Hepatic manifestations of coronavirus disease 2019 infection: Clinical and laboratory perspective

Table 1 Major clinical manifestations and laboratory abnormalities in coronavirus disease 2019

Signs/symptoms
Systemic and respiratory system manifestations
Fever, cough, malaise, dyspnea, fatigue, sputum
Cardiovascular system manifestations
Heart failure, arrhythmia, shock, tight chest, acute myocarditis
Gastrointestinal manifestations
Anorexia, diarrhea, loss of appetite, loss of taste, gastrointestinal bleeding, nausea and vomiting, abdominal pain, mild pancreatitis, mild colitis
Hepatobiliary manifestations
Abnormal liver function tests, jaundice, hypoalbuminemia, new-onset decompensation, acute-on-chronic liver failure, cholangiopathy, acalculous cholecystitis
Kidney manifestations
Acute kidney injury, proteinuria, hematuria
Neurological manifestations
Dizziness, headache, skeletal muscle injury, acute cerebrovascular disease, seizures

Table 2 Rates of hepatic complications in different clinically significant human coronavirus infectious diseases

Hepatic complications	SARS-CoV-2, %	SARS-CoV, %	MERS-CoV, %
Increase in ALT	13.3-28.0	52.5-8.07	11.0-56.3
Increase in AST	22.0-58.0	37.1-86.9	15.0-86.8
Increase in TB	10.5-18.0	30.0	NA
Decrease in serum albumin	36.8	40.4-72.0	NA
Co-morbidity with liver disease	HBV-positive patients were more prone to develop severe disease (32.9%) vs HBV-negative patients (15.3%)	HBV infection was not associated with worse clinical outcomes	NA

ALT: Alanine transaminase; AST: Aspartate transaminase; HBV: Hepatitis B virus; MERS: Middle east respiratory syndrome; NA: Not applicable; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SARS-CoV: Severe acute respiratory distress syndrome; TB: Total bilirubin.

Table 3 Summary of recommendations from various hepatology societies regarding liver transplantation during the coronavirus disease 2019 pandemic

Step	AASLD	EASL	APASL	Indian Transplant Society
Indications	Develop a hospital-specific policy for organ acceptance in consideration to community incidence of COVID-19 infection	Restrict transplant with poor short-term prognosis like ALF, ACLF, high MELD score and HCC at upper limit of Milan criteria	Can limit transplant to urgent cases (ALF, high MELD, high risk of HCC progression) according to resources and infection status of country	Until April 2020, elective transplants were withheld. However, in ALF and ACLF transplant could proceed
Pre- transplant evaluation	Test all recipients and donors for SARS-CoV-2 before transplantation. In case of COVID-19 infection in potential recipient, transplant can be considered after at least 14-21 d if symptoms are resolved and repeat SARS-CoV-2 test is negative. Vaccination of potential recipient is encouraged	All recipients and donors should be tested for SARS-CoV-2 before transplantation. Reduction of hospital stay for transplant evaluation and consultation	All recipients and donors should be tested for SARS-CoV-2 before transplantation. Donor should also be evaluated for evidence of COVID-19 infection on chest CT	All recipients and donors should be tested for SARS-CoV-2 before transplantation
Post-transplant management without COVID-19	Dose reduction/adjustment to current immunosuppression is not recommended. Stable patients could be followed through telemedicine. Encourage COVID-19 vaccination at least 6 wk post-transplant if partially vaccinated pretransplant than vaccination can be completed 1 mo after transplant	Dose reduction/adjustment to current immunosuppression is not recommended. Stable patients could be followed through telemedicine. Encourage vaccination against Streptococcus pneumoniae and influenza	Standard immunosuppression protocols should be followed in new transplant recipient. In cases of long-term transplant dose reduction/adjustment to current immunosuppression is not recommended. Stable patients could be followed through telemedicine. Encourage vaccination against Streptococcus pneumoniae and influenza	Standard immunosuppression protocols should be followed in post-transplant period
Post-transplant management with COVID-19	Consider lowering immunosuppression levels especially anti-metabolite drugs (e.g., azathioprine or MMF). Dose adjustment of immunosuppression should be based on severity of COVID-19. Monitor kidney function and calcineurin inhibitor levels	Dose adjustment of calcineurin- and/or mTOR- inhibitors may be required to avoid drug interactions with anti-viral therapy	Consider lowering immunosuppression levels in patients with moderate COVID-19 infection. Immunosuppression should be reduced in recipients with lymphopenia, fever or worsening pneumonia. Severe COVID-19 should be treated as per local protocol. Drug-to-drug interaction should be considered with anti-viral therapy

AASLD: American Association for the Study of Liver Diseases; ACLF: Acute on chronic liver failure; ALF: Acute liver failure; APASL: Asian Pacific Association for the Study of the Liver; COVID-19: Coronavirus disease 2019; CT: Computed tomography; EASL: European Association for the Study of the Liver; MELD: Model For End-Stage Liver Disease; HCC: Hepatocellular carcinoma; MMF: Mycophenolate mofetil; mTOR: Mammalian target of rapamycin; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.