lesions, such as hemangioma or focal nodular hyperplasia (FNH) occur quite frequently. To describe and diagnose these lesions in terms of dignity and location, knowledge of the macroscopic structure and the relative position of the organ in relation to neighbouring organs are important as well as the histology. The microstructure of the liver and its vascular and biliary vessels are determined by the embryonic development and its function as a central metabolic organ.

Hepatic artery Doppler in trisomy 21 and euploid fetuses at 11-13 weeks.

OBJECTIVE: To determine possible differences in hepatic artery flow between trisomy 21 and euploid fetuses at 11-13 weeks' gestation. METHODS: Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured in fetuses at low risk of aneuploidies (n = 350) and another group at high risk, including 283 euploid and 47 with trisomy 21. The association of hepatic artery PI and PSV with trisomy 21, fetal nuchal translucency (NT) thickness, tricuspid regurgitation, and reversed a-wave in the ductus venosus was investigated. RESULTS: In the low-risk group, the median hepatic artery PSV was 10.0 cm/s and the 95th centile was 14.3 cm/s. The distribution of hepatic artery PI was skewed, but for PI of 2 or more the distribution was Gaussian. In 325 (92.9%) cases, the PI was 2 or more (high PI) and in 25 (7.1%) it was below 2 (low PI). In 33 (70.2%) of the trisomy 21 pregnancies, the PSV was above the 95th centile and the PI was below 2. Multiple regression analysis showed that in the prediction of hepatic artery PSV there were significant contributions from fetal karyotype, tricuspid regurgitation, and reversed a-wave in the ductus venosus, but not delta NT, pregnancy-associated plasma protein-A, or free ß-human chorionic gonadotrophin. CONCLUSION: Trisomy 21 at 11-13 weeks is associated with increased flow in the hepatic artery.

The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology.

The aryl hydrocarbon receptor (AHR) plays a central role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) hepatotoxicity, regulation of xenobiotic metabolism, and hepatovascular development. Each of these processes appears to be dependent on binding of the AHR to dioxin- responsive elements (DREs) within the genome. The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important roles in AHR biology. In the mouse, 8 DREs are located in the 14-kb intergenic region between the Cyp1a1 and Cyp1a2 genes. Seven of these DREs, collectively known as the DRE cluster (DREC), are located 1.4 kb upstream of the Cyp1a1 transcriptional start site and 12.6 kb upstream of the Cyp1a2 start site. To investigate the role of the DREC in each aspect of AHR biology, we generated a DREC-deficient mouse model through homologous recombination. Using this mouse model, we demonstrate that the DREC controls the adaptive up-regulation of both Cyp1a1 and Cyp1a2 genes in vivo. Using selected aspects of acute hepatic injury as endpoints, we also demonstrate that DREC null mice are more sensitive to dioxin-induced hepatotoxicity than WT mice. The results of parallel toxicologic studies using individual Cyp1a1 and Cyp1a2 null mice support the observation that up-regulation of these P450s is not the cause of many aspects of dioxin hepatotoxicity. Finally, we observed normal closure of the ductus venosus (DV) in DREC null mice. Given the 100% penetrance of patent DV in Ahr null mice, these results indicate that Cyp1a1 and Cyp1a2 do not play a dominant role in AHR-mediated vascular development.

[Left hepatic artery: anatomical variations and clinical implications]. / L'artère hépatique gauche, variations anatomiques et implications cliniques.

The presence of a left hepatic artery (LHA) is an anatomical variation related to the persistence after fetal maturation of one of the two embryonic hepatic arteries, who disappear in the modal liver arterial vascularisation (liver vascularisation by a unique hepatic artery originating from the celiac trunk). When present, LHA is originating from the left gastric artery and runs through the pars condensa of the lesser omentum. Its frequency is varying from 12 to 34% according to the different study methods: 14 to 27% in anatomical series, 12 to 20% in angiographic studies and 12 to 24% in liver transplantation series. Laparoscopic detection has the highest sensitivity with reported rates from 18 to 34% of cases. LHA is irrigating a variable liver territory from a part of the left lobe to the whole liver in less than 1% of cases. A satisfactory knowledge of these anatomical variations is mandatory in liver surgery and during liver transplantation but also each time the pars condensa is approached during gastric surgery, hiatal surgery for gastroesophageal reflux and for bariatric surgery. Due to existing anastomosis between liver arteries, LHA ligation is feasible in most cases with a subsequent and transitory elevation of liver enzymes. On the contrary, in case of a unique LHA for the whole liver, the safety of its ligation is not demonstrated.

Vascular development and differentiation during human liver organogenesis.

The vascular architecture of the human liver is established at the end of a complex embryological history. The hepatic primordium emerges at the 4th week and is in contact with two major venous systems of the fetal circulation: the vitelline veins and the umbilical veins. The fetal architecture of the afferent venous circulation of the liver is acquired between the 4th and the 6th week. At the end of this process, the portal vein is formed from several distinct segments of the vitelline veins; the portal sinus, deriving from the subhepatic intervitelline anastomosis, connects the umbilical vein, which is the predominant vessel of the fetal liver, to the portal system; the ductus venosus connects the portal sinus to the vena cava inferior. At birth, the umbilical vein and the ductus venosus collapse; the portal vein becomes the only afferent vein of the liver. The efferent venous vessels of the liver derive from the vitelline veins and are formed between the 4th and the 6th week. The hepatic artery forms at the 8th week; intrahepatic arterial branches progressively extend from the central to the peripheral areas of the liver between the 10th and the 15th week. Hepatic sinusoids appear very early, as soon as hepatic cords invade the septum transversum at the 4th week. They then progressively acquire their distinctive structural and functional characters, through a multistage process. Vascular development and differentiation during liver organogenesis is, therefore, a unique process; many of the cellular and molecular mechanisms involved remain poorly understood.

Congenital hepatic shunts.

Abnormal vascular connections within the hepatic parenchyma are occasionally seen at ultrasonography (US) and require further evaluation. The radiologic findings in 42 children with infantile hepatic hemangioma (n = 28), vascular malformations (n = 10), or infradiaphragmatic total anomalous pulmonary venous return (TAPVR) (n = 4) associated with congenital vascular shunting were retrospectively reviewed. Arteriovenous connections are seen in infantile hepatic hemangiomas and arteriovenous malformations and manifest with aortic tapering at the level of the celiac trunk, hepatic artery enlargement with a low resistivity index (RI), and increased flow velocities in the hepatic veins that may assume an arterialized spectral pattern in late-stage disease. Congenital arterioportal shunts demonstrate a low RI in the hepatic artery, hepatofugal arterialized flow in the portal vein, and rapid development of signs of portal hypertension. Portosystemic shunting may be intra- or extrahepatic. A pulsatile triphasic spectral pattern is seen in the portomesenteric venous system in children with portosystemic shunting, and macroscopic connections between the portal system and the hepatic veins are evident. Infradiaphragmatic TAPVR is associated with a tortuous vessel that parallels the aorta, ends at the intrahepatic left portal vein or the ductus venosus, and has hepatopetal flow. Familiarity with the US features of various congenital abnormal hepatic vascular connections will aid in diagnosis and treatment.

The cystic artery in human foetuses.

The cystic artery varies in origin, course and number and it is important to recognise it during operative procedure. Insufficient recognition of its anatomical variation may contribute to a dangerous situation, especially during laparoscopic cholecystectomy. To prevent iatrogenic injuries of the vessels and bile ducts, correct preparation with clear identification of the anatomic structures is essential. Special attention must be given to the course of the cystic artery through the hepato-billiary triangle (Calot's triangle). The assumption of the present study was recognition of the vasculature of the gallbladder in human foetuses. The purpose of this investigation was to determine the origin of the cystic artery and its relation to Calot's triangle. In this study the cystic artery was most often (97.06%) a single vessel and only in one case (2.94%) was it a double vessel. It arose most often (82.34%) from the right proper hepatic artery, rarely from its trunk (8.82%) or its left branch (5.88%) and most rarely (2.94%) from the gastroduodenal artery. In all but one case the cystic artery coursed within Calot's triangle. Its exceptional course out of Calot's triangle concerned a cystic artery originating from the gastroduodenal artery (2.94%). The cystic artery most frequently (67.66%) runs behind the common hepatic duct, rarely (29.40%) over the common hepatic duct and most rarely (2.94%) on the left side of the cystic duct. In the material examined the cystic artery was not observed running in front of the common hepatic duct. The short type of cystic artery trunk (52.93%) was observed more frequently than the long one (44.13%).

Hepatic artery malformations associated with a primary defect in intrahepatic bile duct development.

BACKGROUND/AIMS: The portal tracts contain bile ducts associated with branches of the portal vein and of the hepatic artery. Hepatic artery malformations are found in diseases in which fetal biliary structures persist after birth (ductal plate malformations). Here we investigated how hepatic artery malformations relate to abnormal bile duct development. METHODS: Hepatic artery and biliary development was analyzed in fetuses with Jeune syndrome or Meckel syndrome, which show ductal plate malformations. We also analyzed hepatic artery development in transgenic mice which exhibit biliary anomalies following inactivation of the genes for hepatocyte nuclear factor (HNF)-6 or HNF-1beta, two transcription factors expressed in biliary cells, but not in arteries. RESULTS: We show that arterial anomalies occurred in fetuses with Jeune syndrome or Meckel syndrome. We provide the first description of hepatic artery branch development in the mouse and show that inactivation of the Hnf6 or Hnf1beta gene results in anomalies of the hepatic artery branches. In the transgenic mice and in the human syndromes, the biliary anomalies preceded the arterial anomalies. CONCLUSIONS: A primary defect in biliary epithelial cells is associated with hepatic artery malformations in mice. Our data provide a model to interpret and study hepatic artery anomalies in humans.

The correlation between portal myofibroblasts and development of intrahepatic bile ducts and arterial branches in human liver.

BACKGROUND/AIMS: The development of the intrahepatic bile ducts most likely requires interactions between epithelial and mesenchymal cells. In view of the epithelial-mesenchymal interactions between portal myofibroblasts (pMFs) and biliary epithelial cells in adult diseases of the bile ducts, we investigated the presence and function of pMFs during the development of intrahepatic bile ducts, as well as the development of intrahepatic branches of the hepatic artery. METHODS: We performed haematoxylin-eosin-stainings and immunohistochemistry for alpha-smooth-muscle actin, cytokeratin 19 and vimentin on serial sections of 45 fetal and postnatal liver biopsies. RESULTS: The mesenchyme of portal tracts in the ductal plate stage devoid of a hepatic artery branch, contained numerous and diffusely scattered pMFs. Portal tracts with a hepatic artery branch were always larger than those without and showed a decreasing number of pMFs. In the remodeling stage, all portal tracts contained a hepatic artery branch, and pMFs were restricted to the periductal mesenchyme. These periductal pMFs disappeared after full incorporation of the bile duct. CONCLUSION: Our findings strongly suggest interactions between pMFs and epithelial cells of the developing bile ducts. The development of the intrahepatic arterial branches always precedes the incorporation of the tubular segments of the ductal plate.

Is the liver of the fetus the 4th preferential organ for arterial blood supply besides brain, heart, and adrenal glands?

In this study we compared the distribution of blood flow to the liver in growth-retarded fetuses whose estimated weight was < 5th centile with normal-weight fetuses. As expected, the relative venous blood flow to the liver was reduced, with blood flowing preferentially through the ductus venosus. However, the total blood supply seemed to be maintained by a concomitant, significant increase in arterial blood flow through the hepatic artery. Absolute flow velocities such as the peak, minimum diastolic and temporal average velocities were changed, as was the flow waveform. Effectively, the deficiency in venous supply was made up for by an increase in arterial blood flow. This compensatory effect may be crucial for maintaining liver function in times of low portal venous blood supply. It thus makes sense to regard the liver as the fourth preferential organ for arterial blood supply in the compromised fetus, besides heart, brain, and adrenals.

Blood flow velocity waveforms of the abdominal arteries in appropriate- and small-for-gestational-age fetuses.

The aim of this study was to describe flow velocity waveforms of abdominal arteries in the appropriate- and small-for-gestational-age fetus. Splenic artery, superior mesenteric artery, hepatic artery and renal artery velocity waveforms were obtained from 57 appropriate-for-gestational-age and nine small-for-gestational-age fetuses with color flow Doppler ultrasonography. The pulsatility index was used to quantify the arterial waveforms. Repeated measure analysis of variance indicated significant differences in the pulsatility index values in both the appropriate-for-gestational-age and small-for-gestational-age fetuses. A multiple comparison test revealed a significantly lower value for the pulsatility index in the splenic artery when compared to that of the other vessels for both the appropriate- and small-for-gestational-age fetuses. In the small-for-gestational-age fetuses, a lower pulsatility index value was observed at the superior mesenteric artery level when compared to the renal artery. Because of its lower frequency of successful insonation, the hepatic artery was not considered for the analysis. In the normal fetus, the splenic artery had the lowest pulsatility index when compared to the other arteries we investigated. This difference remained in small-for-gestational-age fetuses, reflecting a lower vascular resistance at the fetal spleen in both normal and small-for-gestational-age fetuses. It appears that in small-for-gestational-age fetuses the renal artery has a higher pulsatility index than the superior mesenteric artery, suggesting a preferential distribution of blood flow to the bowel.

Variaciones en el origen de la arteria hepática / Variation in the origin of the hepatic artery

Este trabajo analiza las variaciones en el origen y trayecto de la arteria hepática, inusualmente observadas en 4 de 6 cadáveres utilizados para docencia de anatomía humana normal. Las variaciones en el origen incluyen ramas hepáticas aberrantes originadas en la arteria mesentérica superior, como también el origen de la arteria hepática común en la mesentérica superior. Las variaciones en el trayecto consideran la rama hepática propia ubicada al lado derecho del colédoco y las ramas hepáticas aberrantes colocadas detrás de la vena porta, en el borde libre del omento menor. En el texto se discuten las posibles razones embriológicas que explican tales variaciones

Hepatic artery anatomy in relation to reconstruction in liver transplantation: some unusual variations.

The anatomy of the hepatic artery and its variations were studied in 70 donor livers harvested for liver transplantation in the Austin Hospital. Forty three (61.5%) had a 'normal' vascular anatomy and 27 (38.5% had anomalous anatomy. The anomalies were single in 13 instances and multiple in 14 and involved the origin of the right or left hepatic arteries or the coeliac axis. The hepatic artery was reconstructed most frequently by end-to-end anastomosis of the donor to the recipient common hepatic artery (79%). A Carrel patch, an interposition aortic graft and the donor superior mesenteric artery were other techniques used for reconstruction. Two patients (3%) had a postoperative hepatic artery thrombosis, with one of those patients having a further reconstruction. When one vascular anomaly is found, there is a high probability of others being present. The authors' experience confirms that safe hepatic arterial anastomosis can be performed even in the presence of abnormalities of the vascular arterial system.

[The arterial distribution to the abdominal digestive organs in human fetuses].

The arterial supply of the abdominal digestive organs and the developmental process were studied in 25 Japanese fetuses from 3 months to 9 months old into whose arteries latex rubber was injected. The results were as follows: 1) The branching patterns of the celiac trunk were classified into 5 types. The most common type or the complete celiac trunk was found in 18 cases (72%). Four variation types or incomplete celiac trunks were found in 7 cases (28%). 2) The rates at which the following arteries were observed in the stomach were as follows: 100% for the left gastric artery, 100% for the left and right gastroepiploic artery, 100% for the short gastric artery, 100% for the gastroduodenal artery, 92% for the right gastric artery, 24% for the branch of the left inferior phrenic artery, and 16% for the posterior gastric artery arising from the splenic artery. The left gastric artery was better developed than the other arteries in 3-month-old fetuses. 3) The rates at which the following arteries were observed in the liver were as follows: 100% for the proper hepatic artery, 28% for the accessory left hepatic artery and 8% for the accessory right hepatic arteries. The accessory left hepatic artery in 3-month-old fetuses was better developed than in older fetuses. 4) The rates at which the following arteries were observed in the pancreas were follows: 100% for the branches of the splenic artery, 100% for the branches of the gastroduodenal artery and 100% for the branches of the superior mesenteric artery. Further, dorsal pancreatic arteries not arising from the splenic artery were found in 20% of cases. The dorsal and great pancreatic arteries branching from the splenic artery could not be distinguished from one another in younger fetuses. 5) The rates at which the following arteries were observed in the duodenum were as follows: 100% for the branches of the superior and the inferior pancreaticoduodenal arteries. This arterial supply was the same in all the fetuses. 6) The arterial supply of the jejunum and the ileum were as follows: the jejunum and the ileum were supplied only by the branches of the superior mesenteric artery. The minimum number of the branches was 7 and the maximum 12. 7) The arterial supply of the large intestine was as follows: the caecum was supplied only by the ileocolic artery.(ABSTRACT TRUNCATED AT 400 WORDS)

Patterns of arterial supply of the human fetal liver. The significance of the accessory hepatic artery.

One or two aberrant hepatic arteries were found in 30% of human fetal livers. The liver received a triple or double arterial supply. The aberrant artery arises from the left gastric or superior mesenteric arteries and supplies an entire lobe or more without joining the branches of the usual hepatic artery in 38.5%. The artery has an important significance for the arterial supply of the fetal liver.

Accessory blood supply to the liver from the dorsal pancreatic artery: an unusual anatomic variant.

A case of an accessory hepatic artery from the dorsal pancreatic artery is illustrated. A discussion of anatomic variations and embryology of the arterial blood supply to the liver from the celiac axis and aberrant blood supply from other vessels is presented with a consideration of the surgical and diagnostic significance of anatomic variance.

[Origin of the hepatic artery in the embryo and fetus]. / Contribution à l'étude de l'origine de l'artère hépatique chez l'embryon et le foetus

Study of the hepatic artery in 52 human foetuses and 4 embryos. The authors compare their findings to those published on adults. They underline the higher frequency of the hepatic artery arising out of the left gastric artery (67%) in foetuses and embryos, either associated to the common hepatic artery only (55,4%) or to both the common hepatic artery and the right hepatic artery (12,5%). Graphic reconstruction of foetal hepatic arteries shows two important lines of force one coming from the coeliac trunk - the future common hepatic artery, the other arising from the left gastric artery - the future left hepatic artery. At the 19th stage according to Streeter, the definitive disposition is attained.