Like all transplant recipients, patients who have received a liver transplant have complex and unique medical needs. Physicians who are following these patients must be proactive about preventative care, recognize potential complications and manage any post-transplant conditions that develop.
Not surprisingly, the American Society of Transplantation and the American Association for the Study of Liver Diseases (AASLD) recommends COVID-19 vaccination for all transplant recipients.
The AASLD recommends vaccination at least three months post-transplant. Given the potential lethality of infection, vaccination of the liver transplant recipient, as well as their family members and other close contacts, should occur relatively quickly. However, COVID-19 vaccine response rates are suboptimal in immunosuppressed patients, at about 50 percent after the second vaccine dose. As a result, on August 12, the FDA amended the emergency use authorizations for both the Pfizer-BioNTech and Moderna COVID-19 vaccines to allow for the use of an additional dose in certain immunocompromised individuals, specifically, solid organ transplant recipients 28 days or later than the second vaccine dose.
“This action by the FDA gives us the option to boost immunity in some patients who need extra protection from COVID-19,” says Ranjeeta Bahirwani, MD, a transplant hepatologist on the medical staff at Baylor University Medical Center, part of Baylor Scott & White Health. “We expect patients will have a higher spike antibody response. But we don’t want patients to get a third dose, have a positive antibody test and then take off their masks and interact with people in a way that puts them at risk. We have to keep educating patients about the importance of risk reduction strategies.”
Other vaccine recommendations
Before COVID-19, the shingles vaccine was the talk of the town for many years. Many liver transplant recipients 50 and older, who are at higher risk of developing shingles, asked about it. But initially, most transplant centers recommended against it because the old version of the vaccine contained live virus, which the AASLD advises against. There was also concern that the adjuvant in the vaccine could increase the risk of rejection. Studies published in 2018 and 2019 after the introduction of the new inactivated shingles vaccine gave clinicians confidence in recommending it once patients are on a stable dose of immunosuppression.
In addition to the zoster vaccine, vaccines that are recommended for liver patients before transplantation include influenza, pneumococcus, hepatitis A and B, and DTaP, as well as HPV, especially among younger women. The two major vaccines recommended post transplant are a yearly influenza vaccine and the pneumococcal vaccine repeated every three to five years.
Immunosuppression: the dark side
Immunosuppression is a critical part of post-transplant care. However, like many other medications, immunosuppressive drugs can come with unwanted side effects that create their own set of medical issues. Physicians taking care of liver transplant recipients must be aware of the possible side effects, all of which require regular screening, monitoring and, often, treatment.
The use of corticosteroids can result in bone disease, hypercholesterolemia, diabetes and hypertension. Calcineurin inhibitors and mTOR inhibitors can cause kidney injury, hypercholesterolemia, diabetes (especially tacrolimus) and hypertension. The use of mTOR inhibitors may also contribute to the development of pulmonary fibrosis. Mycophenolate mofetil may lead to gastrointestinal issues and bone marrow suppression.
“Immunosuppressive drugs are powerful and their effects on the body can be significant,” Dr. Bahirwani says. “For example, the prevalence of metabolic syndrome in liver transplant recipients ranges from 50 to 60 percent, the prevalence of chronic kidney disease is 30 to 80 percent and the prevalence of hypertension is 40 to 85 percent. It is important to assess for and manage metabolic complications and adjust immunosuppression as cardiovascular comorbidities impact patient outcomes far more than graft loss in the long term.”
Screening for hepatocellular carcinoma
In the past 15 years, hepatocellular carcinoma (HCC) has increased significantly as an indication for liver transplant. Nationally, HCC accounts for approximately 30 to 35 percent of all liver transplants performed. HCC recurrence rates after transplant are less than 10 percent in well- selected patients.
Factors associated with HCC recurrence include:
- Large tumor burden
- Macrovascular invasion at explant
- Tumor rupture
- “Satellite” lesions
- Lymph node involvement
- Poor histologic differentiation
- Elevated alpha-fetoprotein or AFP (> 500 ng/ml)
Surveillance of high-risk patients for recurrence is crucial. At Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, patients considered to be high risk receive post-transplant surveillance imaging with a chest CT and MRI at six months, one year and two years in addition to serum AFP levels.
As a result of immunosuppression, liver transplant recipients have a high incidence of non- melanoma skin cancer. All liver transplant recipients are recommended to have an annual assessment by a dermatologist post transplant to assess any cutaneous lesions.
Liver transplant recipients can experience many of the same dental problems as people in the general population. However, good dental hygiene is especially important for liver transplant recipients. Because of the immunosuppression, recipients can develop infections more easily, which can be a source of sepsis in the peri- and post-transplant setting.
Many transplant programs still provide antibiotic prophylaxis to liver and other transplant recipients prior to dental work. But the American Heart Association current infective endocarditis/valvular heart disease guidelines stipulate that antibiotics are only necessary if the patient is at increased risk of endocarditis due to prior endocarditis, prosthetic cardiac valves and certain forms congenital heart disease.
The American Society of Transplantation recommends that pregnancy should be delayed for at least one year after liver transplant. When pregnancy does occur, it should be at a time with stable allograft function, with maintenance immunosuppression and with good control of any medical complications, such as hypertension and diabetes. Pregnancy should be managed by a high-risk obstetrician in coordination with the patient’s transplant hepatologist.
Earlier data reported intrauterine growth retardation and premature delivery in transplant recipients; however, the largest data from the Transplant Pregnancy Registry International demonstrate favorable outcomes in patients on calcineurin inhibitor-based immunosuppression, the mainstay in transplant recipients.
According to a 2019 study of outcomes of pregnancy in liver transplant recipients published in Clinical Gastroenterology and Hepatology, a higher proportion of patients who conceived more than one year after liver transplantation had live births than of women who conceived before this time.
“Liver transplant outcomes have improved dramatically with the evolution of surgical technique and mastery of immunosuppression,” Dr. Bahirwani says. “Infectious complications and graft loss are uncommon; optimizing metabolic comorbidities and surveillance for malignancy are critical for successful long-term post-transplant care.”