Indocyanine Green Dye Excretion in Bile Reflects Graft Function After Living Donor Liver Transplantation

Abstract

There are many biochemical parameters that can be used to assess the function of partial liver graft; however, a definitive marker remains to be identified. For example, the color of bile has been reported anecdotally to reflect graft function, but its value has not yet been fully evaluated. Recently, indocyanine green (ICG) K value, that is ICG clearance, was found to be valuable in assessing the function of a whole or partial graft after living donor liver transplantation (LDLT) (1). However, the measurement of ICG dye concentrations in serum is not valid in hyperbilirubinemic patients because of interference while using the spectrophotometer (2). We previously reported the value of ICG dye concentration in the bile in an ICG challenge test in patients undergoing liver resection for bile duct cancer, because ICG is a relatively hydrophobic organic anion that has a high hepatic extraction ratio and is excreted extensively and remains unchanged in bile (3). It has also been reported that ICG excretion in bile could be a good parameter for assessing preoperative liver function in biliary drainage patients because it reflects adenosine triphosphate levels in the liver (4, 5). Thus, this study evaluates ICG excretion in bile after LDLT as a potential novel parameter of partial liver graft function. This prospective study was approved by the local institutional review board, and written informed consent was obtained from all patients. Of 37 consecutive patients who underwent liver transplantation between April 2005 and March 2007, 32 patients who received duct-to-duct biliary reconstruction were studied (median age 53 years; right lobe graft:left-sided graft 19:13; and graft volume/standard liver volume median 46%). One week after LDLT, we performed a fasting ICG injection test (0.5 mg/kg; Diagnogreen Inj.; Daiichi Seiyaku, Tokyo, Japan), and bile was collected through biliary external stenting reported earlier (6) while blocking natural light. ICG concentrations in bile at 0, 30, 120, and 360 min after injection were measured by spectrophotometer at a wavelength of 805 nm. Blood samples were also taken before ICG injection and 15 min after injection. All data were expressed as median values with ranges. The pattern of change in ICG excretion after ICG injection showed distinct two patterns. Type I (n=24) showed a steep increase and a peak within 2 hr and returned to baseline within 6 hr, whereas type II (n=8) showed a low peak of less than 1 micromole per liter during the 6-hr observation period. Table 1 shows various detailed parameters of type I and type II patients and their LDLTs. The parameters that correlated with ICG patterns were compared between the two groups, and donor age and graft type were found to have a significant influence on the type of ICG excretion in bile. Also, it shows the relationship between the type of ICG excretion in bile and various graft functions such as jaundice, prothrombin activity, and ICG retention rate at 15 min. In fact, because retention rate of ICG at 15 min after injection was correlated with type of ICG excretion in bile, ICG retention rate at 15 min can substitute the excretion pattern in bile. Several type II patients had prolonged jaundice after LDLT due to outflow block (n=1), acute cellular rejection (n=2), or unknown cause (n=5).TABLE 1: Factors influencing types of ICG excretion in bile and various outcomes after LDLTTo clarify changes in ICG pattern over time, the same challenge test was performed at 3 months after LDLT. Most patients remained or became type I (data not shown). Six of the eight patients who were classified as type II at 1 week after LDLT were classified as type I at 3 months after LDLT. Remaining two patients had prolonged jaundice until approximately 6 months after LDLT and recovered without jaundice. These two patients were complicated with biliary stricture and chronic rejection at 3 months after LDLT. Donor age has been reported to be an important factor of graft quality and liver regeneration (7). In addition, we demonstrate in this study that not only donor age but also graft type affects the bile excretion of the graft liver. Right posterior sector grafts are sometimes problematic because the portal vein is smaller at the second-grade bifurcation, causing relative portal hypertension and biliary stricture (8) Type II pattern at 1 week after LDLT is not a predictor of poor outcome with a partial graft, although prolonged jaundice should be expected. In fact, duration until the disappearance of icterus is of great interest after liver transplantation. This study also demonstrates that ICG excretion in bile is a direct indicator of prolonged severe jaundice. Susumu Eguchi Mitsuhisa Takatsuki Kosho Yamanouchi Masaaki Hidaka Akihiko Soyama Tetsuo Tomonaga Yoshitsugu Tajima Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Sakamoto, Nagasaki, Japan