A 51-year-old male patient was admitted under our care in November-2020 with a diagnosis of ethanol related chronic liver disease (CLD), decompensated with ascites and encephalopathy and was evaluated for living related LT. He did not have any coagulation disorder on routine preoperative workup. All liver transplant recipients at our center are screened for COVID-19 before surgery as per our standard protocol (5). A routine COVID-19 RT PCR sent as part of his evaluation came positive. Symptoms were mild in the form of fever and occasional cough. He was quarantined and was started on a 5-day course of azithromycin in addition to the supportive management, following which his symptoms subsided. A repeat COVID-19 RT PCR after 14-days turned out to be negative. After weighing the potential unknown risks following a recent SARS-CoV-2 infection and the deleterious effects of further decompensation of the liver disease, it was decided to postpone his transplantation for a period of 2-weeks.
Once he was readmitted for transplant, all the investigations were repeated which included the routine set of pre-transplant tests as well as interleukin-6, C-reactive protein, lactate dehydrogenase (LDH), and ferritin. The preoperative investigations have been summarized in Table 1. A high-resolution computed tomography (CT) of chest was done to rule out any sequalae of COVID-19 pneumonia, which revealed small patchy ground glass opacities in the right lower lobe with no interstitial thickening, a CT score of 8/25. The patient and his family members were thoroughly explained regarding the unknown risks of SARS-CoV-2 and the possible impact on graft related outcome. After obtaining adequate consent from the patient as well as required clearances from a multi-disciplinary clinical team, it was decided to go ahead with transplantation procedure 23-days after recovering from COVID-19 disease.
Conduct of anesthesia was done as per our standardized institutional protocol. The dissection phase was complicated by profuse surgical bleeding owing to dense adhesions. Packed red cells were transfused aiming at a hemoglobin level of 9 gm/dl. Administration of platelets, plasma and cryoprecipitate was based on the thromboelastogram (TEG) which was repeated 2-hourly. The intraoperative TEG readings are given in Table 2. Due to significant bleeding from dense perihepatic collaterals, recipient hepatectomy was done with porta-first approach, prolonging the anhepatic time. Despite significant bleeding, and prolonged anhepatic time of 4-hours, it was noticed that the patient maintained a hypercoagulable TEG throughout the surgery, as evidenced by a coagulation index value of more than +3. A total of 20 packed red cell units and 8 units of fresh frozen plasma were transfused intraoperatively. He received the modified right lobe graft (right lobe without middle hepatic vein), and segment 5 and segment 8 veins were reconstructed using a PTFE graft to fashion a neo-middle hepatic vein. Graft implantation was uneventful with standard hepatic vein and portal vein anastomoses. Graft had a single artery which was anastomosed with recipient's right hepatic artery (which originated from common hepatic artery) using interrupted 8-0 prolene sutures. There was no tension, redundancy, or luminal discrepancy in arterial anastomosis. Recipient's left hepatic artery originated from left gastric artery (replaced left gastric artery- type 2 anatomy) and was ligated. The rest of the surgery was uneventful and the patient was shifted to the post-transplant intensive care unit for further management.
Inotropic support was weaned off and the patient was extubated on the 2nd post-operative day. Post-operative antibiotic therapy included cefoperazone-sulbactum, teicoplanin, metronidazole and fluconazole. Low dose immunosuppression was started on the evening of first post-operative day using tacrolimus and mycophenolate mofetil along with tapering doses of methylprednisolone which was later changed to oral prednisolone. Patient tolerated the incremental doses of immunosuppression well which was tailored according to the patients LFT’s and tacrolimus trough levels. As per our standard anticoagulation protocol (discussed later), he did not receive heparin infusion during or in immediate postoperative period due to deranged prothrombin time – international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ratio, both being more than 2, although all postoperative TEGs remained normal to hyper-coagulable.
Anticoagulation was started from 3rd post-operative day in the form of low molecular weight heparin and was discontinued on the 10th post-operative day when aspirin 75-mg once daily was initiated. Early post-operative course was satisfactory with near normalization of liver enzymes by the 7th day post transplantation. As per the protocol at our center, ultrasound doppler of liver graft were done twice daily for first five postoperative days and then once daily from sixth to tenth postoperative day; all doppler studies revealed normal inflows and outflows, homogenous graft and no intra-hepatic biliary dilatation.
While patient's liver function tests showed recovery as expected, a repeat doppler done on the 14th day of transplantation revealed absent hepatic arterial flow. A CT angiography of liver was done immediately which confirmed hepatic artery thrombosis (HAT). Digital subtraction angiography guided thrombolysis/thrombectomy was attempted but was unsuccessful. The patient was taken for emergency re-exploration. Intra-operatively, the graft was homogenous with no signs of ischemia. Graft artery had no visible or palpable pulsations. The arterial anastomosis was disassembled. A fleshy thrombus was present in the recipient artery extending to the root of common hepatic artery. Thrombectomy of the right hepatic artery was done using a 2-Fr Fogarty catheter. Vascular patency was satisfactory after the procedure and he was shifted to the intensive care unit and started on low molecular weight heparin for anticoagulation. Immediately post-exploration, his liver enzymes increased, which started coming down the subsequent days. Unfortunately, he again developed HAT on the 18th day of transplantation (4 days after re-exploration). He was taken up for a re-exploration. Thrombectomy was done and an autologous saphenous vein graft was used as conduit to anastomose the graft hepatic artery with left gastric artery. In view of recurrent HAT, it was decided to initiate him on hyperbaric oxygen therapy. He received a total of 4 cycles of hyperbaric oxygen therapy which were uneventful. By the end of 27th day post-transplant, he had near normalization of LFTs, normal inflows and outflows of the graft and hence he was discharged on the 30th post-operative day continuing low molecular weight heparin and with advices for a strict follow-up.
On the 18th day post discharge, he presented to our hospital with complaints of fever and chills. Abdominal imaging revealed presence of a cholangiolar abscess (Figure 1) with absent hepatic artery flow yet again. He was admitted & initiated on broad spectrum antibiotics. The blood investigations revealed leukocytosis and transaminitis (Table 1). Initially, he was managed with percutaneous drainage of the major abscesses. However, with persistent transaminitis and graft abscess, the patient and his family were counselled regarding the loss of graft and need for a retransplant after control of sepsis, to which he consented. Identifying and evaluating a new donor took us 2 weeks during which we were able to control his infection. He was taken up for re-transplantation 70 days after the initial transplantation.
Surgery for re transplantation was eventful, requiring massive blood transfusion and inotropic support. Once in the ICU, we encountered great difficulty in weaning him off inotropes due to persistent vasoplegia as evidenced by the cardiac output monitor and echo cardiogram. His liver enzymes and bilirubin started increasing by the 3rd post-operative day following a brief period of 2 days where the enzymes seemed to touch baseline. As there were no signs of infection or any vascular & biliary complication, we decided to treat it as acute cellular rejection using steroid pulses and antithymocyte globulin after performing a liver biopsy.
His clinical condition failed to improve with further worsening of hemodynamics & Liver function tests. His liver biopsy revealed centrilobular necrosis with cholestasis and no evidence of inflammatory infiltrate. We rationalized the drugs and performed 2 cycles of plasmapheresis keeping in mind the possibility of acute cellular rejection along with drug induced liver injury. In spite of our best efforts his clinical condition deteriorated with development of multiorgan failure. He suffered an irreversible cardiac arrest 80 days after the initial surgery.