COVID-19 and the Liver: A 2021 Update

Catherine W. Spearman; Alessio Aghemo; Luca Valenti; Mark W. Sonderup


Liver International. 2021;41(9):1988-1998. 

In This Article

Management and Follow-up of Patients With CLD, HCC and Liver Transplant Recipients

The scope of management is dependent on the phase of the pandemic in a given country or region and the demands on healthcare personnel and resource constraints.[66,67] The American Society for the Study of Liver Disease, EASL-ESCMID, World Gastroenterology Organization and APASL have published detailed guidance documents on the management of patients with CLD and liver transplant patients during the COVID-19 pandemic.[66–68,93]

New adult and paediatric patients with clinically significant liver disease should be prioritized viz. patients with jaundice, elevated ALT or AST >500 U/L, recent onset hepatic decompensation or newly diagnosed HCC. When limiting outpatient visits to those who must be seen in person, it is important to ensure an adequate supply of chronic medications and access to telephonic advice. All patients with CLD must receive influenza and pneumococcal vaccines.

Hepatocellular Carcinoma

Mortality in malignancy and COVID-19 is determined by age, gender and comorbidities and not the use of cytotoxic chemotherapy or other anticancer treatment. HCC surveillance must be continued in those at risk viz. cirrhosis, chronic hepatitis B, MAFLD and rising alpha-fetoprotein and done as close to the usual schedule as possible. An arbitrary 2-month delay in surveillance has been proposed as progression with poorer outcomes is associated with delaying interventions beyond two months.[66,94] The risks and benefits of delaying HCC surveillance must be discussed with the patient and the discussion documented. Images of new referrals of liver masses should be reviewed in a multi-disciplinary meeting prior to scheduling in-person visits. HCC systemic and ablative therapies or surgical resection should not be postponed.[66] In patients with COVID-19, the slow median doubling time of HCC supports a short delay in initiating HCC treatment.[95]

An international multicentre study, including 76 centres from Europe, South America, North America, Asia and Africa, revealed that 87% of centres had modified their clinical practice for liver cancer during the first wave with COVID-19: 80.9% modifying their screening programmes and 40.8% their diagnostic procedures; 50% cancelled curative and/or palliative treatments and 44.0% cancelled their liver transplantation programmes. The long-term impact of these modifications includes individuals presenting with advanced disease and no longer being candidates for curative procedures. About 65.2% centres modified their Clinical Trial treatments, and only 58.1% of centres were able to recruit new patients.[96]

Oncology nurses played an important role in the move from face–face visits to telephonic/video consultations. This active involvement of the Oncology nurse should be further developed together with optimal criteria for telephonic/video consultations.[96]

Decompensated Cirrhotics and Management of the Liver Transplant Waiting List

Transplant centres must assess their local situation and the impact of COVID-19 on patients awaiting transplantation on an ongoing basis. Transplant evaluation for patients with high MELD scores, risk of decompensation or HCC progression should be prioritized whilst considering constraints and utilization. Despite listing, potential recipients should be warned about expected reduction in organ recovery due to COVID-19-related limitations on institutional resources, risk of donor-derived disease transmission and concern around nosocomial SARS-CoV-2 infections.[66] There should be a low threshold for admitting transplant wait-listed patients with COVID-19. Any patient presenting with a new decompensation or ACLF must be tested for SARS-CoV-2 given up to 20% have no respiratory symptoms.[18]

Endoscopy is an aerosol-generating procedure and SARS-CoV-2 faecal-shedding persists for over a week after viral clearance from the lungs.[97,98] Swab tests are recommended before procedures if possible, and endoscopists should utilize full PPE, including N95 masks and double gloves. Endoscopic procedures for varices surveillance and treatment; ERCP and stent placement; percutaneous transhepatic cholangiography; TIPS; paracentesis and liver biopsies should be performed, as guided by the local active burden of COVID-19. Population vaccine coverage is as yet an unknown factor in mitigating risk. In patients with COVID-19, procedures should be limited to emergency endoscopic procedures only, for example, for management of variceal bleeds and biliary obstruction.

Liver Transplant Recipients

Minimizing in-person visits for post-transplant patients by maximizing use of telemedicine reduces the risk of nosocomial infections. Liver graft function and immunosuppressant levels can be monitored remotely whilst ensuring an adequate supply of immunosuppressants. The immune response (IL-6; IL-8, TNF-α) may be main driver for pulmonary injury in COVID-19, and thus immunosuppression may be protective. However, the reported mortality rates of COVID-19 in liver and other solid organ transplant recipients are around 25%. Immunosuppression should not be pre-emptively reduced nor MMF stopped as this may precipitate acute rejection.[66] There should be a low threshold for COVID-19 screening in transplant recipients who present with non-specific symptoms. Indications to lower the overall level of immunosuppression especially antimetabolites (azathioprine and MMF) are as usual: drug-induced lymphopenia; superimposed bacterial or fungal infections. Acute kidney injury appears to be more common in transplant recipients with COVID-19, and it is important to monitor calcineurin-inhibitor levels and adjust dosages as necessary. Drug–drug interactions with calcineurin- and mTOR-inhibitors must be considered.[99] Acute cellular rejection as the cause of deranged liver enzymes requires biopsy confirmation.[66] Anti-IL6 has not been shown to increase the risk of acute cellular rejection.