key: cord-0803180-o7lyp7oe
authors: Mallet, Maxime; Allaire, Manon; Thabut, Dominique; Rudler, Marika
title: Liver damage associated with Covid-19: a direct causality is difficult to establish
date: 2021-05-10
journal: nan
DOI: 10.1016/j.liver.2021.100011
sha: 92ce1e13eddb692e4ba7525d20c0a0bc345cf612
doc_id: 803180
cord_uid: o7lyp7oe

nan

showing severe inflammation and intra hepatic cholestasis. These features were however not specific of any aetiology. He finally received a liver transplantation because of end stage liver failure around two months after his first admission to the hospital. According to the authors, the final diagnosis was acute cholestatic liver failure due du Covid-19. This interesting case description must lead to several considerations.

Since the beginning of the Covid-19 pandemic one year ago, the involvement of several organs including the liver has been described 2 . There are however very few cases of ALF attributed to Covid-19. Haji Esmaeil Memar et al. 3 reported the case of an 11-year-old boy presenting with jaundice and abdominal pain, concomitantly with a positive nasopharyngeal SARS-CoV-2 PCR. He subsequently died due to fulminant hepatitis, without any aetiology retrieved except Covid-19. Melquist et al. 4 reported the case of a 35-year-old woman that developed fulminant hepatitis in the context of Covid-19. Fortunately, liver function improved and liver transplantation was not necessary. As this patient had a history of systemic lupus erythematous and a raise in the title of antinuclear antibodies, she was treated with steroids and hydroxychloroquine. The event of an autoimmune hepatitis could thus neither be confirmed nor excluded. Vujaklija Brajkovic et al. 5 described the case of a previously healthy 22 years old man who presented with ALF and cardiac failure. He showed signs of sepsis attributed to Covid-19 but respiratory symptoms were mild. Liver function improved in parallel with the recovery of a normal left ventricular function, suggesting the diagnosis of hypoxic ALF. Off notes, no other causes of cardiac failure except Covid-19 infection were found. Yohanatan et al. 6 described the case of an 18-year-old women who received a liver transplant for ALF. She was initially admitted for respiratory symptoms due to Covid-19. She rapidly developed multi organ failure and required vasopressors, mechanical ventilation and renal replacement therapy. Liver failure with hyperammonemia and encephalopathy persisted in spite of the improvement of respiratory and hemodynamic failures. She was thus listed and fortunately received a liver transplantation (LT). Wilson's disease was diagnosed only after transplantation as quantitative copper dosage on the explanted liver was elevated and genetic testing was positive. In the latter case, COVID 19 probably acts as an aggravating factor leading to liver decompensation. Last, the results of large cohort of 2073 hospitalized COVID 19 patients 7 showed that only 0,5% of patients developed Acute Liver Injury (ALI). The authors pointed that 8/10 patients with ALI were sedated under mechanical ventilation, making the diagnosis of hepatic encephalopathy and thus fulminant hepatitis very difficult. It is also likely that in this context of severe SARS-CoV-2 infection, a combination of factors, such as hypoxia, sepsis, shock, renal failure and drug-induced liver injury (DILI) may lead to liver damage and potentially liver failure, highlighting that a direct causality between SARS CoV2 and liver injury is difficult to establish 8 . In summary, ALF associated with COVID19 can either be related to the decompensation of a pre-existing liver disease 6 , or to another cause of liver failure related to ARDS and sepsis such as heart failure 5 . DILI may also be an aggravating factor. More specifically, exposure to ketamine for prolonged sedation for mechanical ventilation should be examined. Indeed, cholestatic liver injury potentially leading to LT or death has been described in patients who had received high-cumulated doses of ketamine in several contexts including Covid-19 during the first wave of the pandemic 9 . Finally, a direct involvement of SARS-Cov2 in the pathophysiology of liver damage in these patients must be considered as viral replication in liver cells and especially cholangiocytes may occur 2, 10 .

To conclude, it is important to consider the specificity of ALF in the context of Covid-19. It remains a rare event that must be carefully investigated in order to diagnose an underlying liver disease and look for aggravating factors such as sepsis, heart failure or DILI. When possible, the treatment of such aggravating factors may prevent further deterioration of the liver function. Whether SARS-CoV-2 is a direct cause of liver failure in the case described by Pishgar et al 1 . remains uncertain. Nevertheless, in cases when liver failure is not associated with multiple organ failure, the indication of liver transplantation must be evaluated, as it is a lifesaving procedure.

Successful liver transplant in a patient with acute cholestatic liver failure due to COVID-19 infection. A case report

COVID-19 and liver disease: mechanistic and clinical perspectives

Fulminant hepatic failure: A rare and devastating manifestation of Coronavirus disease 2019 in an 11-year-old boy

COVID-19 presenting as fulminant hepatic failure: A case report

Acute liver and cardiac failure in multisystem inflammatory syndrome in adults after COVID-19

Liver transplantation for acute liver failure in a SARS-CoV-2PCR-positive patient

Association of liver abnormalities with in-hospital mortality in patients with COVID-19

Liver Injury in COVID-19 -The culprit may not be COVID-19!

Electronic address: vincent.mallet@aphp.fr

Intravenous ketamine and progressive cholangiopathy in COVID-19 patient

Patterns and prediction of liver injury with persistent cholestasis in survivors of severe SARS-CoV-2 infection