The American Association for the Study of Liver Diseases
(AASLD) has issued preliminary guidance for liver specialists on managing
COVID-19 in patients with liver disease, based on data published up to late
COVID-19 is the disease caused by SARS-CoV 2, the new
coronavirus identified in China in January 2020. SARS-CoV 2 causes a spectrum
of clinical illness ranging from mild symptoms (cough, fever) to severe
pneumonia, lung damage and death.
People with pre-existing health conditions including chronic
kidney disease, cardiovascular disease and chronic obstructive pulmonary
disease are at higher risk of developing serious illness that requires hospital
admission and ventilation.
A meta-analysis of the first 53,000 cases of COVID-19
reported in China, published in 30 studies since late January, found that
chronic liver disease was not associated with a higher risk of severe COVID-19
or death from the disease, although elevated liver enzymes (AST or ALT) were
more common in severe cases at the time of diagnosis.
AASLD convened an expert panel to review the available
evidence and compile clinical insights that can guide healthcare workers.
Liver enzymes elevations and liver injury
People with pre-existing liver disease were more vulnerable
to liver damage if infected with SARS, a related virus. Although it is
plausible that the same might hold true for the new coronavirus, there is little
evidence about its effects in people with liver disease, AASLD concludes.
The AASLD briefing notes that liver injury occurs more often
in severe COVID-19 cases and that liver enzyme elevations in mild COVID-19
cases have usually been transient. Elevated liver enzymes in patients with
Covid-19 should prompt testing for hepatitis B and C, AASLD suggests.
Experimental agents that are being tested as treatments for
COVID-19 may have liver toxicities. Although raised liver enzymes should not be
a bar to experimental use of these drugs, regular monitoring of liver enzymes
should form part of any experimental protocol for COVID-19 treatment.
In cases of suspected hepatocellular carcinoma or ongoing
treatment, specialists should try to minimise clinic visits for patients and
carry out virtual consultations. However, imaging should not be delayed too long;
two months might be reasonable, depending on the patient and facility.
Treatment for HCC should not be delayed.
People awaiting transplant
Limit the number of patients coming into clinics for
transplant evaluation and prioritise visits by those with hepatocellular
carcinoma or those with high MELD scores who are likely to benefit from
immediate listing. Try to move as much management of pre-transplant patients as
Consider RNA testing of recipient and donor when organs
become available. Try to test specimens from multiple sites to overcome lower
sensitivity of nasal and pharyngeal specimen testing. People who test positive
for SARS-CoV 2 are medically ineligible for organ donation.
Liver transplantation during the Covid-19 will be challenged
by a shortage of ICU beds. Nevertheless, liver transplants should still go
ahead, and services may need to prioritise the patients most likely to die on
the waitlist. It is not clear that immunosuppressed patients are at higher risk
for severe COVID-19 but they are known to be more likely to acquire SARS-CoV 2
and are more infectious and have higher viral titres than immunocompetent
people once infected with SARS-CoV 2. These factors need to be considered when
making decisions about immediate or deferred transplantation.
Post-transplant and immunosuppression
It is not clear that immunosuppressed patients are at higher
risk for severe COVID-19 and evidence from outbreaks of SARS and MERS shows
that post-transplant immunosuppression was not a risk factor for death.
Immunosuppressive medication should not be halted. Post-transplant patients
should minimise contacts and continue to practice all hygiene measures
recommended for post-transplant patients.
If post-transplant patients acquire SARS-CoV 2, prednisone
dosage reduction should be considered. The World Health Organization recommends
avoiding the use of corticosteroids for treatment of COVID-19 unless indicated
for another purpose.
Consider drug-drug interactions with immunosuppressive drugs
if using experimental agents to treat COVID-19. Lopinavir/ritonavir is not
proven as an effective treatment for COVID-19 to date but is being tested in
several large randomised clinical trials. Lopinavir/ritonavir is a potent
inhibitor of CYP3A4, which is involved in the metabolism of calcineurin
inhibitors, sirolimus and everolimus. Consider a dosage reduction of tacrolimus
to 2% - 5% of baseline dose due to this drug-drug interaction.
COVID – HEP registry
The University of Oxford has
launched an online registry to record outcomes of patients with liver
disease or undergoing immunosuppressive treatment and liver transplant who
develop laboratory-confirmed COVID-19.
University of North Carolina – Chapel Hill has launched a similar registry for the