Data were derived from a prospectively collected database of all LTs conducted at the West China Hospital of Sichuan University from February 2002 to July 2010. A total of 744 consecutive LTs, including deceased donor liver transplantations (DDLTs) and living donor liver transplantations (LDLTs), were performed at our centre in 726 adult patients suffering from end-stage liver disease. The recipients were 610 men and 116 women, with an age range of 18-69 years (mean age, 44.90 ± 9.98 years). The patients were monitored until December 2012 or their death, and their medical records were retrospectively reviewed. All of the liver grafts were from brain dead donors or living donors. Living and deceased donations were voluntary and altruistic in all cases and were approved by the West China Hospital Ethics Committee. All donations were obtained in accordance with the ethical guidelines of the Declaration of Helsinki. HAT is divided into two categories: early (occurring within less than 1 mo post LT) and late (occurring later than 1 mo post LT).

The detailed surgical techniques for the donors’ and recipients’ operations were previously reported[17,18]. All of the allografts were preserved in the University of Wisconsin (UW) solution at 4 °C. Hepatic arterial reconstruction was performed using microvascular techniques after the adoption of systemic anticoagulation (heparin, 62.5 U/kg, intravenous, 5 min before anastomosis). Administration of alprostadil (20 μg) to maintain artery patency was used in all of the cases after the completion of hepatic arterial reconstruction. The patency of the arterial anastomosis was evaluated by intraoperative Doppler ultrasonography.

Maintenance immunosuppression, which was previously reported, consisted of a triple-drug regimen that included tacrolimus or cyclosporine, mycophenolate and prednisone[19]. All of the recipients received low-molecular-weight heparin (LMWH) subcutaneously (nadroparin, 0.1 mL/10 kg, every 12 h) and alprostadil (20 μg/d) intravenously as thrombosis prophylaxis for the first 7 post-LT days, as soon as the prothrombin time was less than 20 s, the activated partial thromboplastin time was less than 50 s, the platelet count was more than 30 × 10⁹ cells/L, and no evidence of hemorrhagic complications or bleeding tendency was found. All of the patients underwent DUS every 12 h during the first postoperative week and daily during the second postoperative week to confirm hepatic artery patency. The diagnosis of HAT after LT was based on clinical presentations, color DUS findings, and hepatic artery arteriography. If elevated hepatic enzymes, cholestasis, bile leakage, or a high fever in the absence of acute rejection was detected, color DUS, CTA, or selective hepatic artery angiography was performed to establish the diagnosis. If hepatic arterial inflow was not observed by color DUS, contrast-enhanced ultrasound examination was performed in LDLT cases beginning in January 2005[20]. Recipient hepatic arterial inflow was followed regularly with a color DUS scan 3 or 6 mo after discharge.

Donor-related, recipient-related, intraoperative and postoperative factors were compared between the patients with and without early or late HAT, respectively. The donor factors that were considered were gender, age (≤ 60 vs > 60 years), recipient/donor body weight ratio and blood group. The recipient factors were gender, age (≤ 60 years vs > 60 years), aetiology (benign vs malignant liver disease), pretransplantation Child-Pugh class, MELD score, blood group, pretransplantation abdominal operative history, transcatheter arterial chemoembolization (TACE) prior to LT and diabetes status. The intraoperative factors were type of allograft (deceased donor whole liver, living-donor or split liver graft), number of grafts (dual or single graft), complex hepatic arterial reconstruction, method of biliary reconstruction, cold ischemia time (CIT), warm ischemia time (WIT), hepatic artery anastomosis time, duration of LT, and transfusion of blood, cryoprecipitate, fresh frozen plasma (FFP) and platelets. The postoperative factors were posttransplantation rejection episodes, transfusion of blood, cryoprecipitate, FFP and platelets (present, absent), bile leakage, portal vein thrombosis (PVT), infection (including pulmonary, biliary, abdominal or other infection), posttransplantation hyperglycemia/diabetes status and retransplantation. For our study, a “complex hepatic arterial reconstruction” was defined as the presence of bench arterial reconstruction, multiple numbers of anastomoses, or bypass for hepatic arterial reconstruction.

SPSS 17.0 statistical software (SPSS Inc., Chicago, IL, United States) was used to analyse the relevant data. All of the numerical data are presented as mean ± SD or as median. For univariate analysis, categorical variables were compared using χ² test for associations and the Mann Whitney U test was used for nonparametric data analysis. For univariate analysis, P≤ 0.05 was considered significant. Variables with P < 0.05 in the univariate analysis were entered into a forward stepwise logistic regression analysis to estimate the OR of each HAT (dependent variables) and the presence or absence of potential prognostic factors (independent variables). The OR was defined as the exp (β-coefficient) with its 95%CI.

Table 2 shows the donor and recipient characteristics associated with early HAT. In univariate analysis, recipients of ABO-incompatible grafts showed a significantly greater incidence of HAT (16.7%), compared with those who secured ABO-identical (1.8%) or compatible (1.1%) grafts (P = 0.025). Body weight ratio (recipient/donor) greater than 1.15 (n = 112) was associated with an incidence of early HAT of 5.4% compared to 1.3% of the 632 cases with a ratio < 1.15 (P = 0.003). There were no significant differences in the incidences of early HAT between the recipients’ groups by age, gender, aetiology, Child-Pugh class, MELD scores, recipients’ pretransplant history of laparotomy or TACE or diabetes status or the age or gender of the donor.

Early HAT was shown to be associated primarily with intraoperative factors as observed in Table 3. The incidence of early HAT in patients transplanted with dual grafts (n = 10) was 10%, compared to 1.8% occurring in recipients transplanted with a single graft (n = 734), but without reaching statistical significance (P = 0.057). There was a significant difference in the rate of early HAT in cases involving complex hepatic arterial reconstruction (10% of 30 recipients), compared to hepatic artery anastomosis without complex reconstruction (1.5% of 714 recipients, P = 0.001). The incidence of early HAT among recipients with time to hepatic artery anastomosis longer than 80 min (5.2% of 153 cases) was significantly greater than that for those recipients with durations ≤ 80 min (1.0% of 591 cases). Early HAT occurred more frequently in recipients with longer total operative times of more than 10 h, compared with those with operative times within 10 h (4.3% of 208 cases vs 0.9% of 536 cases, P = 0.002). The incidence of HAT reached statistical significance when intra-operative whole blood transfusions of 7 or more units were included (P = 0.01). The infusion of 6 or more units of FFP intraoperatively increased the incidence of early HAT significantly (P = 0.014). Neither the number of units of platelets transfused nor the number of units of cryoprecipitate transfused had any significant impact on the incidence of early HAT. There was no significant difference in the rate of early HAT between recipient groups by type of allograft, methods of biliary reconstruction, CIT, or WIT.

Postoperative factors were also analysed, as shown in Table 4. The incidence of early HAT was significantly greater in patients who required blood transfusions than in those without transfusion requirements of blood (3.7% of 244 cases vs 1.0% of 500 cases, P = 0.011). The transfusion requirement for FFP was significantly associated with early HAT in univariate analysis (P = 0.044), but no association was reported with transfusion requirement for platelets. Postoperative factors, such as posttransplantation rejection episodes, bile leakage, PVT, infection (including pulmonary, biliary, abdominal or other infections), posttransplantation hyperglycemia/diabetes status and retransplantation had no significant impact on the incidence of early HAT.

The factors independently predictive of early HAT are listed in Table 5. After logistic regression, independent risk factors associated with early HAT included recipient/donor weight ratio ≥ 1.15 (OR = 4.499), duration of hepatic artery anastomosis > 80 min (OR = 5.429), the number of units of blood received intraoperatively ≥ 7 (OR = 4.059), and the receiving of blood transfusions postoperatively (OR = 6.898).

In univariate analysis, donor and recipient characteristics and their intraoperative or postoperative associations with the development of late HAT are shown in Table 6. Diabetes was diagnosed preoperatively in 2 of the 40 recipients who developed late HAT, with 4 cases of diabetes diagnosed in the 704 without HAT (P = 0.037). The incidences of late HAT in patients with reduced liver grafts (LDLT and split) were 0.5% and 25%, respectively, reaching statistical significance (P < 0.001). Surgical durations longer than 10 h increased the incidence of late HAT significantly (1.7% of 208 cases, P = 0.034). In total there were 18 regrafts in the 744 transplants in this series. Late HAT occurred in one of these retransplantations (1/18). Retransplantation was found to be a risk factor for late HAT in this study (P = 0.023). The incidence of late HAT among recipients with an episode of rejection (4.2% of 48 cases) was significantly greater than that for those without rejection (0.2% of 696 cases, P = 0.05), and recipients with diabetes preoperatively and those with a high level of blood glucose or diabetes postoperatively (P = 0.025) were also associated with late HAT in univariate analyses. There were no significant differences in the incidences of late HAT between patients grouped by age, gender, aetiology, Child-Pugh class, MELD score, recipient pretransplant history of laparotomy or TACE, age or gender of donor, ABO or Rh blood type and matching, body weight ratio (recipient/donor), duration of arterial reconstruction, method for arterial reconstruction, or type of graft. Intraoperative elements were evaluated for their potential associations with the development of late HAT. Neither the duration of arterial anastomosis nor complex arterial reconstruction increased the incidence of late HAT significantly.

As shown in Table 7, after logistic regression, the independent risk factors associated with late HAT were duration of surgery > 10 h (OR = 6.394), retransplantation (OR = 21.793), and rejection reactions (OR = 16.936).

Liver transplantation (LT) has become the most effective therapy for many patients with acute and chronic end-stage liver disease. Hepatic artery thrombosis (HAT) is the most common and dreaded vascular complication after LT, with a high mortality rate. The identification of risk factors could improve prompt diagnosis of HAT by concentrating on those patients at risk and allowing for appropriate prophylactic treatment.

The real etiology of HAT remains a matter of debate and, in most cases, is unidentifiable. It was traditionally proposed that surgical technique was the most important risk factor for HAT. However, other risk factors such as graft preservation, ischemia reperfusion injury, immunological factors, coagulation abnormalities, infections, donor’s age, rejection episodes, retransplantation, arterial conduits, prolonged operative time, low recipient weight, and genetic factors have also been implicated.

This study was a retrospective analysis of a large case series. Several independent risk factors for early HAT were identified, including a recipient/donor weight ratio ≥ 1.15, duration of hepatic artery anastomosis > 80 min, number of units of blood received intraoperatively ≥ 7 and the receiving of blood postoperatively. Additionally, duration of surgery > 10 h, retransplantation and rejection reactions were found to be independent risk factors for late HAT. These findings include important information for transplant surgeons.

For patients at increased risk for early and late HAT as shown above, prophylactic anticoagulant treatment and daily Doppler ultrasound screening should be considered for the possible prevention or early detection of HAT after LT.

The article by Yi et al “Risk factors associated with early and late HAT after adult liver transplant” is overall well-written and provides a contemporary analysis of a long-standing problem in liver transplantation. The article’s strengths are particularly related to the operative/perioperative phase with regard to the effects of complicated transplants and requirement of blood products in a contemporary era where blood products are overall reduced across the field.