Hiroto Kayashima

Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation.

Backgrounds. Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. Methods and Results. A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). Conclusions. A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC.

Donor Risk in Adult-to-Adult Living Donor Liver Transplantation : Impact of Left Lobe Graft

Background. To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods. Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results. Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions. LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation.

The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft

Small‐for‐size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (−) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate‐ and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight‐to‐standard liver weight (GW‐SLW) ratio of 40% or less (n = 50). Thirty‐one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW‐SLW ratio <40%, and Sp (−) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW‐SLW of 40% or less.

Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Background and aims: MicroRNAs are small non‐coding RNA molecules that post‐transcriptionally regulate gene expression. Liver‐specific microRNA‐122 (miR‐122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR‐122 on HCV in human body is unclear.

Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation

No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium‐99m galactosyl‐human serum albumin (Tc‐GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc‐GSA to the clearance index of Tc‐GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 × graft weight (%) − 0.016 × donor age − 0.008 × Model for End‐Stage Liver Disease score − 0.15 × shunt (if present) + 1.757 (r2 = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin (TB) and prothrombin time international normalized ratio (PT‐INR) in the group with an LHL/HH score ≥ 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT‐INR, and volume of ascites in the group with a predictive score ≥ 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6‐month survival probability was improved in the group with a predictive score ≥ 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short‐term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence. Liver Transpl 14:1007–1013, 2008.

Living Donor Liver Transplantation for Acute Liver Failure: A 10-Year Experience in a Single Center

BACKGROUND Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. STUDY DESIGN Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. RESULTS Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilsons disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2+/-9.2% in left lobe grafts and 50.5+/-3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/-18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. CONCLUSIONS Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated.

Impact of donor age and recipient status on left‐lobe graft for living donor adult liver transplantation

Donor safety is the priority when performing a living donor adult liver transplantation (LDALT). We herein present our findings using left‐lobe graft in LDALT. Data on 119 recipients who underwent the LDALT, and on 119 donors who underwent extended left lobectomy were reviewed. The recipients were divided into groups above (n = 19) and below (n = 100) 50 years of donor age, into groups above (n = 63) and below (n = 56) 40% of graft size (graft volume/standard liver volume, GV/SLV), and above (n = 25) and below (n = 94) 20 of pre‐operative model for end‐stage liver disease (MELD). Total bilirubin (TB), volume of ascites, prothrombin time international normalized ratio on postoperative day 14 or survival rates were compared. TB (mg/dl) or volume of ascites (ml) of the group in donor age < 50 years was better than that of the group in donor age ≥ 50 years (7.4 vs. 14.7 or 788 vs. 1379, P < 0.001 or P < 0.005, respectively). The graft and patient survival rates of the lower MELD group tended to be better than that of the higher MELD group. LDALT can be safely performed using a left‐lobe graft. However, when using the graft from the donor ≥ 50 years, especially for the recipients with the MELD ≥ 20, the indications should be carefully discussed.

Living Donor Hepatectomies with Procedures to Prevent Biliary Complications

BACKGROUND Biliary complications in donor hepatectomies are still common, and occur in approximately 5% of the procedures. STUDY DESIGN To evaluate the usefulness of the management and surgical procedures to prevent the biliary complications in donor hepatectomies, a total of 343 donors were retrospectively studied. The clinical and surgical parameters of the donors and the postoperative biliary complications were evaluated. RESULTS Fourteen donors had biliary complication (BC) during the follow-up period (4.1%). Donors were divided into 2 groups; donors without BC (non-BC group; n = 329) and donors with BC (BC group; n = 14). Mean peak level of total bilirubin, mean duration of hospital stay after surgery, and medical cost in the BC group were significantly higher than in the non-BC group (p < 0.01). As improved procedures to prevent the BC were established at 2005, including the use of a real-time cholangiography by the C-arm, a minimized dissection of the hepatic vessels, the meticulous closure of the bile duct, and/or the use of Pringle maneuver during the parenchymal transection, the donors were divided into 2 groups before and after these establishments (the early period, n = 173; the later period, n = 170). Refinements in the management and surgical procedures reduced the occurrence of biliary complications from 6.4% during the early period to 1.8% during the later period (p < 0.01), and no biliary complications in the last 69 consecutive donors were observed. CONCLUSIONS Technical refinements described in this study might be useful to prevent the occurrence of biliary complications in a donor hepatectomy. It is particularly important to preserve the blood supply for the biliary tract of both the graft and the remnant liver.

Primary Graft Dysfunction After Living Donor Liver Transplantation Is Characterized by Delayed Functional Hyperbilirubinemia

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult‐to‐adult LDLT grafts without anatomical, immunological or hepatitis‐related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH‐20) was used to characterize PGD. DFH‐20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH‐20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT‐INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH‐20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH‐20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.

Accuracy of an age‐adjusted formula in assessing the graft volume in living donor liver transplantation

In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age‐adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age‐adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age‐adjusted formula and 3‐dimensional computed tomography (3D‐CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age‐adjusted formula was created as follows: age‐adjusted GV = 70.767 + (0.703 × GV estimated with 3D‐CT volumetry) + (1.298 × donor age). The mean error ratio for the age‐adjusted formula (9.6%) was significantly lower than that from 3D‐CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age‐adjusted formula is very useful in reducing the error in estimating GV. Liver Transpl 14:1366–1371, 2008.