The Development of the Hepatic Venous System in Man
Authors: Hikspoors Jill , Peeters Mathijs , Mekonen Hayelom , Mommen Greet , Köhler Eleonore , Lamers Wouter 
Published: November 2023

The drainage of the umbilical and vitelline veins into the sinus venosus at 4 weeks of development (Carnegie Stage (CS) 12) is well documented, but to what extent these veins play a role in the development of the hepatic venous system remains to be established. We reinvestigated this issue in a closely spaced series of human embryos between 4 and 7 weeks of development. Embryological structures were visualised with Amira 3D reconstruction and Cinema 4D remodelling software.

In the 5th week (CS13), the vitelline and umbilical veins became enclosed by the expanding mesenchyme of the septum transversum, while the expanding liver primordium enclosed the vitelline veins only. Concomitant with the repositioning of the entrance of the sinus venosus into the right atrium, the most distal part of the right vitelline vein (“hepatocardiac vein”) increased in diameter, whereas the corresponding left portion did not.

In early CS14 embryos (~33 days of development), the liver primordium also enclosed the umbilical veins. While the connection of these veins with the sinus venosus disappeared, a connection (ductus venosus) appeared between the portion of the left umbilical vein that entered the liver and the right hepatocardiac vein. The intrahepatic part of the right vitelline vein temporarily persisted as a fairly large, “C”‐shaped vessel along the right‐sided outer edge of liver until the ductus venosus had acquired a similar size as the umbilical vein. Thereafter, the remaining part of the left and the intrahepatic portion of the right vitelline vein regressed. The right umbilical vein started to regress as soon as it was enclosed by the liver.

In late CS14 embryos (~35 days of development), vessels larger than sinusoids emerged from the right vitelline (portal) vein and the (left‐sided) ductus venosus in the central part of the liver, while a well‐developed sinusoidal network was identifiable in the liver periphery. In CS15 and CS16 embryos, the portal branches extended further into the liver periphery, but remained confined to the right and left hemi‐livers, respectively. Meanwhile, the sinusoidal network extended towards the centre, followed by the appearance of hepatic veins in this network from the hepatocardiac vein towards the liver periphery. In CS16 embryos (~39 days of development), 2 main portal branches with only few side branches had developed in the right hemi‐liver, while the hepatic veins did not yet branch. In contrast, multiple small branches originated from the ductus venosus in the left hemi‐liver and hepatic veins were hardly identifiable. At 7 weeks of development (CS20), only 3 main portal branches remained in the left hemi‐liver and hepatic veins were appearing in between.

Conclusions

The vitelline and umbilical veins contribute to the hepatic venous system, but at their entrance and exit from the liver only. Development of the intrahepatic portal veins precedes that of the hepatic veins and development of the right hemi‐liver precedes that of the left hemi‐liver. The local appearance of hepatic veins does not obey the boundary between left and right hemi‐liver and appears to reflect the emergence of ordered flow patterns in that part of the liver. Our data explain the development and some of the variability of liver segments.