PMC:7242013 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7242013","sourcedb":"PMC","sourceid":"7242013","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7242013","text":"Synthesis of Liver Associations Recommendations for Hepatology and Liver Transplant Care During the COVID‐19 Pandemic\nHepatology and Patient Care During the COVID‐19 Pandemic\nLau and Ward\n\nWatch the interview with the author\nAbbreviations\nAASLD American Association for the Study of Liver Diseases\nALT alanine aminotransferase\nAPASL Asian Pacific Association for the Study of the Liver\nAST aspartate aminotransferase\nCHB chronic hepatitis B\nCHC chronic hepatitis C\nCLD chronic liver disease\nCOVID‐19 coronavirus disease 2019\nEASL European Association for the Study of the Liver\nHBV hepatitis B virus\nHCC hepatocellular carcinoma\nHCV hepatitis C virus\nHCW health care worker\nLT liver transplantation\nNAFLD nonalcoholic fatty liver disease\nNIH National Institutes of Health\nPPE personal protective equipment\nSARS‐CoV‐2 Severe Acute Respiratory Syndrome Coronavirus 2\nTKI tyrosine kinase inhibitor\nULD upper limit of normal\nTo navigate through the stormy unchartered ocean of SARS‐coV‐2 infections and coronavirus disease 2019 (COVID‐19), all practicing hepatologists and other clinicians caring for patients with liver disease need guidance based on the best documented and rapidly evolving knowledge regarding SARS‐CoV‐2 infection and COVID‐19. Prevention of SARS‐CoV‐2 transmission requires the redesign of patient workflow and other measures ensuring delivery of elective and emergency hepatology services without compromising the safety of patients and medical personnel. 1 , 2 Moreover, prevention of severe COVID‐19 and related mortality requires updating management of persons with chronic liver disease (CLD) to diagnose COVID‐19 and being vigilant for drug‐drug interactions and other potential complications of COVID‐19 in persons with CLD. 3 To respond to an urgent need for such information, the Asian Pacific Association for the Study of the Liver (APASL) recently published recommendations of an expert committee to guide infection control and clinical management of patients with CLD during the COVID‐19 pandemic. 4 Previously, two other regional liver associations, American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL), convened expert panels with the same objectives. 5 , 6 This review summarizes the recommendations of the three liver associations for clinical practices to prevent SARS‐CoV‐2 transmission and protect persons with CLD from health risks posed by the emerging COVID‐19 pandemic (Table 1).\nTable 1 Selected AASLD, APASL, and EASL Recommendations for Liver Disease Management During the COVID‐19 Pandemic\nRecommendations AASLD APASL EASL\nLimit nosocomial transmission Prioritize patients to limit in‐person care\nOn arrival, screen patients for COVID‐19 symptoms, exposures; if suggestive of COVID‐19, refer care per clinic’s protocol for symptomatic patients\nUse telemedicine alternatives for routine care\nReduce routine laboratory and imaging monitoring\nPrescribe 90 days of medications\nCancel all elective/nonurgent endoscopic procedures and biopsies\nLimit in‐clinic evaluations for transplant\nLimit clinical trial activity to essential clinical trials\nLimit HCWs providing care or on patient rounds\nHCWs follow recommendations for PPE Use telemedicine alternatives for routine care\nMinimize number of HCWs caring for patients\nMinimize number of HCWs on patient rounds\nCancel elective, nonurgent endoscopies and liver biopsies\nHCWs follow recommendations for PPE Limit in‐person care to urgent cases\nRemodel clinic space for social distancing\nUse telemedicine for routine care; postpone specialist visits\nReduce frequency of laboratory monitoring and obtain locally\nHCWs follow recommendations for PPE\nEvaluate and care for patients with COVID‐19 for liver disease Prioritize for COVID‐19 testing: (1) patients with cirrhosis, (2) patients with CLD receiving immunosuppressive medications, and (3) patients with new‐onset encephalopathy or other acute decompensation\nRegularly monitor liver biochemistries\nConsider non‐COVID‐19 etiologies for liver disease: (1) exacerbation of preexisting CLD or (2) drug‐induced hepatotoxicity\nUse acetaminophen 2 g/day as preferred medication\nUse nonsteroidal anti‐inflammatory drugs as needed\nConsult the University of Liverpool document to assess possible drug interactions Follow WHO guidelines for COVID‐19 diagnosis\nConsider NAFLD as a prognostic factor for severe COVID‐19\nScreen patients for hepatitis B surface antigen\nConsider HBV prophylaxis prior to use of anti‐IL‐6, other immunosuppressive therapy\nMonitor liver function tests of patients with CLD\nBe alert to possible drug hepatotoxicity\nDecompensated CLD and ALT \u003e5 times ULD contraindications for remdesivir therapy\nPrioritize persons with CLD for clinical trials Test for COVID‐19 patients with acute decompensation or acute‐on‐chronic liver and per institution’s practices\nPersons with NAFLD likely to have comorbidity risk factors for severe COVID‐19\nConsider patients with CLD/COVID‐19 for early admission and clinical trial\nUse acetaminophen (2–3 g/day is generally safe)\nLimit use of nonsteroidal anti‐inflammatory drugs\nTest for COVID‐19 patients with acute decompensation or acute‐on‐chronic liver and per institution’s practices\nPersons with NAFLD likely to have comorbidity risk factors for severe COVID‐19\nConsider patients with CLD/COVID‐19 for early admission and clinical trial\nUse acetaminophen (2–3 g/day is generally safe)\nLimit use of nonsteroidal anti‐inflammatory drugs\nManage hepatitis B; hepatitis C Continue HBV and HCV treatment of patients with COVID‐19\nProceed with HBV and HCV treatment in patients without COVID‐19 as clinically warranted\nDo not consider HBV treatment in patients with COVID‐19 unless flare is suspected Continue HBV and HCV treatment of patients with COVID‐19\nProceed with HBV and HCV treatment in patients without COVID‐19 as clinically warranted\nDo not consider HBV treatment in patients with COVID‐19 unless flare is suspected\nDocument discussion with patient regarding CLD diagnosis and management\nManage patients with HCC Continue HCC surveillance schedule for high‐risk subjects; 2‐month delay is acceptable\nDocument discussion of risks and benefits of delaying surveillance with patient\nProceed with HCC treatments as appropriate Continue therapy for non‐COVID‐19 patients\nFor patients with HCC with COVID‐19, postpone elective transplant and resection surgery, withhold immunotherapy Maintain care per guidelines\nAdmit early if COVID‐19 is diagnosed\nConsider postponing HCC therapies\nManage pretransplant and posttransplant patients Screen donors and recipient for COVID‐19\nDo not postpone transplants (an essential medical service, CMS Tier 3b)\nNotify patients of possible extended waiting times on transplant list\nHave low threshold for admitting patients on transplant waiting list diagnosed with COVID‐19\nFor posttransplant patients with moderate COVID‐19, consider reduction of immunosuppression therapy as appropriate\nDo not reduce immunosuppressive therapy in patients with mild COVID‐19 disease Test donors and recipient for COVID‐19\nLimit transplant listing to emergency and urgent cases\nLook for SARS‐COV‐2 prior to organ procurement; defer donors with evidence of infection\nConsider specific COVD‐19 consent for patients on transplant waiting list\nFor posttransplant patient with moderate COVID‐19, consider reduction of immunosuppression therapy as appropriate\nDo not reduce immunosuppressive therapy in patients with mild COVID‐19 disease Maintain care per guidelines\nLimit transplantation listings to patients with poor short‐term prognosis\nVaccinate against pneumonia and flu\nAvoid reductions in immunosuppressive therapy\nDo not reduce immunosuppressive therapy in patients with mild COVID‐19\nJohn Wiley \u0026 Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.\n\nHow to Protect Medical Personnel and Patients With Liver Diseases From SARS‐CoV‐2 Infection?\nTo this end, all three associations recommend physical distancing by limiting face‐to‐face consultations to urgent situations, routine patient contact via telemedicine and phone visits, and use of local laboratories and pharmacies to reduce clinic and hospital visits and patient travel. AASLD guidance is most stringent by discouraging clinic entry of anyone with fever or other COVID‐19 symptoms and SARS‐CoV‐2 testing of these patients. All recommend COVID‐19 testing of liver transplant donors and recipients and patients with encephalopathy or acute decompensation. Recent data showed that many SARS‐CoV‐2–infected patients are asymptomatic, yet capable of transmitting the disease. 7 Ideally, all patients with a history of close contact with cases of possible or confirmed COVID‐19 or from high‐prevalence regions should be tested. APASL recommends SARS‐CoV‐2 testing based on clinical and epidemiological factors. EASL recommends following an institution’s practice. AASLD and APASL describe the personal protective equipment (PPE) requirements for endoscopy and other procedures. Like SARS‐CoV‐2 testing, the limiting factor is the availability of PPE. Without adequate supply, many elective procedures will need to be canceled.\nModifications of the practice of liver transplantation (LT) are recommended by all three associations. With the potential risks of SARS‐CoV‐2 transmission, aggravated by the limited supply of PPE and other resources, many governments have restricted elective medical procedures, including LT. However, in the United States, LTs are considered “high‐acuity surgery” and can proceed as medically warranted. 8 All associations recommend limiting LT to patients with high Model for End‐Stage Liver Disease scores, risk for decompensation, or hepatocellular carcinoma (HCC) progression.\n\nShould LT be Performed in COVID‐19 Recipients, and Should One Use Organs Procured From COVID‐19 Donors?\nAASLD recommends against LT in patients with COVID‐19. LT can proceed 21 days after symptom resolution and negative diagnostic tests in recipients. APASL suggests balancing risks of delaying LT against risks of transmission to health care workers (HCWs). EASL does not specifically address this issue. To minimize the risk to HCWs, APASL recommends LT be performed only in patients with COVID‐19 with at least two consecutive negative SARS‐CoV‐2 nucleic acid results and the presence of antibodies. Finally, there is debate whether immunosuppression should be reduced during the COVID‐19 pandemic. So far there are no data to suggest that posttransplant immunosuppression is a risk factor for severe COVID‐19. In contrast, reducing immunosuppression may increase the risk for graft rejection. All three associations recommend against reducing immunosuppressive therapy in LT patients with mild COVID‐19. The dose of azathioprine, mycophenolate, and calcineurin inhibitor may be reduced in the setting of severe lymphopenia or worsening pulmonary status.\n\nWhat Are the Roles of a Hepatologist in the Management of a Patient With COVID‐19?\nElevation of serum transaminase levels is commonly observed in patients with COVID‐19, and a hepatologist might therefore be consulted. All of the guidance suggests that the underlying cause of liver injury may be related to SARS‐CoV‐2 infections, exacerbation of preexisting CLD, or drug‐induced hepatotoxicity. AASLD and APASL provide an algorithm to clinical evaluations (Fig. 1). A key question is whether patients with CLD have a higher risk for severe COVID‐19. AASLD and APASL suggest nonalcoholic fatty liver disease (NAFLD) as an independent prognostic factor, and patients with CLD should be prioritized as candidates for COVID‐19 drug trials. EASL and AASLD mention that patients with NAFLD are more likely than others to have other comorbidity risks for severe COVID‐19. To date, there is no evidence that patients with stable CLD due to chronic hepatitis B (CHB) or chronic hepatitis C (CHC) have increased susceptibility to SARS‐CoV‐2 infection. It is controversial whether there is an increased risk for flare‐up of CHB or CHC during COVID‐19 and whether prophylactic therapy should be started. Both AASLD and APASL recommend continuing treatment for CHB or CHC in patients with COVID‐19. APASL recommends prophylactic hepatitis B therapy for those planned for anti‐IL‐6 or other immunosuppressive therapy. Initiating prophylactic hepatitis C therapy is not recommended. If there is any suggestion of a flare‐up, therapy should be initiated in patients who are not already receiving hepatitis B or hepatitis C treatment.\nFig 1 Approach to the patient with COVID‐19 and elevated serum liver biochemistries. Reproduced with permission from Hepatology. 5 Copyright 2020, American Association for the Study of Liver Diseases. On May 1, 2020, remdesivir, a nucleotide RNA polymerase inhibitor, was authorized by the US Food and Drug Administration under Emergency Use Authorization for treatment of those patients hospitalized with severe COVID‐19. 9 APASL and AASLD recommend close monitoring of liver function in patients, especially those with CLD, who are treated with remdesivir. Patients with decompensated CLD and those with alanine aminotransferase (ALT) \u003e5 times upper limit of normal should not be treated with remdesivir.\n\nHow Should We Modify Management of Patients With HCC?\nTo avoid SARS‐CoV‐2 exposures, all associations recommend reducing patient visits and a delay in HCC ultrasound surveillance. It is uncertain whether HCC treatment should be deferred or started as usual in patients with COVID‐19 with newly diagnosed HCC, and whether tyrosine kinase inhibitors (TKIs) or checkpoint inhibitors should be stopped in patients with COVID‐19 who are already receiving such therapy. Delaying or withdrawing treatment increases the risk for HCC progression with detrimental outcomes, whereas surgical resection may increase risk for transmission to health care personnel, and checkpoint inhibitors might worsen COVID‐19 by exacerbating a cytokine storm. AASLD recommends HCC treatments should proceed. EASL recommends locoregional therapies should be postponed whenever possible and immune‐checkpoint inhibitor therapy be temporarily withdrawn. TKI in nonsevere COVID‐19 should be taken on a case‐by‐case basis. APASL recommends postponing elective transplant/resection surgery, whereas radiofrequency ablation, transcatheter arterial chemoembolization, TKI, or immunotherapy can be initiated with change of immunotherapy schedules to every 4 to 6 weeks.\n\nHow to Conduct Clinical Trials?\nBoth APASL and AASLD recommend using alternative physical distancing processes for study assessments to reduce SARS‐CoV‐2 exposure. APASL specifically recommends seeking local regulators and institutional review board approval of the contingency measures during the COVID‐19 pandemic, obtaining trial participant’s consent, and documentation of all deviations from the contingency measures. These recommendations align with US National Institutes of Health (NIH) revised guidance for NIH‐supported clinical research. 10\n\nSummary\nAPASL, AASLD, and EASL strongly recommend changes in patient workflow and clinical procedures to protect HCWs and patients from SARS‐CoV‐2 infection. Similarly, the associations generally agree on approaches to evaluation and treatment of patients with COVID‐19 for liver disease, and management of patients with HCC and post–liver transplant patients with slight differences in the populations targeted for SARS‐CoV‐2 testing. These recommendations will evolve with further clinical experience and data from randomized controlled trials. For now, the liver associations provide the best available advice for the management of CLD during the COVID‐19 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