Influence of Transplantation on Liver Surgery

Liver Growth and Regeneration

The liver occupies a central role in the complex metabolic interactions among organ systems during stress and illness. This delicate homeostasis is further balanced by the remarkable capacity of the liver to expand hepatocyte mass rapidly in response to changing metabolic demands or significant hepatic injury. Simultaneous advances in critical care, perioperative management, pharmacology, and oncology have paralleled the advances in liver transplantation over the last 5 decades, stimulating a rapid growth of research in hepatic regeneration, ischemia-reperfusion injury, and acute liver failure.

Gene expression profiles of regenerating hepatocytes continue to be analyzed and are helping to refine our understanding of the role of hepatocyte growth factors accumulating in the serum after partial resections. Growth factors may be synthesized in the liver or other tissues and include insulin, glucagon, norepinephrine, vasopressin, and complement components, among others. The discovery that early activation of the cytokines interleukin-6 and tumor necrosis factor-α serves to trigger the regenerative response has been further explored. The generation of genetically modified mice with alterations in the expression levels of growth factors, cytokines, and their receptors and the use of these mice in liver regeneration studies have provided some exciting results, including characterization of synergistic functions of transforming growth factor-β and activin, the role of insulin-like growth factors and the insulin system in liver regeneration, and the contribution of hepatocyte growth factor. Finally, growing evidence suggests that the same cytokine-dependent activation processes that drive hepatic regeneration are also responsible for the physiological and histological changes typically seen in posttransplant ischemia-reperfusion injury. This research is potentially applicable to treatment of patients with loss of liver substance from a variety of causes, including cirrhosis, inflammation, infection, trauma, and surgical resection. It may offer a better understanding of the phenomenon of small-for-size syndrome, characterized by prolonged cholestasis and graft dysfunction after partial and living donor liver grafts. Liver transplantation has also spurred investigations into the generation of liver progenitor cells and stem cells and liver assist devices as an alternative to the use of whole organ transplantation.

Hepatic Vascular and Biliary Anatomy

The donor and recipient hepatectomy procedures offer a broad experience in upper abdominal surgery and provide supreme lessons in surgical anatomy, including exposure, surgical approach, mobilization techniques, and hepatic vascular isolation, as well as an appreciation for the variations of hepatic vascular and biliary anatomy. Arterial variants have long been recognized, and portal venous and biliary anomalies are also recognized with growing frequency. The UCLA series of donor hepatectomies shows that specific variations in hepatic arterial anatomy are particularly common ( Fig. 4-1 ). In this series ( Table 4-1 ), subsequently corroborated by others, 24% of donor livers had anomalous hepatic arterial supply, most often a replaced or accessory right hepatic artery arising from the superior mesenteric artery (11%), followed by a replaced or accessory left hepatic artery arising from the left gastric artery (10%). Aberrant portal venous anatomy is present in 20% to 35% of livers. Portal vein trifurcation or an aberrant branch from the left portal vein supplying the right anterior lobe was the most frequent anomaly ( Table 4-2 ).

The high incidence of biliary complications after split and living donor liver transplantation has led to a greater interest in the common variants of biliary anatomy ( Table 4-3 ). These include trifurcation of the common hepatic duct into left, right anterior, and right posterior ducts, with no significant length of right hepatic duct (12%), and aberrant drainage of the right segmental duct into the left hepatic duct (6%). The increasing experience with split and living donor liver transplantation and the wider application of surgical treatment for hepatic malignancies obligate familiarity with these anatomical variations, which will provide challenges in complex reconstructions.

Recognition of the anatomy of the dual hepatic blood supply and dependence of hepatocellular carcinoma on the arterial supply has enabled transcatheter techniques to direct chemotherapy, radioactivity, and embolization material via the hepatic artery to treat these tumors. The dual hepatic blood supply has also led to increased use of portal vein embolization before major liver resection to augment the size of the liver that will remain postoperatively.