SURGICAL COMPLICATIONS OF LIVER TRANSPLANTATION Maher Osman, MD, Ph.D National Liver Institute Menoufiya University

INTRODUCTION Liver Tx has evolved over the past 4 decades to be the standard treatment for patients with a variety of acute and chronic liver diseases. The living donor procedure was developed as a result of: The inevitable problem of organ shortage, The obvious success of reduced-size and split-liver innovations, Unacceptance of deceased donor transplantation because of cultural difficulties with the concept of brain death.

INTRODUCTION cadaveric The recipient operation for living donor procedures is identical to that of the deceased donor procedure, except that the recipient cava must be left in situ & a direct hepatic vein to vena caval anastomosis is used. Care must be taken to ensure that adequate recipient portal vein & hepatic artery are preserved. The biliary reconstruction can be either duct to duct or using a choledochojejunostomy. cadaveric

INTRODUCTION The technique of LDLTx has been hindered by three factors: The concern over donor safety (mortality ranges from 0.1 to 1% & morbidity from 10-20%). Inappropriate technique for profoundly ill patients (hepato-renal syndrome patients) or big body built recipients. Absence of backup re-transplantation whenever indicated. Despite these limitations, LDLTx has become a standard option for pediatric patients & for adult patients in areas where deceased donor livers are in short supply.

INTRODUCTION Postoperative complications following LTx are very common because of: The degree of preoperative debilitation, The complexity of the operative procedure, The additional burden of immunosuppression These complications have a significant impact on: Resource utilization Cost mortality

POSTOPERATIVE COMPLICATIONS CLASSIFICATION Extrahhepatic complications: Pulmonary (atelectasis, pleural effusion, etc) Neurologic (in about 12-20%) Renal Gastrointestinal complications: Postoperative bleeding Perforation Infectious complications: Bacterial Fungal viral

POSTOPERATIVE COMPLICATIONS CLASSIFICATION 4. Surgical complications: Hepatic artery stenosis Hepatic artery thrombosis Portal caval stenosis and thrombosis Inferior vena cava stenosis and obstruction Biliary complications (leak, stenosis, ampullary dysfunction) 5. Allograft-related complications: Primary non-function Acute cellular rejection

POSTOPERATIVE COMPLICATIONS GRADES Grade I: altered ideal postoperative course with recovery or easily controlled complications (ex. Steriod responsive rejection). Grade II: any complication that is potentially life-threatening or results in ICU stay greater than 5 ds or a hospital stay greater than 4 ws but does not result in residual disability or permanent illness ( ex. Infection, bleeding or primary graft dysfunction)

POSTOPERATIVE COMPLICATIONS GRADES Grade III: complications with residual or lasting functional disability or development of malignant disease (ex. Renal failure). Grade IV: complications that lead to retransplantation (IVa) or death (IVb).

SURGICAL COMPLICATIONS Hepatic Artery Stenosis (HAS) Develops in 4-5% of cases. Sonographic findings include: Resistive index of less than 0.5, Systolic acceleration , Increase in focal peak velocity. Angiographic diagnosis of HAS is by reduction in caliber by greater than 50% of the normal lumen. Management is according to the time of diagnosis.

SURGICAL COMPLICATIONS Hepatic Artery Stenosis (HAS) Early diagnosis: Direct arterial reconstruction, Reconstruction with placement of an infrarenal arterial conduit. Late diagnosis (> 1 m): Percutaneous hepatic angioplasty, Complications of angioplasty include: intimal dissection, arterial rupture, or pseudoaneurysm formation).

SURGICAL COMPLICATIONS Hepatic Artery Thrombosis (HAT) Occurs in 5-10% of liver transplants & is more common in children. Suspected clinically by: Elevated transaminases, Biliary problems. Diagnosed by: Doppler US, MRI Angiography (the gold standard)

SURGICAL COMPLICATIONS Hepatic Artery Thrombosis (HAT) Risk factors of HAT include: Anatomical Factors: Poor inflow due to celiac trunk atherosclerosis, Arcuate ligament compression, The need for reconstructive angioplasty in the presence of non standard donor anatomy, Technical Factors: Intimal dissection, Anastomotic stenosis. Other important Factors: Post-transplant acute rejection (within first week), Placement of CMV+ve organ into CMV –ve recipient, Donor smaller significantly than the recipient, History of smoking.

SURGICAL COMPLICATIONS Hepatic Artery Thrombosis (HAT) Routine ligation of the recipient gastroduodenal artery during implantation is important to prevent vascular steal phenomenon through the gastroduodenal artery away from the graft. The presentation of HAT is variable and depends on: The timing of its occurrence, The presence of collaterals. HAT in the 1st w post-transplant: Complete biliary stenosis, Graft failure, Thrombectomy is the treatment (successful in ½ of cases), intrarterial injection of urokinase & antibiotic for sepsis.

SURGICAL COMPLICATIONS Hepatic Artery Thrombosis (HAT) Late HAT( ms or ys) following LTx: Does not always lead to graft failure, Some patients develop biliary stricture &/or hepatic abscesses, Approximately a 1/3 of patients do well without intervention. The association between rejection and HAT may be the result of: Decrease in hepatic artery flow (the graft is swollen & edematous) The release of procoagulants into the microcirculation (inflammatory injury). Most centers recommend prophylactic aspirin to prevent HAT in children

SURGICAL COMPLICATIONS Portal Vein Thrombosis /Stenosis (PVT) Much less common than HAT, occurring in 1-3% ofcases Occurs more frequently in reduced-size LTx than in whole LTx because of the limited length of PV that can be obtained from the donor. Risk Factors include: Decreased PV inflow, The presence of portosystemic shunt before Tx, Previous splenectomy, Twisting or kinking of the vascular conduit, Tension in the PV interposition graft Previous splenorenal shunt should be disconnected at the time of LTx because it usually associated reduced flow through the PV.

SURGICAL COMPLICATIONS Portal Vein Thrombosis /Stenosis (PVT) Presentation & diagnosis: Symptoms & signs of portal hypertension, Doppler US (the first diagnostic tool), Mesenteric arteriography with portal phase view, Direct percutaneous transhepatic portography (PTP) (stenosis or thrombosis). Portal vein stenosis: PTP is useful to measure the pressure gradient across a stenotic area, Balloon dilatation is done via the PTP catheter (angioplasty), In case of restenosis & elastic stenosis a metallic stent can be used. Portal Vein thrombosis: Can be effectively treated by continuous injection of urokinase via the balloon catheter retained in the SMV. If identified in the immediate postoperative period, reexploration & attempted thrombectomy.

SURGICAL COMPLICATIONS Hepatic Vein Outflow Obstruction Occurs in 2-4% of patients. Restrictions of hepatic blood flow may result for kinking of the suprahepatic cava, which can be suspected when: the donor is small relative to the recipient, the suprahepatic anastomosis is left long. Hepatic V obstruction can present with: Ascites, Renal dysfunction, May be presented early in the 1st w after Tx or months later. The diagnosis can be suspected on the basis of: Doppler US, Inferior cavography. Hepatic vein stenosis responds very well to balloon dilatation

SURGICAL COMPLICATIONS Biliary Leak or Obstruction Common surgical complication after LTx with an incidence of 10-30%, & mortality rate of 10%. Mortality continues to be a significant problem in patients with biliary tract complications because of delay in diagnosis. The laboratory diagnosis depends on elevation in serum bilirubin, gamma-glutamyltransferase, & alkaline phosphatase levels.

SURGICAL COMPLICATIONS Biliary Leak or Obstruction Most biliary complications occur within the first 3 ms, with most leaks occurring in the 1st m after Tx & strictures developing later. The diff. diagnosis of elevations in the previous lab parameters include: Sepsis, Graft injury secondary to ischemia, Rejection. Primary imaging modalities used in diagnosis include: US to detect biliary dilatation, Cholangiography to evaluate for leaks or strictures, Cholescintigraphy using 99mTc-labelled hepatoiminodiacetic acid to look for leaks from the cut surface of the liver or from anastomosis.

SURGICAL COMPLICATIONS Bile Leaks Diagnosis: PTC, ERCP Etiologty: Anastomotic complications, Hepatic artery thrombosis, T-tube exit-site leaks, Leaks from the aberrant ducts, Leaks from the cut liver surface Management: T- tube exit-site leaks by endoscopic nasobiliary drainage, Intraperitoneal biloma be percutaneous drainage, Leaks after CD-J by operative intervention.

SURGICAL COMPLICATIONS Biliary Obstruction Etiology: Anastomotic causes, Hepatic artery stenosis or thrombosis, Recurring cancer or recurrent disease, Sequelae of ischemic injury. Management: Document hepatic artery patency Obstruction after CD-CD treated either by balloon dilatation & stenting or by conversion to CD-J. Stricture of CD-J treated by PTD or by surgical redo in refractory cases. Multiple diffuse IH strictures treated by PTC & drainage with either external or internal drainage and balloon dilatation or metallic stents.

SURGICAL COMPLICATIONS Hemorrhage Postoperative bleeding occurs in 7-15% of patients, and requires exploration in 50% of cases. The most sensitive indication of bleeding is lack of urine output (oliguria). In many patients a specific bleeding point cannot be identified at reoperation (coagulopathy rather than failure of hemostasis). The bleeding will cease spontaneously due to: Intrabdominal pressure, Restoration of normal synthetic function by the new liver .

SURGICAL COMPLICATIONS Hemorrhage Gastrointestinal bleeding can occur due to: GI-Ulcers, Viral enteritis, Portal hypertensive lesions, Roux-en-Y bleeds. Most episodes occur within the first 3 ms postoperatively. The occurrence of variceal bleeding after LTx is usually associated with PVT & mandates emergent US or angiography to document PV patency. Medical coagulopathy may worsen all episodes of bleeding and should be corrected. Thrombocytopenia is common after LTx and maybe due to: Splenic sequestration, Drug toxicity, Immunologic factors

SURGICAL COMPLICATIONS SUMMARY The cost and impact of early post-transplant complications continue to be high. Diagnosis and management involves a high index of suspicion, rapid diagnostic and therapeutic interventions, and eliminations of technical problems. Preoperative assessment of the donor and recipient medical condition and meticulous attention to detail during the performance of LTx are the mainstays in achieving a good outcome.