Arushi Bidhuri
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Written By: Arushi Bidhuri | Published : September 4, 2021 5:23 PM IST
Outcome of COVID-19 infection in liver transplant recipients under immunosuppression
SARS-CoV-2, the virus that causes Covid-19 infection, is associated with a higher mortality rate among patients suffering from an underlying disease such as diabetes, coronary artery disease, kidney disease and non-alcoholic fatty liver disease. Experts have also warned that patients who have had organ transplants are more vulnerable to Covid-19 infections even after a second dose of the vaccine. An independent study conducted by the Department of Gastroenterology and Hepatology and Centre for Liver & Biliary Sciences, Max Super Speciality Hospital, Saket under the aegis of Prof (Dr) Subhash Gupta, Chairman, Centre for Liver & Biliary Sciences, Max Super Speciality Hospital, Saket has suggested that uncomplicated liver transplant recipients without comorbidities, who get affected by Coronavirus/SARS-CoV-2 do not have a poor outcome.
For the study, the researchers examined 2,182 adult Indian patients who had undergone liver transplantation at the Centre for Liver & Biliary Sciences since 2006 and on regular follow-up.
Commenting on the reason behind conducting the study, Dr Gupta said, "It is an established fact that patients who have undergone liver transplantation (LT) are on long-term immunosuppressive medications which predispose them to infections. The study is significant because the data regarding the impact of SARS-CoV-2 infection in post LT patients is conflicting, and risk factors for the outcome are also not well defined. While initial studies suggested that patients on immunosuppressive medications, such as liver transplant recipients, are at increased risk of severe COVID-19 and mortality, subsequent evidence did not support this finding. Since India is one of the worst affected countries in this pandemic, our study, approved by the MAX HEALTHCARE institute's ethical committee, shares the clinical characteristics, demographics and outcomes of SARS-CoV-2 infection in our post LT population."
Of the 3096 patients who underwent a liver transplant at the centre since 2006, 2182 adult recipients were under regular follow-up and in communication with the centre during the pandemic. Of these, 88 patients (3.71%) reported SARSCoV-2 infection, six adults and a child were excluded from the analysis, and 81 patients were included. The average age of SARS-CoV-2 infected patients in the study was 51.3 years, and 74 patients (91.4%) were males. 21 (25.9%) patients infected with SARS-CoV-2 underwent liver transplants within one year. 36 (44.4%) patients received a transplant between one and five years while 24 (29.6%) patients were transplanted more than 5 years ago.
A total of COVID infected 81 patients received transplants for Alcohol-related liver disease (29.6%) patients, NASH related cirrhosis (27.2%), cryptogenic cirrhosis (18.5%) and HBV-related cirrhosis (9.9%). 22 patients i.e. 27.1% of the SARS-CoV-2 infected patients had diabetes mellitus (DM) as the most common comorbidity while hypertension was present in 3.7% of patients, and 7.4% of patients had DM2 with hypertension. Four of them had chronic kidney disease (CKD) along with DM2, of which one had stage 2 CKD and the other three patients had stage 3 CKD. 59 or 72.8% were on two immunosuppressants - CNIs and mycophenolate mofetil. 10 or 12.3% of them were receiving three immunosuppressive drugs calcineurin inhibitors (CNIs), mycophenolate mofetil and prednisolone. 11 or 13.5% of patients were taking single immunosuppressive medication (tacrolimus) only. One patient was on steroids with tacrolimus and everolimus due to a recent rejection episode.
Based on the duration since liver transplant, patients who were infected with SARS-CoV-2 were divided into three groups. Group A had 21 patients who got the disease within one year of a liver transplant, Group B had 36 patients who got LT 1 5 years ago and group C had 24 patients who got LT more than 5 years ago. Of these groups, only one or 4.8% of patients died in group A as compared to 6 or 16.7% and 7 or 29.2% in groups B and C respectively. Although mortality was higher in group C, the difference was not statistically significant.
In the study group, 35 or 43.2% of the patients had one or more comorbidities. Eleven or 31.4% of patients died because of COVID-19 in this group. Only 3 or 6.5% of patients' death occurred due to SARS-CoV-2 infection among transplant recipients without any comorbidity. (P = 0.003). On logistic regression analysis, advanced age and presence of comorbidities were independent predictors of death due to COVID-19.
In the observational study of 81 liver transplant recipients with SARS-CoV-2 infection, 14 (17.3%) patients died because of COVID-19. Most of the patients had mild disease only and recovered completely. Eighty-one (3.71%) adult liver transplant recipients reported SARS-CoV-2 infection as compared to the 2.06% prevalence of laboratory-confirmed cases in the general population.
However, true seroprevalence in the general population is likely to be much higher due to under testing and a large proportion of asymptomatic cases. Deaths were more common in patients with comorbidities and advanced age. The presence of DM2 and chronic kidney disease has been strongly associated with poor outcomes in individuals with SARS-CoV-2 infection. Thus, rather than the post-liver transplantation status, it was the presence of comorbidities or other risk factors such as advanced age which may have been responsible for mortality."
Talking about the conclusion of the study, Dr Gupta said, "In our study, all patients except one who died had received a liver transplant more than a year ago. After 1-year of transplantation, a dose of immunosuppressive medication is usually significantly reduced and therefore the cytokine storm may not be ameliorated. In our study population, COVID-19 related mortality was 17.3% which is comparable to the 18.2 % mortality seen in older patients with co-morbidities. Our study suggests that uncomplicated liver transplant recipients who acquire SARSCoV-2 do not necessarily have higher mortality as compared to similar non transplanted populations. However, more studies are needed with the larger patient population and matched control groups to reach a firm conclusion."
Discussing the limitations of the study, Dr Gupta said, "Although testing for SARS-CoV-2 infection was liberal in our country, it may still be underdiagnosed in our study population as asymptomatic and mildly symptomatic patients who recovered swiftly may have avoided testing. We did not compare mortality in our liver transplant recipients with immunocompetent matched COVID-19 patients. That could have provided a better understanding of the role of immunosuppressants in COVID-19 related immune dysregulation. This should be addressed in future studies. We could not study the impact of individual comorbidities on mortality due to a limited number of patients. In addition, details of inflammatory markers and serum level of immunosuppressive medications were not included in the study as only 43% patients were hospitalized, and remaining patients were managed at home."
