Until the present time, the first experimental liver transplant which led to the development of human liver transplantation is attributed to C. Stuart Welch who performed a heterotopic transplant in ...the canine species in 1955. In 1956, Jack Cannon is credited with the first animal orthotopic liver transplant although the species was not disclosed. This report is intended to set the historical record straight by acknowledging that Vittorio Staudacher in 1952 was the first to perform a liver transplant in a large animal model.
This article credits Vittorio Staudacher from Milan, Italy, who in 1952 was the first surgeon/investigator in the Western world to perform a liver transplant in a large animal model.
A retrospective data analysis on liver transplantation for Wilson's disease (WD) was performed among Italian Liver Transplant Centers. Thirty‐seven cases were identified. The main indication for ...liver transplantation was chronic advanced liver disease in 78% of patients. Mixed hepatic and neuropsychiatric symptoms were recorded in 32.3%. Eight patients presented with fulminant liver failure; 44.8% were on medical treatment. Patient and graft survival at 3 months, 12 months, 3 years, 5 years, and 10 years after transplantation were, respectively, 91.8%, 89.1%, 82.9%, 75.6%, and 58.8%, and 85.3%, 83.0%, 77.1%, 70.3%, and 47.2%. Neurological symptoms significantly improved after orthotopic liver transplantation (OLT), but the survival of patients with mixed hepatic and neuropsychiatric involvement was significantly lower than in patients with liver disease alone (P = 0.04). WD characterized by hepatic involvement alone is a rare but good indication for liver transplantation when specific medical therapy fails. Patients with neuropsychiatric signs have a significantly shorter survival even though liver transplantation has a positive impact on neurological symptoms. In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment. (Liver Transpl 2005;11:1056–1063.)
Tissue damage during cold storage and reperfusion remains a major obstacle to wider use of transplantation. Vascular endothelial cells and complement activation are thought to be involved in the ...inflammatory reactions following reperfusion, so endothelial targeting of complement inhibitors is of great interest. Using an in vitro model of human umbilical vein endothelial cells (HUVEC) cold storage and an animal model of ex vivo liver reperfusion after cold ischaemia, we assessed the effect of C1‐INH on cell functions and liver damage. We found that in vitro C1‐INH bound to HUVEC in a manner depending on the duration of cold storage. Cell‐bound C1‐INH was functionally active since retained the ability to inhibit exogenous C1s. To assess the ability of cell‐bound C1‐INH to prevent complement activation during organ reperfusion, we added C1‐INH to the preservation solution in an animal model of extracorporeal liver reperfusion. Ex vivo liver reperfusion after 8 h of cold ischaemia resulted in plasma C3 activation and reduction of total serum haemolytic activity, and at tissue level deposition of C3 associated with variable level of inflammatory cell infiltration and tissue damage. These findings were reduced when livers were stored in preservation solution containing C1‐INH. Immunohistochemical analysis of C1‐INH‐treated livers showed immunoreactivity localized on the sinusoidal pole of the liver trabeculae, linked to sinusoidal endothelium, so it is likely that the protective effect was due to C1‐INH retained by the livers. These results suggest that adding C1‐INH to the preservation solution may be useful to reduce complement activation and tissue injury during the reperfusion of an ischaemic liver.
Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma ...(HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child‐Turcotte‐Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions (P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases. (Liver Transpl 2005;11:1117–1126.)
Anatomic variations of the arterial supply to donor liver grafts often require complex hepatic artery reconstructions on the back table. Therefore, because of the additional anastomoses, there is a ...greater risk of arterial thrombosis and graft loss. Among the 620 orthotopic liver transplantations (OLT) in 549 adult and pediatric patients performed from June 1983 through August 2004, the rates and types of donor hepatic artery variations (HAV) and the type of reconstructions were reviewed as well as the 1- and 5-year grafts and patient survival rates after OLT. At least 1 HAV was present in 133 liver grafts (21.4%). The most frequent variations were as follows: right hepatic artery (RHA) from superior mesenteric artery (SMA) (44 cases); RHA from aorta (4 cases); and RHA from SMA, combined with a left hepatic artery (LHA) from left gastric artery (3 cases). No graft was discarded. Fifty-six of 133 (42%) HAV required arterial reconstructions, generally a termino-terminal (TT) anastomosis between RHA and splenic artery (26 cases, 46.4%). Less frequently performed anastomoses were the “fold-over” technique (15 cases, 26.8%) and the anastomosis between the RHA and the gastro-duodenal artery (6 cases, 10.6%); rare reconstructions were performed in 9 cases (16.0%). The rate of hepatic artery thrombosis was 5.4% (3 of 56 OLT) in complex hepatic artery reconstructions and 2.2% in other grafts. One- and 5-years graft and patient actuarial survival rates have been respectively 73.2%– 71.4% in hepatic artery reconstructions and 78.6%–76.8% in the absence of an artery reconstruction, respectively.
Hepatitis C virus (HCV) recurrence in HCV+ liver transplant recipients is almost inevitable and may be promoted by immunosuppression. We compared the amount of liver damage with regard to usage of ...steroids and basiliximab.
A total of 140 HCV+ adult liver transplant recipients were randomly allocated to basiliximab + steroids or basiliximab + placebo (plus cyclosporine and azathioprine). Primary endpoint: hepatitis C histological recurrence (liver damage as for Ishak grading score >or=8 by biopsy at 12 months); secondary endpoints: treatment failure (death, graft loss, patient withdrawal), biopsy proven acute rejection (BPAR), treated acute rejection (tAR), allograft and patient survival rates at 12 months.
Any significant difference has been observed in the 12-month hepatitis C histological recurrence rate (41.2% basiliximab + steroids, 37.5% basiliximab + placebo, P = 0.354). The treatment failure rate was significantly higher in basiliximab + steroids (28.8%) than in basiliximab + placebo (15.6%), P = 0.03; the combination test for the evaluation of the joint hypothesis resulted in a borderline nonsignificant overall result (P = 0.059). BPAR rate was significantly lower in the group treated with steroids (24.3% basiliximab + steroids, 39.4% basiliximab + placebo, P = 0.04), while the tAR rate was similar (29.7% basiliximab + steroids and 37.9% basiliximab + placebo). Any significant differences in 1-year graft and patient survival rates have been observed (72.9% and 84.8% basiliximab+steroids; 81.5% and 89.0% basiliximab + placebo).
Results suggest that steroid-free therapy is associated with a significantly lower treatment failure rate, although histological recurrence rate of hepatitis C is similar in the two groups. This benefit is not offset by an evident increase in graft rejection rate requiring treatment.
In situ split liver transplants represent a technical progression from ex situ split procedures conceived to retrieve grafts for pediatric recipients. The transection line runs along the falciform ...ligament, so the main artery to the right graft is the right proper artery, whereas the left graft retains the main arterial axis with the celiac trunk. Although the major advantages are for pediatric recipients, due to the expanded pool of grafts available, for adult recipients the results of right split in situ grafts must be compared with whole grafts. We considered two groups of consecutive grafts transplanted since 1993 as first grafts: 20 of the former and 261 of the latter. Groups were comparable for donor gender, recipient age and gender, perfusion solution, ischemia time, and follow-up time, but not for donor age and for the number of arterial anastomoses. Although there were more major surgical complications in the former compared with the latter group (40% vs 25%), the only statistically significant difference was found in retransplantation rate for arterial complications (15% vs 2.2%). No statistical difference was observed in graft or patient actuarial survival rates at 1, 3, or 6 years after transplantation; for right split grafts these were 85%, 69%, and 69% and 95%, 79%, and 79%, respectively.
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