key: cord-1024661-zxwzc71w
authors: Pahari, Hirak; Shellagi, Nikhil; Nath, Barun
title: Deceased Donor Liver Transplantation in India in the COVID-19 Era: Current Scenario and Future Perspectives
date: 2020-06-11
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2020.06.004
sha: a9b5b87f0634018abe36fac458c08b0eb1868035
doc_id: 1024661
cord_uid: zxwzc71w

Abstract Coronavirus Disease 2019 (COVID-19) has been recently declared a global pandemic. As of June 5, 2020, over 75,000 cases have been reported with nearly 2,500 deaths in India alone. COVID-19 has severely impacted deceased donor liver transplant (DDLT) programs throughout the world. Acceptance of deceased liver donors have decreased worldwide due to the unknown risks associated with COVID-19 transmission or post-operative infection in the immediate post-transplant period, along with the risks to the healthcare workers in a multidisciplinary setting. In India, DDLT has come to a standstill in the setting of a national lockdown. Many national guidelines have emerged on how to safely perform transplantation as well on immunosuppressive regimes and care of the post-transplant patients. Here, we take a look at the current situation and summarize the different guidelines and future perspectives of DDLT in India in the COVID-19 era.

Coronavirus Disease 2019 (COVID -19) has been recently declared a global pandemic. As of June 5, 2020, over 75,000 cases have been reported with nearly 2,500 deaths in India alone. COVID-19 has severely impacted deceased donor liver transplant (DDLT) programs throughout the world. Acceptance of deceased liver donors have decreased worldwide due to the unknown risks associated with COVID-19 transmission or post-operative infection in the immediate posttransplant period, along with the risks to the healthcare workers in a multidisciplinary setting. In India, DDLT has come to a standstill in the setting of a national lockdown. Many national guidelines have emerged on how to safely perform transplantation as well on immunosuppressive regimes and care of the post-transplant patients. Here, we take a look at the current situation and summarize the different guidelines and future perspectives of DDLT in India in the COVID-19 era.

In December 2019, the first case of Coronavirus disease 2019 (COVID-19) infection was reported in Wuhan, China, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). [1] As of June 4, 2020, about 6.6 million cases have been diagnosed worldwide with over 380,000 deaths. [2,3] In India alone, over nearly 75,000 cases have been reported with over 2,400 deaths. [2,4] On March 11, 2020, the World Health Organization (WHO) declared COVID-19 as a global pandemic. [3] The healthcare sector around the world has been at the forefront of fighting against this epidemic, has led to strain on the economy and availability of resources. [5] COVID-19 has severely impacted solid-organ transplant programs throughout the world. The risk and outcomes of COVID-19 infection in liver transplant recipients are being studied all around the world. [6] [7] [8] There is still paucity of information regarding the overall safety of liver transplant recipients in the COVID-19 era. There is also the risk of transmission of COVID-19 from donor to recipient, surgical teams and other healthcare professionals involved in a multidisciplinary program like liver transplantation. Elective surgeries like Living Donor Liver Transplantation (LDLT) have been temporarily suspended in many countries according to their national guidelines. However, many countries continue to perform Deceased Donor Liver Transplantation (DDLT) based on modified donor and recipient criteria. [9] [10] [11] 

Acceptance of deceased liver donors in the past few months have decreased worldwide due to the unknown risks associated with COVID-19 transmission or post-operative infection in the immediate post-transplant period. [10, 12, 13] The risk of viremia in a liver donor (upto 15% cases) potentially places all recipients at risk of acquiring it through organ transplantation. [14, 15] Donor screening before acceptance has become mandatory around the world, using a combination of clinical, radiological and laboratory criteria. This varies in different countries between universal Nucleic Acid Testing (NAT) or Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) using nasopharyngeal (NP) swabs or bronchoalveolar lavage (BAL). [12] Recipient screening is also being done in a few countries using NAT or RT-PCR. [12] The American Society of Transplant Surgeons (ASTS) COVID-19 strike force has recommended testing in all donors. [15] The International Liver Transplant Society (ILTS) has issued a general guideline which suggests avoiding transplanting and immunosuppressing someone with developing or active disease. [16] Most countries have deferred transplantation for non-urgent indications, including LDLT, while DDLT has been continued for urgent indications such as Acute Liver Failure (ALF) or Acute on Chronic Liver Failure (ACLF) with appropriate consent. [7, [10] [11] [12] [17] [18] [19] [20] [21] So far, no donor derived infection has been reported.

India responded relatively early to the COVID-19 pandemic and because of early restriction and quarantine practices, spread has been limited. Yet community transmission is now prevalent with a surge predicted in the upcoming periods. The use of RT-PCR in Indian Council of Medical Research (ICMR) approved laboratories has been prevalent here, with 2 negative tests considered as confirmatory. Despite LDLT being the predominant type, DDLT has been progressively on the rise over the years between 2007 and 2018. [22] After the advent of COVID-19, many national and international guidelines have been put in place for appropriate With the advent of lockdown in India on March 29, 2020, NOTTO officially declared for DDLT to stop throughout the country until further notice. As a result of this, only 1 DDLT was performed throughout the country in the month of April, 2020. In May, 2020, the policy of phased relaxation of curfew measures, with gradual re-opening of business activity, was resumed. Eventually, in the second week of May, 2020, 2 cases of DDLT were performed. At present, transplant centers should attempt to minimize exposure of recipients to the healthcare setting by reducing the frequency of clinic visits and laboratory testing in a stable patient. All elective procedures such as stent removal or protocol biopsies can be deferred. We fell that transplant centers should develop their own guidelines to determine which symptomatic patients need evaluation, testing and management by the transplant center and which patients can be followed up closely by telephone or telemedicine.

At the time of writing this article, no universal agreements exist on the modification of immunosuppression in the immediate post-transplant period. There is a potential concern for higher risk of COVID-19 infection in solid organ transplant recipients. However, as of now, there is no clinical evidence of the risks of immunosuppression and standard immunosuppressive protocol should be used in the post-transplant period. [21, 22, 28, 29] However, during an active infection of COVID-19 in a post-transplant recipient, reduction of immunosuppressant may be considered, although withdrawal may result in acute rejection. [30] A study from New York has described their general approach to hold antimetabolites while reducing the dosage of other immunosuppressive agents as per clinical judgment. [7] 

The risk of COVID-19 infection in post solid organ transplant (SOT) recipients and their outcomes are being evaluated worldwide. In their initial report of 90 patients, Pereira et al.

reported the most common presenting features as fever, cough and dyspnea. Just over 50% of them required ICU care with a mortality rate of 18% (16 patients [31, 32] Despite these reports, more data will be required to determine the risk factors for mortality in COVID-19 infection in this population, as well as the optimal management strategies for both the treatment of COVID-19 and the immunosuppressive regimens.

As India continues its journey in the community transmission phase, the relaxation of the curfew and the growing burden on the economy will ultimately result in a phased return to normalcy. This will be followed by a resumption of the DDLT programs around the country, and eventually LDLT programs. Although, the anticipation of a peak in the country will make transplant surgeons wary of performing avoidable cases in the near future. The promise of a vaccine or a cure, though probable, is still a distant reality. Eventually, we may also have to succumb to the age-old strategy of herd immunity while we wait for a research breakthrough. Until then, with proper donor and recipient selection strategies, DDLT will try to strike a fine balance between life and death on the liver transplant waiting list.

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We would like to thank the National Organ and Tissue Transplant Organization (NOTTO) for their support.

The authors have no conflicts of interest to disclose.

We hereby certify that all the authors have NO affiliations with or involvement in any organization or entity with any financial interest or non-financial in the subject matter or materials discussed in this manuscript.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study