Liver Transplant
Page updated spring 2021.
Disclaimer: Medicine is an ever-changing science. We have been witnessing changes in diagnostic and therapeutic modalities and guidelines during last several years. We have used official sources or sources believe to be reliable for purpose of this webpage. However, due to possibility of human error or changes in medicine, readers are required to confirm the information provided in this website with other sources. Readers are specially required to read all parts of the product information sheet included in the package of each drug they plan to administer and follow those instructions. Readers are also needed to follow instructions of FDA and other regulatory bodies and their own department in this regard. Doses need to be adjusted per manufacturer and FDA publications. This website serves as a general framework. We and other users would adjust the approach per departments policies and patients situation.
MELD Score
Eligibility age: At least 12 years old
Ranges from 6 to 40
Per OPTN policies, median MELD at transplant (MMaT) is calculated by using the median of the MELD scores at the time of transplant of all recipients at least 12 years old who were transplanted at hospitals within 250 nautical miles of the candidate’s listing hospital ina prior 365 day period.
Per OPTN policies, the MMaT and MPaT calculations exclude recipients who are either of the following: 1. Transplanted with livers from living donors, DCD donors, and donors from donor hospitals more than 500 nautical miles away from the transplant hospital 2. Status 1A or 1B at the time of transplant.
MELD or PELD Score Exceptions
Per OPTN policies:
Cholangiocarcinoma (CCA)
Cystic fibrosis
Familial amyloid polyneuropathy
Hepatic artery thrombosis
Hepatopulmonary syndrome
Metabolic disease
Portopulmonary hypertension
Primary hyperoxaluria
Hepatocellular Carcinoma
HCC Exception
Per OPTN policies:
Candidates with T2 HCC lesions are eligible for a standardized MELD or PELD exception if they have an alpha-fetoprotein (AFP) level less than or equal to 1000 ng/mL and either of the following:
One lesion greater than or equal to 2 cm and less than or equal to 5 cm in size.
Two or three lesions each greater than or equal to 1 cm and less than or equal to 3 cm in size.
For lesions Eligible for Downstaging Protocols, refer to OPTN policies.
For requirements for MELD or PELD Score Exceptions for each of above conditions, refer to OPTN policies.
Adult Status 1A
Per OPTN policies, the candidate’s transplant program may assign the candidate adult status 1A if all the following conditions are met:
1. The candidate is at least 18 years old at the time of registration
2. The candidate has a life expectancy without a liver transplant of less than 7 days and has at least one of the following conditions:
a. Fulminant liver failure
Defined as the onset of hepatic encephalopathy within 56 days of the first signs or symptoms of liver disease. In addition, the candidate:
i. Must not have a pre-existing diagnosis of liver disease. For purposes of this section, any diagnoses of liver disease that occurred prior to a subsequent liver transplant do not constitute pre-existing liver disease.
ii. Must currently be admitted in the intensive care unit
iii. Must meet at least one of the following conditions:
1. Is ventilator dependent
2. Requires dialysis, continuous veno-venous hemofiltration (CVVH), or continuous veno-venous hemodialysis (CVVHD)
3. Has an international normalized ratio (INR) greater than 2.0
b. Anhepatic
c. Primary non-function of a transplanted whole liver within 7 days of transplant
With aspartate aminotransferase (AST) greater than or equal to 3,000 U/L and at least one of the following:
International normalized ratio (INR) greater than or equal to 2.5
Arterial pH less than or equal to 7.30
Venous pH less than or equal to 7.25
Lactate greater than or equal to 4 mmol/L
All laboratory results reported for the tests required above must be from the same blood draw taken 24 hours to 7 days after the transplant.
d. Primary non-function within 7-days of transplant of a transplanted liver segment from a deceased or living donor
Evidenced by at least one of the following:
INR greater than or equal to 2.5
Arterial pH less than or equal to 7.30
Venous pH less than or equal to 7.25
Lactate greater than or equal to 4 mmol/L
e. Hepatic artery thrombosis (HAT) within 7-days of transplant
With AST greater than or equal to 3,000 U/L and at least one of the following:
INR greater than or equal to 2.5
Arterial pH less than or equal to 7.30
Venous pH less than or equal to 7.25
Lactate greater than or equal to 4 mmol/L
All laboratory results reported for the tests required above must be from the same blood draw taken 24 hours to 7 days after the transplant.
f. Acute decompensated Wilson’s disease
Immunosuppression
Per EASL guidelines, induction agents are safe when used together with CNIs, allowing a reduction of CNI dose especially in patients with pre-transplant renal impairment.
Per EASL guidelines, IL-2R antibodies with delayed and low dose Tacrolimus plus MMF and steroids is safe and significantly improves renal function after liver transplant.
Per EASL guidelines, CNI-based immunosuppression is still the cornerstone of immunosuppressive regimens in liver transplant.
Per EASL guidelines, MMF in combination with CNI reduction of at least 50% is associated with significant improvement in renal function and it has a low risk of acute rejection.
Per AASLD guidelines, the reduction or withdrawal of calcineurin inhibitor (CNI)-associated immunosuppression is an appropriate response to the development of chronic kidney disease (CKD) in LT recipients.
Per EASL guidelines, conversion to Sirolimus can be done safely and provide adequate immunosuppression without increased incidence of rejection, graft loss or infection in liver transplant recipients
CMV Prophylaxis
Per EASL guidelines, CMV prophylaxis for at least 3 months should be used in patients at a higher risk of developing CMV infection.
Per AASLD guidelines, prophylaxis against cytomegalovirus (CMV) should be resumed whenever LT recipients receive anti-lymphocyte therapy for the treatment of rejection and should be continued for 1 to 3 months after the treatment of rejection.
PCP Prophylaxis
Per EASL guidelines, prophylaxis against P. jirovecii with trimethoprim-sulphamethoxazole should be given to all liver transplanted patients for 6-12 months.
Candida prophylaxis
Per EASL guidelines, oral prophylaxis against Candida species is recommended during the first months, as it reduces mortality due to fungal infection.
Surgical Complications
Impaired coagulation
Per EASL guidelines, in patients with impaired coagulation, a temporary packing of 48 hours may be necessary.
Biliary anastomosis leakage
Per EASL guidelines, if a biliary anastomosis leakage in the post-transplantation period is diagnosed, initial ERCP with sphincterotomy is recommended. If the leakage persists, a temporary biliary stent can be used.
Hepatic artery thrombosis
Per EASL guidelines, it is necessary to prevent hepatic artery thrombosis during LT and post-operative period. The occurrence of this complication requires retransplantation in 50% of cases.
Per AASLD guidelines, Hepatic artery thrombosis (HAT) or stenosis is most readily assessed initially by Doppler ultrasound, but angiography is usually required to confirm the diagnosis and plan therapy.
Ischemic cholangiopathy
Per EASL guidelines, in advanced cases of ischemic cholangiopathy, the final treatment is retransplantation.
Stenosis of the biliary anastomosis
Per EASL guidelines, in cases of stenosis of the biliary anastomosis without improvement after conservative treatment, it is recommended to perform a hepatico-jejunostomy.
Acute Rejection
Per AASLD guidelines, rejection can be reliably diagnosed only on the basis of liver histology; a biopsy sample should be taken before treatment initiation and classified according to the Banff criteria.
Per AASLD guidelines, in mild cases of cellular rejection, an increase in maintenance levels of immunosuppression may be sufficient, whereas in histologically moderate or severe cases, the treatment should be a short course of increased immunosuppression (eg, methyl prednisone at 500 mg/day or prednisolone at 200 mg/day for 3 days) followed by an increase in the baseline immunosuppression.
Recurrent Liver Disease
Per EASL guidelines, all patients with a prior diagnosis of alcoholic liver disease should be encouraged to remain abstinent from alcohol after LT.
Per EASL guidelines, liver biopsy may be required to confirm recurrent or de novo NAFLD/NASH and to exclude other causes of elevated biochemical liver tests. No specific recommendation regarding prevention and treatment of NAFLD and NASH in LT recipients can be made, except to avoid excessive weight gain and to control diabetes, dyslipidaemia and arterial hypertension.
Per EASL guidelines, recurrent autoimmune and cholestatic liver disease should be confirmed by liver biopsy and/or cholangiography (PSC). There is no evidence for prophylactic use of ursodeoxycholic acid in patients transplanted for PBC and PSC.
PTLD
Per EASL guidelines, PTLD should always be suspected in liver transplanted patients, especially those at high risk, presenting with fever, weight loss, night sweats, and even in the absence of lymphoadenopathy.
Hepatitis C Infection
Per AASLD guidelines, antiviral treatment is recommended for all adults with acute or chronic HCV infection, except those with a short life expectancy that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy.
Per AASLD guidelines, patients with a Model for End-Stage Liver Disease (MELD) score >20 or severe portal hypertension complications may be less likely to improve and might be better served by transplantation than antiviral treatment.
Per AASLD guidelines, real-world data comparing direct-acting antiviral (DAA) response rates demonstrate that patients with cirrhosis and hepatocellular carcinoma (HCC) have lower SVR rates than cirrhotics without HCC.
Antiviral treatment will be given after liver transplant, if it is not given already.
Organ Transplantation From HCV Viremic Donors to HCV (-)Recipients
Informed consent should be taken.
Transplant centers should have a programmatic strategy for this option.
Treatment of HCV(-) recipient of Allograft from HCV viremic donor
Per AASLD guidelines, prophylactic/preemptive DAA therapy with a pangenotypic regimen is recommended.
Options:
Mavyret -an 8-week course of the pangenotypic daily fixed-dose combination of glecaprevir (300 mg)/ pibrentasvir (120 mg) is recommended.
Epclusa -A 12-week course of the pangenotypic daily fixed-dose combination of sofosbuvir (400 mg)/ velpatasvir (100 mg) is recommended.
Harvoni- A 12-week course of the daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) is recommended for patients with genotype 1, 4, 5, or 6 only.
Hepatitis B Infection- Decompensated Cirrhosis
Per AASLD guidelines, HBs Ag positive adults with decompensated cirrhosis should be treated with antiviral therapy indefinitely regardless of HBV DNA level, HBeAg status, or ALT level to decrease risk of worsening liver-related complications. Entecavir and tenofovir (TDF) are recommended drugs.
Liver Transplant Recipients With Hepatitis B
Per AASLD guidelines, all HBsAg-positive patients undergoing liver transplantation should receive prophylactic therapy with nucleos(t)ide analogues (NAs) with or without HBIG posttransplantation regardless of HBeAg status or HBV-DNA level pretransplant.
Per AASLD guidelines, HBIG monotherapy should not be used.
Per AASLD guidelines, entecavir, and tenofovir (TDF, and TAF) are preferred antiviral drugs because of their low rate of resistance with long-term use.
Per AASLD guidelines, HBIG for 5-7 days or no HBIG is reasonable in low-risk patients.
Per AASLD guidelines, combination antiviral therapy and HBIG may be the best strategy for those at highest risk of progressive disease posttransplantation, such as HDV and HIV coinfected patients. Nonadherent patients may benefit from combination prophylaxis with HBIG plus antivirals. Prophylactic therapy should be lifelong.
HBsAg Negative Patients Receiving anti-HBc Positive grafts
Per AASLD guidelines, all HBsAg negative patients who receive HBsAg negative but anti-HBc–positive grafts should receive long-term antiviral therapy to prevent viral reactivation. Although lamivudine has been used successfully in this scenario, entecavir, TDF, and TAF are preferred choices. Prophylactic therapy should be lifelong.
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