Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury

Table 1 Main characteristics related to liver injury in patients with coronavirus disease 2019 based on a series of case reports

Ref.	Sample size	Liver injury	Elevated ALT		Elevated AST	Elevated TBIL	Elevated ALP	Elevated GGT	Factors related to liver injury
[25]	1099	NA	21.3%: Severe 28.1%, Non-severe 19.8%	22.2%: Severe 39.4%, Non-severe 18.2%		10.5%: Severe 13.3%, Non-severe 9.9%	NA	NA	NA
[26]	548	NA	23.1%: Severe 24.1%, Non-severe 22.3%	33.1%: Severe 43.4%, Non-severe 23.3%		4.4%: Severe 6.4%, Non-severe 2.3%	NA	NA	NA
[27]	417	21.5%	41.2%: Severe 82.4%, Non-severe 50.2%	47.2%: Severe 75.3%, Non-severe 36.9%		64.2%: Severe 75.3%, Non-severe 60.1%	10.9%: Severe 12.2%, Non-severe 10.5%	48.5%: Severe 75.3%, Non-severe 39.1%	Older, male, higher BMI, Underlying liver diseases (NAFLD, alcoholic liver disease and chronic hepatitis B), drugs (lopinavir/ritonavir)
[28]	324	NA	15.7%	10.5%		6.5%	1.2%	0.9%	NA
[29]	298	14.8%	NA	NA		NA	NA	NA	NA
[30]	274	NA	22.0%: Deceased 27.0%, Recovered 19.0%	31.0%: Deceased 52.0%, Recovered 16.0%		NA	NA	NA	NA
[31]	148	37.2%	18.2%	21.6%		6.1%	4.1%	17.6%	Male, higher levels of procalcitonin and CRP. PCT, LDH, received lopinavir / ritonavir
[32]	85	38.8%	61.2%	NA		NA	NA	NA	Older, lactic acid, myoglobin, neutrophils, critical illness, aCRP, alymphocyte count
[33]	79	36.7%	31.6%	35.4%		5.1%	NA	NA	Male, white blood cell counts, neutrophils, CRP, athe extent of pulmonary alesions on CT
[34]	40	55%	52.5%	40%		25%	NA	NA	Many types of drugs, large amounts of hormones, underlying diseases, lymphocyte count, acritical illness
[35]	82	78%	30.6%	61.1%		30.6%	NA	NA	NA

^aRepresents independent risk factors for liver injury in coronavirus disease 2019. ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; COVID-19: Coronavirus disease 2019; CRP: C-reactive protein; CT: Computed tomography; GGT: Gamma-glutamyl transpeptidase; LDH: Lactate dehydrogenase; NA: Not available; NAFLD: Non-alcoholic fatty liver diseases; PCT: Procalcitonin; TBIL: Total bilirubin.

Table 2 Management of coronavirus disease 2019 patients with liver disease

	Management of COVID-19 patients with liver disease
Out-patient care	Use telemedicine or visits by phone wherever possible. Consider seeing in person only patients with urgent issues and clinically significant liver disease (e.g., jaundice, elevated ALT or AST > 500 U/L, or recent onset of hepatic decompensation)[40,84,86]. Seeing at the fever clinic[40]
Hospital treatment	Separate management from non-COVID-19 patients[40,85]. Monitor liver biochemistries regularly, particularly in patients treated with remdesivir or tocilizumab[40]. Avoid ultrasound or other advanced imaging unless it is likely to change management, for example, clinical suspicion for biliary obstruction or venous thrombosis[40]. Hospitalize COVID-19 patients with advanced liver disease as soon as possible[85]
Patients with hepatitis B, hepatitis C	Document discussion with patient regarding CLD diagnosis and management[84]. Delay starting DAA therapy until after their recovery from COVID-19 disease if there is no suspicion of advanced liver disease[87]. Continue treatment and provide 90-d supplies for HBV oral antiviral drugs or a full course of DAA medications to complete HCV treatment[87]
Patients with autoimmune liver disease	Continue immunosuppressive therapy in stable patients with AIH[87]. Lower the doses of azathioprine or mycophenolate mofetil when patients develop lymphopenia[87]. Avoid liver biopsy and start empiric therapy in new patients presenting with features of AIH[87]. Avoid high doses of prednisone in AIH patients on corticosteroids[87]
Patients with HCC	Continue HCC surveillance schedule for high-risk subjects[40]. Document discussion of risks and benefits of delaying surveillance with patient[40]. Proceed with HCC treatments as appropriate[40]. Postpone elective transplant and resection surgery, withhold immunotherapy[84]
Pretransplant and post-transplant patients	Have low threshold for admitting patients on transplant waiting list diagnosed with COVID-19[40,84]. Consider reduction of immunosuppression therapy as appropriate for posttransplant patients with moderate COVID-19[40,84]. Avoid reductions in immunosuppressive therapy in patients with mild COVID-19 disease[40,84]

AIH: Autoimmune hepatitis; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CLD: Chronic liver disease; COVID-19: Coronavirus disease 2019; DAA: Direct acting antiviral; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.