A third dose of the BNT162b2 mRNA vaccine sufficiently improves the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients.

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. Methods: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. Result: The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. Conclusion: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls.

Liver transplantation recovers hepatic N-glycosylation with persistent IgG glycosylation abnormalities: Three-year follow-up in a patient with phosphomannomutase-2-congenital disorder of glycosylation.

Phosphomannomutase-2-congenital disorder of glycosylation (PMM2-CDG) is the most common CDG and presents with highly variable features ranging from isolated neurologic involvement to severe multi-organ dysfunction. Liver abnormalities occur in in almost all patients and frequently include hepatomegaly and elevated aminotransferases, although only a minority of patients develop progressive hepatic fibrosis and liver failure. No curative therapies are currently available for PMM2-CDG, although investigation into several novel therapies is ongoing. We report the first successful liver transplantation in a 4-year-old patient with PMM2-CDG. Over a 3-year follow-up period, she demonstrated improved growth and neurocognitive development and complete normalization of liver enzymes, coagulation parameters, and carbohydrate-deficient transferrin profile, but persistently abnormal IgG glycosylation and recurrent upper airway infections that did not require hospitalization. Liver transplant should be considered as a treatment option for PMM2-CDG patients with end-stage liver disease, however these patients may be at increased risk for recurrent bacterial infections post-transplant.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.

Orthotopic Liver Transplantation of a SARS-CoV-2 Negative Recipient from a Positive Donor: The Border between Uncertainty and Necessity in a Pandemic Era- Case Report and Overview of the Literature.

(1) Introduction: Liver transplantation represents the gold-standard therapy in eligible patients with acute liver failure or end-stage liver disease. The COVID-19 pandemic dramatically affected the transplantation landscape by reducing patients' addressability to specialized healthcare facilities. Since evidence-based acceptance guidelines for non-lung solid organ transplantation from SARS-CoV-2 positive donors are lacking, and the risk of bloodstream-related transmission of the disease is debatable, liver transplantation from SARS-CoV-2 positive donors could be lifesaving, even if long-term interactions are unpredictable. The aim of this case report is to highlight the relevance of performing liver transplantation from SARS-CoV-2 positive donors to negative recipients by emphasizing the perioperative care and short-term outcome. (2) Case presentation: A 20-year-old female patient underwent orthotropic liver transplantation for Child-Pugh C liver cirrhosis secondary to overlap syndrome, from a SARS-CoV-2 positive brain death donor. The patient was not infected nor vaccinated against SARS-CoV-2, and the titer of neutralizing antibodies against the spike protein was negative. The liver transplantation was performed with no significant complications. As immunosuppression therapy, the patient received 20 mg basiliximab (Novartis Farmacéutica S.A., Barcelona, Spain) and 500 mg methylprednisolone (Pfizer Manufacturing Belgium N.V, Puurs, Belgium) intraoperatively. Considering the risk of non-aerogene-related SARS-CoV-2 reactivation syndrome, the patient received remdesivir 200 mg (Gilead Sciences Ireland UC, Carrigtohill County Cork, Ireland) in the neo-hepatic stage, which was continued with 100 mg/day for 5 days. The postoperative immunosuppression therapy consisted of tacrolimus (Astellas Ireland Co., Ltd., Killorglin, County Kerry, Ireland) and mycophenolate mofetil (Roche România S.R.L, Bucharest, Romania) according to the local protocol. Despite the persistent negative PCR results for SARS-CoV-2 in the upper airway tract, the blood titer of neutralizing antibodies turned out positive on postoperative day 7. The patient had a favorable outcome, and she was discharged from the ICU facility seven days later. (3) Conclusions: We illustrated a case of liver transplantation of a SARS-CoV-2 negative recipient, whose donor was SARS-CoV-2 positive, performed in a tertiary, university-affiliated national center of liver surgery, with a good outcome, in order to raise the medical community awareness on the acceptance limits in the case of COVID-19 incompatibility for non-lung solid organs transplantation procedures.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS: In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS: Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION: Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING: National Institutes of Health and US Department of Veterans Affairs.

Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Effect of COVID-19 Pandemic on Patients Who Have Undergone Liver Transplantation Because of Hepatocellular Carcinoma.

BACKGROUND AND AIM: Many clinical studies have shown that the COVID-19 case fatality rate is higher in older patients, those with comorbidities, those with immunosuppressive conditions, and those who stay in the intensive care unit. This study aims to evaluate the clinical outcomes of 66 liver transplant (LT) patients with primary liver cancer who were exposed to COVID-19 infection. METHODS: Demographic and clinical data of 66 patients with primary liver cancer (hepatocellular carcinoma = 64, hepatoblastoma = 1, cholangiocarcinoma = 1) who underwent LT in our institute and were exposed to COVID-19 infection between March 2020 and November 2021 were analyzed in this cross-sectional study. The following data of the patients were recorded: age, sex, body mass index (kg/m2), blood group, underlying primary liver disease, smoking, tumor characteristics, post-transplant immunosuppressive agents, COVID-19 symptoms, hospitalization, intensive care unit stay, intubation, and other clinical features. RESULTS: There were 55 (83.3%) male and 11 (16.7%) female patients, with a median age of 58 years. Sixty-four patients were exposed to COVID-19 only once, whereas the remaining 2 patients were exposed 2 and 4 times, respectively. After exposure to COVID-19, it was determined that 37 patients used antiviral drugs, 25 were hospitalized, 9 were followed in the intensive care unit, and 3 were intubated. One intubated patient was under hospital follow-up because of biliary complications before exposure to COVID-19, and this patient died from sepsis. CONCLUSION: The low mortality rate of LT patients with primary liver cancer exposed to COVID-19 infection can be attributed to background immunosuppression that prevents cytokine storm. However, it is appropriate to support this study with multicenter studies to make strong comments on this issue.

Two Cases of Possible Exacerbation of Chronic Rejection After Anti-SARS-CoV-2 Messenger RNA Vaccination: A Case Report.

In post-liver transplant recipients, SARS-CoV-2 infection is a health threat, and novel messenger RNA vaccines such as Pfizer BioNTech BNT162b2 and Moderna mRNA-1273 are aggressively recommended. However, there are few reports on their adverse effects, some of which may be potentially fatal. We have experienced 2 post-liver transplant recipients with exacerbated chronic rejection after vaccination, one of whom had to undergo retransplant and the other who is still in the process of liver function without improvement. These alarming cases will be presented as case reports.

OPTN/SRTR 2021 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Etiology of Severe Acute Hepatitis in a Pediatric Transplant Center in Japan.

The proportion of pediatric cases with severe acute hepatitis of unknown etiology in the coronavirus disease 2019 era was higher than that in the pre-coronavirus disease 2019 era in Japan's largest pediatric transplant center. Further research and monitoring are essential.

Analysis of Antibody Responses After COVID-19 Vaccination in Liver Transplant Recipients: A Single-Center Study.

BACKGROUND: Liver transplant (LT) recipients were considered a vulnerable population during the coronavirus disease 2019 (COVID-19) pandemic. The clinical efficacy of the COVID-19 vaccine is unknown in immunocompromised patients. The purpose of this study was to provide evidence of antibody responses after COVID-19 vaccination in LT recipients. METHODS: This study enrolled 46 patients who underwent LT at Samsung Medical Center (Seoul, Korea) before implementation of the one-dose vaccine in Korea. Those who completed the two-dose COVID-19 vaccine between August 2021 and September 2021 were included and followed through December 2021. Semiquantitative anti-spike serologic testing was performed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (Roche Diagnostics, Rotkereuz, Switzerland) with a positive cutoff of at least 0.8 U/mL. RESULTS: Among all 46 participants, 40 (87%) demonstrated an antibody response after the second dose of a COVID-19 vaccine, while six (13%) had no antibody response after the second dose. Upon univariate analysis, patients with higher antibody titer had longer years since LT (2.3 ± 2.8 vs. 9.4 ± 5.0, P < 0.001). A lower median tacrolimus (TAC) level before vaccination and after the second dose of COVID-19 vaccine indicated a significantly higher antibody response (2.3 [1.6-3.2] vs. 7.0 [3.7-7.8], P = 0.006, 2.5 [1.6-3.3] vs. 5.7 [4.2-7.2], P = 0.003). Period between 2nd vaccination and serologic testing was significantly higher in the antibody-response group compared to the no-antibody-response group (30.2 ± 24.0 vs. 65.9 ± 35.0, P = 0.012). A multivariate analysis of antibody responses revealed TAC level before vaccination as a statistically significant factor. CONCLUSION: A higher TAC level before vaccination resulted in less effective vaccination in LT patients. Booster vaccinations are required, especially for patients in the early stage after LT who have compromised immune function.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

COVID-19 in Liver Transplant Patients: A University Hospital Experience.

BACKGROUND: We aimed to examine the comorbidity, disease progress, and vaccination status of liver transplant patients followed up in our hospital who had COVID-19. METHODS: Liver transplant patients with COVID-19 were included between 11 March 2020 and 15 September 2022. Demographic data, disease progress, and COVID-19 vaccines were recorded. The SPSS 24.0 (IBM SPSS, Inc, Armonk, NY, United States) program was used for analysis. The data were analyzed using the χ2 test. P values < .05 were considered clinically significant. RESULTS: Sixteen SARS-CoV-2 polymerase chain reaction (+) patients were detected. Twelve (75.0%) patients were male; the mean age was 49.56 ± 14.0 years (24-76 years). The mean transplant time was 156.69 ± 54.05 months. Four (25.0%) of the 5 (31.3%) patients with comorbidities had hypertension, and 1 (6.3%) had diabetes. None of the patients had an underlying lung disease. All the patients received immunosuppressive therapy, and the most common combination was antimetabolite and calcineurin inhibitor (9 patients [69.2%]). Nine patients (56.3%) had a fever, whereas 6 (37.5%) had respiratory symptoms. Two (33.3%) had pneumonia. Five (31.4%) patients were hospitalized, and 1 (20%) was admitted to the intensive care unit due to non-invasive mechanical ventilation needs. No patient died due to COVID-19. A statistically significant correlation was found between the presence of fever, respiratory symptoms, and hospitalization (P < .05). Of those vaccinated, 10 (66.7%) were infected before the COVID-19 vaccination. CONCLUSIONS: The course of COVID-19 in liver recipients without any underlying disease other than transplantation is not different from that in the healthy population. Immunosuppressive therapy was continued in patients with the disease, and two-thirds did not require hospitalization.

SARS-CoV-2 infection in adult liver transplantation recipients: a systematic review of risk factors for mortality and immunosuppression role.

OBJECTIVE: Data on mortality, immunosuppression, and vaccination role regarding liver transplant (LT) recipients affected by COVID-19 are still under debate. This study aims to identify risk factors for mortality and the role of immunosuppression in COVID-19 LT recipients. MATERIALS AND METHODS: A systematic review of SARS-CoV-2 infection in LT recipients was performed. The primary outcomes were risk factors for mortality, the role of immunosuppression and vaccination. A meta-analysis was not performed as there was a different metric of the same outcome (mortality) and a lack of a control group in most studies. RESULTS: Overall, 1,343 LT recipients of 1,810 SOT were included, and data on mortality were available for 1,110 liver transplant recipients with SARS-CoV-2 infection. Mortality ranged between 0-37%. Risk factors of mortality were age >60 years, Mofetil (MMF) use, extra-hepatic solid tumour, Charlson Comorbidity Index, male sex, dyspnoea at diagnosis, higher baseline serum creatinine, congestive heart failure, chronic lung disease, chronic kidney disease, diabetes, BMI >30. Only 51% of 233 LT patients presented a positive response after vaccination, and older age (>65y) and MMF use were associated with lower antibodies. Tacrolimus (TAC) was identified as a protective factor for mortality. CONCLUSIONS: Liver transplant patients present additional risk factors of mortality related to immunosuppression. Immunosuppression role in the progression to severe infection and mortality may correlate with different drugs. Moreover, fully vaccinated patients have a lower risk of developing severe COVID-19. The present research suggests safely using TAC and reducing MMF use during the COVID-19 pandemic.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.