Patients with cirrhosis during the COVID-19 pandemic: Current evidence and future perspectives

Table 1 Clinical characteristics of cirrhotic patients infected with SARS-CoV-2

Reference	Patientnumber (n)	Region	Etiology	CirrhosisSeverity1	ACLF2	Acute decompensation
Qi et al[33]	21	China	HCV: 9.5%	CTP-A: 76.2%	4.8%3	Variceal bleeding: 19%
			HBV: 42.9%	CTP-B: 14.3%
			ALD: 9.5%	CTP-C: 9.5%		Ascites: 23.8%
			AIH: 4.8%	MELD: 8 (7-11)
Liu et al[32]	17	China	HCV: 11.8%	CTP-A: 88.2%	APASL:11.8%	Variceal bleeding: 5.9%
			HBV: 70.6%	CTP-B: 5.9%
				CTP-C: 5.9%
Iavarone et al[31]	50	Italy	HCV: 28%	CTP-A: 40%	EASL: 28%	HE: 22%
			HBV: 10%	CTP-B: 28%
			ALD: 24%	CTP-C: 32%
			NAFLD: 6%	MELD: 9 (6-15)
Sarin et al[14]	43	Asia	Viral: 60.4%	CTP-A: 53.8%	APASL: 11.6%	AD event: 9.3%
			MAFLD: 32.5%	CTP-B: 37.2%		Variceal bleeding: 9.3%
			ALD: 4.6%	CTP-C: 9%		HE: 7%
			AIH: 2.3%			Ascites: 23.3%
						Jaundice: 23.3%
						SBP: 7%
Moon et al[19]	103	International	HCV: 10.5%	CTP-A: 44.7%	N/A	AD event: 25.7%
			HBV: 11.8%	CTP-B: 29.1%		Variceal bleeding: 1%
			ALD: 19.7%	CTP-C: 26.2%		HE: 16.5%
			NAFLD: 22.4%	MELD: 10		Ascites: 27.2%
						SBP: 2.9%
Lee et al[22]	14	Korea	HCV: 14.3%	CTP-A: 64.3%	N/A	Secondary infection: 7.1%
			HBV: 35.7%	CTP-B: 35.7%
			ALD: 35.7%	MELD: 8 (7-12)
			AIH: 7.1%
Bajaj et al[23]	37	United States	HCV: 24.3%	MELD: 17.6 ± 8.6	NACSELD: 30%	Variceal bleeding: 14%
			ALD: 24.3%
						HE: 14%
			NASH: 24.3%
Kimet al[21]	227	United States	N/A	Compensated: 59%	N/A	AD event: 29.5%
						Variceal bleeding: 3.1%
				Decompensated: 41%
						HE: 10.1%
						Ascites: 4.8%
Shalimar et al[30]	26	India	HCV: 7.7%	CTP: 8.6 ± 2.3	EASL: 34.6%	AD event: 61.5%
			HBV: 11.5%	MELD: 18.1 ± 9.6		Variceal bleeding: 30.8%
			ALD: 34.6%			Ascites: 7.7%
			NAFLD: 7.7%
			AIH: 15.4%
Marjot et al[18]	386	International	HCV: 11%	CTP-A: 52%	EASL: 23%	AD event: 46%
			HBV: 21%	CTP-B: 30%		Variceal bleeding: 3%
			ALD: 38%	CTP-C: 17%		HE: 27%
			NAFLD: 26%	MELD: 12 (8-19)		Ascites: 28%
						SBP: 3%
Jeon et al[28]	67	Korea	N/A	N/A	N/A	Variceal bleeding: 3%
						Ascites: 3%
						HE: 4.5%

¹Cirrhosis severity based on Child-Turcotte-Pugh classification and model for end-stage liver disease score.

²Definition of acute-on-chronic liver failure (ACLF) based on the The North American Consortium for the Study of End-Stage Liver Disease, Asian Pacific Association for the Study of the Liver, and The European Association for the Study of the Liver guidelines.

³Definition of ACLF was not mentioned in the study.

ACLF: Acute-on-chronic liver failure; AD: Acute decompensation; HCV: Hepatitis C virus; HBV: Hepatitis B virus; ALD: Alcohol-related liver disease; AIH: Autoimmune hepatitis; CTP: Child-Turcotte-Pugh; MELD: Model for end-stage liver disease; APASL: Asian Pacific Association for the Study of the Liver; NAFLD: Nonalcoholic fatty liver disease; EASL: The European Association for the Study of the Liver; SBP: Spontaneous bacterial peritonitis; HE: Hepatic encephalopathy; MAFLD: Metabolic-associated fatty liver disease; NASH: Nonalcoholic steatohepatitis; NACSELD: The North American Consortium for the Study of End-Stage Liver Disease

Table 2 Clinical complications and outcomes of cirrhotic patients infected with SARS-CoV-2

Reference	Patient number (n)	COVID-19 severity	COVID-19 complications	Mortality
Qi et al[33]	21	N/A	ICU: 23.8%	23.8%
			MV: 14.3%
			Shock: 14.3%
			ARDS: 28.6%
			RRT: 9.5%
			ECMO: 9.5%
Liu et al[32]	17	Mild1: 64.7%	ICU: 17.6%	17.6%
		Severe1: 35.3%	MV: 11.8%
			Shock: 11.8%
			ARDS: 29.4%
Iavarone[31] et al	50	N/A	ICU: 4%	34%
			MV: 4%
			Shock: 8%
			ARDS: 52%
Sarin et al[14]	43	Severe2: 18.6%	ICU: 25.6%	16.3%
			MV: 23.2%
			Shock: 14%
Moon et al[19]	103	N/A	ICU: 23.3%	39.8%
			MV: 17.5%
			RRT: 4.9%
Lee et al[22]	14	N/A	ICU: 35.7%MV: 21.4%	28.6%
			RRT: 7.1%
			Shock: 28.6%
			ARDS: 35.7%
Bajaj et al[23]	37	N/A	ICU: 43%	30%
			MV: 38%
			Shock: 30%
			RRT: 19%
Kim et al[21]	227	N/A	Death, hospitalization, oxygen support, ICU, vasopressor support, or MV: 70.5%	25.1%
Shalimar et al[30]	26	Mild3: 57.7%	N/A	42.3%
		Moderate3: 7.7%
		Severe3: 34.6%
Marjot et al[18]	386	N/A	ICU: 28%	32%
			MV: 18.4%
			RRT: 5.4%
Jeon et al[28]	67	N/A	ICU: 3%	9%
			Shock: 6%
			RRT: 1.5%

¹Severe COVID-19 was defined as severe pneumonia (i.e., SpO2 < 93% despite high -flow nasal cannula O2 or a respiratory rate (RR) > 30 per minute), features of acute respiratory distress syndrome (ARDS), acute kidney, heart or circulatory failure, altered sensorium or a combination of the above.

²Mild, moderate, and severe coronavirus disease-2019 (COVID-19) were defined as the presence of only upper respiratory tract symptoms without any signs of breathlessness and hypoxia, the presence of pneumonia with a RR between 24 and 30/min and SpO2 between 90% and 94% on room air, and the presence of pneumonia with a RR > 30/min or SpO2 < 90% on room air or severe respiratory distress, respectively.

³Severe COVID-19 was defined when patients had 1 of the following criteria: (1) RR ≥ 30/min; (2) Resting SpO2 < 93%; or (3) Oxygenation index of 300 mm Hg or less. Mild COVID-19 was defined as mild clinical symptoms without pneumonia on imaging.

COVID-19: Coronavirus disease-2019; ICU: Intensive care unit; MV: Mechanical ventilator; ARDS: Acute respiratory distress syndrome; RRT: Renal replacement therapy; ECMO: Extracorporeal membrane oxygenation.

Table 3 Guidelines recommended for the management of cirrhosis patients during the COVID-19 pandemic

	EASL	AASLD	APASL
Outpatient	Common rules of physical distancing	Limited outpatient visitsWearing mask and keeping appropriate distancing	Phone or telemedicine
	Early admission for patient infected with SARS-CoV-2	Limited family or friend accompanied	Limited travel
	Prevent decompensation (e.g., variceal bleeding, HE, SBP) and avoid admission	Video conference, phone or telemedicine	Continue hepatitis B and C treatment
	Telemedicine or remote monitor	Provide prescriptions for 90 d instead of 30 dLimited travel
	Continue hepatitis B and C treatment	Continue hepatitis B and C treatment
	Receive vaccination for Streptococcus pneumoniae and influenza
Inpatient	Designate non-COVID-19 ward	Designate non-COVID-19 ward	Option of palliative treatment for advanced liver disease with COVID-19 disease
	Perform SARS-CoV-2 testing in patient with new or worsening decompensation or ACLF	Perform SARS-CoV-2 testing in patient with new or worsening decompensation or ACLF
	Option of palliative treatment for patient with advanced liver disease with COVID-19	Minimize interaction and transport for patient
		Telemedicine equipmentLimit patient visitors
Endoscopy	Limit to emergency (e.g., GI bleeding or bacterial cholangitis) in patient with COVID-19	Limit to emergency (e.g., GI bleeding or bacterial cholangitis) in patient with COVID-19	Limit to emergency (e.g., GI bleeding or bacterial cholangitis) in patient with COVID-19
	SARS-CoV-2 testing prior to endoscopic procedureNo delay in endoscopy in areas with low COVID-19 burden	SARS-CoV-2 testing prior to endoscopic procedure	PPE used in endoscopy for patient and staff
	Noninvasive tool for variceal surveying	PPE used in endoscopy for patient and staff	Variceal survey can be arbitrary postponed 3 mo depend on COVID-19 outbreak.
		Clean and disinfect the operation room	Noninvasive tool for variceal survey
		Prophylaxis with beta-blocker instead of endoscopic screening	Prophylaxis with beta-blocker instead of endoscopic screening
HCC surveillance	Deferred in patients with COVID-19 until recovery	Deferred in patients with COVID-19 until recovery	Prioritized for patients at high risk
	Prioritized for patients at high risk (e.g., elevated alpha-fetoprotein level or advanced cirrhosis	Continued radiological surveillance, but an arbitrary delay of 2 mo is reasonable	Continued radiological surveillance, but an arbitrary delay of 3 mo is reasonable

EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Disease; APASL: Asian Pacific Association for the Study of the Liver; COVID-19: Coronavirus disease-2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; HE: Hepatic encephalopathy; SBP: Spontaneous bacterial peritonitis; ACLF: Acute on chronic liver failure; GI: Gastrointestinal; PPE: Personal protective equipment; HCC: Hepatocellular carcinoma