Outcome of Liver Cancer Patients With SARS-CoV-2 Infection

An International, Multicentre, Cohort Study

Sergio Muñoz-Martínez; Victor Sapena; Alejandro Forner; Jordi Bruix; Marco Sanduzzi-Zamparelli; José Ríos; Mohamed Bouattour; Mohamed El-Kassas; Cassia R. G. Leal; Tudor Mocan; Jean-Charles Nault; Rogerio C. P. Alves; Helen L. Reeves; Leonardo da Fonseca; Ignacio García-Juárez; David J. Pinato; María Varela; Saleh A. Alqahtani; Mario R. Alvares-da-Silva; Juan C. Bandi; Lorenza Rimassa; Mar Lozano; Jesús M. González Santiago; Frank Tacke; Margarita Sala; María Anders; Anja Lachenmayer; Federico Piñero; Alex França; Maria Guarino; Alessandra Elvevi; Giuseppe Cabibbo; Markus Peck-Radosavljevic; Ángela Rojas; Mercedes Vergara; Chiara Braconi; Sonia Pascual; Christie Perelló; Vivianne Mello; Carlos Rodríguez-Lope; Juan Acevedo; Rosanna Villani; Clemence Hollande; Valérie Vilgrain; Ahmed Tawheed; Carmem Ferguson Theodoro; Zeno Sparchez; Lorraine Blaise; Daniele E. Viera-Alves; Robyn Watson; Flair J. Carrilho; Carlos Moctezuma-Velázquez; Antonio D'Alessio; Massimo Iavarone; Maria Reig


Liver International. 2022;42(8):1891-1901. 

In This Article

Abstract and Introduction


Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.

Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered.

Results: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84–11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24–12.74], 11.76% [95% CI 4.73–22.30], 20.69% [95% CI 11.35–31.96] and 34.52% [95% CI 17.03–52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49–4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29–7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection.

Conclusions: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.


After the start of the Coronavirus Disease 2019 (COVID-19) in 2019, all countries worldwide made a huge effort to face up to the health issues derived from the pandemic. In December 2020 the first SARS-CoV-2 vaccine was authorized by the U.S. Food and Drug Administration, while it was granted a conditional marketing authorization by the European Medicines Agency.[1] Nevertheless, just after the first wave, further waves emerged and the sequelae of the pandemic will probably continue for years. Our previous study[2] showed that all treatments, except systemic therapy, had relevant interruptions during the first wave around the World. Indeed, 48% of the centres decreased the number of physicians devoted to managing liver cancer. Gandhi et al.[3] also assessed the impact on COVID-19 in 14 Asia-Pacific countries and observed similar results. One of the main harms of the pandemic according to Muñoz et al.[2] was the delay in liver cancer diagnosis because of the modification of screening, reported in 80.9% of the participating centres. A similar impact of COVID-19 was also reported for other cancers[4–7] and in the current study, here we characterize the profile and evolution of those patients incidentally diagnosed with liver cancer as a result of the assessments done because of COVID-19 infection diagnosis and those who had a history of liver cancer.

A microsimulation model on five cancers (breast, cervix, colorectal, prostate and stomach) found that delays in diagnosis will result in a worse cancer stage at presentation, leading to worse survival outcomes.[8] Liver cancer was not represented in that model and such data should be confirmed in the liver cancer realm. A second harm of the pandemic is the COVID-19-related and non-COVID-19-related mortality.[9] In the liver cancer setting, the mortality analysis is complex because almost all hepatocellular carcinoma (HCC) patients and some of the intrahepatic cholangiocarcinoma (iCCA) patients present underlying cirrhosis.

Iavarone et al.[10] evaluated the 30-day mortality rate in cirrhotic patients but only 22% of them had active or history of liver cancer. Thus, there is neither mortality data nor information about the impact of the liver cancer stage in the outcome of patients diagnosed as a result of SARS-CoV-2 diagnosis. Lai et al.[11] analysed the indirect excess deaths (because of pandemic-induced healthcare service reconfiguration) on cancer patients from the United Kingdom. They concluded that cancer services had only partially recovered with the lockdown easing. They also suggested that this situation may contribute to substantial excess mortality and multimorbidity among cancer patients. According to their analysis, the 1-year liver cancer mortality in patients without comorbidities or with one or two comorbidities are 50.2%, 50.3% and 49.5% respectively. Here, again there is neither information about the liver cancer stage nor the impact of the 30-day mortality rate. They pointed out the urgent need to better understand and mitigate these excess mortality risks. The present analysis is the second part of the Liver cancer outcome in the COVID-19-pandemic (CERO-19) which aims to address the outcome of SARS-CoV-2 on liver cancer patients and to understand the confounding factors at the time of analysing their mortality.

The specific aims of the present analysis were (1) to describe the profile of patients with liver cancer as a result of the tests performed because of SARS-CoV-2 infection as well as their outcome; (2) to analyse the 30-day mortality rate of liver cancer patients with SARS-CoV-2 infection. This information will be key to understand the outcome of liver cancer patients who started oncologic treatments before or during the pandemic as well as the evolution of new liver cancer diagnosed during SARS-CoV-2 infection.