Good outcomes of living donor liver transplant in primary sclerosing cholangitis: an experience from North India.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. In the absence of effective medical therapy, liver transplant is the definitive treatment for advanced stage. However, recurrence of PSC after liver transplant is of concern which can lead to graft failure and may require retransplant. There are limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are genetically related there can be an increased risk of recurrence. We conducted this retrospective study to analyze the outcomes of LDLT in PSC at a tertiary liver transplant center in north India. METHODS: We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients had PSC as indication for liver transplantation (PSC = 24, PSC-AIH overlap = 2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence, and survival. RESULTS: Mean age of study group was 42 (± 13.8) years and 19 patients (73.1%) were males. All patients had decompensated cirrhosis at the time of transplant. Mean CTP score and MELD score were 9.5 (± 1.8) and 18.9 (± 7.1), respectively. Sixteen patients received modified right lobe graft, seven extended right lobe graft and five patients received left lateral graft. Median graft weight and mean graft to recipient weight ratio (GRWR) were 633.5 (IQR 473.5-633.5) grams and 1.23 (± 0.42), respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19 (73.1%) while duct to duct anastomosis was performed in 7 (26.9%) patients. Median follow-up was 96 (36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and were managed successfully with steroid pulses. Three patients died during early post-transplant period while seven deaths occurred during long-term follow-up including one death due to COVID-19. Five (21.73%) patients had recurrence of PSC of which two patients had graft loss including one after retransplantation. The one year graft and patient survival rate was 88.5%. CONCLUSION: LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about one-fifth patients.

Initiation of Liver Transplant in Nepal: A Milestone.

Background: The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal's first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. Method: A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient's demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Results: Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Conclusion: Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal.

Living donor liver transplant outcomes during the COVID-19 pandemic: does a decrease in case volume impact the overall outcomes?

Background: High-volume centers (HVCs) are classically associated with better outcomes. During the coronavirus disease 2019 (COVID-19) pandemic, there has been a decrease in the regular liver transplantation (LT) activity at our center. This study analyzed the effect of the decline in LT on posttransplant patient outcomes at our HVC. Methods: We compared the surgical outcomes of patients who underwent LT during the COVID-19 pandemic lockdown (April 1, 2020 to September 30, 2020) with outcomes in the pre-pandemic calendar year (April 1, 2019 to March 31, 2020). Results: During the 6 months of pandemic lockdown, 60 patients underwent LT (43 adults and 17 children) while 228 patients underwent LT (178 adults and 50 children) during the pre-pandemic calendar year. Patients in the pandemic group had significantly higher model for end-stage liver disease (MELD) scores (24.39±9.55 vs. 21.14±9.17, P=0.034), Child-Turcotte-Pugh scores (11.46±2.32 vs. 10.25±2.24, P=0.03), and incidence of acute-on-chronic liver failure (30.2% vs. 10.2%, P=0.002). Despite performing LT in sicker patients with COVID-19-related challenges, the 30-day (14% vs. 18.5%, P=0.479), 3-month (16.3% vs. 20.2%, P=0.557), and 6-month mortality rates (23.3% vs. 28.7%, P=0.477) were lower, but not statistically significant when compared to the pre-pandemic cohort. Conclusions: During the COVID-19 pandemic lockdown the number of LT procedures performed at our HVC declined by half because prevailing conditions allowed LT in very sick patients only. Despite these changes, outcomes were not inferior during the pandemic period compared to the pre-pandemic calendar year. Greater individualization of patient care contributed to non-inferior outcomes in these sick recipients.

Critical Update on the Diagnosis and Management of COVID-19 in Advanced Cirrhosis and Liver Transplant Recipients.

The novel coronavirus disease 2019 (COVID-19) pandemic has impacted health care worldwide, with specific patient populations, such as those with diabetes, cardiovascular disease, and chronic lung disease, at higher risk of infection and others at higher risk of disease progression. Patients with decompensated cirrhosis fall into the latter category and are a unique group that require specific treatment and management decisions because they can develop acute-on-chronic liver failure. In liver transplant recipients, the atypical immunity profile due to immunosuppression protects against downstream inflammatory responses triggered by COVID-19. This exhaustive review discusses the outcomes associated with COVID-19 in patients with advanced cirrhosis and in liver transplant recipients. We focus on the immunopathogenesis of COVID-19, its correlation with the pathogenesis of advanced liver disease, and the effect of immunosuppression in liver transplant recipients to provide insight into the outcomes of this unique patient population.

"SARS-CoV-2 Infection in Liver Transplant Recipients - Immunosuppression is the Silver Lining?"

BACKGROUND: COVID-19 is associated with higher mortality among patients who have comorbidities. However, evidences related to COVID-19 among post liver transplant recipients are scarce and evolving. METHODS: Adult Indian patients who had undergone liver transplantation at our centre since 2006 and were under regular follow-up, were contacted either telephonically or on email. Data were recorded related to symptoms and diagnosis of COVID-19, need for hospitalization, and need for ICU stay and mortality. RESULTS: Eighty one (3.71%) of the 2182 adult Liver transplant (LT) recipients on regular follow-up reported SARS-CoV-2 infection between 1st April 2020 and 31st May 2021. Mean age was 51.3(±9.8) years, and 74(91.4%) were males. Thirty five (43.2%) patients had one or more comorbidities. Twenty one (25.9%) patients were transplanted less than 1 year ago. Forty four (54.3% ) patients had mild disease only while 23(28.4%) patients had severe COVID-19 disease. Of the 81 patients 14 patients died and overall mortality was 17.3. CONCLUSION: Uncomplicated liver transplant recipients without comorbidities who acquire SARS-CoV-2 do not have poor outcome.

Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.

Protocol to ensure continued pediatric liver transplantation service during the COVID pandemic and the encouraging outcomes.

Coronavirus disease 2019 is a global pandemic, and to deal with the unexpected, enormous burden on healthcare system, liver transplantation (LT) services have been suspended in many centers. Development of robust and successful protocols in preventing the disease among the recipients, donors and healthcare workers would help in re-starting the LT programs. We adapted a protocol at our center, which is predominantly a living donor liver transplant center based in north India, and continued the service as the pandemic unfolded and peaked in India with good results and shared the experience of the same. Between March 24 and June 7, 2020, during the government-enforced public curfew-"lockdown"-7 children received LT. The protocols of infection control were drafted in our team by local customization of published guidelines. The number of pediatric LT done during the lockdown period in 2020 was similar to that done in corresponding pre-COVID period in 2019. The outcomes were of 100% survival, and none of recipients developed COVID. One potential donor was asymptomatic positive for COVID, responded well to conservative treatment, and was later accepted as a donor. LT program during the COVID pandemic can successfully function after putting in place standard protocols for infection control. These can be implemented with minimal extra involvement of healthcare infrastructure, hence without diversion of resources from COVID management. In conclusion, pediatric liver transplantation services can be continued amid COVID-19 pandemic after establishing a properly observed protocol with minimum additional resources.