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Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma

Hypothetical studies that favour living donor liver transplantation (LDLT) for early hepatocellular carcinoma (HCC) assumed a comparable outcome after LDLT and deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcome after LDLT with that after DDLT, and to identify factors that might account for any differences.

Impact of postoperative complications on long-term outcome of curative resection for hepatocellular carcinoma

The aim of this retrospective study was to determine the impact of postoperative complications on the long‐term outcome of curative liver resection for hepatocellular carcinoma (HCC).

Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: a randomised controlled trial

Background: Previous studies suggested that somatostatin given before endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. However, the routine use of somatostatin in all patients undergoing ERCP is not likely to be cost effective. This study evaluated whether intravenous bolus somatostatin given after diagnostic cholangiopancreatography could reduce the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP procedures. Methods: In a randomised, double blind, controlled trial, the effect of intravenous bolus somatostatin 250 μg given immediately after diagnostic cholangiopancreatography was compared with that of placebo in patients who required endoscopic sphincterotomy or other therapeutic procedures. The primary end point was the incidence of post-ERCP clinical pancreatitis, and a secondary end point was the incidence of hyperamylasemia. Results: A total of 270 patients were randomised. The somatostatin group (n = 135) and the placebo group (n = 135) were comparable in age, sex, indications for treatment, and types of procedure. The frequencies of clinical pancreatitis (4.4% v 13.3%; p = 0.010) and hyperamylasemia (26.0% v 38.5%; p = 0.036) were both significantly lower in the somatostatin group compared with the placebo group. Conclusions: A single dose of intravenous bolus somatostatin, given immediately after diagnostic cholangiopancreatography, is effective in reducing the incidence of pancreatitis after therapeutic ERCP. This novel approach of administering prophylactic somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment.

Efficacy of a Pre‐S Containing Vaccine in Patients Receiving Lamivudine Prophylaxis after Liver Transplantation for Chronic Hepatitis B

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double‐doses (20 ug) of third‐generation recombinant pre‐S containing vaccine (Sci‐B‐Vac™) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390–2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti‐HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti‐HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci‐B‐Vac™ is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

Effects of the intermittent Pringle manoeuvre on hepatic gene expression and ultrastructure in a randomized clinical study

The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min. The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre.

Right lobe living donor liver transplantation with or without venovenous bypass

Venovenous bypass was considered necessary to maintain haemodynamic stability and avoid splanchnic and retroperitoneal congestion during the anhepatic phase of liver transplantation. It was essential for right lobe living donor liver transplantation (LDLT) in which the inferior vena cava needed to be cross‐clamped to construct wide and short hepatic vein anastomoses. However, many complications related to venovenous bypass have been reported. This study aimed to determine whether venovenous bypass was necessary for right lobe LDLT.

Graft‐versus‐host disease after liver transplantation: documentation by fluorescent in situ hybridisation and human leucocyte antigen typing

Graft‐versus‐host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. Skin biopsy showed characteristic changes of GVHD. Using Y‐chromosome‐specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal–epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti‐thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA‐identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.

Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival.

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small‐for‐size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small‐for‐size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat‐derived hormone adiponectin (anti‐steatosis) plus immunomodulator FTY720 (anti‐inflammatory) in a rat liver transplantation model using small‐for‐size fatty liver grafts, and investigated the underlying protective mechanism such as anti‐steatosis, intra‐graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7‐day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7‐day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra‐graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat‐derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small‐for‐size fatty liver graft injury.

Rapamycin attenuates liver graft injury in cirrhotic recipient--the significance of down-regulation of Rho-ROCK-VEGF pathway.

To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small‐for‐size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7‐day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small‐for‐size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small‐for‐size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down‐regulated by rapamycin at 48 h both in whole and small‐for‐size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down‐regulation of Rho‐ROCK‐VEGF pathway.