key: cord-0705407-k3467rtk authors: Yohanathan, Lavanya; Campioli, Cristina C.; Mousa, Omar Y.; Watt, Kymberly; Friedman, Daniel Z. P.; Shah, Vijay; Ramkissoon, Resham; Hines, Alexander S.; Kamath, Patrick S.; Razonable, Raymund R.; Badley, Andrew D.; DeMartino, Erin S.; Joyner, Michael J.; Graham, Rondell; Vergidis, Paschalis; Simonetto, Doug A.; Sanchez, William; Taner, Timucin; Heimbach, Julie K.; Beam, Elena; Leise, Michael D. title: Liver transplantation for acute liver failure in a SARS‐CoV‐2 PCR‐positive patient date: 2021-05-05 journal: Am J Transplant DOI: 10.1111/ajt.16582 sha: 2d49fc9325c796fbfb1f6f92ab85701bfb7d8c0c doc_id: 705407 cord_uid: k3467rtk Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18‐year‐old, previously healthy African‐American woman diagnosed with COVID‐19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS‐CoV‐2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID‐19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS‐CoV‐2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS‐CoV‐2 PCR test eventually became negative. Three months following transplantation, the patient has made a near‐complete recovery. This case highlights that COVID‐19 with SARS‐CoV‐2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID‐19 pandemic need to be validated in future studies. Most patients with COVID-19 have a mild or asymptomatic disease course; however, about 19% require admission to an intensive care unit (ICU) because of multiorgan failure. 1 These severe infections can result in up to 60% mortality. 2, 3 Furthermore, signs of hepatobiliary damage have been observed in 14%-53% of patients with severe presentations of COVID-19. 4 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly damage the biliary ducts by binding to angiotensin-converting enzyme 2 (ACE2) on the surface of cholangiocytes; the particularly low abundance of ACE2 on hepatocyte surfaces suggests that SARS-CoV-2 may not directly infect the liver parenchyma. 4 Other potential mechanisms of hepatotoxicity include hyperinflammation and hypoxia-associated metabolic derangements. 5 Histopathologic changes in the liver include hepatic steatosis, portal fibrosis, ductal proliferation with lymphocytic infiltrates, lobular cholestasis, and acute liver-cell necrosis with central-vein thrombosis. 6, 7 Patients with pre-existing cirrhosis appear to be at higher risk of mortality from COVID-19. 8 Acute liver failure (ALF) attributable to COVID-19 is exceptionally rare. 9, 10 Liver transplantation (LT) remains the best treatment option for decompensated cirrhosis and ALF. However, Transplantation Society Guidelines recommend that LT candidates have resolved COVID-19 symptoms with two negative PCR tests done at least 24 hours apart before proceeding to LT. 4 Herein, we report a case of ALF resulting in LT in a patient with COVID-19 and ongoing SARS-CoV-2 polymerase chain reaction (PCR)-positivity. The patient's timeline is shown in Figure 1 . She was admitted to a dedicated COVID-19 ICU. Intermittent hemodialysis (IHD) was initiated (day 4) and continuous renal replacement therapy (CRRT) was started on day 6. Treatment for SARS-CoV-2 included 2 units of convalescent plasma (day 5-6). Hepatic and renal failure precluded the use of remdesivir. Due to a direct antiglobulin test (gel-based assay) that was positive (regular direct antiglobulin test, tube-based assay, was negative) and ongoing hemolysis, intravenous (IV) methylprednisolone 125 mg daily was administered. She also had severe weakness in a lower motor neuron pattern and diffuse muscle pain. Creatinine kinase was elevated to a peak of 6512 U/L and urine myoglobulin was positive indicating rhabdomyolysis. There was concern for COVID-19-related myopathy; prednisone was initiated at 60 mg per os daily with significant improvement in myalgias. An EMG demonstrated a diffuse myopathic process. A deltoid muscle biopsy showed severe, active myopathy, myosinolysis, and denervation atrophy favoring critical illness myopathy, but a superimposed process could not be ruled out given prior empiric prednisone treatment. Creatinine kinase normalized on day 39. She was dismissed home after a physical rehabilitation stay and is without cognitive or neurologic deficits. We present a case of LT in the setting of a persistently positive SARS-CoV-2 PCR. Although there have been reports on COVID-19 in transplant recipients in the postoperative period, to our knowledge, this is the first intentional LT performed in a patient with active SARS-CoV-2 PCR positive infection. 13 One other case has been reported; however, the patient was PCR negative prior to LT. 14 Liver injury is widely reported in the setting of COVID-19, although ALF due to COVID-19 seems to be exceedingly rare and reported cases have potential competing diagnoses for ALF. 9 infection. 13, 16, 17 We used our standard renal-sparing immunosuppression protocol (basiliximab, corticosteroids, mycophenolate mofetil), except we held mycophenolate mofetil given her active SARS-CoV-2 infection and data suggesting increased mortality in LT recipients on mycophenolate mofetil. 12 We started remdesivir immediately after Given the potential for excellent long-term outcome for LT performed for ALF due to WD, and the near-certainty of mortality without transplantation, we opted to proceed to LT despite active SARS-CoV-2. At present, the patient has excellent graft function and has returned home. Given the high prevalence of SARS-CoV-2 infection, and the low incidence of reported ALF, it is imperative to look for another cause of liver disease when patients with ALF test positive for SARS-CoV-2. Although it is difficult to provide a general conclusion for proceeding to LT in the context of ongoing SARS-CoV-2 infection, we demonstrated that it is possible to do so successfully Additional supporting information may be found online in the Supporting Information section. 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Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement Copper-induced acute rhabdomyolysis in Wilson's disease Covid-19-associated myopathy caused by type I interferonopathy Acute liver failure as the initial manifestation of Wilson disease triggered by human parvovirus b19 infection Acute varicella infection heralding Wilsonian crisis Repeat COVID-19 molecular testing: correlation of SARS-CoV-2 culture with molecular assays and cycle thresholds when the underlying reason for ALF is not driven by SARS-CoV-2, there is limited pulmonary involvement and significant improvement in the "cytokine storm" as determined by inflammatory markers. The criteria applied herein for patient selection and LT timing needs to be validated in future studies. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Deidentified data are available on reasonable request.