Indications for liver transplantation
Acute liver failure due to
Acetaminophen overdose
Idiosyncratic drug-induced liver injury
Acute fatty liver of pregnancy
Toxin exposure—Amanita phalloides (mushroom poisoning)
Acute viral hepatitis—hepatitis A–E, herpes simplex virus, Epstein–Barr virus, cytomegalovirus
Decompensated liver disease due to
Chronic viral hepatitis—hepatitis B, C
Alcoholic liver disease
Nonalcoholic fatty liver disease
Autoimmune hepatitis
Cholestatic liver disease—primary sclerosing cholangitis, primary biliary cirrhosis
Metabolic and genetic disorders
Wilson’s disease
Hemochromatosis
α1-Antitrypsin deficiency
Glycogen storage disease
Primary oxaluria
Familial amyloidosis
Urea cycle enzyme deficiencies
Tyrosinemia
Cystic fibrosis
Complications of chronic liver disease
Hepatocellular carcinoma
Cholangiocarcinoma
Hepatopulmonary syndrome
Portopulmonary hypertension
Vascular disorders
Budd–Chiari syndrome
Sinusoidal obstruction syndrome
The leading indication for LT in the USA is chronic hepatitis C virus (HCV) infection, now accounting for approximately 40 % of all recipients [12, 13]. In Europe, 36 % of graft recipients have alcoholic cirrhosis, slightly surpassing HCV as the primary indication for transplantation [4]. Rates of LT for HCV cirrhosis are expected to increase in the coming years as the HCV population ages [14]. It is estimated that as many as 30 % of adults in Western countries have nonalcoholic fatty liver disease (NAFLD), of which up to 12 % have nonalcoholic steatohepatitis (NASH), and this number is expected to increase in concert with rising rates of associated factors such as obesity and the metabolic syndrome [15, 16]. Accordingly, NASH-related cirrhosis is already the fourth most common indication for LT in the USA and is anticipated to become the leading indication for transplantation in the next 10–20 years [17, 18]. Patients with ALF receive priority listing for LT and account for approximately 10 % of the USA and European transplants [19].
Hepatocellular Carcinoma and Other Priorities in Organ Allocation
An increasing proportion of liver transplants are performed for patients with nonresectable hepatocellular carcinoma (HCC) [20]. Drawing on LT experiences in France, Spain, Germany, and Italy, excellent 5-year survival rates were shown for patients with a solitary HCC lesion ≤ 5 cm or with up to three nodules each ≤ 3 cm in size, which became known as the Milan criteria [21]. To mitigate the risk for tumor progression beyond Milan criteria, patients with HCC within Milan criteria may receive priority in organ allocation beyond their actual MELD score. Expansion of tumor burden limits beyond the Milan criteria has been proposed and implemented by several transplant centers without adversely impacting patient survival, but this practice has not been universally adopted [22]. Locoregional therapies such as chemoembolization and radiofrequency ablation are often used to downstage patients to within Milan criteria in order to facilitate listing for LT, but this practice is also controversial [23].
In addition to HCC, other etiologies may receive priority when the risk of death or drop-off from the waitlist is not accurately represented by the MELD score (e.g., hepatopulmonary syndrome (HPS)) [24]. Priority is also assigned for certain metabolic diseases with extrahepatic manifestations even when liver function is not compromised (e.g., primary hyperoxaluria, familial amyloidotic polyneuropathy) [24]. These livers can sometimes be used to replace the diseased liver of another patient in a sequential or so-called domino transplant [25]. At many transplant centers, there is a mechanism to petition for priority on a case-by-case basis.
Liver Transplant Evaluation
Formal evaluation for LT involves a multidisciplinary team approach to rigorously examine the need for transplantation and exclude medical, psychiatric, social, or financial factors that would limit successful recovery and survival (Table 27.2). Not all patients with compensated cirrhosis will require LT. Indeed, it has been shown that the survival benefit associated with LT is greatest among those with the highest risk of pre-transplant death [26]. Accordingly, patients should be referred for formal transplant evaluation once there is evidence of hepatic decompensation resulting in an MELD score ≥ 15 or the development of an index complication, such as ascites , HE, or variceal hemorrhage [11].
Table 27.2
Evaluation for liver transplantation
Evaluation for liver transplantation |
|---|
Medical evaluation |
Determine/confirm etiology of liver disease |
Explore medical management options |
Evaluate medication adherence history |
Assess functional status and exercise tolerance |
Laboratory evaluation |
Assess hepatic and renal function |
Exclude alternative or concomitant causes of liver disease |
Perform infectious disease workup: testing for viral hepatitis, cytomegalovirus, human immunodeficiency virus, syphilis, tuberculosis |
Radiographic evaluation |
Doppler ultrasonography to document hepatic vascular anatomy and portal venous system patency |
Consider contrast-enhanced computed tomography or magnetic resonance imaging to assess for and characterize any hepatocellular carcinoma or cholangiocarcinoma |
Cardiopulmonary evaluation |
Plain chest film |
Noninvasive evaluation with electrocardiogram and 2D echocardiography |
Pharmacological stress testing, consider coronary angiography for patients with cardiac risk factors |
Consider pulmonary function testing for patients with signs, symptoms, or a known history of chronic lung disease |
Age-appropriate cancer screening |
Colonoscopy for patients with age ≥ 50 years or a history of primary sclerosing cholangitis |
Pap smear for females sexually active > 3 years or age ≥ 21 years |
Mammogram for females with age ≥ 50 years |
Prostate-specific antigen level measurement for males with age ≥ 40 years |
Surgical consultation |
Identify factors that may complicate transplantation, such as morbid obesity, prior abdominal surgery, extensive portal venous thrombosis, or generalized deconditioning |
Social work evaluation |
Ensure adequate social support and identify any potential social or financial barriers to transplantation |
Additional case-specific assessments |
Psychiatric consultation to assess for substance abuse disorders or untreated psychiatric comorbid illnesses |
Dental assessment for patients with poor dentition |
Anesthesia evaluation for patients with high perioperative risk |
Nutritional assessment if nutritional needs or problems identified |
Renal Dysfunction
Acute and chronic kidney injury in patients with cirrhosis is associated with a poor prognosis. Outcomes vary by etiology, and patients with hepatorenal syndrome, particularly type I, have the worst survival [27, 28]. The majority of patients with good baseline renal function will remain without renal dysfunction following transplantation [29]. MELD-based allocation has resulted in an increase in simultaneous liver–kidney transplantation (SLK) [30]. Guidelines for SLK continue to evolve in response to the growing number of LT candidates with renal dysfunction and the ongoing organ shortage (Table 27.3) [31].
Table 27.3
Criteria for simultaneous liver–kidney transplantation
Criteria for SLK transplantation |
|---|
1. Persistent AKI for ≥ 4 weeks, with one of the following: |
(a) stage 3 AKI as defined by modified RIFLE (threefold increase in serum Cr from baseline, serum Cr ≥ 4 mg/dL with an acute increase ≥ 0.5 mg/dL or on renal replacement therapy) |
(b) estimated GFR ≤ 35 mL/min or GFR ≤ 25 mL/min by iothalamate clearance, and |
2. CKD for 3 months, with one of the following: |
(a) estimated GFR ≤ 40 mL/min or GFR ≤ 30 mL/min (iothalamate clearance) |
(b) proteinuria ≥ 2 g daily |
(c) kidney biopsy showing > 30 % global glomerulosclerosis or > 30 % interstitial fibrosis |
(d) metabolic disease |
Coronary Artery Disease
Coronary artery disease (CAD) rates among LT candidates are comparable to those of the general population [32], and graft recipients with CAD may have a postoperative mortality rate as high as 50 % at 1 year [33]. All transplant candidates should undergo cardiac evaluation, including electrocardiogram and transthoracic echocardiography. Noninvasive cardiac stress testing, including pharmacological stress echocardiography or nuclear medicine imaging, should be considered for all LT candidates on the basis of CAD risk factors, followed by cardiac catheterization if indicated [34]. Noninvasive cardiac testing to screen for CAD has limited sensitivity in cirrhotics and coronary angiography should be performed in candidates with significant cardiac risk factors [35]. Coronary revascularization should be considered in patients with significant coronary artery stenosis [11].
Age
The average age of graft recipients has increased steadily during the past decade [3, 4]. Overall, data do not support exclusion from LT on the basis of age alone, as favorable outcomes have been observed among recipients aged 70 years or older [36]. This may be in large part due to better selection of patients and exclusion of patients with significant comorbid illnesses or poor functional status.
Obesity
In parallel with the increasing prevalence of obesity in the general population, the proportion of transplant recipients with obesity continues to increase [3]. Obesity is associated with increased perioperative morbidity and mortality after major surgical procedures [37]. Among LT recipients, obesity is associated with significantly increased cardiovascular mortality with a higher prevalence of graft nonfunction and poorer 5-year survival rates [37]. In many centers, a BMI ≥ 40 kg/m2 is a relative contraindication to LT and should only be pursued in carefully selected cases. All obese patients require diet and counseling regarding weight loss. Concomitant bariatric surgery with LT has been performed successfully in a small number of obese patients with decompensated cirrhosis, but this approach requires careful planning and considerable surgical expertise [38].
Hepatopulmonary Syndrome
LT improves survival in patients with HPS, with 5-year survival rates nearly three times greater among liver allograft recipients compared to patients who are not transplanted [39]. Moreover, LT reverses HPS in nearly all patients who survive more than 6 months, and for these reasons, patients with HPS are often granted priority in LT allocation [40]. All potential transplant recipients should be screened for HPS using pulse oximetry , with further evaluation using arterial blood gases and agitated saline contrast echocardiography in those with hypoxemia [41].
Portopulmonary Hypertension
All patients evaluated for LT must be screened for portopulmonary hypertension (POPH) by echocardiography given the increased perioperative mortality associated with moderate-to-severe POPH [42]. Patients with elevated Doppler-estimated pulmonary artery systolic pressure should undergo right heart catheterization. Posttransplant mortality increases dramatically with increasing mean pulmonary artery pressure (MPAP), approaching 100 % in patients with severe POPH (MPAP ≥ 45 mmHg) [43]. As such, severe POPH is an absolute contraindication to LT, and patients with moderate POPH (MPAP 35–44 mmHg) should be considered for pulmonary vasodilator therapy. POPH does not necessarily resolve following LT and many patients may require chronic pulmonary vasodilator therapy posttransplant [44, 45].
Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) infection was once considered a contraindication to LT; however, more recently, LT in HIV-infected individuals has resulted in acceptable graft and patient survival rates [46]. An increased rate of HIV-related complications or rapid HIV disease progression has not been observed, but antiretroviral and immunosuppressant medication adjustments are frequently needed to manage complex drug interactions and side effects [47]. Poor outcomes have been observed among HIV patients coinfected with HCV, particularly among patients with low BMI and the need for SLK transplantation [46]. LT in HIV recipients is primarily pursued at centers with expertise in the care of HIV patients.
Patient Outcomes and Postoperative Complications
Donor Selection
Ideal deceased liver donors are young, previously healthy persons who meet criteria for brain death. Generally speaking, there are few absolute medical contraindications to organ donation apart from malignancy and the presence of transmissible infections that can adversely affect the recipient. Donor factors associated with adverse posttransplant outcomes include advanced age, female sex, donor–recipient gender mismatch, moderate-to-severe hepatic steatosis, hypernatremia, and prolonged circulatory shock. Technical factors, such as cold ischemia time and donor–recipient ABO mismatch, also impact graft viability. In response to the significant organ shortage, several important boundaries to graft utilization have been successfully overcome, including the use of HCV-positive donors in HCV-positive recipients, HIV-positive donors in HIV-positive recipients, and the use of non-heart-beating (donation after cardiac death) donors [48]. The donor risk index, developed using data derived from over 20,000 transplants, can aid physicians in selecting appropriate donors [49].
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