Impact of the COVID-19 Pandemic on Patients with End-Stage Liver Disease: One Virus—A Plethora of Consequences

The COVID-19 pandemic has been a once in a lifetime (hopefully) bitter experience for humanity in recent times, and has left an indelible mark on our lives. More than anything, it overwhelmed healthcare systems worldwide, and led to a tumultuous time for medical institutions, health professionals, and more so for patients who suffered from lack of medical care for non-COVID related ailments too. Prominent among them were end-stage liver disease patients waiting for a life-saving organ transplant, especially from deceased donors, since the whole process of identifying and maintaining a prospective donor, as well as actually realising a deceased donor liver transplant (DDLT) was a far-fetched dream during these times.

In the current issue of JCEH, Jothimani et al. report a retrospective single-center study evaluating the impact of the COVID-19 pandemic on the clinical outcome of patients waitlisted for DDLT. During the 2-year peak of the COVID-19 pandemic (2020–21), less number of patients were listed for a transplant, and less than a quarter of the patients listed actually underwent a DDLT. Almost half of the patients listed unfortunately died without a transplant in the year 2021, with a shorter time to death on the waitlist. These figures demonstrate the stark reality of the impact of the pandemic on healthcare resources and outcomes in patients with end-stage liver disease who were under-served due to a lack of resources, and a low organ donation rate. A competing risk survival model could also provide a more concrete idea of the significant impact of the pandemic on the wait list mortality in such a situation. Further, the organ donation to waitlist mortality ratio would have been worse in States where more hospitals were sharing the limited number of deceased donor organs donated within that region.

Several published studies showed that COVID-19 infection was associated with significant morbidity and mortality in patients with cirrhosis, especially those with decompensated cirrhosis.^{1, 2, 3, 4} Further, the incidence of ACLF (acute on chronic liver failure) significantly increased in patients with cirrhosis and concurrent COVID-19 infection, with associated higher mortality.^{1,2,5, 6, 7} The fear of acquiring COVID-19 infection, before or after liver transplantation (LT) lead to a significant reduction in LT numbers, and patients with decompensated cirrhosis remained at a risk of wait list mortality.⁸ Also, those who did undergo LT were sicker, with higher MELD scores, and hence, post operative morbidity was higher.

Jothimani et al. report an experience from South India, a region where the organ donation rate is higher as compared to the rest of the country, and consequently the number of DDLTs performed are higher. Living donor liver transplantation (LDLT) is by far the predominant type of LT performed in India (85% LDLTs vs. 15% DDLTs). The LDLT scenario was also significantly affected by the pandemic, because in addition to the risk of infection in the recipient, healthy living donors were also at a risk perioperatively. The Liver Transplant Society of India, the Indian Society of Organ Transplantation and the NOTTO tried their best to keep pace with, and smoothen the path for transplant professionals and Institutes to some extent, by proposing (and updating) guidelines for transplantation and vaccination from time to time.^{9, 10, 11}

During this period, studies in recipients (in the early and late post-LT period) showed that the risk of mortality due to COVID-19 was generally driven by higher age and comorbidities, including diabetes, kidney disease, history of malignancy.^{12, 13, 14, 15, 16} It was found that while immunosuppression could attenuate inflammatory response to COVID-19, it had the potential to also increase virological injury and risk of secondary infections and could prolong viral shedding.

Despite all these concerns, it was encouraging to note how some transplant centers managed to continue their LT activity, with acceptable outcomes in selected patients (albeit sicker, with higher MELD scores). LDLT proved to be the silver lining in some situations where urgent transplants were required, although the involvement of a living donor (and the risk of infection) did not make the process easy.¹⁷ Centers needed to formulate and follow not only isolation and care protocols for patients and donors, but also for the surgical teams, where the entire team was divided into sub-units working alternately so that if any member was infected, the other team could be functional. In short, an entire restructuring of the LT program was required before transplant activity could be restarted and continued.^18,19

The COVID-19 pandemic affected patients with liver disease (and those who initially did not have liver disease too) in many ways beyond just the lower chance of having a transplant, or the poor outcomes thereof. Several pertinent publications from Indian Centers focussed on occurrence of liver disease following intake of drugs or COVID-19 vaccines used for prevention of infection^20,21; post COVID-19 cholangiopathy requiring even salvage LT in some cases²²; and the collateral impact on patients with liver diseases (even without actually acquiring the infection).²³

The COVID-19 pandemic forced patients as well as doctors and medical Institutions into experiencing a true sense of helplessness and hopelessness at times. Thousands were fighting for survival due to severe COVID infection, and healthcare resources were far from adequate. Consequently, patients with decompensated liver disease were one of those cohort of patients who suffered most, due to their inability to seek medical support following restricted travel, and lack of priority or availability of emergency measures including endoscopy, interventional procedures and of course liver transplants. The pandemic was more than just a wake-up call for the healthcare sector and us medical professionals to strengthen protocols, policies and infrastructure to tackle such unforeseen catastrophes. It was a lesson too, that in the most difficult times, selfless efforts (individual as well as team work) coupled with restructuring of the system, could actually help accomplish the seemingly impossible task of saving lives with a liver transplant, as was demonstrated by some centers in India.

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