RESUMO
Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. METHODS: We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. RESULTS: All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. CONCLUSIONS: The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.
RESUMO
The case of a 57-year-old male patient with jaundice, high-grade fever, and upper abdominal pain who was recovering from a mild coronavirus disease-19 (COVID-19) infection is reported. Laboratory analysis showed liver injury with high levels of AST and ALT, as well as an elevated serum ferritin level. The patient underwent a bone marrow biopsy which showed features of hemophagocytic lymphohistiocytosis (HLH), a systemic syndrome caused by immune activation. The patient was successfully treated with etoposide and dexamethasone and kept on maintenance therapy with cyclosporine, with resolution of the HLH. The discussion highlights that COVID-19 infection may cause liver injury, and in severe cases, patients may develop HLH as a cause for liver injury. The incidence of HLH in adults with severe COVID-19 infection is estimated to be lower than 5%. The association between HLH and COVID-19 infection has been studied due to immunological hyperactivation. Signs such as persistent high fever, hepatosplenomegaly, and progressive pancytopenia should raise suspicion for the diagnosis of overlapping HLH. A specific approach using steroids and etoposide, followed by maintenance therapy with cyclosporine, is proposed in the HLH-94 protocol as the mainstay of treatment. It is suggested that HLH should be suspected in patients with laboratory signs of liver injury following COVID-19 infection, especially in patients with high-grade fever and a history of rheumatic conditions.
Assuntos
COVID-19 , Ciclosporinas , Linfo-Histiocitose Hemofagocítica , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , COVID-19/complicações , Etoposídeo/uso terapêutico , Medula Óssea , FebreRESUMO
Since the spread of the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection much progress has been made in understanding the disease process. However, we are still facing the complications of coronavirus disease 19 (COVID-19). Multiple sequelae may appear as a consequence of acute infection. This set of entities called post-COVID-19 syndrome involves a wide variety of new, recurrent or persistent symptoms grouped together as a consequence of the acute disease process. One of those that has attracted the most attention is the liver and bile duct involvement called post-COVID-19 cholangiopathy. This is characterized by elevation of liver markers such as alkaline phosphatase, bilirubin and transaminases as well as alterations in the bile ducts in imaging studies. Thus, a narrative review of the cases reported until the end of 2021 was carried out. From the findings found, we concluded that patients who have had COVID-19 or during the process have required hospitalization should remain under follow-up for at least 6 months by a multidisciplinary team.