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.     

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.     

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.     

Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study

OBJECTIVE: To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS) on major hepatectomy. SUMMARY BACKGROUND DATA: While steatosis of a liver graft is an established risk factor in transplantation, its impact on major hepatectomy remains unclear. METHODS: Fifty-eight steatotic patients who underwent major hepatectomy were matched 1:1 with patients with normal liver according to age, gender, ASA score, diagnosis, extent of hepatectomy, and need of hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively. Primary endpoints were mortality and complications. RESULTS: Pure MaS and MiS were present in only 10 and 3 patients, respectively, while mixed steatosis was noted in 45 patients. Forty-four patients had mild (10%-30%) and 14 moderate/severe (>30%) steatosis. Steatotic patients had significantly higher serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased in steatotic patients. Complications were higher in steatotic patients when considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P = 0.001) complications. Patients with pure MaS had increased mortality (MaS: 20% vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS: 50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis was a highly significant risk factor for mortality in patients with hepatic steatosis. CONCLUSION: Steatosis per se is a risk factor for postoperative complications after major hepatectomy and should be considered in the planning of surgery. Caution must be taken to perform major hepatectomy in steatotic patients with preexisting cholestasis.     

Hepatocellular proliferation and changes in microarchitecture of right lobe allografts in adult transplant recipients.

Imaging studies show complete restoration of liver volume in adult recipients of right lobe allografts within 2-3 weeks of living donor transplantation (LDLT). However, it is not known if this growth is associated with restoration of hepatic microarchitecture. We compared 21 biopsies without significant pathology from LDLT recipients with 23 biopsies from adult recipients of cadaveric donor liver transplantation (CDLT) performed within 3 months of transplantation. The difference in the number of portal tracts per cm was statistically significant (P < .0001) between CDLT (9.08 +/- 1.74) and LDLT recipients within 3 months (6.26 +/- 1.62), as well as after 3 months following transplantation (6.56 +/- 1.44). The coefficient of correlation between length of biopsy specimens and the number of portal tracts in these 3 groups was .94, .93, and .85, respectively. Proliferative activity demonstrated by immunohistochemical staining for MIB-1 was seen predominantly in hepatocytes in both groups; bile ducts only occasionally stained positive. The difference between labeling indices of hepatocytes was statistically significant (P = .00056) between CDLT and LDLT recipients within 3 months of transplantation (.82 +/- .63 and 4.53 +/- 3.72), and between LDLT recipients within 3 weeks and after 3 weeks of transplantation (5.97 +/- 3.78 and 1.80 +/- 1.37, P = .0074). In conclusion, restoration of liver volume following LDLT occurs by proliferation of hepatocytes in the immediate posttransplant period. There is a decrease in number of portal tracts in these volume-restored allografts. Volume restoration is therefore, not accompanied by restoration of hepatic microarchitecture.     

Expansion of hepatic progenitor cell in fatty liver graft after living donor liver transplantation

Although it is known that steatotic livers have a reduced ability to regenerate, most individuals with steatosis show generally benign prognosis. We hypothesized that a proliferative blockade in steatotic hepatocytes results in the compensatory expansion of hepatic progenitor cells (HPC) during fatty liver regeneration. Fifty‐four cases of living donor liver transplantation (LDLT) with a liver biopsy performed at the postoperative 10th day were examined. HPC were counted by immunofluorescence histochemical dual‐staining technique using cytokeratin 7 and Ki‐67, and the replicative arrest of hepatocytes was assessed by p21 immunohistochemistry. The degree of ductular proliferation during regeneration 10 days after LDLT correlated both with the degree of steatosis and the number of HPC (P < 0.001). There was no difference in the average number of HPC and the replicative arrest index between donors with or without steatosis before LDLT (P = 0.111 and P = 0.062). However, degree of steatosis correlated with both the expansion of HPC and the replicative arrest index during liver regeneration 10 days after LDLT (P < 0.001 and P < 0.001, respectively). Moreover, increased replicative arrest was strongly associated with HPC expansion (P < 0.001). In conclusion, the compensatory expansion of HPC as a result of impaired hepatocyte replication occurred during steatotic liver regeneration after LDLT.     

Prognostic value of p53, proliferating cell nuclear antigen, and Ki-67 expression in undifferentiated nasopharyngeal carcinomas

In this study the prognostic importance of p53, proliferating cell nuclear antigen (PCNA), and Ki-67 expression was analyzed along with the clinical parameters in 35 consecutive patients with undifferentiated nasopharyngeal carcinomas. Immunohistochemistry was used to detect p53, PCNA, and Ki-67 staining. Among the clinical findings, stage IV disease (P = 0.01), cranial nerve paralysis (P = 0.02), and lymph node metastasis (P = 0.06) were associated with shorter survival. The p53 positivity correlated with the presence of lymph nodes, but it was not a significant factor to predict the outcome. PCNA expression was not found to be a prognostic indicator. On the other hand, the proliferative value of Ki-67 staining was suggestive of prognosis. A proliferation index of Ki-67 less than 10% indicated longer survival (P = 0.03). There was no correlation between Ki-67 staining and PCNA index. As a result, the prognostic value of Ki-67 may alert the physician to more aggressive and adjuvant treatment modalities.     

Competition between native liver and graft in auxiliary liver transplantation in a rat model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were 相似文献   

Impact of polysol, a newly developed preservation solution, on cold storage of steatotic rat livers.

Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 degrees C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728+/-824 in HTK vs. 3107+/-718 in Polysol; P < 0.001) but also mitochondrial (GLDH (IU/L); 3189+/-773 vs. 1282+/-365; P < 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9+/-2.7 vs. 7.8+/-1.5 mmHg; P < 0.05), hepatic O2 consumption (0.291+/-0.047 vs. 1.056+/-0.053 micromol/g liver/min; P < 0.001), tissue ATP content (0.695+/-0.086 vs. 1.340+/-0.157 micromol/g dry-liver; P < 0.005), bile production (0.79+/-0.11 vs. 4.08+/-0.66 microL/g liver/45-min; P < 0.001), malondialdehyde into the perfusate (1.922+/-0.198 vs. 0.573+/-0.094 nmol/L; P < 0.0001) and wet/dry-weight ratio of the liver tissues (5.20+/-0.31 vs. 3.85+/-0.15; P < 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs.     

Regenerative capacities of normal and cirrhotic livers following 70% hepatectomy in rats and the effect of alpha-tocopherol on cirrhotic regeneration

BACKGROUND: The regeneration of normal and cirrhotic liver has been very well demonstrated after partial hepatectomy; although the tissue regenerated by cirrhotic liver is also cirrhotic. The structural differences of the regenerated tissues between normal and cirrhotic livers may also indicate different regeneration capacities. The objective of this study was to compare the regeneration capacities of normal and cirrhotic livers by bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling indices in replicating nuclei and mitotic figures in cells in partially hepatectomized normal and cirrhotic rats and to study the effect of alpha-tocopherol on cirrhotic liver regeneration. METHODS: Five groups of adult Wistar rats comprised normal livers, cirrhotic livers, regenerated normal livers, regenerated cirrhotic livers, and alpha-tocopherol-treated regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Liver regeneration capacities in normal and cirrhotic rats and following partial hepatectomy in normal and cirrhotic rats and cirrhotic rats that were administered alpha-tocopherol were evaluated through BrdU incorporation, PCNA labeling, and mitotic indices. RESULTS: BrdU and PCNA labeling and mitotic indices were zero for normal rats and 4.3 +/- 3.5, 6.5 +/- 5, and 2.5 +/- 1.5 for cirrhotic rats, respectively. The values after partial hepatectomy in normal and cirrhotic rats were 46.2 +/- 8.7 and 27.8 +/- 7.5 for BrdU labeling, 83.7 +/- 6.5 and 51.3 +/- 6.8 for PCNA labeling, and 31.8 +/- 4.2 and 18.6 +/- 3.4 for mitotic index, respectively. For the fifth group comprising cirrhotic rats that were administered alpha-tocopherol and had undergone partial hepatectomy, BrdU incorporation, PCNA labeling, and mitotic indices were 37.5 +/- 6.3, 76.5 +/- 6.2, and 27.2 +/- 4.2, respectively. When the cirrhotic liver regeneration group was compared with the normal liver regeneration group, rates of liver regeneration in the cirrhotic group were significantly depressed (P < 0.01). Although the BrdU incorporation and PCNA labeling indices of the alpha-tocopherol-administered cirrhotic liver regeneration group indicated significantly lower rates of liver regeneration when compared with the normal liver regeneration group (P < 0.05), the liver regeneration rates of the alpha-tocopherol-administered cirrhotic group were also significantly higher than those of the cirrhotic liver regeneration group that was not administered alpha-tocopherol (P < 0.01). CONCLUSIONS: Cirrhotic livers revealed a significantly depressed capacity for regeneration following partial hepatectomy. alpha-Tocopherol administration seemed to improve the rates of regeneration in cirrhotic rats with respect to the BrdU incorporation, PCNA labeling, and mitotic indices.     

Hepatocyte morphology and kinetics after portal vein embolization

BACKGROUND: Macroscopic volume changes after portal vein embolization (PVE) can be assessed accurately by computed tomography, but histological changes remain poorly understood. The aim of this study was to clarify hepatocyte morphology and kinetics after PVE. METHODS: The resected livers from 25 patients who underwent extended hepatectomy after PVE and five normal livers were examined using hepatocyte paraffin 1 staining for histomorphometric analysis of hepatocytes. Cell kinetics were determined by Ki-67 staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay. Kupffer cells were examined by CD68 immunostaining. RESULTS: The number of hepatocytes was similar in the embolized lobe, non-embolized lobe and normal liver, but hepatocyte volume was greater in the non-embolized lobe than in the embolized lobe (P = 0.017). The Ki-67 labelling index was higher in the non-embolized lobe (P < 0.001) whereas the apoptotic index was higher in the embolized lobe (P < 0.001). There were more Kupffer cells per unit area in the embolized lobe (P < 0.001). CONCLUSION: Hepatocyte hypertrophy and replication leads to volume enlargement of the non-embolized hepatic lobe, whereas hepatocyte atrophy and apoptosis causes a decrease in volume of the embolized lobe.     

Renoportal anastomosis in right lobe living donor liver transplantation: report of a case

End-stage liver disease is often accompanied by thrombosis of the portal vein and the formation of splanchnic collateral vessels. Successful liver transplantation in such situations is more likely if the surgeon uses a strategy to establish a graft inflow. A 59-year-old male with a decompensated liver secondary to idiopathic portal hypertension underwent living donor liver transplantation (LDLT) using a right lobe liver graft donated from his son. His portal venous trunk was atrophied and a splenorenal shunt drained the mesenteric venous flow into the systemic circulation. LDLT was performed with renoportal anastomosis (RPA) using his right internal jugular vein as an interposed venous graft, without dissecting the collateral vessels. Although he developed temporary functional hyperbilirubinemia, he was discharged from the hospital 23 days after LDLT. This case suggests that RPA is a useful technique to manage patients with an obstructed portal vein and a splenorenal shunt.     

Optimal portal venous circulation for liver graft function after living-donor liver transplantation

BACKGROUND: Previous studies have shown poor outcome after living-donor liver transplantation (LDLT) as a result of excessive portal venous pressure (PVP), excessive portal venous flow (PVF), or inadequate PVF. We investigated optimal portal venous circulation for liver graft function after LDLT in adult recipients retrospectively. METHODS: Between June 2003 and November 2004, 28 adult patients underwent LDLT in our institution. We modulated PVP under 20 mmHg in these 28 cases by performing a splenectomy (n=4) or splenorenal shunt (n=1). The PVF and PVP were measured at the end of the operation. Compliance was calculated by dividing PVF by PVP. RESULTS: PVF and compliance showed a significant inverse correlation with peak billirubin levels after LDLT (r = -0.63: r=-0.60, P<0.01), and with peak international normalized ratio after LDLT (r=-0.41: r=-0.51, P<0.05). Compliance was higher in right-lobe graft with middle hepatic vein cases (148+/-27 ml/min/mmHg), and lower in left-lobe graft cases (119+/-50 ml/min/mmHg). CONCLUSIONS: Liver graft function was better when PVF and graft compliance were higher and PVP was maintained under 20 mmHg.     

Preservation of steatotic livers in IGL-1 solution.

A new Institut Georges Lopez (IGL-1) solution was used to preserve steatotic livers. Steatotic (obese [Ob]) and nonsteatotic (lean [Ln]) livers from Zücker rats (n = 16, 8 Ln and 8 Ob) were preserved for 24 hours at 4 degrees C in University of Wisconsin (UW) or IGL-1 solution, respectively, and then perfused ex vivo for 2 hours at 37 degrees C. Additionally, Ob and Ln livers (n = 16, 8 Ln and 8 Ob) were preserved in IGL-1 plus Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME). Hepatic injury and function (aminotransferases, bile production, bromosulfophthalein clearance), and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion injury, such as oxidative stress, mitochondrial damage, and vascular resistance, were studied. Nitric oxide (NO) production and constitutive and inducible NO synthase were also measured. Steatotic and nonsteatotic livers preserved in IGL-1 solution showed lower transaminases, malondialdehyde, glutamate dehydrogenase levels, and higher bile production than UW-solution-preserved livers. IGL-1 solution protected against oxidative stress, mitochondrial damage and the alterations in vascular resistance associated with cold ischemia-reperfusion. Thus, at the end of reperfusion period, aspartate aminotransferase levels in steatotic livers were 281 +/- 6 U/L in UW vs. 202 +/- 10 U/L in IGL-1 solution. Glutamate dehydrogenase was 463 +/- 75 U/L in UW vs. 111 +/- 4 U/L in IGL-1 solution, and oxidative stress was 3.0 +/- 0.1 nmol/mg prot in UW vs. 2.0 +/- 0.1 nmol/mg prot in IGL-1 solution. These beneficial effects of IGL-1 solution were abolished by the addition of L-NAME, which implicates NO in the benefits of IGL-1. In conclusion, IGL-1 solution provided steatotic livers with better protection against the deleterious effects of cold ischemia-reperfusion injury than did UW solution.     

Successful Use of Extended Criteria Donor Grafts With Low to Moderate Steatosis in Patients With Model for End-Stage Liver Disease Scores Below 27

Liver transplantation may be performed using extended criteria donor grafts (ECDg). The characteristics of ECDg include age >60 years, long intensive care unit (ICU) stay, history of malignancy or steatosis. Grafts are often discarded due to steatosis, which can be macrovesicular (MaS) or microvesicular (MiS). MaS is the variety most frequently involved with unfavorable outcomes due to primary nonfunction (PNF) or primary dysfunction (PDF). As of January 2000, all livers referred to our institution were considered potentially transplantable. Steatosis was defined as the presence of fat droplets in more than 5% of hepatocytes. We observed 35 steatotic grafts. Grafts were stratified according to MaS and MiS as follows: low steatosis (5%–15%), mild steatosis (16%–30%), moderate steatosis (31%–60%), or severe steatosis (>60%). Fifteen grafts with moderate (n = 2) or severe (n = 13) MaS were discarded. Twenty grafts were harvested: 18 of them were transplanted at our institution, the remaining 2, discarded by our donor team, were transplanted by other Italian centers. Low MaS was detected in 10 grafts (50%), mild MaS in 4 (20%), and moderate MaS in 2 (10%). Low MiS was detected in 8 grafts (40%), mild MiS in 5 (25%), and moderate MiS in 1 (5%). Steatotic grafts were transplanted only into recipients with model for end-stage liver disease (MELD) scores <27. The 6-month graft survival was 80%; the PNF rate was 10%; and the PDF rate was 15%. The careful use of ECDg with low to moderate steatosis is possible if particular care is taken to avoid additional risk factors related to the recipient.     

Experimental radiofrequency ablation near the portal and the hepatic veins in pigs: differences in efficacy of a monopolar ablation system

BACKGROUND: We sought to compare the efficacy of a monopolar radiofrequency ablation system in vivo near the portal vein and the hepatic veins in porcine liver. MATERIALS AND METHODS: Radiofrequency ablation of healthy livers near the portal vein and the hepatic veins was performed in 10 pigs with a multitined expandable electrode. Volumes and diameters of zones of ablation were assessed by magnetic resonance imaging. RESULTS: Volumes (16.0 +/- 5.5 mL, P = 0.001) and diameters (4.0 +/- 0.7 cm, 3.3 +/- 0.7 cm, 3.0 +/- 0.6 cm, P 相似文献   

Fibronectin-alpha4beta1 integrin interactions modulate p42/44 MAPK phosphorylation in steatotic liver cold ischemia-reperfusion injury

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-alpha4beta1 integrin interactions upon cell signaling, leukocyte migration, and secretion of proinflammatory cytokines, in a well-established steatotic rat liver model using ex vivo cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers prior and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplantation (OLT) received an additional 3-day course of CS1 peptides post-OLT. CS1 peptide-treated steatotic OLTs harvested at 1, 3, and 7 days showed moderated levels of p42/44 mitogen-activated protein kinase (MAPK) phosphorylation, comparable to those observed in steatotic naive livers. In contrast, p42/44 MAPK phosphorylation was found up-regulated in 1- to 3-day damaged control OLTs. However, 7-day control OLTs were characterized by virtually lack of p42/44 MAPK phosphorylation. Lack of p42/44 MAPK phosphorylation in 7-day control OLTs was correlated with massive presence of leukocytes in the grafts and elevated levels of proinflammatory cytokines. CS1 peptide-treated OLTs at 7 days showed a profound decrease in T-cell (10 +/- 3 vs 56 +/- 20, P < .03) and monocyte/macrophage (+/++ vs +++) infiltration and significantly reduced levels of cytokine expression, such as IL-2 (approximately sixfold), and IFN-gamma (approximately three- to fourfold), as compared with controls.     

Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.     

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.