Liver transplantation complications

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Liver trasnsplantation Microchapters
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Patient Information
Overview
Historical Perspective
Indications
Pre-surgical management
Choice of donor
Epidemiology and Demographics
Techniques
Complications
Acute rejection
Immune therapy
Post-surgical infection
Prognosis

Overview

Complications of liver transplantation include vascular, biliary, and immunosuppression drugs complications. Hepatic artery complications include thrombosis, stenosis, and pseudoaneurysm. IVC complications include thrombosis and stenosis, usually at the site of surgical anastomosis. Biliary complications include stenosis, fistula, obstruction, stone formation, dysfunction of the Oddi sphincter, and recurrent biliary disease. Complications of immunosupression include infections, metabolic syndrome, hypertension, diabetes mellitus, obesity, dyslipidemia, coronary heart disease, acute and chronic renal disease, metabolic bone disease, and malignancy.

Post-surgical complications

Vascular Disorders

Hepatic Artery

• Hepatic artery complications include thrombosis, stenosis, and pseudoaneurysm.
• A normal hepatic artery waveform obtained at the porta hepatis does not exclude a hepatic artery obstruction.

Thrombosis

• The incidence of hepatic artery thrombosis is 4%–12% in adults and 42% in children.
• The mortality rates are 30% due to fulminant hepatic necrosis.
• Arterial thrombosis may lead to biliary necrosis.
• Most cases require retransplantation.
• Gadolinium-enhanced MR imaging is an accurate and noninvasive method for evaluating the hepatic vessels.

Stenosis

• Hepatic artery stenosis incidence rates are 5%–11% of liver transplant recipients.
• This complication usually occurs at the site of anastomosis within 3 months after transplantation.
• Causes of hepatic artery stenosis may include injury from a perfusion catheter, or disruption of the vasa vasorum with resultant ischemia of the arterial ends.
• Doppler US is the method of choice for postoperative screening of liver transplant recipients because it is capable of depicting any focal increase in peak systolic velocity at the site of stenosis and any poststenotic turbulent flow.
• Both at contrast-enhanced CT and at MR angiography, this arterial lesion appears enhanced.

Portal Vein

• Portal vein thrombosis occurs in about 1%–2% of cases.
• It most commonly results from technical problems (vessel misalignment, differences in the caliber of the anastomosed vessels, or stretching of the portal vein at the anastomotic site), previous portal vein surgery or previous thrombosis, increased downstream resistance due to a supra-hepatic stricture of the inferior vena cava (IVC), decreased portal inflow, and hypercoagulable states.
• Portal vein stenosis has a reported incidence of 1% after liver transplantation.
• The treatment in symptomatic cases is thrombolysis or surgery (thrombectomy, venous graft)
• CT and MR angiography provide excellent depiction of filling defects and focal narrowing of the portal vein.
• Transhepatic or transjugular portography may be necessary to achieve a definitive diagnosis.

Inferior Vena Cava (IVC)

• IVC complications include thrombosis and stenosis, usually at the site of surgical anastomosis.
• The anastomosis gained wide acceptance internationally and is the preferred technique for orthotopic liver transplantation at many institutions.
• However, it is especially vulnerable to two types of complications:
• Hemorrhage due to hepatic injury during surgery
• Budd-Chiari syndrome due to inadequate venous drainage
• An obstruction of hepatic venous outflow may be treated with placement of a balloon-expandable stent.
• Cross-sectional modalities such as CT and MR imaging are commonly used to confirm suspicions aroused by doppler US findings.

Biliary Disorders

• Biliary complications include stenosis, fistula, obstruction, stone formation, dysfunction of the Oddi sphincter, and recurrent biliary disease.
• MR cholangiography is the best noninvasive technique for evaluation of the biliary tree. It does not provide a means of therapeutic intervention, it can be used for percutaneous, endoscopic, and surgical treatments.
• Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography provide high-quality images of the biliary tree and allow therapeutic intervention.

Obstruction and Stenosis

• Obstruction is the most common biliary complication both in adults and in pediatric patients and is frequently caused by stenosis at the anastomotic site.
• Anastomotic strictures usually result from fibrotic proliferation with narrowing of the biliary lumen less frequently, they are due to ischemia caused by hepatic artery thrombosis or stenosis.
• The possible causes of nonanastomotic strictures include pretransplantation biliary diseases such as primary sclerosing cholangitis, biliary ischemia, and infection.
• Some patients with clinical and biochemical evidence of biliary obstruction may have dilatation of both the donor and the recipient bile ducts.
• Diffuse ductal dilatation may result from papillary dyskinesia due to devascularization or denervation of the papilla of Vater during transplantation.

Bile Leak

• The incidence of bile leaks in liver transplant recipients is 5%.
• Bile leaks usually occur in more than 70% occur within the 1st postoperative month.
• Leaks occur most often at the T-tube site.
• Bile may leak freely into the peritoneal cavity or may form a perihepatic collection.
• Treatment includes stent placement and drainage of collections.

Ductal Ischemia

• Bile duct ischemia is usually a consequence of stenosis or thrombosis of the hepatic artery; the bile ducts are entirely dependent on the hepatic artery for their blood supply.
• This leads to necrosis, bile leak, fibrosis, and bile collection.
• A ductal stenosis may be treated with balloon dilation, which frequently is used in drainage procedures.
• However, in most cases, retransplantation ultimately is necessary.

Fluid Collections

• Seromas and hematomas are commonly observed near areas of vascular anastomosis and biliary anastomosis.
• Pleural fluid also is a common finding.
• US is highly sensitive for the detection of fluid collections, it is not specific.
• CT and MR imaging are more useful for differentiating hematomas from seromas because blood has higher attenuation at CT than do other fluids.
• The other role of imaging is to guide interventional diagnostic or therapeutic procedures.

Complications of immunosupression

Infections

• The leading cause of mortality following liver transplantation is infection.
• Serious infections occur most frequently within the first three months post-transplantation.

Metabolic syndrome

• The metabolic syndrome is common among patients who have undergone liver transplantation.
• It is defined by a combination of hypertension, insulin resistance, dyslipidemia, and obesity.
• Liver transplant recipients may meet criteria for the metabolic syndrome prior to transplantation, in which case immunosuppressive medications can exacerbate the problem.
• In addition, many patients will develop the metabolic syndrome de novo.
• Fifty-two percent had metabolic syndrome following transplantation, compared with only 5 percent prior to transplantation.
• The rate of obesity increased from 24 percent four months after transplantation to 41 percent three years after transplantation.

Immunosuppressant use is associated with all aspects of the metabolic syndrome:

• Hypertension: Glucocorticoids, cyclosporine, tacrolimus
• Diabetes mellitus: Glucocorticoids, tacrolimus, cyclosporine
• Obesity: Glucocorticoids, cyclosporine
• Dyslipidemia: Glucocorticoids, cyclosporine. tacrolimus, sirolimus

Hypertension

• Approximately 65 to 70 percent of liver transplant recipients develop hypertension following transplantation.
• Patient's blood pressure be assessed at home with self-monitoring every week for six months after the surgery.
• The cause of hypertension is multifactorial but is mostly related to the use of calcineurin inhibitors and glucocorticoids.

Diabetes mellitus

• Glucocorticoids, cyclosporine, tacrolimus, and weight gain predispose to the development of diabetes following liver transplantation.
• The risk also appears to be increased in patients transplanted for hepatitis C virus.
• Fasting plasma glucose levels or hemoglobin A1C are sceened every six months and annual eye examinations to look for cataracts or diabetic changes.

Obesity

• Over one-third of patients after liver transplantation are obese.
• Approximately one-third of patients who are normal weight at the time of transplantation will become obese following transplantation.
• Body weight tends to increase during the first two years after transplantation and then stabilizes.

Dyslipidemia

• Dyslipidemia is common after liver transplantation.
• Hypertriglyceridemia usually develops within the first month post-transplantation and then remains stable throughout the first year.
• Serum cholesterol increases gradually and plateaus at six months.
• Patients should have a fasting lipid profile obtained annually.

Cardiovascular risk

• Coronary heart disease is common after liver transplantation.
• Ten-year risk of cardiovascular events was 14 percent and was particularly high among those with the metabolic syndrome.
• Factors that have been associated with cardiovascular events include older age at transplantation, male sex, post-transplantation diabetes, post-transplantation hypertension, history of coronary artery disease, and use of mycophenolate mofetil.

Acute and chronic renal disease (CNI)

• Acute and chronic kidney injuries are common in liver transplantation.
• Important contributing factors are preexisting chronic kidney disease, renal failure prior to liver transplantation, acute tubular necrosis around the time of transplantation, hypertension, and diabetes mellitus.
• CNI-related acute renal failure is due to renal vasoconstriction and improves with dose reduction.
• Chronic renal disease can also be induced by these drugs, warranting continued monitoring of the plasma creatinine concentration and urinalysis.
• Nephrotoxicity in liver transplant recipients is more common with cyclosporine or tacrolimus.

Metabolic bone disease

• Bone mineral density is assessed prior to transplantation and every other year after transplantation to assess for osteoporosis.
• The majority of osteopenia and fractures occur within the first six months following transplantation, and fractures often involve the spine.
• Patients transplanted for cholestatic liver disease are particularly vulnerable to the development of osteoprosis before liver transplantation.

Malignancy

• The incidence of malignancy is increased in liver transplant recipients.
• Intensive screening than is done in the general population.