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Liver transplantation for alcoholic liver disease.

Although increasing numbers of alcoholic patients are being referred to liver transplant centres, liver transplantation for alcoholic liver disease still remains controversial, essentially because we are in an era of organ shortage. In fact, the main issue is the likelihood of relapse and its influence on outcome, because it is the possibility of returning to alcohol use that separates patients with alcoholic liver disease from those with other forms of chronic liver disease. In all proposed clinical guidelines of indications for referral and assessment for liver transplantation for alcoholic liver disease, the authors emphasize the risk of alcoholism recurrence and, thus, a multidisciplinary approach is required to select patients who are likely to comply with follow-up and not return to a damaging pattern of alcohol consumption after transplantation. It emerges from all clinical studies that when we take into account the usual criteria of success for liver transplantation, i.e. patient and graft survival, rejection rate and infection rate, alcoholic liver disease is a good indication for liver transplantation. Predictive factors for alcoholic relapse after liver transplantation have been assessed in numerous studies, often with contradictory results making these difficult to analyse and compare. Several predictive factors for alcoholic relapse have been studied: length of abstinence before transplantation, associated psychiatric problems, social conditions, associated drug addiction, age. Abstinence after transplantation is the goal, but the necessary treatment for alcoholic disease can result in considerable improvement, even when complete abstinence is not achieved. Finally, the good results obtained with liver transplantation for alcoholic liver disease should help us to educate the general population about alcoholic disease.

Journal Article↗

The effect of age upon liver volume and apparent liver blood flow in healthy man.

The aim of this study was to determine the effect of aging upon liver volume and apparent liver blood flow in healthy man. Sixty-five subjects between 24 and 91 years of age were recruited. Liver volume was quantitated by a gray scale B ultrasound scan method. Apparent liver blood flow was determined from the plasma clearance of indocyanine green, based on an assumption of no change in hepatic extraction of the dye with age. A significant negative correlation was observed between age and both liver volume and apparent liver blood flow (p less than 0.001), whether expressed in absolute terms or per unit body weight. Similarly, a significant negative correlation was observed between apparent liver blood flow per unit volume of liver (liver perfusion) and age (p less than 0.005). The reduction in liver volume, apparent liver blood flow and perfusion may at least partly account for the decline in the clearance of many drugs undergoing liver metabolism which has been noted to occur with aging in man.

Adult↗

Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver.

Gut-derived, endotoxin-mediated hepatocellular damage has been postulated to play a crucial role in the pathogenesis of alcohol-induced liver injury in rodents. Endotoxins induce production of tumor necrosis factor alpha (TNF-alpha) by Kupffer cells via Toll-like receptor (TLR) 4 and contribute to liver injury. This study addressed the contribution of other TLRs and ligands to alcoholic fatty liver. C57Bl6/J mice were fed a modified Lieber-DeCarli diet. Serum aminotransferase measurements, histological analysis, and quantification of liver TNF-alpha and TLR1-9 messenger RNA (mRNA) were performed. The effect of TLR ligands on liver injury was assessed in vivo. Neomycin and metronidazole or diphenyleneiodonium sulfate (DPI) were administered to evaluate the role of gut bacteria and NADPH oxidase activity, respectively, in hepatic TLR expression. Enteral ethanol (EtOH) exposure induced steatosis and increased liver weight, aminotransferase levels, and expression of TLR1, 2, 4, 6, 7, 8, and 9 liver mRNA. Injection of lipoteichoic acid, peptidoglycan (PGN), lipopolysaccharide (LPS), loxoribine, and oligonudeotide containing CpG (ISS-ODN) increased TNF-alpha mRNA expression more in the livers of EtOH-fed mice than in control mice. PGN, LPS, flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but not control mice. Addition of antibiotics reduced the severity of alcoholic fatty liver without affecting TLR expression, whereas daily DPI injections reduced the EtOH-mediated upregulation of TLR2, 4, 6, and 9 mRNA. In conclusion, EtOH-fed mice exhibited an oxidative stress dependent on upregulation of multiple TLRs in the liver and are sensitive to liver inflammation induced by multiple bacterial products recognized by TLRs.

Animals↗

Two-stage total hepatectomy and liver transplantation for acute deterioration of chronic liver disease: a new bridge to transplantation.

Two-stage total hepatectomy and liver transplantation has been reported for acute liver disease such as fulminant hepatic failure, primary graft failure, severe hepatic trauma, and spontaneous hepatic rupture secondary to hemolysis, elevated liver function tests, low platelets syndrome, and preeclampsia. This is the first report of patients with cirrhosis to undergo a 2-stage total hepatectomy and liver transplantation. From 1984 to 2002, our institution performed 2008 orthotopic liver transplantations. We identified 4 patients with chronic liver disease who underwent a 2-stage hepatectomy and liver transplantation. This is a retrospective review of these 4 patients and a review of the literature on this procedure. All 4 patients were young men with an age range of 29-31 years and had underlying cirrhosis as well as a previous transjugular intrahepatic portosystemic shunt (TIPS)procedure. Acute decompensation fulfilling Ringes' criteria for toxic liver syndrome secondary to an upper gastrointestinal bleed occurred in all patients. The approximate average time between hepatectomy and liver transplantation was 20 hours (range: 8-42 hours). In all cases, the explanted liver showed histological changes of acute hepatic necrosis within the background of cirrhosis. After hepatectomy, vasopressor requirements were well documented in 2 patients. For 1 patient, there was a clear improvement in their hemodynamic status. The mean hospital stay of the 4 patients was 63 days. All patients were discharged from the hospital and are alive and well with adequate liver function at 6 to 37 months follow-up. Two-stage total hepatectomy and liver transplantation may be a life-saving procedure in highly selected cirrhotic patients with acute hepatic decompensation and multiorgan dysfunction.

Adult↗

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.

Bezafibrate↗

Liver transplantation for adult polycystic liver disease.

Patients with adult polycystic liver disease and massive cystic replacement of the liver may present with severe debilitation and impairment of functional performance or, rarely, with signs of portal hypertension or hepatic dysfunction. In those patients incapacitated by severe hepatomegaly secondary to massive cystic replacement with predominantly small cysts (2 cm) without areas of parenchymal sparing, liver transplantation is a therapeutic option. Five patients with incapacitating symptoms from polycystic liver disease underwent liver transplantation as a final therapeutic procedure. Two patients had previous fenestration procedures without significant relief. All patients had radiographic evidence of concomitant polycystic kidney disease; two of these patients were dialysis-dependent at the time of liver transplantation. One patient underwent combined liver-kidney transplantation, whereas another received a six-antigen matched kidney transplant 64 months after liver transplantation. Four of five patients are alive 84, 39, 20, and 8 months after successful liver transplantation. All four have returned to normal functional status with complete resolution of symptoms. Liver transplantation is a suitable option for the patient with bilobar small cystic liver disease without areas of parenchymal sparing. However, only patients with severely compromised functional status should be offered this therapy. Concomitant renal evaluation is mandatory, and a knowledge of the natural history of this disease will aid in the decision of whether a combined liver-kidney transplantation is indicated.

Adult↗

T1 relaxation times for viability evaluation of the engrafted and the native liver in a rat model of heterotopic auxiliary liver transplantation: a pilot study.

Following a heterotopic auxiliary liver transplantation, commonly used measurements are either invasive or non-indicative of individual viability of the coexisting engrafted and native livers. Magnetic resonance imaging (MRI) was therefore tested for its potential to monitor the post-transplant hepatic viability in a rat model. Thirteen Wistar rats were systematically evaluated with MRI and serum biochemical liver parameters. Post-transplant complications and the causes of animal death were identified by autopsy and histo-pathological examinations. The data of the healthy survivors were compared with those of the rats that developed complications. On MRI, the hepatic complications could be depicted in the individual livers. A specific pattern of signal evolution was found in the livers of the healthy survivors: the mean T1 relaxation times of the engrafted livers increased immediately after transplantation (476 +/- 64 ms, mean +/- standard deviation, pre-operative; 730 +/- 48 ms, week 1) and then declined steadily to a 3 month value of 489 +/- 246 ms, while, following a transient first rise (476 +/- 64 ms, pre-operative; 589 +/- 28 ms, week 1), the mean T1 value of the native livers increased again 4 weeks after surgery and reached a 3 month value of 859 +/- 43 ms. However, in the rats with various complications, the mean T1 relaxation times of the engrafted livers continued to increase throughout the first post-operative month (760 +/- 48 ms, week 1; 922 +/- 76 ms, week 4), while that of the native liver only varied mildly (546 +/- 25 ms, week 1; 473 +/- 25 ms, week 4). After the first post-transplant week, the healthy engrafted livers could already be distinguished from those with complications by a significant decrease in T1 relaxation times. These data suggest that, besides demonstrating major complications, MRI may allow one to monitor the viability of each liver by analysing the relative signal intensity and T1 relaxation times after a heterotopic auxiliary liver transplantation.

Alanine Transaminase↗

Morphometric measurement of collagen in liver tissue with posthepatitis liver cirrhosis portal hypertension.

A correct estimation of the collagen content in cirrhosis liver tissue and analysis of its relation to the degree of liver function injury are important to the clinician in the establishment of the diagnosis in the liver diseases. The author has performed the morphometric measurement of collagen with liver tissue pathological section by using TJTY-300 image analysis system. It was found that the cirrhotic liver tissue's collagen area and collagen average grey degree were notably higher than those in normal men (P < 0.05), average optical density was markedly lower than that in normal men (P < 0.05), integral optical density had no significant difference (P > 0.05) between patients and normal controls, but the integral optical density in cirrhotic liver was 1.21 times that of normal men. It suggests that the collagen content in cirrhotic liver tissue increased obviously, the average density of the increased collagen was lower than that in the normal liver tissue and the density of increased collagen was not homogeneous. Comparison between normal controls and patients with different Child-Pugh liver function grades in liver tissue collagen parameters revealed that the cirrhotic liver's collagen content can, to different degree, directly reflect the function status of cirrhotic liver.

Adult↗

Diagnosis of chronic liver disease from liver scintiscans by artificial neural networks.

Artificial neural networks were used in the diagnosis of chronic liver disease based on liver scintiscanning. One hundred and thirty-seven patients with chronic liver disease (12 with chronic persistent hepatitis, 39 with chronic aggressive hepatitis, and 86 with cirrhosis) and 25 healthy controls were studied. Sixty-five subjects (10 healthy controls, 20 patients with chronic hepatitis, and 35 patients with cirrhosis of the liver) were used in the establishment of a neural network. Liver scintiscans were taken starting 20 min after the intravenous injection of 111 MBq of Tc-99m-phytate. The neural network was used to evaluate five items judged from information on liver scintiscans: the ratio of the sizes of the left and right lobes, splenomegaly, radioactivity in the bone marrow, deformity of the liver and distribution of radioactivity in the liver. The neural network was designed to distinguish between three liver conditions (healthy liver, chronic hepatitis and cirrhosis) on the basis of these five items. The diagnostic accuracy with the neural network was 86% for patients with chronic hepatitis and 93% for patients with cirrhosis. With conventional scoring, the accuracy was 77% for patients with chronic hepatitis and 87% for patients with cirrhosis. Our findings suggest that artificial neural networks may be useful for the diagnosis of chronic liver diseases from liver scintiscans.

Case-Control Studies↗

Liver transplantation for acute liver failure: analysis of applicability.

BACKGROUND: Liver transplantation has emerged as the most important advance in the therapy of acute liver failure. To assess the applicability of liver transplantation in this setting, the outcome of 62 patients with acute liver failure consecutively admitted to hospital was analyzed. METHODS: Criteria for indicating liver transplantation were grade III-IV hepatic encephalopathy or progression of encephalopathy following a transient improvement. In subfulminant cases, liver transplantation was also indicated when no improvement was observed after a 3-day period of conservative treatment. RESULTS: Thirteen (21%) of the 62 patients never met criteria for transplant indication; all of them were discharged after receiving conventional therapy. Twenty-one (34%) patients with criteria for indicating liver transplantation could not receive the transplant because of either contraindications (17 patients; only 1 being discharged from hospital) or death before donor organ availability (4 patients). Finally, 28 (45%) patients received a liver transplant and 22 were discharged from hospital. CONCLUSIONS: The applicability of liver transplantation in acute liver failure is relatively low. Considering the high survival rate (79%) obtained in the patients with transplantations and the poor survival rate (6%) observed in those who could not be transplanted, efforts should be made to increase liver transplant applicability to improve the prognosis in acute liver failure.

Adolescent↗

Predicting recidivism after orthotopic liver transplantation for alcoholic liver disease.

With appropriate selection criteria, patients with end-stage alcoholic liver disease who undergo orthotopic liver transplantation have similar graft and patient survivals as patients undergoing transplantation for other causes. However, because of the possibility of recidivism after orthotopic liver transplantation there is still reluctance to transplant alcoholic patients. This study examined the association between pretransplant psychosocial variables and the risk of recidivism after orthotopic liver transplantation. At our institution, 43 patients received orthotopic liver transplantation for the referral diagnosis of alcoholic liver disease from February 1, 1988 to May 1, 1991. This represented 17% of all first transplants (43 of 257) performed during this period. Patients were interviewed before orthotopic liver transplantation by a single psychiatrist and responses to a defined set of questions were entered into a clinical database. All 43 patients diagnosed with alcoholic liver disease and a comparison group of patients transplanted for diagnoses other than alcoholic liver disease received a postoperative questionnaire regarding past and present alcohol use. Patients enrolled in the study all had at least 7 mo of follow-up, with the median follow-up being 21 mo. Eighty-six percent of alcoholic liver disease patients (37 of 43) and 86% of patients in the comparison group (37 of 43) of ALD patients agreed to participate in the study. Nineteen percent of alcoholic liver disease patients (7 of 37) and 24% of patients in the comparison group (9 of 37) admitted to having used alcohol after orthotopic liver transplantation, wtih 8% (3 of 37) and 11% (4 of 37) currently using alcohol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease.

BACKGROUND/AIMS: Alcoholic cirrhosis is a common indication for liver transplantation. The present study was aimed to assess the influence of superimposed alcoholic hepatitis on the outcome of liver transplantation in patients with alcoholic cirrhosis. METHODS: Survival rates of 68 patients transplanted for alcoholic cirrhosis were compared with those of 101 patients transplanted for miscellaneous causes. Within the alcoholic group, explanted livers were searched for data of acute alcoholic hepatitis. The survival rate of patients with alcoholic hepatitis superimposed on liver cirrhosis was compared to that of patients with liver cirrhosis alone. Clinical severity of alcoholic hepatitis was assessed with Maddrey's score. RESULTS: Survival was similar in alcoholics and patients with other causes of liver disease. Among patients transplanted for alcoholic cirrhosis, survival was similar in patients with superimposed alcoholic hepatitis (n=36) and in cases with liver cirrhosis alone (n=32). There was no difference in survival between patients with mild (n=26) and severe (n=10) alcoholic hepatitis. Seven alcoholics (10%) returned to ethanol consumption. Recidivism was not associated with either alcoholic hepatitis in the explanted liver or graft loss. CONCLUSIONS: Survival after liver transplantation in patients with alcoholic cirrhosis plus alcoholic hepatitis detected in the explanted liver is similar to that of patients transplanted for other reasons. Even the presence of severe alcoholic hepatitis does not worsen the outcome of liver transplantation for end-stage alcoholic liver disease.

Adult↗

Serum bile acids in patients with liver failure supported with a bioartificial liver.

BACKGROUND: Serum bile acids are increased in liver failure, but the composition of the bile acid pool in this condition has not been studied in detail. This information is of interest because of dihydroxy bile acid toxicity. METHODS: We measured serum bile acids by gas chromatography-mass spectrometry in 13 patients with fulminant liver failure and five patients with acute-on-chronic liver failure. Furthermore, serum bile acids were analysed in the same patients after 6 h of treatment with a bioartificial liver, consisting of a hollow-fibre cartridge with microcarrier-attached porcine hepatocytes and a charcoal column. RESULTS: Pre-bioartificial liver serum bile acids demonstrated a high dihydroxy/trihydroxy ratio and were higher in patients with acute-on-chronic liver failure than in those with fulminant liver failure (452.8 +/- 98.6 vs. 182.1 +/- 39.7 micro mol/L; P < 0.05). Bioartificial liver treatment decreased significantly serum bile acids in patients with fulminant liver failure (-38.8%) and acute-on-chronic liver failure (-35.8%), with a decreased dihydroxy/trihydroxy ratio. In vitro, porcine hepatocytes in the bioreactor cleared most conjugated bile acid species from pooled patient plasma. CONCLUSIONS: Acute liver failure is associated with very high serum levels of toxic bile acids that could contribute to the pathogenesis of the syndrome. Bioartificial liver treatment reduces both serum bile acid concentrations and the hydrophobicity of the bile acid pool.

Adolescent↗

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice.

Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-gamma were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-gamma release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-gamma release (-66% or -41%, -95% or -94%, and -70% or -70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell- and macrophage-dependent cytokines.

Animals↗

The F(ab')2 fragment of an anti-ICAM-1 monoclonal antibody attenuates liver injury after orthotopic liver transplantation.

Long-term storage of liver grafts results in increased adhesion of leukocytes onto the sinusoidal walls. This eventually leads to posttransplant graft damage through disturbances of hepatic microcirculation. Intracellular adhesion molecule-1 (ICAM-1) is known to be involved in attachment of leukocytes. This study was designed to examine whether ICAM-1 participated in the pathogenesis of posttransplant liver injury. Inbred Lewis rats were used as both donors and recipients to avoid immunoreactivity. Donor livers were stored for either 1 or 6 hr in ice-cold Euro-Collins solution and subsequently implanted. Expression of ICAM-1 was examined immunohistochemically. In some rats that received livers stored for 6 hr, the intact IgG (1.0 mg/kg) or the F(ab')2 fragment (0.5 mg/kg) of an anti-ICAM-1 mAb (1A29) was administered via the tail vein immediately after reperfusion of portal blood. In the group receiving livers stored for 6 hr, ICAM-1 began to be expressed on the sinusoidal endothelial cells as early as 15 min after reperfusion of the portal blood. Strong ICAM-1 expression was observed from 2 hr up to 24 hr after reperfusion. In contrast, expression of ICAM-1 was not evident at any time point after surgery in the 1-hr storage group as well as in untransplanted, normal livers. Serum alanine aminotransferase (ALT) levels were significantly higher in the 6-hr storage group compared with those of the 1-hr storage group (1-hr: 171 +/- 9 IU/L; 6-hr: 825 +/- 109 IU/L, P < 0.05; mean +/- SEM) 24 hr after transplantation. Serum ALT levels were markedly reduced by treatment with the F(ab')2 fragment of 1A29 (247 +/- 34 IU/L, P < 0.05 vs. 6-hr storage group). This was associated with reduced accumulation of leukocytes in the liver. In marked contrast, treatment with the intact IgG of 1A29 increased serum ALT levels dramatically (5297 +/- 634 IU/L, P < 0.05 vs. 6-hr storage group) and reduced serum complement. Histological examination revealed focal hepatocellular necrosis 24 hr after surgery in the 6-hr storage group. Treatment with the F(ab')2 fragment decreased the liver damage; in marked contrast, treatment with the intact IgG strikingly aggravated the injury, as characterized by massive necrosis throughout the liver. Liver damage caused by the intact IgG might be related to activation of the complement system by the Fc portion of the antibody. Taken together, these results indicate that ICAM-1 is involved in the mechanism of postoperative liver injury following liver transplantation.

Animals↗

Functional metabolic characteristics of intact pig livers during prolonged extracorporeal perfusion: potential for a unique biological liver-assist device.

BACKGROUND: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases. METHODS: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation. RESULTS: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery. CONCLUSIONS: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.

Ammonia↗

Maintenance of the celiac trunk with the left-sided liver allograft for in situ split-liver transplantation.

BACKGROUND: It has been shown that in situ split-liver transplantation (SLT) expands the cadaveric donor pool, decreases recipient waiting time, and decreases pretransplant morbidity. However, the technique as previously described requires a microvascular left hepatic artery anastomosis. In an attempt to decrease the incidence of hepatic artery thrombosis and to increase collaboration among transplant teams, in the current report, we describe a modification of the in situ SLT technique that maintains the celiac trunk with the left-sided liver allograft. METHODS: Twelve in situ split-liver procurements resulted in 24 segmental liver allografts; 11 right trisegments, 11 left lateral segments, 1 right lobe, and 1 left lobe. The common bile duct and main portal vein were maintained with the right-sided liver allograft in all cases. The right hepatic artery was divided, and the celiac trunk was maintained with the left-sided liver allograft in nine cases. In one case the left hepatic artery was divided and the celiac trunk was maintained with the right-sided allograft. Two of the 12 donors had a completely replaced left hepatic artery originating from the left gastric artery, which was divided at its origin from the celiac trunk. When the celiac trunk was maintained with the left-sided allografts, arterial reconstruction of the right-sided allograft was performed with an external iliac arterial interposition graft. Nineteen of the 24 split-liver allografts were transplanted at our center. The remaining five liver allografts were shared with regional liver transplant centers. RESULTS: In this series, 1-year actuarial patient and allograft survival rates are 100% and 96%, respectively. Hepatic artery thrombosis (HAT) did not occur in any patient receiving a left-sided split allograft in which the celiac trunk or left gastric artery was maintained; in addition, HAT did not occur in any of the right-sided allografts. HAT did occur immediately after transplantation in the one patient who was transplanted with a left lateral segment without the celiac trunk. This allograft was salvaged by early thrombectomy and interposition grafting. One patient required retransplantation, owing to portal vein thrombosis. Hepatic venous outflow obstruction did not occur in any of the patients. Two patients required reexploration in the posttransplant period because of arterial anastomotic site bleeding, and one of the left lateral segment allograft recipients had a cut-surface bile leak, which was managed nonoperatively. All of the patients are alive and well, including the five patients who received their transplants at other centers, with a median follow-up of 10 months (range, 1-27 months). CONCLUSIONS: In summary, our data demonstrate that maintaining the celiac trunk with the left-sided allograft in SLT provides excellent early survival results with low complication rates. This technical modification obviates the need for a left hepatic artery microvascular anastomosis and should lower the incidence of hepatic artery thrombosis in the small-caliber left hepatic artery. We have also shown that this technique allows sharing among liver transplant centers without compromise in patient or allograft survival rates. It is hoped that this modification in SLT will increase the number of livers split, and will promote sharing among transplant centers to truly optimize the number of liver allografts available from the cadaveric pool.

Adolescent↗

Investigation of liver parenchymal flow using contrast-enhanced ultrasound in patients with alcoholic liver disease.

BACKGROUND: Peripheral hepatic blood flow has not been investigated using contrast-enhanced ultrasound. The aim of this study was to assess the characteristics of peripheral blood flow within the liver parenchyma using Levovist in patients with alcoholic liver disease (ALD). METHODS: The study population comprised 160 patients: 7 normal control subjects (NC), 89 with chronic viral hepatitis (CVH), 8 with alcoholic liver injury (ALI), 18 with viral liver cirrhosis without portosystemic shunting (VLCwoPSS) plus 11 with PSS (VLCwPSS), and 12 with alcoholic liver cirrhosis without PSS (ALCwoPSS) plus 15 with PSS (ALCwPSS). First, continuous spectral Doppler ultrasound was performed to assess peripheral blood flow within the liver parenchyma. We defined the arrival time (AT) as the time when signals began to increase in the region of interest after the injection of Levovist, whereas the peak time (PT) was the time between the AT and the maximum signal. Second, stimulated acoustic emission imaging was compared between the liver parenchyma and the right kidney at 20 sec, 90 sec, and 5 min after injection of Levovist. RESULTS: The average AT was as follows: NC, 18.4 sec; CVH, 18.7 sec; ALI, 15.5 sec; VLCwoPSS, 18.2 sec; VLCwPSS, 12.5 sec; ALCwoPSS, 13.5 sec; and ALCwPSS, 12.7 sec. In patients with ALI and cirrhosis (excluding VLCwoPSS), the AT was earlier than in NC and CVH. The average PT was as follows: NC, 18.3 sec; CVH, 19.4 sec; ALI, 20.3 sec; VLCwoPSS, 19.3 sec; VLCwPSS, 9.0 sec; ALCwoPSS, 10.7 sec; and ALCwPSS, 4.9 sec. In patients with cirrhosis (excluding VLCwoPSS), the PT was earlier than in the other groups. As PSS developed, the PT of ALC became much earlier. In NC, the stimulated acoustic emission study showed no enhancement of the liver parenchyma at 20 sec. However, most of the patients with ALD showed marked enhancement of the liver at 20 sec. It is interesting that only slight enhancement of the liver was seen in ALCwPSS, although NC showed marked liver enhancement at 5 min. CONCLUSIONS: Our results suggest that ALD is accompanied by regional hepatic and systemic hemodynamic changes, such as hyperdynamic circulation and arterialization of the liver, before progression to cirrhosis.

Aged↗