Guo-Ling Lin , Min Xio , Li Zhung , Yu Yng , Qi-Yong Li , Jin-Fng Lu , Meng-Xi Li , Shu-Sen Zheng , d, *

a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China

b Division of Hepatobiliary and Pancreatic Surgery, Department of Nursing, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China

c Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University School of Medicine, Hangzhou, China

d Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

Liver transplantation (LT) is the only way to cure end-stage liver disease with or without tumors in the last few decades [1] . However, critical issues such as how to rebuild portal flow in pa- tients with portal vein thrombosis (PVT) or superior mesenteric vein (SMV) thrombosis have been challenging for surgeons. Ade- quate portal flow is critical in LT because more than 75% of the liver’s blood supply comes from the portal vein and the rest comes from the hepatic artery. PVT is a universal problem in LT. PVT was divided into grades I-IV by Yerdel et al. in 20 0 0 [2] . For patients with grade I-III PVT, they could be managed through thrombec- tomy or reconstruction. The most severe grade IV PVT is defined as complete portal vein and entire SMV thrombosis [2–4] . For grade IV PVT, direct anastomosis of the donor’s portal vein to the recipi- ent’s portal vein is not feasible even if vascular allograft is used.

Renoportal anastomosis (RPA) has been proposed as an al- ternative strategy to establish a portal inflow in grade IV PVT [5–9] . The recipient’s left renal vein (LRV) and the allograft’s portal vein are typically end-to-end anastomosed [ 10 , 11 ] or rarely end-to-side anastomosed [12] . A systematic literature review re- ported by D’Amico et al. [13] showed that the overall survival of 66 cases who received RPA was 80%, and almost every case received RPA complicated with pre-LT spleno-renal shunt (SRS). Moreover, approximately 5%–10% of all cases with PVT without SRS could be successfully transplanted [13] . Hence, how to establish a portal in- flow in grade IV PVT recipients without sufficient SRS remains un- clear.

We reported a new protocol combining RPA and inferior mesen- teric vein-portal anastomosis (IMV-PA) in LT. A 50-year-old male patient with chronic hepatitis B for more than 20 years was ad- mitted to our department with complaint of a liver mass. A CT scan showed a large hepatocellular carcinoma (HCC) lesion with a diameter of about 10 cm in the patient’s right liver lobe accompa- nied by PVT, cavernous transformation of portal vein (CTPV), tiny SRS and liver cirrhosis. No metastatic lesion was found in other organs. The model for end-stage liver disease score was 18 based on the total bilirubin (TBil) 197μmol/L, international normalized rate (INR) 1.21 and serum creatinine (Scr) 56μmol/L. This patient received piggyback LT on July 5, 2019 at our center and the organ was donated by a donor after cardiac death. During the surgery, we located the portal vein, removed the thrombosis and then anasto- mosed the recipient’s portal vein with a diameter of 6 mm to the donor’s portal vein with a diameter of 10 mm. The left portal vein flow and right portal vein flow on day 1 and day 2 after LT was 13 cm/s, 10 cm/s and 12 cm/s, 10 cm/s, respectively, as measured by B ultrasound. Acute PVT occurred on day 3 after LT and we re- constructed the portal vein image through abdominal enhanced CT scan ( Fig. 1 A). Peripheral intravenous heparin therapy was given for the next few days, but failed, and the thrombosis rapidly devel- oped into grade IV PVT. Without portal blood supply, this patient presented liver failure although we used artificial liver support sys- tem to sustain his life. Thereafter, he received the second LT on July 16, 2019. During the surgery, we successfully anastomosed the recipient’s LRV to the donor’s portal vein and anastomosed the re- cipient’s IMV to the donor’s portal vein through a section of iso- lated iliac artery bypass. The portal vein system was established as a protocol combining RPA and IMV-PA ( Fig. 2 ). RPA was end-to- end connected by the recipient’s left renal vein to the donor’s SMV. One terminal of IMV-PA was end-to-side connected by the recipi- ent’s IMV to isolated iliac artery and another terminal was end-to- side connected by isolated iliac artery to the donor’s portal vein ( Fig. 2 A and B). Reconstructed portal vein image on day 5 after re-transplantation showed the entire portal vein, IMV, LRV, splenic vein and SRS ( Fig. 1 B). Left and right portal flow measured by B ul- trasound was 22 cm/s and 20 cm/s at that time. Immunosuppres- sive regimen was traditional protocol including tacrolimus and my- cophenolate mofetil. Liver function test including alanine amino- transferase (ALT), aspartate aminotransferase (AST), albumin (ALB), TBil, prothrombin time (PT) and INR gradually returned to normal in the next four weeks after re-transplantation, and was main- tained within normal levels for 1-year follow-up. However, Scr, which reflects the patient’s renal function, remained at a higher level (100–120μmol/L) than the normal value. The urine volume of the patient was normal during one year after surgery.

Fig. 1. A: Reconstructed image of vein system through abdominal enhanced CT scan before re-transplantation (we cannot see portal vein and inferior mesenteric vein); B: reconstructed image of vein system through abdominal enhanced CT scan after re-transplantation.

Patients with grade IV PVT are more complex. RPA, cavoportal hemitransposition, or multivisceral transplant may be feasible in selected patients. Considering the new formation of SRS after the first LT, RPA would be the preferable strategy. Successful RPA re- quires SRS. Only five out of 66 patients had no SRS in the study by D’Amico et al. [13], but three out of those fvie patients died after LT. LRV could collect the blood supply from spleen and intes- tine through a thick SRS. If the recipients have concomitant portal hypertension, SRS receives other blood flow from newborn collat- eral circulation like left gastric vein. With the addition of blood from left kidney, LRV can provide sufficient flow to the donor’s portal vein. In our patient, SRS with the largest diameter of 6 mm dislodged because of the acute PVT after the first LT. After mul- tidisciplinary discussion, we recommended this patient to receive re-transplantation through RPA due to liver failure. However, we were concerned whether the portal flow was sufficient for simple RPA because the SRS diameter was smaller than that reported in other studies [1 0, 14] . We demonstrated a protocol combining RPA and IMV-PA (F ig. 2C ). Portal vein could collect blood supply from spleen through SRS, from intestine through IMV-PA, and from left kidney through LRV. Fig. 1 B shows the complete portal vein re- construction image. PVT did not occur in the next year. As ex- pected, the patient’s liver function gradually returned to normal. After this surgery, the LRV pressure was close to PV pressure, and it was much higher than LRV pressure in normal scenario. This could explain why the Scr was maintained at a higher level af- ter surgery. However, the urine volume of the patient was always normal in 1-year follow-up after LT, which suggested that filtration and metabolic function of the kidneys were normal.

Fig. 2. A and B: photograph during the surgery of renoportal anastomosis and inferior mesenteric vein-portal anastomosis; C: a sketch of renoportal anastomosis and inferior mesenteric vein-portal anastomosis. HA: hepatic artery; PV: portal vein; IIA: isolated iliac artery; LRV: left renal vein; IVC: inferior vena cava; IMV: inferior mesenteric vein; SMV: superior mesenteric vein; LRV: left renal vein; PVT: portal vein thrombosis; SRS: spleno-renal shunt.

In conclusion, a new method combining RPA and IMV-PA dur- ing LT was suitable and achieved positive result in this case. To the best of our knowledge, this is the first case to be reported. To ex- amine whether this method is feasible for grade IV PVT recipients without large SRS, further studies are warranted by enrolling more appropriate cases in the future.

Acknowledgments

None.CRediTauthorshipcontributionstatement

Guo-LingLin:Conceptualization, Funding acquisition, Writing – original draft.MinXiao:Conceptualization, Writing – original draft.LiZhuang:Resources, Writing – review & editing.YuYang:Methodology, Data curation, Investigation.Qi-YongLi:Resources, Writing – review & editing.Jian-FangLu:Resources, Writing – re- view & editing.Meng-XiaLi:Methodology, Data curation, Investi- gation.Shu-SenZheng:Supervision, Validation.

Funding

This study was supported by a grant from the National Key Re- search and Development Program of China ( 2018YFC20 0 050 0 ).

Ethicalapproval

This study was approved by the Ethics Committee of Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shu- lan International Medical College. Written informed consent was obtained from the patient.

Competinginterest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the sub- ject of this article.