In liver transplant recipients or patients with autoimmune hepatitis on immunosuppressive therapy, acute cellular rejection or disease flare should not be presumed in the face of active coronavirus disease 2019 (COVID-19), according to the American Association for the Study of Liver Diseases (AASLD).
Signs that would normally be interpreted as flare or rejection need to be considered more cautiously now because the virus attacks the liver, and elevated aspartate aminotransferase, alanine aminotransferase, and slightly elevated bilirubin are common, ranging from a prevalence of 14% to 53% in COVID-19 patients. Acute liver injury is possible, especially in more severe cases, the group said.
The advice comes from a recently released document from AASLD, called “Clinical Insights for Hepatology and Liver Transplant Providers During the Covid-19 Pandemic,” to help hepatologists and liver transplant providers negotiate the pandemic, according to the latest data. It’s a far-ranging work that contains a lot of now familiar steps for providers to take to protect themselves and patients from the virus, but also much advice specific to liver medicine.
For instance, the group said it’s important to keep in mind that experimental treatments for the infection, including statins, remdesivir, and tocilizumab, can be hepatotoxic. Abnormal liver biochemistries are not a contraindication, but liver biochemistries need to be followed regularly in COVID-19 patients, especially those treated with remdesivir or tocilizumab, regardless of baseline values.
Also, lopinavir/ritonavir is a potent inhibitor of cytochrome P450 enzymes involved with calcineurin inhibitor metabolism, so if it’s used, AASLD said to reduce tacrolimus dosages to 1/20–1/50 of baseline.
The group cautioned against anticipatory adjustments to immunosuppressive drugs or dosages in patients without COVID-19, but if immunosuppressed liver disease patients do get the infection, prednisone doses should be reduced but kept above 10 mg/day to avoid adrenal insufficiency. In the setting of lymphopenia, fever, or worsening COVID-19 pneumonia, it advised reduction of azathioprine and mycophenolate dosages and reduction of, but not stopping, calcineurin inhibitors.
Liver transplants should not be postponed. However, to minimize exposure to the hospital environment, AASLD advised to “consider evaluating only patients with HCC [hepatocellular carcinoma] or those patients with severe disease and high MELD [model for end-stage liver disease] scores who are likely to benefit from immediate liver transplant.”
“An argument that has been put forward to justify deferring some transplants is concern about immunosuppressing patients during the COVID-19 pandemic,” the group said, but “data suggest the innate immune response may be the main driver for pulmonary injury due to COVID-19 and [that] immunosuppression may be protective. ... Posttransplant immunosuppression was not a risk factor for mortality associated with” the severe acute respiratory syndrome pandemic in 2003-2004 or the ongoing Middle East respiratory syndrome pandemic, both also caused by coronaviruses.
AASLD advised against reducing immunosuppression or stopping mycophenolate for asymptomatic patients after transplant, but COVID-19 prevention measures should be emphasized, including frequent hand washing and staying away from large crowds.
People who test positive for COVID-19 are ineligible for organ donation. Bronchoalveolar lavage is the most sensitive test (93%), followed by nasal swabs (63%) and pharyngeal swabs (32%).
In general, the group said elective procedures should be postponed, but urgent ones, such as biliary surgery and transjugular intrahepatic portosystemic shunts for bleeding varices, in addition to liver transplants, should not.
Also, HCC patients “should not wait until the pandemic abates to undergo [surveillance] imaging because the prospective duration of the pandemic is unknown. ... An arbitrary delay of 2 months is reasonable” for imaging based on patient and facility circumstances, but otherwise, “proceed with HCC treatments rather than delaying them due to the pandemic,” the group said.
As for who to bring into the office for an initial consult, “consider seeing in person only new adult and pediatric patients with urgent issues and clinically significant liver disease (e.g., jaundice, elevated ALT or AST above 500 U/L, recent onset of hepatic decompensation),” AASLD said.