A modified surgical model of fulminant hepatic failure in the rat.

in Journal of Surgical Research (2013), 181

BACKGROUND: There is a need for better animal models of fulminant liver failure (FHF). Eguchi et al described an interesting surgical model of FHF in the rat. This model includes 68% partial hepatectomy ... [more ▼]

BACKGROUND: There is a need for better animal models of fulminant liver failure (FHF). Eguchi et al described an interesting surgical model of FHF in the rat. This model includes 68% partial hepatectomy, ischemia of 24% of the liver mass, and 8% of remnant liver left intact. In the original description by Eguchi et al, rats were administered subcutaneous glucose. However, the authors found that normothermic FHF rats with subcutaneous glucose died from deep hypoglycemia. In this report, we describe a modification of that model, and show that administration of intravenous glucose allows better survival and development of intracranial hypertension. METHODS: We operated on FHF rats using the procedure described by Eguchi et al, kept them normothermic, and maintained normoglycemia by continuous intravenous glucose injection (glucose 10%, 1 mL/h). At 24 h, we monitored liver blood tests (n = 5), intracranial pressure (n = 5), clinical encephalopathy, and survival (n = 10), and compared them with sham and 68% hepatectomy rats. RESULTS: The FHF rats developed acute cytolysis, cholestasis, and liver failure, as demonstrated by the liver blood tests. They experienced progressive encephalopathy and intracranial hypertension leading to death. Mean survival was 45.9 h. Of 10 FHF rats from the survival evaluation cohort, one survived 7 d. Laparotomy showed necrosis of lateral liver lobes and enlargement of omental lobes with a normal hepatic aspect, suggesting liver recovery. CONCLUSIONS: This surgical rat model mimics the features of human FHF and seems interesting for further research into the pathophysiology and therapeutic management of the disease. [less ▲]

Retrospective analysis of Belgian experience with intestinal transplantation

Conference (2013, March 21)

Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results ... [more ▼]

Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results compared to other organ Tx. Therefore ITx has been rarely applied in Belgium. In a multicenter retrospective review, we analyzed the overall Belgian experience with ITx. Methods: The Belgium Liver Intestine Committee organized a survey among all Belgian Tx centers, based on the patient-specific data form of the international ITx registry. Overall activity and indications were reviewed. Patient/graft survival was calculated (Kaplan-Meier). Nutritional (TPN) independence and Quality of Life (QoL) (Karnofsky score) were analyzed. Results: 21 ITx were performed in 20 patients (03/99-11/12), distributed among 5 centers: KUL (12), ULg (5), UZG (2), UCL (1), UZA (1). Median age was 38y(8mo-56y). Male/female ratio was 10/10. 5 were pediatrics (<18y) and 15 adults. Indications were anatomical or functional short bowel syndrome: intestinal ischemia(5), volvulus(5), Crohn(2), chronic intestinal pseudo-obstruction(2), splanchnic thrombosis(2), Churg-Strauss(1), necrotizing enterocolitis(1), microvillus inclusion(1), intestinal atresia(1) and chronic rejection of a first ITx(1). Most patients also suffered from TPN-associated com- plications (infection/shortage of venous access or liver failure). An isolated small bowel was trans- planted in 9 patients (plus kidney Tx in 2; plus pancreas Tx in 1); 10 received a combined liver and ITx; 2 received a multivisceral Tx. At time of Tx, 11 patients were hospitalized and 10 at home. 20 grafts were procured from deceased donors; one segmental intestinal graft was procured from a living donor. ABO blood group was identical in 63%, compatible in 37%. Median cold ischemia time was 5h30 ́(3h17 ́-9h31 ́). All patients received tacrolimus-based immunosuppression. Basiliximab (anti-IL2 receptor antibody) induction was administered in 16 patients. In 11 patients donor specific blood was transfused as part of an immunomodulatory protocol. 5-year patient and graft survival is 59% and 55.6%, respectively. 8 patients died: 6 to sepsis, 1 to intracerebral hemorrhage; 1 sudden death re- mained unexplained. 1 patient developed postTx lymphoma. 2 chronic rejections occured for which one reTx was performed. Of 12 survivors (median follow-up 1870 days), 11 are nutritionally independent (TPN-free) and 10 have a Karnofsky score >90%. Conclusions: ITx has come of age in Belgium. During the last 13 years, 21 ITx were performed in 5 centers. A 5-year patient/graft survival of 59%/55.6% is achieved, which is similar to results reported by the International ITx registry. In Belgium, awareness should grow that ITx represents a life-saving (and QoL improving) treatment in selected patients with reduced life expectancy due to significant complica- tions from TPN and intestinal failure. [less ▲]

What is the potential increase in the heart graft pool by cardiac donation after circulatory death?

Conference (2013, February 09)

Delayed graft function (DGF) does not harm the results of controlled donation-after-cardiovascular death (DCD) in kidney transplantation.

Poster (2013, February 08)

Renal function following transplantation with kidneys from donation after brain death (DBD) or cardiac death (DCD)

Poster (2013, February 08)

Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof-of-concept study using discarded human livers.

in Liver Transplantation (2012), 18(12), 1495-507

The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk ... [more ▼]

The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk livers is the development of objective criteria for assessing their condition before transplantation. Compared to simple cold storage, hypothermic machine perfusion (HMP) provides a unique window for evaluating liver grafts between procurement and transplantation. In this proof-of-concept study, we tested basic parameters during HMP that may reflect the condition of human liver grafts, and we assessed their morphology after prolonged HMP. Seventeen discarded human livers were machine-perfused. Eleven livers were nontransplantable (major absolute contraindications and severe macrovesicular steatosis in the majority of the cases). Six livers were found in retrospect to be transplantable but could not be allocated and served as controls. Metabolic parameters (pH, lactate, partial pressure of oxygen, and partial pressure of carbon dioxide), enzyme release in the perfusate [aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)], and arterial/portal resistances were monitored during HMP. Nontransplantable livers released more AST and LDH than transplantable livers. In contrast, arterial/portal vascular resistances and metabolic profiles did not differ between the 2 groups. Morphologically, transplantable livers remained well preserved after 24 hours of HMP. In conclusion, HMP preserves the morphology of human livers for prolonged periods. A biochemical analysis of the perfusate provides information reflecting the extent of the injury endured. Liver Transpl, 2012. (c) 2012 AASLD. [less ▲]

Effects of Large-Pore Hemofiltration in a Swine Model of Fulminant Hepatic Failure.

in Artificial Organs (2012), 36(11), 981-987

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation ... [more ▼]

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m(2) , large-pore (78 A) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels. [less ▲]

Transplantation et don d'organes en Belgique

Conference (2012, September 29)

Donation after cardio-circulatory death liver transplantation.

in World Journal of Gastroenterology (2012), 18(33), 4491-506

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ ... [more ▼]

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT. [less ▲]

Liver transplantation for unresectable hepatocellular carcinoma in normal livers.

in Journal of Hepatology (2012), 57(2), 297-305

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for ... [more ▼]

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation <12months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC. [less ▲]