P0838 - SARS-CoV-2-Associated Cholestatic Liver Injury: A Case Series in Critically Ill Patients

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Anthony Rainho, MD

University of Virginia
Charlottesville, VA, United States

Anthony Rainho, MD¹, Edward C. Oldfield, MD¹, Zachary Dickson, MD², Stephen H. Caldwell, MD¹, Nicolas M. Intagliata, MD³
¹University of Virginia, Charlottesville, VA; ²University of Virginia Gastroenterology Fellowship, Charlottesville, VA; ³University of Virginia Health System, Charlottesville, VA

Introduction: Hepatocellular injury has been documented in 14% to 76% of patients suffering from Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with increased rates of intubation and mortality. SARS-CoV-2 enters target cells by binding to angiotensin-converting enzyme 2 present in the lungs, small intestine, cholangiocytes, and hepatocytes. While most patients experience mild acute liver injury, some critically ill patients develop a prolonged cholestatic injury pathologically similar to secondary sclerosing cholangitis. Histologic assessments have demonstrated microvesicular steatosis, diffuse intrahepatic vascular thrombosis, and chronic fibrous endothelial thickening. We present five cases of cholestatic liver injury in critically ill patients, including a novel case of severe hepatic arteriopathy during endoscopic retrograde cholangiopancreatography (ERCP).

Case Description/Methods: We identified 5 patients without preexisting liver disease who developed prolonged cholestatic liver injury following severe COVID-19 infection requiring mechanical ventilation, antibiotics, and prolonged hospitalization (Table 1). Four patients developed shock requiring vasopressor support and two required extracorporeal membrane oxygenation. Additionally, Patient 1 underwent ERCP which revealed friable hepatic parenchyma and vascularture that appeared angiographically similar to secondary sclerosing cholangitis. While liver chemistries were normal or mildly elevated at the time of COVID-19 diagnosis, all patients experienced significant cholestasis with predominantly elevated alkaline phosphatase levels ranging from the 900s to 4000s. In patients who survived their initial hospitalization, liver chemistries remained elevated months beyond resolution of their pulmonary and renal injuries, and none had returned to baseline as of this writing.

Discussion: We described several cases of prolonged cholestasis in patients with severe COVID-19 infection without preexisting liver disease. While a component of this acute liver injury could be attributed to drugs or ischemia, the timeframe and degree of injury suggest a different etiology, which we postulate may be a combination of secondary sclerosing cholangitis and direct hepatic injury from SARS-CoV-2. Additional research and longitudinal monitoring of these patients is needed to better characterize this type of injury and determine the risk of clinically relevant, long-term liver dysfunction.

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Demographics
Age (years)	58	52	49	37	39
Sex	F	M	M	M	M
Ethnicity	Hispanic	Hispanic	Hispanic	Hispanic	Hispanic
Pre-Existing Conditions
Hypertension	No	No	Yes	No	No
Diabetes Mellitus	Yes	Yes	No	No	Yes
Obesity	No	Yes	No	Yes	No
Chronic Kidney Disease	No	No	No	No	No
Characteristics of COVID-19(1) Infection
Need for Mechanical Ventilation	Yes	Yes	Yes	Yes	Yes
Need for Vasopressors	Yes	Yes	Yes	No	Yes
Acute Kidney Injury	Yes	Yes	Yes	No	Yes
Need for Hemodialysis	Yes	No	No	No	No
Need for Extracorporeal Membrane Oxygenation	No	No	Yes	Yes	No
Other Diagnoses Treated	Bacterial Pneumonia, Hemorrhagic Shock, Malnutrition, Acute Encephalopathy, Iatrogenic Hepatic Artery Dissection	ARDS(2), Non-Occlusive Pulmonary Embolism, Distributive Shock, Atrial Fibrilation, Heart Failure with Preserved Ejeciton Fraction	ARDS, Aspiration Pneumona, Distributive Shock, Pneumomediastinum, Pneumoperitoneum, Pneumothorax, Hematuria, Urinary Retention	ARDS, Acute Encephalopathy, Catheter Associated Urinary Tract Infection, Loculated Pleural Effusion, Hemopneumothorax, Superficia Venous Thrombi	Distributive Shock, Ventilator Associated Pneumonia, Pneumothorax, Acute Sinusitis, Hyperglycemia, Hypernatremia
Hydroxychloroquine	Yes	No	No	No	No
Azithromycin	Yes	Unknown	Yes	Yes	Yes
Tocilizumab	Yes	No	Yes	No	No
Corticosteroids	No	Yes	Yes	Yes	Yes
Remdesivir	No	Yes	No	Yes	Yes
Convalescent Plasma	No	Yes	No	Yes	No
Antibiotics	Yes	Yes	Yes	Yes	Yes
Admission Survival	No	No	Yes	Yes	Yes
Serum Liver Chemistries on Day 0 of COVID-19 Infection
Aspartate Aminotransferase (U/L)	31	46	132	50	70
Alanine Aminostransferase (U/L)	29	21	135	72	55
Alkaline Phosphatase (U/L)	122	8	178	72	78
Total Bilirubin (mg/dL)	0.5	0.4	0.8	0.7	0.7
Peak Serum Liver Chemistries
Aspartate Aminotransferase (U/L)	423	235	159	102	238
Alanine Aminostransferase (U/L)	227	77	497	206	310
Alkaline Phosphatase (U/L)	4,632	2,953	1,085	600	951
Total Bilirubin (mg/dL)	44.2	8.4	0.9	0.6	1.5
Last Documented Serum Liver Chemistries at Discharge or Death
Aspartate Aminotransferase (U/L)	97	235	115	50	40
Alanine Aminostransferase (U/L)	87	55	246	79	52
Alkaline Phosphatase (U/L)	2,776	2,132	1,085	289	472
Total Bilirubin (mg/dL)	39.4	6.6	0.5	0.4	0.4
Hepatobiliary Characteristics
Cirrhosis	No	No	No	No	No
Hepatomegaly	Yes	No	No	No	No
Intrahepatic Biliary Ductal Dilatation	Yes	No	No	No	No
Extrahepatic Biliary Ductal Dilatation	Yes	No	No	No	No

Table: Table 1: Patient Characteristics
(1) COVID-19, Coronavirus Disease 2019
(2) ARDS, Acute Respiratory Distress Syndrome

Disclosures:

Anthony Rainho indicated no relevant financial relationships.

Edward Oldfield indicated no relevant financial relationships.

Zachary Dickson indicated no relevant financial relationships.

Stephen Caldwell indicated no relevant financial relationships.

Nicolas Intagliata indicated no relevant financial relationships.

Anthony Rainho, MD¹, Edward C. Oldfield, MD¹, Zachary Dickson, MD², Stephen H. Caldwell, MD¹, Nicolas M. Intagliata, MD³. P0838 - SARS-CoV-2-Associated Cholestatic Liver Injury: A Case Series in Critically Ill Patients, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.