Primary liver transplantation vs liver resection followed by transplantation for transplantable hepatocellular carcinoma:Liver functional quality and tumor characteristics matter

Liver resection(LR) and primary liver transplantation(LT) are two potentially curative treatment modalities for patients with hepatocellular carcinoma(HCC).If an underlying chronic liver disease exists,however,making a decision on which method should be selected is difficult.If a patient has no chronic liver disease,LR may be the preferable option with salvage transplantation(ST) in mind in case of recurrence.Presence of a moderate-to-severe liver failure accompanying HCC usually warrants primary LT.The treatment of patients with HCC and early-stage chronic liver disease remains controversial.The advantages of "LR-followed-by-STif-needed" strategy include less complicated index operation,no need for immunosuppression,use of donor livers for other patients in today's organ shortage setting and comparable survival rates.However,primary LT has its own advantages as it also treats underlying chronic liver disease with carcinogenic potential,removes undetected tumor nodules and potentially eliminates need for a ST.An article recently published by Fuks et al in Hepatology offers an approach by which selecting between LR-followed-by-ST and immediate LT might be easier.Here we discuss the results of the aforementioned report in the light of currently available knowledge.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature

Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.

Early graft dysfunction following adult-to-adult livingrelated liver transplantation:Predictive factors and outcomes

AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is characterized by EGD when the graft-to-recipient body weight ratio(GRBWR)is below 0.8%.However, patients transplanted with GRBWR above 0.8%can develop dysfunction of the graft.In 73 recipients of LRLT(GRBWR>0.8%),we identified 10 patients who developed EGD.The main measures of outcomes analyzed were overall mortality,number of re-transplants and length of stay in days(LOS).Furthermore we analyzed other clinical pre-transplant variables,intraoperative parameters and post transplant data.RESULTS:A trend in favor of the non-EGD group(3-mo actuarial survival 98%vs 88%,P=0.09;3-mo graft mortality 4.7%vs 20%,P=0.07)was observed as well as shorter LOS(13 d vs 41.5 d;P=0.001)and smaller requirement of peri-operative Units of Plasma (4 vs 14;P=0.036).Univariate analysis of pre- transplant variables identified platelet count,serum bilirubin,INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P=0.025,OR:1.175)and pretransplant platelet count(P=0.043,OR:0.956)were independently associated with EGD. CONCLUSION:EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.

Transjugular intrahepatic portosystemic shunt for liver transplantation

Objectives: To assess transjugular intrahepatic porto- systemic shunt (TIPSS) as an effective bridge be- tween the control of variceal bleeding or refractory ascites and orthotopic liver transplantation (OLTx) and to examine whether TIPSS influences the opera- tive procedures of OLTx. Methods: Five patients treated by TIPSS prior to OLTx were retrospectively reviewed. Results: The patients were followed up for 2-7 months (average 4.2 months) after transplantation. Transplantation was performed at a mean of 9. 6 months (range 0.2-24.7) after TIPSS insertion. In four patients, stents were predominantly intrahepatic and they did not interfere with OLTx. In one pa- tient, the stent extended into the portal vein, requi- ring removal during OLTx by division of the stent with the recipient portal vein. All patients are alive and none has portal vein thrombosis. No difference was observed in operation time, blood transfusion, and the length of hospital stay. Conclusions: TIPSS is an effective bridge to OLTx for the control of variceal hemorrhage or refractory ascites. Our results suggest that TIPSS does not in- crease surgical morbidity or mortality, but optimal TIPSS placement within the liver is emphasized to fa- cilitate subsequent OLTx.

肝脏移植术后的外科并发症

目的 探讨肝移植术后外科并发症的防治。方法 根据美国匹兹堡大学医疗中心Starzl移植研究所的经验 ,介绍与外科操作技术有关的术后常见并发症的防治方法。结果与结论 术后腹腔出血、肝动脉血栓形成、门静脉血栓形成、胆漏、胆道梗阻、胃肠道穿孔、胃肠道出血等是与外科技术操作有关的外科并发症。对肝脏移植术后异常情况的快速诊断和及时处理 ,是减少外科并发症的发生率和死亡率的重要措施。

成人原位活体部分肝移植4例报告

目的 :报道成人活体部分肝移植的临床经验。方法 :回顾性研究 4例临床资料。结果 :所有病人年龄均大于 18岁 ;2例施行左半肝移植术 ,2例施行右半肝移植术。供体平均手术时间大约 7h ,平均失血量为 40 0ml,无一发生术后并发症。受体平均手术时间是 6 .8h ,移植肝重量介于 34 0 g～ 870g ,移植肝重量与体重的比例介于 0 .80 %～ 0 .91%;1例发生肝动脉部分栓塞 ,3个月后因胆道并发症而再次行原位移植 ,无近期手术死亡率。结论 :无论左半肝还是右半肝移植术 ,均能达到较好疗效 ,为成年病人的肝移植提供了新的供肝来源和选择。

Bioartificial liver assist devices in support of patients with liver failure

Bioartificial liver assist devices (BALs) offer anopportunity for critical care physicians and transplantsurgeons to stabilize patients prior to orthotopic livertransplantation. Such devices may also act as a bridgeto transplant, providing liver support to patientsawaiting transplant, or as support for patients post liv-ing-related donor transplant. Four BAL devices thatrely on hepatocytes cultured in hollow fiber membranecartridges (Circe Biomedical HepatAssist (r), VitagenELADTM, Gerlach BELS, and Excorp Medical BLSS)are currently in various stages of clinical evalua-tion. Comparison of the four devices shows that severalunique approaches based upon the same overall systemarchitecture are possible. Preliminary results of theExcorp Medical BLSS Phase I safety evaluation at theUniversity of Pittsburgh, after treating four patients(F, 41, acetominophen-induced, two support periods;M, 50, Wilson's disease, one support period; F, 53, a-cute alcoholic hepatitis, two support periods; F, 24,chemotherapy-induced, one support period) are pre-sented. All patients presented with hypoglycemia andtransient hypotension at the start of extracorporealperfusion. Hypoglycemia was treated by IV dextroseand the transient hypotension responded positively toIV fluid bolus. Heparin anticoagulation was used onlyin the second patient. No serious or adverse eventswere noted in the four patients. Moderate biochemicalresponse to support was noted in all patients. Morecomplete characterization of the safety of the BLSSrequires completion of the Phase I safety evaluation.

D-galactosamine based canine acute liver failure model

Background: Appropriate preclinical evaluation of a bioartificial liver assist device (BAL) demands a large animal model, as presented here, that demon- strates many of the clinical features of acute liver failure and that is suitable for clinical qualitative and quantitative evaluation of the BAL. A lethal canine liver failure model of acute hepatic failure that re- moves many of the artifacts evidenced in prior canine models is presented. Methods: Six male hounds, 24-30 kg, under isoflu- rane anesthesia, were administered 1.5 g/kg D- galactosamine intravenously. Canine supportive care followed a well-defined management protocol that was guided by electrolyte and invasive monitoring consisting of arterial pressure, central venous pres- sure, extradural intracranial pressure (ICP), pul- monary artery pressure, and end-tidal CO_2. The animals were treated until death-equivalent, defined as inability to sustain systolic blood pressure>80 mmHg for 20 minutes despite maximal fluids and 20 μg·kg^(-1)·min^(-1) dopamine infusion. Results: The mean survival time was 43.7±4.6 hours (mean±SE). All animals showed evidence of progressive liver failure characterized by increasing liver enzymes (aspartate transaminase from 26 to 5977 IU/L; alanine transaminase from 32 to 9740 IU/L), bilirubin (0.25 to 1.30 mg/dl), ammonia (19. 8 to 85. 3 μmol/L), and coagulopathy (pro- thrombin time from 8.7 to 46 s). Increased lability and elevations in intracranial pressures were ob- served. All animals were refractory to maintenance of cerebral perfusion pressure even with only mode- rately elevated intracranial pressure. Severe neuro- logic obtundation, seen in 2 of 6 animals, was associ- ated with elevations of ICP above 50 mmHg. Post- mortem liver histology showed evidence of massive hepatic necrosis. Postmortem blood and ascites mi- crobial growth was consistent with possible transloca- tion of intestinal microbes. Conclusions: The improved lethal canine liver failure model presented here reproduces many of the clinical features of acute liver failure. The model may prove useful for qualitative and quantitative evaluation of BALs.