Liver Transplant Waitlist Outcomes and the Allocation of Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception Points at a Low-Volume Center.

BACKGROUND: Organ scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review. METHODS: The waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0. RESULTS: One hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5-43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14-16 points (7%) but lower than those with 17-19 points (16%). CONCLUSIONS: Hepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population.

Donor-Derived Candida dubliniensis Resulting in Perigraft Abscesses in a Liver Transplant Recipient Proven by Whole Genome Sequencing: A Case Report.

BACKGROUND: The transmission of fungi via transplant, although well-known, has not often been molecularly proven. We describe a case of donor-derived candidiasis verified by whole genome sequencing. CASE DESCRIPTION: The multiorgan donor was a 42-year-old woman with subdural hemorrhage. Procurement of the thoracic organs was performed followed by the abdominal organs. Tissue from the left bronchus grew Candida dubliniensis. The liver recipient was a 63-year-old woman with cryptogenic liver cirrhosis. She was noted to have worsening leukocytosis on postoperative day (POD) 9. Computed tomography of the abdomen and pelvis showed multiple rim-enhancing collections around the graft. Percutaneous drainage was performed. Fluid cultures grew C dubliniensis. C dubliniensis isolated from the donor's left bronchus and the liver recipient's abscesses were verified to be related by whole genome sequencing. We postulate that C dubliniensis colonizing the donor's transected trachea could have contaminated the inferior vena cava when the former was left open after explant of the donor's lungs. A portion of the donor's contaminated inferior vena cava was transplanted along with the liver graft, resulting in the infected collections in the recipient. CONCLUSIONS: Our case report highlights the importance of maintaining a sterile field during organ procurement, especially in a multiorgan donor whose organs are explanted in succession.

The viability of liver graft for transplantation after prolonged warm ischaemia.

Maximum duration of warm ischaemia within which the liver graft is viable for transplantation remains undefined. Published data on porcine allogeneic liver transplantation (LTx) using non heart beating donors (NHBDs) are conflicting because technical details like the hepatic artery status, systemic heparinisation of donor animals and duration of rewarming were not addressed. We described a novel porcine model which simulate conditions of transplantation from NHBDs. The pigs were divided into three groups of 6 each. Groups I, II and III were subjected to 60, 90 and 120 minutes of warm ischaemia, respectively. Liver viability was assessed using four parameters: serum liver function tests (serum bilirubin and transaminase), dynamic liver function test i.e. the monoethylglycinexylidide (MEGX) formation test, morphological assessment and animal survival. All animals in groups I and II (90 minutes of warm ischaemia or less) survived but 50% of animals in group III died of massive liver failure. Given that rewarming period required in actual allogeneic LTx is about 60 minutes, the safe period for intervention in NHBDs is determined to be about 30 minutes. Allogeneic porcine LTx using NHBDs with 30 minutes of cardiac arrest were performed in 5 animals. All of them survived.

Augmentation of portal blood flow improves function of human cirrhotic liver.

In cirrhotic livers, the intrahepatic resistance is increased and drug elimination and portal transhepatic flow are decreased. The aim of our work was to study the effect of a twofold increase in portal blood flow during 2 hr on the hemodynamic parameters, drug elimination and hepatic viability in eight isolated perfused human cirrhotic livers. Using an oxygenated recirculating system with independent arterial and portal flows, we perfused livers with Kreb's buffer bicarbonate solution, bovine serum albumin (20 gm.L-1) and human red blood cells (hematocrit 20%). The flow was maintained at a basal level of 0.713 +/- 0.19 L/min for 1 hr and then increased and maintained for 2 hr at twice the basal flow. Portal pressure-portal flow curve slopes were linear (27.04 +/- 21.06 mm Hg.L-1 x min; range = 6.43 to 60.8) and correlated with intrahepatic resistance during the basal-flow period (r = 0.87, p < 0.01). Parameters registered during the basal- and high-flow periods were compared by use of Student's t test: portal pressure increased from 23.5 +/- 7 to 37.3 +/- 16.7 mm Hg (p < 0.05); arterial pressure increased from 80.3 +/- 19 to 103.5 +/- 26 mm Hg (p < 0.005); hepatic artery flow resistance increased 31.9% (from 690.1 +/- 218 to 899.4 +/- 269 mm Hg.L-1 x min; p < 0.005); indocyanine green clearance increased by 28.2% (from 86.0 +/- 58.3 to 109.2 +/- 74.8 ml.min-1 x kg liver-1; p < 0.04). No significant differences were observed in enzyme release, biliary flow (n = 5) and oxygen consumption. Histological examinations demonstrated sinusoidal dilatations in six of eight cases.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ retrovirus-mediated gene transfer into dog liver.

Dogs were used as a large animal model to assess the feasibility and safety of a surgical method for gene transfer into hepatocytes in vivo. This method, which we previously described in rats, consists of a partial hepatectomy aimed at inducing liver regeneration, followed by the selective in situ perfusion of the remnant liver parenchyma with a retrovirus preparation. Isolation of the liver was obtained by clamping the afferent and efferent blood vessels, a procedure that prevented retroviral vector dissemination and genetic modification of nonhepatic organs. A helper-free retrovirus vector encoding beta-galactosidase targeted to the nucleus was perfused in the liver of 5 golden retriever dogs. Volumes up to 1,650 ml of fresh or concentrated vector stocks were perfused and the procedure was well tolerated. Gene transfer, observed in 3 of 5 treated dogs when documented on liver biopsy fragments obtained at day 4, involved 0.15-0.6% hepatocytes and persisted at equivalent levels at the time of sacrifice, 6 weeks later. No propagation of the vector to other tissues was detected. These observations suggest that the selective perfusion of the regenerating liver might be considered an alternative to liver transplantation for the treatment of certain severe genetic liver disorders, or for the delivery of a therapeutic protein into the serum.

Augmented portal flow in the isolated perfused cirrhotic rat liver: a haemodynamic and morphological study.

1. Isolated perfused cirrhotic rat livers were used to study the effects of an increase in portal perfusion pressure and portal flow on the microcirculation and viability of the hepatocytes. Cirrhosis was induced by CCl4, and Krebs-Ringer bicarbonate buffer solution was used as the perfusate. Portal perfusion pressures were increased incrementally between 25 and 45 cm H2O. The viability of the livers was assessed and histological studies were performed under light and electron microscopy. 2. An increase in portal perfusion pressure induced an increase in hepatic flow in all the experiments (P < 0.05). Hepatic flow was 2.52 ml min-1g-1 of liver (SD 0.67; n = 5) at basal pressure compared with 4.19 ml min-1g-1 of liver (SD 0.93; n = 5) and 5.91 ml min-1g-1 of liver (SD 0.63; n = 5) when pressures were raised to 25 and 45 cmH2O, respectively. Portal perfusion pressure and hepatic flow were correlated (r = 0.908; P < 0.001; n = 30). 3. Production of the enzyme alanine aminotransferase (EC 2.6.1.2) increased significantly from 5.69i.u. ml-1min g-1 of liver (SD 3.62; n = 5) to 23.53i.u. ml-1min g-1 of liver (SD 16.7; n = 5) when the perfusion pressure was raised from baseline to 30 cmH2O. In all the cases the porto-caval gradient of enzyme production was within the normal range. No correlation existed between the release of enzyme and portal perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative risks of complications in giant and nongiant gastric ulcers.

There are two divergent views regarding giant gastric ulcers. Traditionally, they have been regarded as a virulent disease prone to massive hemorrhage, intractability, and perforation. Recently, an entirely opposing viewpoint has developed that considers them no different from ordinary gastric ulcers. In this study between 1984 and 1989, 62 patients with giant ulcers (greater than or equal to 3 cm) were compared with 476 benign gastric ulcer patients to evaluate their relative risks of ulcer complications. The results showed that giant ulcers are more prone to severe hemorrhage (44% versus 27%; chi 2 test: p less than 0.009) but not more prone to free perforation. Penetration into contiguous organs occurred more frequently with giant gastric ulcers (45% versus 10%; chi 2 test: p less than 0.0001). The risk of the presence of microscopic malignancy in the macroscopically benign-looking giant ulcer is significantly greater than in the nongiant type (13% versus 3%; Fisher's exact test: p = 0.0013). The data showed that patients with giant gastric ulcers are more at risk for the development of life-threatening complications and, hence, more likely to require surgery.