1. Volume 66, Issue 4, Pages 778-786 (April 2017)
Human liver regeneration in advanced cirrhosis is organized by the portal tree 
Katalin Dezső, András Rókusz, Edina Bugyik, Armanda Szücs, András Szuák, Bence Dorogi, Mátyás Kiss, Ágnes Nemeskéri, Péter Nagy, Sándor Paku 
Journal of Hepatology 
Volume 66, Issue 4, Pages (April 2017)
DOI: /j.jhep
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

2. Fig. 1
Relationship of the ductular reaction to the portal venous (A–D) and arterial (E–G) system. (A) 3D reconstruction of 16 serial sections which shows the intricate relationship of ductules to the capillaries supplied by the portal venous system. Arrows of different color on the 3D reconstruction and on selected sections (B–D) of the series indicate the position of ductules (yellow color) and vessels (other colors). The sections are stained for CD34 (brown) to highlight endothelial cells and smooth muscle actin (SMA; red) which marks the arterioles. The terminal portal venule (black arrows) terminates in strongly CD34 positive capillaries (green, purple, red arrows) which meander among the ductules. For clarity, not all ductules and capillaries were reconstructed. Note that no branching of the arterioles into capillaries could be observed in this area through the series. (E–G) Arteriole giving off a capillary branch (large arrow) which courses between the ductules. Arrowhead marks the termination of the smooth muscle coverage of the arteriole. Small arrows points at vessel segments, which are continuous with capillary branching of the arteriole on other sections of the series. Pv, portal vein. Scale bar for A–G: 50μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

3. Fig. 2
Relationship of the regenerative nodules to the terminal portal venules. Serial sections of three nodules from alcoholic liver disease (A, B), hepatitis C virus (C–E), and primary sclerosing cholangitis (F–H) case. The nodules are supplied by one terminal portal venule. (A, B) Portal area with a nodule. The portal vessel (Pv) is accompanied by an arteriole (Ar) and a bile duct (Bd). A CD34 positive (brown) terminal portal venule (arrows) enters into the nodule and continues in a strongly CD34 positive capillary (arrowheads) which runs towards the center of the nodule. (C–E) Portal area with a small nodule of which only the cap is visible. The short terminal portal venule (arrow) continues in a capillary (arrowheads) which runs on the surface of the nodule and turns into its center on D, E (Pv; portal vein, Ar; arteriole, Bd; bile duct). (F–H) Portal tract with a large nodule. The CD34 positive terminal portal venule (arrows) is partially incorporated into the nodule and ramifies in the center of the nodule into CD34 negative sinusoid-like vessels. CD34 positive capillaries are only visible close to the surface of the nodule. The terminal portal venule is continuous with the portal vein on H (arrowhead). Note the absence of large bile ducts (Pv, portal vein; Ar, arteriole). Scale bar for A–E: 50μm; F-H: 100μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

4. Fig. 3
Relationship of small regenerative nodules to the portal venous system. (A) Low power micrograph of an extinct area with five regenerative nodules in the liver from an alcoholic liver disease patient. The section is stained for CD34 (brown) and SMA (red). On the right side, a large portal area is visible with portal veins (asterisks), bile duct (X), and numerous arteries. A smaller portal vein originates from the lower large portal vessel and runs straight to the left. The boxed area visible on (A) was reconstructed from 28, 5μm thick serial sections (B). Terminal branches of the portal vessel visible on the right lower corner of the boxed area (pink arrow) directly supplies two (number 2, 3) of the five nodules as it can be seen in the 3D reconstruction (B). Portal vessels on the reconstruction are marked by blue and the regenerative nodules by brownish color. Arrows of different colors on selected sections of the series (C–F) indicate the position of the vessels in the reconstruction. Nodule 1 on (A) is in contact only with CD34 positive capillaries, no direct connection with larger portal vein branches could be detected. Nodule 4 is supplied by another branch (its direction is indicated by large arrowhead) originating from the large portal area (A). The two entering portal vessels into nodule 4 could be detected 23 and 33 sections apart of this section. Nodule 5 is supplied by a portal branch located at the upper part of the picture. The entry of the terminal portal vessel into nodule 5 is marked by a small arrowhead. The portal vessels located in the upper part of the picture are out of the sectioning plane but their run is indicated by the presence of accompanying arteries (red). Scale bar for A: 500μm, for B–F: 100μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

5. Fig. 4
Relationship of large regenerative nodules to the portal venous system and determination of localization of portal and central veins by casting of cirrhotic human livers with resins of different colors. (A–C) 3D reconstruction of large cirrhotic nodules and the supplying portal vessels of the primary sclerosing cholangitis case (the position of arteries and bile ducts are also shown). 120 sections were used for the reconstruction. For clarity only the large trunks of the three systems were reconstructed. Through the series in 4 nodules (1–4) the supplying portal vein could be detected (arrows 1–4). Arteries and bile ducts run in the connective tissue outside the nodules (white arrowheads). Note the large, long arterial branches running between the nodules (white arrowhead 1). (B) The organization of the three systems without the nodules, which originate from a large portal triad at the bottom of the picture (black arrowhead). The portal veins which enter nodules are numbered. (C) The side view of the reconstruction without the nodules. White arrows point at intact portal triads running in the connective tissue. The portal veins of these triads did not enter nodules through the examined serial sections. The portal veins which enter nodules are numbered. (D) Low power micrograph of section number 93 of the series which is stained for CD34 (brown), and SMA (red). The connective tissue appears red because of the slight staining of myofibroblasts by SMA. The nodules in which supplying portal vein is present are numbered. Nodules 1 and 2 are fused. The portal vein which supplies nodule 1 is visible (arrow 1). The large portal vein from which this portal branch originates is marked by arrowheads. CD34 positive capillaries are only visible close to the surface of the nodule. Scale bar for A–D: 1mm. (E) Section number 117 of the series stained for CD34 (brown) and SMA (red). The portal vein supplying nodule number 3 is visible. Note the SMA positivity of the wall of this portal vein branch. From this vessel an SMA negative terminal portal venule originates (arrow) which branches into sinusoids (arrowheads). Scale bar for E: 100μm. (F, G) Unstained, frozen thick sections (30μm) of a casted alcoholic liver disease cirrhotic liver. Hematoxylin counterstaining was omitted for better visibility of the colored resins. The portal venous system was filled by a blue resin, the central veins by a red. (F) Small cirrhotic nodule (asterisk) is supplied by a portal vessel (blue). Arrow points at the inlet venule. Inset shows at high power the narrow inlet venule (arrow). Arrowhead points at a central vein located in the connective tissue. (G) From the portal vessel (arrow) located close to the center of a large nodule the resin spreads radially towards the periphery of the nodule. Note the compressed central veins (arrowheads) close to the surface of the nodule. Scale bar for F, G: 500μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

6. Fig. 5
Relationship of small regenerative nodules to the arterial system. (A) Alcoholic liver disease case, the section is stained for CD34 (brown) and SMA (red). Regenerative nodule with centrally located supplying terminal portal venule (small arrows). No arterioles are visible in the nodule. The larger portal venule (large arrow) from which the supplying terminal portal venule originates is accompanied by an arteriole outside the nodule (arrowhead). (B) A small arteriole (small arrowhead) is present at the periphery of the nodule. Unlike the larger portal venule (large arrow) the centrally located terminal portal venule (small arrows) is not accompanied by an arteriole. Large arrowhead points at the accompanying arteriole. In the upper left corner other arterioles are located in the connective tissue. Scale bars for A, B: 50μm. (C–H) Serial sections of a peripheral area of a cirrhotic nodule. An arteriole (arrows) is passing through the nodule. No capillary branch is given off by the arteriole within the nodule. Scale bar for C–H: 100μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

7. Fig. 6
Relationship of the regenerative nodules to the portal and central veins in the CCl4 induced experimental cirrhosis model in rat. Serial sections of a cirrhotic liver filled through the portal vein by blue resin and through the central vein by red resin. The individual nodule in the center of the pictures (not present on A and O but its position is marked by large arrowheads) is supplied by a portal venule marked by arrows in D-H. The resin injected to the portal vein starts to spread towards the periphery of the nodule visible on G. Another slightly compressed nodule, (asterisks) visible through G-L, has also a centrally located portal venule (white arrow on L). Central veins (red) are scattered in the connective tissue outside the nodules. Scale bar: 100μm.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

8. Journal of Hepatology 2017 66, 778-786DOI: (10. 1016/j. jhep. 2016. 11
Copyright © 2016 European Association for the Study of the Liver Terms and Conditions