Hepatic steatosis is associated with intrahepatic cholestasis and transient hyperbilirubinemia during regeneration after living donor liver transplantation

A clear understanding of the mechanisms in steatotic livers that trigger cholestasis or hyperbilirubinemia after living donor liver transplantation (LDLT) remains elusive. We hypothesized that microarchitectural disturbance might occur within regenerating steatotic livers without impairment of hepatic proliferative activity. Liver biopsy specimens from 67 LDLT recipients taken at the 10th postoperative day were scored for the numbers of portal tracts per area (nPT/A) of liver tissue and for intrahepatic cholestasis, and immunostained by proliferating cell nuclear antigen (PCNA) and Ki-67. The preoperative degree of macrovesicular steatosis (MaS) was independently associated with cholestasis after LDLT (P < 0.001). Serum total bilirubin results on the 1st, 3rd, and 7th days post-LDLT in MaS+ (5-30% of MaS; n = 37) patients were significantly higher than those in MaS- (<5% of MaS; n = 30) patients (P = 0.030, 0.042, and 0.019, respectively). Mean numbers of positively stained hepatocytes were 53.1 +/- 12.0 in patients with MaS and 48.0 +/- 17.1 in those without MaS by PCNA (P = 0.390), and 24.4 +/- 10.5 and 24.0 +/- 14.0 by Ki-67 (P = 0.940). However, a significant negative correlation was found between the degree of MaS and nPT/A (P = 0.013), and nPT/A was correlated with the grade of histological cholestasis (r = 0.350, P = 0.039). Intrahepatic cholestasis and hyperbilirubinemia after LDLT could be caused by scanty morphologic change of portal tract during steatotic liver regeneration.     

The hepatic regeneration power of mild steatotic grafts is not impaired in living-donor liver transplantation.

The aim of this study was to assess histologic changes in steatotic grafts, regenerative capacity, and the outcome of steatotic grafts in living-donor liver transplantation (LDLT). Between September 2002 and February 2004, 55 cases of LDLT with a liver biopsy performed on the 10th postoperative day were enrolled. Patients were grouped according to the intraoperative histologic degree of macrovesicular steatosis (MaS) as follows: Group 1, <5% (n = 24); Group 2, 5 to 15% (n = 24); and Group 3, 15 to 30% (n = 7). The intraoperative microscopic findings and the findings on the 10th postoperative day were compared. Immunohistochemistry was performed using antibody of proliferating cell nuclear antigen (PCNA) and Ki-67 to assess the regeneration power of grafts on the 10th postoperative day. The histologic degree of MaS on postoperative day 10 decreased from 5.22 +/- 1.04% (mean +/- standard deviation) to 2.17 +/- 1.90 in Group 2 (P < .001) and from 21.4 +/- 8.02 to 4.43 +/- 2.70 in Group 3 (P = .003). The number of positively stained hepatocytes in 10 high power fields was 48.0 +/- 17.1, 53.8 +/- 14.4, and 51.5 +/- 4.1 in each group by PCNA (P = .681), and 24.0 +/- 14.0, 25.5 +/- 11.8, and 21.6 +/- 6.8 by Ki-67 (P = .825), respectively. No primary graft nonfunction (PNF) or delayed graft function (DGF) occurred. Major complications were comparable among groups. In conclusion, in LDLT, steatosis disappeared immediately after transplantation and hepatic regeneration power was not impaired in grafts with less than 30% of MaS. Furthermore, a mildly steatotic graft did not increase the risk of graft dysfunction or morbidity in LDLT.     

Severe steatosis increases hepatocellular injury and impairs liver regeneration in a rat model of partial hepatectomy

OBJECTIVE: The aim of this study was to assess the influence of severe steatosis with inflammation on hepatocellular recovery after 70% hepatectomy in a rat model of diet-induced steatosis. BACKGROUND: Patients with steatosis have an increased risk of inflammatory complications after liver resection. This might be attributable to Kupffer cell-mediated inflammation in steatotic livers causing progressive injury. METHODS: Male Wistar rats were fed a standard methionine- and choline-deficient diet for 1 or 5 weeks. A 70% partial hepatectomy (PH) was performed, after which rats were killed at 24, 48, or 72 hours. The extent of steatosis and inflammation was determined by assessment of hepatic triglycerides, cytokine content, and histopathology. Outcome parameters were: liver regeneration (MIB-5 proliferation rate, mitotic index, and regenerating liver mass), hepatocellular injury (plasma aminotransferases, lipid peroxidation, histopathology, and apoptosis), Kupffer cell-mediated proinflammatory response (TNF-alpha, IL-1beta, IL-6, IL-10 in plasma and liver) and antioxidant content (total glutathione). RESULTS: Methionine- and choline-deficient diet induced uncomplicated steatosis after 1 week (<30% hepatocytes affected without inflammation) and severe steatosis after 5 weeks (>60% hepatocytes affected, including prominent inflammation) as confirmed by histopathology. After PH, liver regeneration was impaired at all time points in the severe steatosis group as compared with the mild and control groups (P < 0.05). Hepatocellular injury was significantly increased in the severe steatosis group at all time points (P < 0.05). Kupffer cell-mediated inflammatory responses were aggravated in the severe steatosis group along with decreased antioxidant content (P < 0.05). Necrosis was the main type of cell death in severe steatotic livers compared with mainly apoptotic cell death in mild steatotic and normal livers. CONCLUSION: Steatosis with prominent inflammation impaired liver regeneration probably because of increased hepatocellular lipid peroxidation and damage in concert with Kupffer cell-mediated proinflammatory responses. These results suggest an increased risk of performing extensive liver resection in the presence of severe steatosis.     

Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers – a retrospective study

The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia-free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3-year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.     

Mild steatosis impairs functional recovery after liver resection in an experimental model

BACKGROUND: Mild steatosis has been thought not to affect outcome after liver resection. However, recent studies have reported impaired postoperative recovery of patients with mild steatosis. This study evaluated the recovery of hepatic functional reserve during regeneration in a rat model of mild steatosis and liver resection. METHODS: Male Wistar rats had a standard methione- and choline-deficient diet to induce mild steatosis before 70 per cent liver resection. Evaluation of hepatobiliary function was by (99m)Tc-labelled mebrofenin scintigraphy. Mebrofenin uptake rate, the time for maximum uptake (T peak) and the time required for peak activity to decrease by 50 per cent (T(1/2) peak) were assessed 1, 2, 3 and 7 days after liver resection, along with regeneration of the remnant liver, hepatocellular and sinusoidal damage, and hepatic adenosine 5'-triphosphate (ATP) levels. RESULTS: Liver regeneration and proliferative response in mild steatotic rats were no different from those in controls. However, the mebrofenin uptake rate was lower (P < 0.050) and the recovery of hepatic ATP impaired (P < 0.050) in animals with mild steatosis. Hepatocellular damage was increased (P < 0.050) but sinusoidal endothelial cell function was not affected after liver resection in mildly steatotic rats. CONCLUSION: Mild steatosis impaired functional recovery and increased hepatocellular damage after liver resection.     

Factors associated with low graft regeneration in the early phase after living donor liver transplantation

Appropriate graft regeneration after living donor liver transplantation (LDLT) is crucial to avoid small‐for‐size syndrome. We enrolled 44 recipients who underwent ABO‐identical/compatible LDLT from December 2007 to August 2016 and determined possible factors associated with low graft regeneration after LDLT. Liver regeneration was calculated by the ratio of the graft size on postoperative day (POD) 7 ± 1 day (calculated by CT volumetry) to the size of the donated liver at implant. Postoperative outcomes were compared between the low and high regeneration groups. Median regeneration rate was 1.65‐fold. Regeneration rate was negatively correlated with graft‐to‐recipient weight ratio. Postoperative morbidity rates on POD 14‐90 were significantly higher in the low group compared with the high group (63% vs 18%, P = .03). Graft and patient survival in the low group were significantly worse than the high group (1‐year graft survival 73% vs 100%, P = .002; patient survival 82% vs 100%, P = .01). Cold ischemia time (CIT; per 10 minute; odds ratio [OR] =1.37) and platelet count <60 000/μL on POD 5 (OR = 14.32) were independently associated with low regeneration. In conclusion, longer CIT and postoperative thrombocytopenia were associated with low graft regeneration in the early phase after LDLT, which could consequently lead to poor graft and patient survival.     

Mechanism of primary graft non‐function in a rat model for fatty liver transplantation

Abstract We established a fatty liver model in rat suitable for the model of human liver with steatosis by cholesterol enriched chow, and investigated the mechanism of primary graft non‐function in fatty liver transplantation (LTx) using this model. Grafts with steatosis caused primary graft dysfunction after LTx following even short cold preservation; however, no significant difference was recognized in mitochondrial function of the graft during preservation. Morphological findings were not different at 1 h after reperfusion between non‐steatotic and steatotic livers. Focal necrosis of hepatocytes was seen and the sinusoidal endothelial cells were injured 24 h after reperfusion. In addition, the fluidity of the plasma membrane decreased in fatty liver. Our results indicate that deterioration of sinusoidal endothelial cells after reperfusion causes graft dysfunction in LTx of steatotic liver.     

Pediatric living‐donor liver transplantation for acute liver failure: analysis of 57 cases

We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto University Hospital in Japan over a period of 15 years to compare the etiology and the long‐term outcome of infants and children after living donor liver transplantation (LDLT). Patients were divided into two groups according to age at the time of liver transplantation, infants group (<1 year, n = 20), and children group (1–18 years, n = 37). The overall survival rates were 73.6%, 69.5% and 67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the time of LDLT had a strong impact on their outcome, Children had significantly better outcome than infants (P = 0.001). Surgical complications were comparable between both groups. Infants had higher rates of acute cellular rejection (ACR), which was associated with features of hepatitis in many cases. Refractory ACR was the leading cause of death in eight out of 12 infants, while it resulted in loss of one child only. Cox’s proportional hazard regression model was used to examine potential risk factors for graft loss and it shows that age <1 year was associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961–76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children and refractory ACR was the leading cause of death. Using additional immunosuppressant for cases with severe and atypical rejections is recommended.     

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel–Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel–Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.     

Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm

The aim of this study was to assess the long‐term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single‐center, 10‐yr follow‐up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low‐risk recipients. This study initially compared fat assessment based on frozen‐section Ehrlich's hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30–60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non‐function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.     

Saying "Yes" to obese living liver donors: short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean+/-SEM], P=0.0028). Body weight and BMI were significantly reduced (73.7+/-3.2 kg vs. 66.9+/-2.9 kg, P=0.0033, 26.4+/-0.7 kg/m(2) vs. 24.1+/-0.8 kg/m(2), P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steatosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.     

Prediction of early allograft dysfunction using serum phosphorus level in living donor liver transplantation

Serum phosphorus is greatly affected by liver surgeries, but its change after liver transplantation has not yet been clarified. We investigated the predictive role of serum phosphorus for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT). Perioperative factors, including serum phosphorus level, of 304 patients who underwent LDLT were retrospectively studied and compared between patients with and without EAD after LDLT. Potentially significant factors (P < 0.15) in univariate comparisons were subjected to multivariate logistic regression analysis to develop a prediction model for EAD. A total of 48 patients (15.8%) met the EAD criteria. Patients with EAD experienced more severe preoperative disease conditions, higher one‐month mortality and more elevated serum phosphorus concentrations during the first week after surgery compared with patients without EAD (P = 0.016). Multivariate analysis showed that a serum phosphorus level ≥4.5 mg/dl on postoperative day 2 was an independent predictor of EAD occurrence after LDLT (relative risk: 2.36, 95% confidence interval [1.18–4.31], P = 0.017), together with a history of past abdominal surgery, emergency transplantation and preoperative continuous veno‐venous haemodiafiltration. These data indicate that hyperphosphataemia during the immediate postoperative days could be utilized as a predictor of EAD after LDLT.     

Resolution of severe graft steatosis following dual-graft living donor liver transplantation.

Although severely steatotic liver grafts are not suitable for transplantation, they have been used when other, more optimal donors were not available, especially for living donor liver transplantation (LDLT) using two liver grafts. Here we present two cases of dual-graft LDLT in which the recipients showed rapid and complete clearing of fat from livers with previously severe steatosis. In the first case, two left lateral segment grafts were used, one of which was 70% steatotic. Preoperative and posttransplant two-week liver-to-spleen computed tomography-value (L/S) ratios were 0.48 and 1.25, respectively. A liver biopsy taken two weeks after transplantation showed that the fatty changes had almost disappeared. The second case used one left lobe and one left lateral segment graft, the latter of which was 80% steatotic. Preoperative and two-week L/S ratio were 0.58 and 1.34, respectively, and a liver biopsy taken two weeks after transplantation showed less than 3% steatosis. The two donors of the severely steatotic liver grafts recovered uneventfully. These findings show that the fat content of the liver grafts was rapidly removed after transplantation. This observation is helpful in understanding the recovery sequences following transplantation of steatotic liver grafts, as well as expanding the acceptability of steatotic liver grafts.     

Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.     

18F‐FDG‐PET/CT predicts early tumor recurrence in living donor liver transplantation for hepatocellular carcinoma

The prognosis including ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG‐PET/CT) for the early recurrence for hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) was not well established. Consecutive patients who underwent ¹⁸F‐FDG‐PET/CT and subsequent LDLT for HCC from March 2005 to June 2011 were enrolled. The 191 patients with a median follow‐up of 26.1 months were evaluated. There were 20 patients (10.5%) with early recurrence (≤6 months), 18 patients (9.4%) with late recurrence (>6 months), and 153 patients (80.1%) with no recurrence. Fifty‐five patients (28.8%) displayed increased PET/CT tumor uptake. Three‐year overall and disease‐free survival for PET/CT‐positive patients were 65.5% and 57.1%, respectively, while PET/CT‐negative patients showed respective values of 89.8% and 86.8% (P = 0.001 vs. P < 0.001). Tumor variables associated with PET/CT‐positive finding were preoperative AFP level, Milan, UCSF criteria, maximum tumor size, total tumor size, differentiation, vascular invasion, and serosal invasion. PET/CT‐positive status was identified as an independent prognostic factor for disease‐free survival influencing early recurrence in multivariable analysis (HR 3.945, 95% CI 1.196–13.016, P = 0.024). ¹⁸F‐FDG‐PET/CT is an independent and significant predictor of early tumor recurrence in LDLT for HCC.     

Diffuse reflectance spectroscopy: toward real‐time quantification of steatosis in liver

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real‐time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy‐eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery.     

Use of severely steatotic grafts in liver transplantation: a matched case-control study

BACKGROUND: Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers. METHODS: We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers. RESULTS: During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%-100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (> or =21 days) and hospital (> or =40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient. CONCLUSION: Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.     

Mild hepatic steatosis is not a major risk factor for hepatectomy and regenerative power is not impaired

BACKGROUND: An understanding of the regeneration power and operative risk of steatotic livers after hepatectomy is still unclear. We evaluated the volume regeneration and outcome of steatotic livers after donor hepatectomy. METHODS: Fifty-four, consecutive living liver donors from September 2002 to December 2003 were evaluated prospectively by volumetric analysis, liver-spleen ratio, and liver attenuation index; the latter has been shown by serial computed tomographic scanning to be correlated strongly with histologic steatosis. Donors were followed up completely for at least 1 year (460-915 days) and were allocated according to histologic degree of macrovesicular steatosis: group 1, <5% (n = 36); group 2, 5%-30% (n = 18). RESULTS: No mortality or hepatic failure was observed, and no donor required reoperation or intraoperative transfusion. The results of serial liver function tests, and major and minor morbidities were comparable between groups. Liver-spleen ratio and liver attenuation index remained at a constant level above normal values postoperatively in group 1, but increased rapidly above normal values in group 2. No difference in the rate of liver regeneration at 10 days after hepatectomy was found between the groups (P = .487), but the liver regeneration rate at 3 months after hepatectomy in group 1 was slightly higher than that in group 2 (P < .044). However, no difference was observed between the 2 groups at 1 year after hepatectomy (P = .4). CONCLUSIONS: Mild hepatic steatosis is cleared immediately after hepatectomy, and early regeneration power is impaired, but the long-term regenerative power is comparable. Hepatectomy in donors with mild steatosis can be performed with low morbidity.     

Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma

Tumor markers [alpha‐fetoprotein (AFP) or des‐gamma‐carboxyprothrombin (DCP)] and neutrophil/lymphocyte ratio (NLR) reportedly correlate with long‐term outcomes for hepatocellular carcinoma (HCC). However, no standardized method has been established for evaluating the pretransplant data. One hundred and twenty‐four patients who underwent living donor liver transplantation (LDLT) were retrospectively reviewed. The best predictive parameters for tumor recurrence were maximum values for AFP or DCP and 90‐day mean values for NLR, respectively, and multivariate analysis confirmed these values were correlated with tumor recurrence. However, receiver operating characteristic analysis revealed that discriminative powers were sufficient only in maximum AFP [area under the curve (AUC) 0.88, P < 0.001] and maximum DCP (AUC 0.76, P < 0.001), while mean NLR was less predictive (AUC 0.62, P = 0.20). When incorporating AFP and DCP to the Tokyo criteria (≤5 tumors with each tumor ≤5 cm), the presence of at least two of the following factors: (i) beyond the Tokyo criteria, (ii) AFP>250 ng/ml, and (iii) DCP > 450 mAu/ml (>450 ng/ml), was correlated with a worse 5‐year disease‐free survival rate (20.0% vs. 96.8%, P < 0.001) and 5‐year overall survival rate (20.0% vs. 84.0%, P < 0.001). The prognosis of patients undergoing LDLT for HCC strongly relies on maximum AFP or DCP values before transplantation, while the prognostic impact of NLR is limited.     

Association of thrombocytopenia with outcome following adult living donor liver transplantation

This study aimed to evaluate the association of postoperative thrombocytopenia with outcome following adult living donor liver transplantation (LDLT) for end‐stage liver disease (ESLD). It was a prospective study of 120 consecutive adult LDLT from September 2012 to May 2015. Preoperative platelet counts (PLTs) and postoperative PLTs were recorded at regular intervals till 3 months after LDLT. Univariate and multivariate analyses were performed. The median pretransplant PLT was 61 × 10⁹/l. The lowest median PLT after LDLT was observed on POD 3. Patients were stratified into low platelet group (n = 83) with PLT <30 × 10⁹/l and high platelet group (n = 37) with PLT ≥30 × 10⁹/l. Patients with PLT <30 × 10⁹/l had statistically significant higher grade III/IV complication (P = 0.001), early graft dysfunction (P = 0.01), sepsis (P = 0.001), and prolonged ascites drainage (P = 0.002). On multivariate analysis, PLT<30 × 10⁹/l was identified as an independent risk factor for grade III/IV complications (P = 0.005). Overall, patients survival was significantly different between two groups (P = 0.04), but this predictive value was lost in patients who survived more than 90 days (P = 0.37). Postoperative PLT of <30 × 10⁹/l was a strong predictor of major postoperative complications and is associated with early graft dysfunction, prolonged ascites drainage, and sepsis. The perioperative mortality rate was high in the thrombocytopenia group.