"Small-for-flow" syndrome: shifting the "size" paradigm

Abstract

The "small-for-size" syndrome and "post-hepatectomy liver failure" refers to the development of liver failure (hyperbilirubinemia, coagulopathy, encephalopathy and refractory ascites) resulting from the reduction of liver mass beyond a certain threshold. This complication is associated with a high mortality and is a major concern in liver transplantation involving reduced liver grafts from deceased and living donors as well as in hepatic surgeries involving extended resections of liver mass. The limiting threshold for liver resection or transplantation is currently predicted based on the mass of the remnant liver (or donor graft) in relation to the body weight of the patient, with a ratio above 0.8 being considered safe. This approach, however, has proved inaccurate, because some patients develop the "small-for-size" syndrome despite complying with the "safe" threshold while other patients who surpass the threshold do not develop it. We hypothesize that the development of the "small-for-size" syndrome is not exclusively determined by the ratio of the mass of the liver remnant (or graft) to the body weight, but it is instead strictly determined by the hemodynamic parameters of the hepatic circulation. This hypothesis is based in recent clinical and experimental reports showing that relative portal hyperperfusion is a critical factor in the development of the "small-for-size" syndrome and that maneuvers that manipulate the hepatic vascular inflow are able to prevent the development of the syndrome despite liver-to-body weight ratios well below the "limiting" threshold. Measurements of hepatic blood flow and pressure, however, are not routinely performed in hepatic surgeries. Focusing on the "flow" rather than in the "size" may improve our understanding of the pathophysiology of the "small-for-size" syndrome and "post-hepatectomy liver failure" and it would have important implications for the clinical management of patients at risk. First, hepatic hemodynamic parameters would have to be measured in hepatic surgeries. Second, these parameters (in addition to liver mass) would be the principal basis for deciding the "safe" threshold of viable liver parenchyma. Third, the hepatic hemodynamic parameters are amenable to manipulation and, consequently, the "safe" threshold may also be manipulated. Shifting the paradigm from "small-for-size" to "small-for-flow" syndrome would thus represent a major step for optimizing the use of donor livers, for expanding the indications of hepatic surgery, and for increasing the safety of these procedures.