SARS-CoV-2 infection in liver transplant recipients: collaboration in the time of COVID-19

In The Lancet Gastroenterology & Hepatology, Gwilym Webb and colleagues present a multicentre analysis of outcomes for 151 liver transplant recipients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with data collected from March 25, 2020, to June 26, 2020.¹ The study, which included liver transplant recipients from 18 countries, represents the largest reported series of liver transplant recipients with confirmed SARS-CoV-2 infection to date. The study is also the first to include a comparison with patients with COVID-19 who have not received a liver transplant (n=627), having collected data from the electronic patient records of group of four hospitals in Oxford, UK. Importantly, the report provides an estimation of the risks for liver transplant recipients—who must balance the need for ongoing medical care with the need to remain isolated to reduce exposure to SARS-CoV-2—and also demonstrates the power of international collaboration in solving critical health-care challenges.

The study found no difference in the proportion of patients hospitalised between the liver transplant (124 [82%] patients) and the non-liver transplant cohort (474 [76%] patients; p=0·106). Despite an increased need for invasive ventilation support among recipients of liver transplants (30 [20%] vs 32 [5%] in the comparison cohort, p<0·0001), mortality was significantly lower in liver transplant recipients (28 [19%]) than in patients who had not received a liver transplant (167 [27%]; p=0·046). In a propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI −7·7 to 10·4]).

COVID-19 lung disease was the main cause of death in both groups and, importantly, there were no liver-related deaths among the transplant recipients. Multivariable analysis showed that factors associated with death among liver transplant recipients included age and creatinine concentration, as well as the presence of non-liver malignancy, whereas time from transplantation and type of immunosuppression were not related to risk of death. In the control population, multivariable analysis showed age, male sex, and diabetes to be the major risk factors for death. An additional notable finding was the higher rates of gastrointestinal symptoms in the liver transplant cohort, with 30% having abdominal pain, vomiting, or diarrhoea at diagnosis compared with just 12% of the control group having abdominal symptoms (p<0·0001).

There are some important caveats to the current analysis, such as the significant differences between the two cohorts. Although age, a key risk factor, was higher in the comparison cohort (median 73 years [IQR 55–84]) than the liver transplant cohort (median 60 years [47–66]), the liver transplant group had significantly greater proportions of men (68% vs 52% in the comparison cohort) and patients with diabetes (43% vs 23% in the comparison cohort). In addition, testing rates and thresholds for hospitalisation and admission to an intensive care unit might have differed across different centres and between the cohorts. Furthermore, the liver transplant cohort might have been subject to reporting bias because the data were collected from two registries of clinician-submitted cases; those clinicians might have been more likely to be aware of, and thus submit data on, hospitalised liver transplant recipients with more severe infections (as compared with the comparison cohort, which was drawn from consecutive cases of patients testing positive for SARS-CoV-2). However, this bias would only serve to strengthen the main conclusion that liver transplant recipients are not at a higher risk of death than patients who have not undergone transplantation.

It is essential to note that the median time from transplantation in this liver transplant cohort was 5 years (IQR 2–11), and thus the current experience cannot be extrapolated to patients who might acquire SARS-CoV-2 infection in the perioperative period.

Despite these limitations, Webb and colleagues' study¹ represents the largest experience of SARS-CoV-2 infection in liver transplant recipients to date, and found no adverse effect of liver transplantation on survival following COVID-19 compared with a UK population cohort of patients without liver transplant.

A recently published single-centre study of 36 kidney transplant recipients in the USA showed a similar rate of hospitalisation (78%), with a potentially higher rate of death (28%), although, unlike the present series of liver transplant recipients, at least some kidney transplant recipients were within weeks of transplantation.² A larger multicentre series of 144 kidney transplant recipients, which included only hospitalised patients, found a mortality rate of 32% in a cohort with a median time from transplantation of 5 years, although that study also included some patients with less than 1 year since transplantation.³

Whether there are actually differences in outcome between patients undergoing liver or kidney transplantation, or transplantation of other organs, remains to be determined, although the question is likely to be answered best by large collaborative efforts, as reflected in Webb and colleagues' study.¹ Despite the unprecedented challenges imposed by the current pandemic on all aspects of our lives, centres across the globe were able to work together to collect and analyse detailed outcome data for more than 700 patients with SARS-CoV-2 infection, thus providing crucial information on a potentially at-risk population, with an efficiency and scale only possible through international collaboration.