Hepatic Artery Thrombosis: Conservative Management or Retransplantation? Professor Nigel Heaton Kings Health Partners Institute of Liver Studies Kings College Hospital London

Hepatic Artery Thrombosis: Conservative vs Retransplantion Topics to be covered Arterial anatomy of the liver and biliary tree Definition of early and late hepatic artery thrombosis Incidence Pathophysiology Decision making and outcomes :conservative management or retransplantation Prevention? Personal data

Schematic of 3 & 9 o’clock arteries 38% Arterial contributions to the bile duct axial distal supply dominant 2% 60% Northover and Terblanche, BJS 1979

Early Hepatic Artery Thrombosis: Incidence Definition not agreed – varying from 2 weeks to 3 months Early HAT – within one month of transplant Incidence: mean 3.9%, median 4.4% Adults 2.9%, Children 8.3% Era effect 1982-1996 6.9% 1993 – 2006 3.8% Higher incidence in lower volume centers (< 30 LTx) 5.8% vs 3.2%) Bekker et al, AJT 2009; 9: 757

Late Hepatic Artery Thrombosis One month to more than 3 months Bekker et al, AJT 2009; 9: 757

Hepatic Artery Thrombosis: Pattern of injury - Early Depends on the speed and efficiency of collateralisation Bile duct ischemia Infection Cholangiolitic abscesses Parenchymal necrosis Liver failure and death Personal data

Hepatic Artery Thrombosis: Pattern of injury - late Non-anastomotic/complex biliary stricture Cast formation on damaged biliary epithelium Recurrent infection – cholangitis Biliary abscesses and infarction Malnourishment and ill health Personal data

Hepatic Artery Thrombosis: Factors influencing collateralisation Site of arterial thrombosis Graft type? split / reduced grafts Roux loop Children vs adults Multiple arteries Timing after transplantation

Early Hepatic Artery Thrombosis: Mortality Overall mortality 33% (0-80%) Important cause of graft loss 53% Mortality 33% Clinical burden of retransplantation Financial burden and escalating cost Bekker et al, AJT 2009; 9: 757

Early Hepatic Artery Thrombosis Surgical Causes Retrieval injury – tear, dissection, hematoma Anastomotic stenosis Kinking – short length of artery Multiple arteries/arterial reconstruction Use of arterial conduits Pseudo-aneursym Retransplantation

Early Hepatic Artery Thrombosis Non-Surgical Causes Pro-coagulant states JAK-2, Anticardiolipin antibody, Factor V Lieden High hematocrit Liver disease – PSC, HIV, FAP Massive ascites Drugs eg aprotinin, sirolimus? Smoking

Early Hepatic Artery Thrombosis Non-Surgical Causes Pediatric recipients - Small artery – neonatal liver graft CMV negative recipient Long cold ischemic time Large graft Small for size syndrome ABO incompatibility

Early Hepatic Artery Thrombosis Presentation Early asymptomatic Presentation – unexplained fever - bacteremia, septicemia - liver dysfunction – transaminitis, cholestasis - biliary leak/stricture - Pseudo-aneurysm Personal data

Early Hepatic Artery Thrombosis Evolution of ischemia Asymptomatic – no ischemia on CT (collateralisation) Patchy parenchymal ischemia Extensive parenchymal necrosis Cholangiolytic abscesses Biliary leak Personal data

Early Hepatic Artery Thrombosis Interventions Revacularisation Thrombectomy Revision of vascular anastomosis Thrombolytic drug therapy Retransplantation Conservative management Combination of above

Early Hepatic Artery Thrombosis Intervention: Surgical Revascularisation Revascularisation in 257 out of 510 cases from 47 studies 163 out of 315 - clear reporting of intervention and outcome Revascularisation attempted in 75% adults and 54% of children Overall success 56% Correlation between early occurrence and successful revascularisation Frequent (daily USS) associated with successful outcome - 66% vs 45% Adults 61% vs 45% and children 92% vs 58%. Retransplantation in 30% of attempted revascularisations Bekker et al, AJT 2009; 9: 757

Early Hepatic Artery Thrombosis Intervention: Retransplantation Revascularisation in 260 cases in 43 studies Treatment of choice in 53% Retransplantation in 50% of adults and 62% of children Limited reporting of data Mortality 50% (30-70%) Outcome same for adults and children? Bekker et al, AJT 2009; 9: 757

Hepatic Artery Thrombosis: Conservative Management or Retransplantation Varying results of revascularization Type of revascularization Varying threshold for retransplantation between centers Recipient and graft status at the time of revascularization Time post hepatic artery thrombosis (extent of ischemia)

Hepatic Artery Stenosis Doppler Ultrasound Recognition Tardus parvus waveform on Doppler ultrasound to identify stenosis Low positive predictive value and high false positive rate Tardus parvus defined as a waveform with a resistive index of < 0.5 and a systolic acceleration time of < 0.08 sec Combined with optimal peak systolic velocity < / = 48cm/sec Improved specificity to 99% and positive predictive rate of 88% and false positive rate to 1% but decreasing sensitivity Park et al, Radiology 2011; 260: 884

Endovascular treatment of recurring hepatic artery stenosis 941 LTx 1998-2010 48 (5.1%) with HAS 6 patients underwent arterial and biliary surgical repair 5 retransplants for biliary stricture 37 treated with transluminal intervention 3 complications – dissection, haematoma Outcome – HAS recurrence 9 (24%), HAT 4 (11%) Repeat interventions -10 in 8 patients Median follow up 66m with HA patency of 94.6% 5 year graft and patient survival of 82% and 87% Sommacale et al. Transplant Int 2013; 26: 608-615

Proposed management – LFTs and CT angiography Hepatic Artery Thrombosis: Conservative Management or Retransplantation Proposed management – LFTs and CT angiography Early recognition, normal transaminases, no graft ischemia on CT urgent revascularization Late recognition, transaminitis, parenchymal or biliary ischemia Conservative management or retransplanatation Significant or progressive ischemia Liver retransplantation

Hepatic Artery Thrombosis: Prevention? Microvascular techniques? Immediate postoperative Doppler ultrasound Daily ultrasound for first week (or ultrasound probe) Management of hematocrit Replacement of coagulation factors for ascitic loss Use of heparin/aspirin prophylaxis Parvus tardus – investigate with early intervention

Hepatic Artery Thrombosis: Conservative Management or Retransplantation: Summary Early and late HAT: continue to be a challenge Role for daily ultrasound for early recognition CT angiography – key to management decisions Role for early revascularisation Morbidity and mortality associated with early retransplantation Conservative management for late recognition with collateralisation