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.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays. METHODS: At our institution, 2 strategies for providing DAA therapy to HCV- recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies. RESULTS: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients. CONCLUSIONS: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

The Prevalence and Pathobiology of Nonalcoholic Fatty Liver Disease in Patients of Different Races or Ethnicities.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common cause of liver disease in the United States. The prevalence varies dramatically when comparing individuals of different races and ethnicities. Rates are highest in Hispanic patient populations compared with non-Hispanic whites and African Americans, despite similar rates of the metabolic syndrome and risk factors. This observation remains poorly characterized; variations in genes that effect lipid metabolism may play a role. This article describes the prevalence of NAFLD in patients of different races or ethnicities, and discusses pathophysiologic mechanisms that may explain why these differences exist.