Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Post-COVID-19 Cholangiopathy: A Novel Entity.

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.

Secondary sclerosing cholangitis in critically ill patients: a rare disease precipitated by severe SARS-CoV-2 infection.

A previously well 59-year-old man required a prolonged intensive care unit stay due to severe COVID-19 symptoms. During the admission, he developed a cytokine storm, also known as secondary haemophagocytic lymphohistocytosis, and multiorgan failure. Despite recovering from his other organ failures, his liver function continued to deteriorate. Magnetic resonance cholangiopancreatography and subsequent endoscopic retrograde cholangiopancreatography revealed extensive intrahepatic duct dilatation with 'beading' but common bile duct sparing. Given the patient had no primary liver disease prior to admission, we considered secondary causes of cholestatic liver injury; this led us to an unusual diagnosis of secondary sclerosing cholangitis in critically ill patients. This case demonstrates a rare disease that has developed specifically in the context of SARS-CoV-2 infection. A review of current literature and the underlying pathophysiology for this rare disease are discussed, particularly in relation to COVID-19.

Recurrent Acute Pancreatitis in a Patient with COVID-19 Infection.

BACKGROUND The novel COVID-19 disease has infected more than 2 million people worldwide, causing more than 120 000 deaths. While the disease is known to primarily affect the respiratory system, gastrointestinal manifestations can also occur. However, little is known about the development of acute pancreatitis in COVID-19. The present report highlights a patient with no precipitating risk factors for pancreatitis who presented with recurring acute pancreatitis following the diagnosis of SARS-CoV-2 infection. CASE REPORT An otherwise healthy 38-year-old man presented to the Emergency Department (ED) with fever and epigastric pain. Laboratory testing revealed a lipase level of 10 255 ukat/L. An abdominal ultrasound showed no gallstones. After ruling out the possible causes of acute pancreatitis, a diagnosis of idiopathic acute pancreatitis was made. He received conservative management and was discharged home after being medically stabilized. Of note, the patient tested positive for SARS-CoV-2 infection at a local testing center 1 week prior to presenting to the ED. One week following the discharge, the patient returned with recurrent severe epigastric pain. Laboratory testing showed a lipase level of 20 320 ukat/L. An abdominal CT revealed acute pancreatitis. Further workups, including abdominal ultrasound, hepatitis serology, and immunoglobulin G for autoimmune pancreatitis, were unrevealing. Repeated SARS-CoV-2 testing produced positive results. CONCLUSIONS The temporal relationship between clinical presentation of acute pancreatitis and SARS-CoV-2 infection in this patient with no precipitating risk factors for pancreatitis suggests COVID-19-associated acute pancreatitis. Our review of the literature found a handful of reported cases of acute pancreatitis in patients with coexisting SARS-CoV-2 infection, and this report presents the first presumptive case of COVID-19-associated recurring acute pancreatitis.