COVID-19-associated hepatic injury differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

COVID-19-associated hepatic Injury must be differentiated from other conditions that cause elevation of liver enzymes.

Differential Diagnosis

COVID-19-associated hepatic Injury must be differentiated from other conditions that cause elevation of liver enzymes.

Disease		Clinical manifestations					Laboratory findings			Additional findings
		Symptoms			Signs		Transaminitis (elevated AST and ALT)	Viral markers	Autoimmune markers
		Nausea & vomiting	Abdominal pain	Arthralgia	Jaundice	Hepatomegaly
Acute viral hepatitis	Hepatitis A	+++	++	+	+++	+	+++	HAV Ab	---	Fecal-oral transmission Usually acute and self limit Fever usually present
	Hepatitis B	+++	++	++	+++	+	+++	HBs Ag, HBc Ab, HBe Ag	---	Percutaneous transmission most common May cause acute hepatic failure or may become chronic Fever usually present
	Hepatitis C	+++	++	++	+++	+	+++	HCV Ab	---	Percutaneous transmission is most common Higher rate of chronic progression Associated with extra hepatic manifestation such as cryoglobulinemia and membranoproliferative glomerulonephritis Fever usually present
	Hepatitis E	++	++	+/-	++	+	+++	HEV Ab	---	Fecal-oral transmission May cause fulminant disease in pregnancy Fever usually present
	CMV hepatitis	+/-	++	-	+	+	++	CMV-specific immunoglobulin (Ig)M antibody	--	Usually manifests as mononucleosis syndrome fever usually present
	EBV hepatitis	+/-	++	-	+/-	+	++	Heterophile antibody test, monospot test	--	Systemic manifestations as mononucleosis syndrome Fever usually present
Autoimmune hepatitis		-	+	+/-	++	+	+++	---	ANA, ASMA, anti SLA/LP, ANCA, ALKM-1 antibodies	Liver biopsy may be required for diagnosis
Alcoholic hepatitis		+/-	+	-	+	-	AST>ALT	---	---	History of alcohol intake
Drug induced hepatitis		+/-	+	-	+	+	++	---	---	May cause either cholestatic or hepatocellular injury
COVID-19-associated hepatic Injury		+	+	-	-	+	++	IgG/IgM Antibodies	---	May cause both cholestatic or hepatocellular injury