Infrahepatic cavocavostomy: Expanding the armamentarium for the liver transplant surgeon

Infrahepatic vena cavocavostomy, a modification of the piggyback technique for liver transplantation. Khanmoradi K, Defaria W, Nishida S, Levi D, Kato T, Moon J, et al. Am Surg 2009;75:421-425.

COMMENTS

Every liver transplant surgeon has a preferred technique for performing arterial anastomosis, biliary anastomosis, portal vein anastomosis, and inferior vena cava anastomosis. The unique anatomy of every patient influences the type of anastomosis that is chosen. To meet specific anatomical challenges, surgeons must modify their preferred techniques to ensure successful outcomes for all patients.

The evolution of caval implantation was reviewed in a previous Liver Transplantation Worldwide column.¹ Every technique needs modification in some patients. One modification of the piggyback technique for caval implantation is the infrahepatic cavocavostomy. In the performance of infrahepatic cavocavostomy, either the end of the inferior vena cava is used for the anastomosis, or the posterior wall of the donor's infrahepatic cava is cut longitudinally cephalad starting from the inferior edge. The donor's suprahepatic inferior vena cava is oversewn or closed with a patch so that it does not obstruct the hepatic veins. A longitudinal cavostomy is made in the recipient's inferior vena cava for the anastomosis.

Quintini et al.² described the use of infrahepatic cavocavostomy as a rescue technique in cases in which the liver allograft's venous outflow became obstructed because of stenosis of the piggyback anastomosis. Lima et al.³ reported on cases in which infrahepatic cavocavostomy was the primary caval anastomosis, and they suggested the use of infrahepatic cavocavostomy in selected patients. Nishida et al.⁴ described the use of end-to-side infrahepatic cavocavostomy in 5 domino recipients receiving livers from donors having familial amyloidotic polyneuropathy.

In this review, Khanmoradi et al. report on 109 infrahepatic cavocavostomies performed in 1400 liver transplant operations between May 1997 and January 2006. These 109 anastomoses were performed in 101 patients. There were 87 primary transplants and 22 retransplants. The reasons for using infrahepatic cavocavostomy were problems with either the recipient hepatic veins or the donor suprahepatic cava. Problems with the recipient hepatic veins included the presence of a transjugular intrahepatic portosystemic shunt with damage to the hepatic veins, retransplantation, thin-walled friable hepatic veins, and Budd-Chiari syndrome. Problems with the donor suprahepatic cava included a short suprahepatic cava resulting from a domino liver procurement, reduced or split liver grafts, and mismatch of the inferior vena cava size between the donor and recipient. Outflow problems developed in only 2 of the 109 anastomoses. There was no graft loss related to hepatic venous outflow abnormalities. Patients undergoing infrahepatic cavocavostomy had significantly more need for blood transfusions than patients undergoing the standard piggyback technique. There was no difference in long-term survival between patients undergoing the standard piggyback technique and patients undergoing infrahepatic cavocavostomy.

The option of infrahepatic cavocavostomy as an alternative to the piggyback technique will be useful to the liver transplant surgeon in the right circumstances.

Abbreviations

ALD, alcoholic liver disease; DCD, donation after cardiac death; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NASH, nonalcoholic steatohepatitis.

REFERENCES

Defatting the Fatty Liver with Normothermic Perfusion of the Liver Allograft

Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo. Nagrath D, Xu H, Tanimura Y, Zuo R, Berthiaume F, Avila M, et al. Metab Eng 2009. doi://10.1016/j.ymben.2009.05.005. Available at: http://www.sciencedirect.com.

COMMENTS

Machine perfusion (both hypothermic and normothermic) of liver allografts has been studied for several years.^1–6 Because of logistic and cost issues, however, machine perfusion has not yet been a viable clinical option. If machine perfusion were to allow transplantation of heretofore rejected livers, this would motivate solutions for logistic and cost issues, encouraging the routine clinical use of machine perfusion.⁷

Donor livers are being seen with increasing amounts of steatosis and are being rejected for transplantation.⁸ Verran et al.⁹ reported that the higher grades of donor liver steatosis are associated with poorer initial allograft function. Briceño et al.¹⁰ also found that liver graft survival decreased as donor liver steatosis increased and that hepatitis C virus recurrence increased with increasing grades of donor liver steatosis. Spitzer et al.¹¹ suggested that for purposes of classifying the highest risk donors, donor age, macrovesicular fat percentage, cold ischemia time, and donation after cardiac death (DCD) are the most important factors. Overcoming the detrimental effects of macrovesicular fat and DCD donation would improve transplantation success rates and increase the number of liver transplants.

In this review, Nagrath et al. discuss their exploration of several compounds that increase lipid export and/or oxidation. These investigators studied the effects of a combination of amino acids on lipid metabolism in ex vivo perfused fatty livers. The goal was to metabolically precondition liver allografts to reduce the fat content of steatotic livers to an amount within a normal range before transplantation. Livers (obese and lean) from Zucker rats were perfused with 40 mL of perfusate pumped through an oxygenator with a 95% O₂/5% CO₂ gas mixture and a heat exchanger. Outflow from the livers was returned to the perfusion chamber, recycled, and changed hourly. The livers were subjected to 3 hours of perfusion at a flow rate of 2.5 mL min⁻¹ with the temperature maintained between 35.6 and 37°C. Compared with a control perfusate containing no defatting agents, the defatting cocktail led to greater bile production. Histologically, significant defatting effects were observed in the periportal region but not in the perivenous region. The defatting cocktail increased secretions of triglyceride by 40% over the control perfusate. In summary, Nagrath et al. found that a mixture of these amino acids significantly up-regulates pathways involved in fatty acid oxidation and triglyceride secretion, causing a rapid reduction in lipid storage.

Another high-risk donor factor is DCD donation. St Peter et al.¹² used a pig model to discover that DCD livers undergoing normothermic machine perfusion recovered liver function significantly better than livers in cold storage. Livers were subjected to 1 hour of warm ischemia before preservation. No liver undergoing cold storage in University of Wisconsin solution for 24 hours had viable function. All livers undergoing normothermic machine perfusion for 24 hours had viable function. Gong et al.¹³ reported that pig livers undergoing normothermic machine perfusion were significantly more viable than those stored in cold histidine-tryptophan-ketoglutarate solution. In a rat model, Tolboom et al.¹⁴ found that normothermic liver perfusion optimized the preservation of DCD livers.

If normothermic perfusion can successfully improve clinical care by allowing the use of fatty livers and livers from DCD donors, it will gain prominence among organ preservation methods.

REFERENCES

Is Survival After Liver Transplantation for Hepatocellular Carcinoma Influenced by the Etiology of the Liver Disease?

Liver transplantation in patients with nonalcoholic steatohepatitis-related hepatocellular carcinoma. Malik SM, Gupte PA, de Vera ME, Ahmad J. Clin Gastroenterol Hepatol 2009;7:800-806.

COMMENTS

Fattovich et al.¹ reviewed the incidence of hepatocellular carcinoma (HCC) associated with various etiologies of cirrhosis. Cirrhosis secondary to hepatitis C virus (HCV) infection was associated with the highest HCC incidence, and it was followed by hereditary hemochromatosis, hepatitis B virus (HBV) infection, alcoholic liver disease (ALD), and primary biliary cirrhosis. Coinfection with HBV/HCV increased the HCC risk 2- to 4-fold. Fattovich et al. additionally commented that HCC secondary to nonalcoholic steatohepatitis (NASH) needed further study. Hashimoto et al.² found that more women experienced NASH-HCC than HCC from ALD. Regimbeau et al.³ stated that obesity and diabetes are risk factors for HCC. Bugianesi^4,5 suggested that the incidence of NASH-related HCC is expected to increase, and HCC that develops in patients with cryptogenic cirrhosis may actually be a complication of NASH. Several authors have recommended screening for HCC in patients with NASH.^6–8

With the increasing incidence of HCC in patients with NASH, does the etiology of the underlying cirrhosis influence survival after liver transplantation for HCC?

In this review, Malik et al. studied the prevalence of HCC among patients undergoing liver transplantation for NASH-related cirrhosis and their outcomes in comparison with controls after transplantation. Patients with NASH cirrhosis (98 patients) were compared in a 1:2 ratio with patients in each of 3 control groups (588 patients in all) who underwent transplantation for primary biliary cirrhosis/primary sclerosis cholangitis, ALD, or HCV. The patients were matched for age, sex, Model for End-Stage Liver Disease score, and year of transplantation. Patients were considered to have a diagnosis of NASH cirrhosis through histopathological findings, absence of ALD history, and exclusion of other forms of chronic liver disease. Of the NASH patients, 17 (17.3%) were diagnosed with HCC. In the 4 groups, the incidence of total HCC (ie, cases known pre-transplantation and cases discovered incidentally in the explanted liver) was 17.3% in the patients with NASH, 7.1% in the patients with primary biliary cirrhosis/primary sclerosing cholangitis, 13.6% in the patients with ALD, and 27.8% in the patients with HCV. There was no difference in 5-year survival between patients transplanted for NASH cirrhosis with HCC and patients transplanted for NASH cirrhosis without HCC. Likewise, there was no difference between patients transplanted for NASH with HCC and all patients transplanted with the diagnosis of HCC at the authors' center over a 15-year period.

This finding that the etiology of cirrhosis has no effect on survival is consistent with a report by Chan et al.⁹ on the risk of HCC recurrence after liver transplantation. In this study, the etiology of HCV, HBV, or ALD was not seen to influence HCC recurrence.

In the absence of additional data showing otherwise, it seems that the etiology of cirrhosis does not affect the posttransplant survival of patients who undergo transplantation for HCC.

REFERENCES

Should Intraportal Insulin Administration Become Routine in Clinical Transplant Care?

Initial clinical effect of intraportal insulin administration on liver graft regeneration in adult patients who underwent living donor right lobe liver transplantation. Xu MQ, Yan LN, Li B, Wen TF, Zeng Y, Zhao JC, et al. Transplant Proc 2009;41:1698-1702.

COMMENTS

In 1977, Starzl et al.1 noted that insulin is the single most important hepatotrophic factor. These investigators discovered that insulin infusion into a portally deprived liver minimized liver atrophy. Using a rat model, Rokicki et al.2 found that intraportal insulin infusion enhanced rat liver regeneration, as evidenced by a rapid increase in liver DNA and RNA levels. The most significant changes occurred in the first 24 hours after partial hepatectomy.

Intraportal insulin therapy has been used in clinical care. Wang et al.3 reported on intraportal insulin infusion after partial hepatectomy in patients with hepatoma who had insulinopenia. A 16-gauge catheter was inserted into a reopened umbilical vein and fixed in place for administration of the intraportal infusion. Regular insulin was administered just after the operation at a rate of 2 U/hour for 2 to 3 weeks. Wang et al. concluded that intraportal insulin infusion after hepatectomy promotes recovery of the remnant liver.

In this review, Xu et al. consider the clinical effects of intraportal insulin administration on liver graft regeneration in adult liver transplantation. These authors compared one group of 15 recipients of right lobe living donor livers who were given intraportal insulin therapy to another group of 15 right lobe graft recipients who were not given insulin. To prepare for the intraportal insulin therapy, an 18-gauge catheter was inserted into the right gastro-omental vein and passed through the abdominal wall. Recombinant human insulin (20 U/mL) was administered at a dose of 2 U/hour. On postoperative day 7, the levels of total bilirubin, aspartate aminotransferase, and alanine aminotransferase in the patients who received the intraportal insulin infusion were significantly lower than those in the patients who did not receive the infusion. The regenerated graft volumes, as measured by computed tomography volumetric analysis at 1 week after transplantation, were significantly larger at 1081 ± 82.4 cm³ in the patients who received intraportal infusion in comparison with 952.1 ± 60.8 cm³ in the patients without intraportal insulin administration. The graft regeneration rates at 1 week were significantly higher in the group receiving intraportal insulin than in the group not receiving insulin. There was no difference between groups in the liver function tests, liver volumes, or regenerative rates at 1 month following transplantation.

Intraportal insulin infusion will require further study before becoming routine in clinical practice.