Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause.

BACKGROUND: Since January 2022, there has been an increase in reports of cases of acute hepatitis of unknown cause in children. Although cases have been reported across multiple continents, most have been reported in the United Kingdom. Investigations are ongoing to identify the causative agent or agents. METHODS: We conducted a retrospective study involving children referred to a single pediatric liver-transplantation center in the United Kingdom between January 1 and April 11, 2022. These children were 10 years of age or younger and had hepatitis that met the case definition of the U.K. Health Security Agency for confirmed acute hepatitis that was not hepatitis A through E and did not have a metabolic, inherited or genetic, congenital, or mechanical cause, in the context of a serum aminotransferase level greater than 500 IU per liter. We reviewed medical records and documented demographic characteristics, clinical features, and results of liver biochemical, serologic, and molecular tests for hepatotropic and other viruses, as well as radiologic and clinical outcomes. The outcomes were classified as an improving condition, liver transplantation, or death. RESULTS: A total of 44 children had hepatitis that met the confirmed case definition, and most were previously healthy. The median age was 4 years (range, 1 to 7). Common presenting features were jaundice (in 93% of the children), vomiting (in 54%), and diarrhea (in 32%). Among the 30 patients who underwent molecular testing for human adenovirus, 27 (90%) were positive. Fulminant liver failure developed in 6 patients (14%), all of whom received a liver transplant. None of the patients died. All the children, including the 6 who received liver transplants, were discharged home. CONCLUSIONS: In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established.

Successful liver transplantation for hepatitis B-related acute liver failure in a patient with active COVID-19.

The emergence of coronavirus disease 19 (COVID-19) has significantly disrupted liver transplantation worldwide. Despite significant, collective experience in treating liver transplant recipients with COVID-19, there remains a paucity of data to guide the management of transplant candidates with acute COVID-19 who require urgent transplantation. We present the case of an otherwise well, 39-year-old female presenting for urgent liver transplantation for acute liver failure secondary to hepatitis B, with concomitant acute, mild COVID-19 due to Omicron BA.2. COVID-19 antivirals were not administered pre-transplant as the potential risk of hepatotoxicity precipitating further deterioration of liver function was not felt to outweigh the small, potential benefit of antiviral therapy. No effective SARS-CoV-2 monoclonal antibodies were available; however, the patient was previously vaccinated against SARS-CoV-2 with evidence of anti-spike antibodies at the time of COVID-19. Transplantation surgery and recovery were uncomplicated with no progression of COVID-19 post-transplant, hospital discharge was at day 14. At 30 days post-transplant the patient had recovered, with normal liver function and SARS-CoV-2 was not detectable on nasopharyngeal PCR. While the safety of transplantation of patients with acute COVID-19 cannot be assured by a single case, ours highlights the complex decision-making process undertaken and competing priorities that need to be balanced when assessing patients with acute COVID-19 who require urgent transplantation.

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

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.

Successful orthotopic liver transplantation in a patient with a positive SARS-CoV2 test and acute liver failure secondary to acetaminophen overdose.

SARS-CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on expert opinion, on managing patients with COVID-19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS-CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID-19 manifestations and plasma exchange peri-operatively. We recommend a full work-up for OLT in COVID-19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID-19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.

Liver transplantation in the era of COVID-19.

Liver transplantation is considered the ultimate solution for patients with end-stage chronic liver disease or acute liver failure. Patients with liver transplant need special care starting from preoperative preparation, surgical intervention ending with postoperative care. Transplanted patients have to receive immunosuppressive therapy to prevent rejection. Such a state of immune suppression could predispose to different types of infections in liver transplant recipients. Currently, the world is suffering a pandemic caused by a new strain of the coronavirus family called COVID-19. Certain infection control precautions are needed to protect immunocompromised and vulnerable patients, including liver transplant candidates and recipients from acquiring COVID-19 infection. Restricting non-transplant elective surgical procedures, managing transplant patients in separate outpatient clinics, and in-patient wards can prevent transmission of infection both to patients and healthcare workers. Telemedicine can help in the triage of patients to screen for symptoms of COVID-19 before their regular appointment. Management of immunosuppressive therapy and drug-drug interactions in liver transplant recipients infected with COVID-19 should be cautiously practiced to prevent rejection and effectively treat the underlying infection. In this report, we are trying to summarize available evidence about different aspects of the management of liver transplant candidates and recipients in the era of COVID-19.