COVID-19 associated liver injury: A general review with special consideration of pregnancy and obstetric outcomes

Table 1 Clinical characteristics and management of COVID-19 and perinatal liver diseases

	COVID-19	PEC/severe PEC	HELLP	ICHP	AFLP
Epidemiology	-	5.0%-7.5%	1%	0.3%-5.6%	0.005%-0.010%
Symptoms	Respiratory +/- GI symptoms	Variable: Headache, swelling, vision changes (or none)	Variable: Headache, nausea, vomiting, RUQ pain (or none)	Pruritis; starting at palms + soles (can be diffuse)	Nausea, vomiting, abdominal pain
Pathophysiology of liver disease	SARS-CoV-2 infection and systemic inflammation	Inflammation and imbalanced endothelial activity	Thrombotic micro-angiopathy	Hormonal cholangiopathy	Mitochondrial dysfunction + fatty acid accumulation in hepatocytes
Increased transaminases	13%-42%, 2-5 × ULN	Approximately 50%, > 2 × ULN	Typical, > 2 × ULN	Typical, > 2 × ULN	Always, < 10 × ULN
Jaundice	Rare (unclear%)	Rare	Rare (< 5%)	Uncommon (< 25%)	Mostly (> 70%)
Other findings	Radiographic lung disease	HTN, ↑ sFLT-1/PIGF	↓ PLC; ↓ haptoglobin; ↑ LDH ↑ D-dimer	↑ ALP; ↑ bile acids	Coagulopathy; hypoglycemia
Diagnosis	Viral antigen PCR or Nucleic acid amplification test (NAAT)	HTN ≥ 140/90 + organ dysfunction (proteinuria not required)	Tennessee or Mississippi classification	Bile acids (BA); > 10 umol/L	Swansea criteria; biopsy if unclear
Management	Anti-virals +/- Steroids Mono-clonal antibodies	HTN control; delivery if > 37 wk GA or > 34 wk if severe	Delivery after 34 wk GA	Ursodiol; delivery at 36 wk GA if BA > 100 or 36-39 wk if BA < 100	Prompt delivery
Complications	↑ Risk of post-partum hemorrhage; ↑ multi-systemic organ failure	↑ Complications; mortality: 1%-5%; ↑ Neonatal respiratory distress + mortality	↑ Complications Mortality: 1%-3%	↑ Neonatal complications	↑ Maternal + neonatal complications; morality: 20% (mother); 6%-77% (neonate)

Comparison of the clinical presentation and management of Coronavirus disease 2019 (COVID-19) complicated by COVID-19 associated liver injury (COVALI) in pregnant compared to liver diseases specific to pregnancy[105-107,134-138]. Many of the diseases present along a spectrum however, they each have features that can help narrow the differential diagnosis. Importantly, management of perinatal liver diseases includes early delivery in most cases based on American College of Obstetrics and Gynecology recommendations, whereas management of COVALI does not involve decisions about pregnancy delivery. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; PEC: Pre-ec clampsia; HELLP: Hemolysis, elevated liver enzymes, low platelets; Ahellp: atypical HELLP; AFLP: Acute fatty liver of pregnancy; ICHP: Intrahepatic cholestasis of pregnancy/obstetric cholestasis; LDH: Lactate dehydrogenase; PLC: Platelet count.