Worldwide management of hepatocellular carcinoma during the COVID-19 pandemic

Table 1 Recommendations from main international liver society

	APASL	HC-FMUSP	EASL-ESCMID	ILCA	AASLD
Liver resection	Generally, liver resection with curative intent should not be delayed. However, in cases of high risk of decompensation or comorbidities, surgical intervention should be postponed or alternative therapy such as ablation should be adapted	The indications for surgical resection are the same as those during the prepandemic period and are as follows (18-21): In patients without cirrhosis: Solitary or oligonodular HCCs; in patients with chronic liver disease: Solitary tumors (regardless of size), preserved liver function (Child–Pugh A), and absent or mild portal hypertension (small caliber esophageal varices and platelets 100000/mm3)			Can consider bridging locoregional therapy (TACE/TARE/SBRT), systemic therapy, or active monitoring if necessary to delay surgery
LT	LT for patients with poor short-term prognosis should not be delayed. Elective living donor transplantation may be suspended. In patients with complete response to bridging therapy on transplant list, transplantation may be suspended	LT is the treatment of choice for patients with early HCC (BCLC-A) and impaired liver function (Child–Pugh B/C), clinically significant portal hypertension, and those with early HCC who are not candidates for resection	Patients on the LT waiting list with decompensated cirrhosis are at high risk of severe COVID-19 and death following SARS-CoV-2 infection. We therefore recommend that LT centers aim to restore transplantation services following the peak of the COVID-19 epidemic wherever possible. In centers with ongoing resource limitations, LT should be prioritized for patients with poor short-term prognosis including those with acute liver failure, ACLF, high MELD score (including exceptional MELD points), and HCC at the upper limits of the Milan criteria	Unique considerations of COVID-donor derived infection and immunosuppression post-transplant. Consider cessation of LDLT (lower MELD) and delaying transplant in those with complete response	Limit the number of patients coming to clinic for transplant evaluations. Consider evaluating only patients with HCC or those patients with severe disease and high MELD scores who are likely to benefit from immediate liver transplant listing
Ablation	Ablation with curative intent should not be delayed. Ablation is an acceptable alternative to resection for cases of three or fewer tumors, each 3 cm or smaller, and of Child–Pugh class A or B liver dysfunction	Radiofrequency ablation can be performed in patients with very early (BCLC-0) or early (BCLC-A) HCC and have solitary nodules < 3 cm in size			Reserve for those with best chance of response (size < 3 cm) and can consider SBRT
Vascular intervention	Vascular interventions may be postponed because they are used as cytoreductive treatments in most cases. Vascular interventions should be suspended in cases of risk of decompensation or comorbidities that increase the risk of severe COVID-19	TACE/TAE: Can be performed in patients with solitary nodules > 3 cm in size as local disease control or as a “bridge treatment” to surgery			Consider TACE for single or multifocal HCC. Consider TAE, DEB-TACE or TARE instead of TACE and perhaps systemic therapy in some patients with large tumor burden
Radiation therapy	Radiation therapy for cases of symptom control or at low risk of progression may be postponed. However, radiation therapy for function- or life-threatening situations have to be treated without delay. The course of radiation should be shortened when appropriate	SBRT: Can be considered in patients who have contraindications to RFA or TACE/TAE
Systemic therapy	Oral tyrosine kinase inhibitors would be better than infusion regimens during the pandemic. The impact of immunotherapy on the course of COVID-19 is not known	Systemic therapy: May be used as a “bridge therapy” for surgery in patients with contraindications to other treatments

ILCA: International Liver Cancer Association; AASLD: American Association for the Study of Liver Disease; SBRT: Stereotactic body radiation therapy; COVID-19: Coronavirus disease 2019; TACE/TAE: Transarterial chemoembolization/embolization; LT: Liver transplantation; HCC: Hepatocellular carcinoma; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; LDLT: Living donor liver transplantation; MELD: Model for end-stage liver disease; ACLF: Acute-on-chronic liver failure; EASL-ESCMID: European Association for the Study of the Liver-European Society of Clinical Microbiology and Infectious Diseases; APASL: Asian-Pacific Association for the Study of the Liver society; RFA: Radio frequency ablation; TARE: Transarterial radioembolization; BCLC: Barcelona Clinic Liver Cancer; DEB-TACE: Drug-eluting bead transarterial chemoembolization; HC-FMUSP: São Paulo Clínicas Liver Cancer Group Multidisciplinary Consensus Statement.