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.

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.

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.

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.

Pyogenic liver abscesses in liver transplant recipients versus non-transplant population. Outcome and risk factors of patient survival.

Pyogenic liver abscess (PLA) is a life-threatening infection in both liver transplant (LT) and non-LT patients. Several risk factors, such as benign and malignant hepatopancreatobiliary diseases and colorectal tumors have been associated with PLA in the non-LT population, and hepatic artery stricture/thrombosis, biliary stricture, and hepaticojejunostomy in the LT patients. The objective of this study is to compare the outcomes of patients with PLA in LT and non-LT patients and to determine the risk factors associated with patient survival. From January 2000 to November 2020, a total of 296 adult patients were diagnosed of PLA in our institution, of whom 26 patients had previously undergone liver transplantation (LTA group), whereas 263 patients corresponded to the non-LTA population. Seven patients with PLA who had undergone previous kidney transplantation were excluded from this retrospective study. Twenty-six patients out of 1503 LT developed PLA (incidence of 1.7%). Median age was significantly higher in non-LTA patients (p = .001). No significant differences were observed in therapy. PLA recurrence was significantly higher in LTA than in non-LTA (34.6% vs. 14.8%; p = .008). In-hospital mortality was greater in the LT group than in the non-LT group (19.2% vs. 9.1% p = .10) and was identified in multivariable analysis as a risk factor for mortality (p = .027). Mortality rate during follow-up did not show significant differences between the groups: 34.6% in LTA patients versus 26.2% in non-LTA patients (p = .10). The most common causes of mortality during follow-up were malignancies, Covid-19 infection, and neurologic disease. 1-, 3-, and 5-year actuarial patient survival rates were 87.0%, 64.1%, and 50.4%, respectively, in patients of LTA group, and 84.5%, 66.5%, and 51.0%, respectively, in patients with liver abscesses in non-LTA population (p = .53). In conclusion, LT was a risk factor for in hospital mortality, but not during long-term follow-up.

ABO-Incompatible Living Donor Liver Transplant From a Blood Type A2 Donor to a Type B Recipient: A Note of Caution.

Standardization of immunomodulation protocols has enabled ABO-incompatible liver transplants with outcomes similar to those of ABO-compatible liver transplants. Patients with the A2 blood group are unique because they have a diminished expression of the A antigen. Despite rare immune complications, this phenomenon of diminished expression has led to treatment of type A2 donors according to the regimen for type O blood group donors in ABO-incompatible liver transplants. Additionally, the requirement for pretransplant recipient immunomodulation is consi dered minimal when considering these donors. The transplant of a type A2 donor kidney to a type B recipient is well recognized; however, for liver donation the A2-to-B transplant is rare. Here, we present a case of 48-year-old male patient with blood group type B who underwent ABO-incompatible liver transplant of a right lobe liver graft from a type A2 donor. Postoperatively, despite adequate immunosuppression and initiation of thera - peutic plasma exchange, the patient developed severe and refractory antibody-mediated rejection that ultimately abated with a splenectomy. This report highlights the low but tangible risk of antibody-mediated rejection in ABO-incompatible liver transp lants from type A2 donors and emphasizes the importance of serial monitoring of anti-A isohemag glutinin titers and posttransplant splenectomy to ensure that liver grafts with antibody-mediated rejection can be rescued.

Evaluation of an Abnormal Liver Panel After Liver Transplantation.

Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing.

Coronavirus Disease-2019 and Implications on the Liver.

The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.

Does COVID-19 infection significantly affect liver transplantation? Results of liver transplantation in the COVID-19 era at a single, high-volume centre.

BACKGROUND: Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events. MATERIAL AND METHODS: In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected. RESULTS: This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting. CONCLUSION: This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.

Liver transplantation in alcohol-associated liver disease: ensuring equity through new processes.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.

SARS-CoV-2 vaccine alleviates disease burden and severity in liver transplant recipients even with low antibody titers.

BACKGROUND AND AIMS: We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. PATIENTS AND METHODS: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). RESULTS: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. CONCLUSION: Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave.

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

Changes in Physical Activity Due to Fear of COVID-19 and Its Impact on Depression Among Post-Liver Transplant Patients in Japan: A Longitudinal Survey Study.

BACKGROUND Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. MATERIAL AND METHODS This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. RESULTS Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. CONCLUSIONS Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

Bickerstaff's brainstem encephalitis mimicking herpetic encephalomyelitis in a liver transplant patient with anti-GQ1b antibodies.

A woman in her late 70s with a history of liver transplant presented with ophthalmoplegia, ataxia, areflexia, positive Babinski's sign and reduced consciousness. This followed an antecedent illness in the form of a herpes zoster infection. MRI of the brain/spinal cord, cerebrospinal fluid analysis with viral PCR and routine blood tests were normal, and tacrolimus neurotoxicity was ruled out. Serum anti-GQ1b antibodies were positive. A diagnosis of Bickerstaff's brainstem encephalitis was made, forming part of the continuum that involves Miller-Fisher syndrome, entitled the 'anti-GQ1b syndrome'. Complete recovery ensued without intravenous immunoglobulins or plasma exchange. The role of monitoring anti-ganglioside pattern change to predict or confirm disease recurrence and disease severity is further discussed.

Secondary sclerosing cholangitis after COVID-19 pneumonia: a report of two cases and review of the literature.

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare disease characterized by chronic cholestasis. The underlying pathophysiology of SC-CIP is not fully understood, and prognosis in severe cases remains poor with liver transplantation remaining the only curative treatment option. There is a growing amount of literature describing patients with chronic cholangiopathy after COVID-19 infection. The vast majority of the patients described in these reports were male and had a poor outcome. While the exact percentage of patients with COVID-19-related SC-CIP cannot be estimated accurately due to a lack of larger studies, an increase in patients with long-term complications of chronic cholestatic liver disease after severe COVID19-pneumonia can be expected in the upcoming years. Treatment options remain limited and further research is needed to improve the dismal prognosis of SC-CIP. Here, we present the cases of two patients who developed SC-CIP after prolonged intensive care unit stay due to severe COVID-19 pneumonia. Both patients required invasive ventilation for 31 and 141 days, respectively, as well as extra-corporal membrane oxygenation for 23 and 87 days. The patients suffered from jaundice and severe pruritus, and typical features of SC-CIP were present by MRCP and ERC. Repeated removal of biliary casts resulted in some alleviation of their clinical symptoms, but cholestasis parameters remain elevated. Furthermore, an increased liver stiffness was indicative of advanced fibrosis in both patients. In addition to these two case reports, we provide a concise review of the literature of SC-CIP after COVID-19 infection and discuss risk factors, treatment options and prognosis.

Early Liver Transplant In Patients With Liver Cirrhosis Recovered From COVID-19 Infection.

OBJECTIVES: Coronavirus disease 2019 has resulted in significant morbidities and mortalities in nearly all parts ofthe world. There remain major concerns about management, timing, and safety of liver transplant in patients who have recovered from COVID-19. We aimed to study the clinical course and outcomes of patients with liver cirrhosis who recovered from COVID-19 and underwent liver transplant from deceased donors. MATERIALS AND METHODS: A retrospective study was conducted on liver transplant recipients who underwent liver transplant from April 1, 2020, to January 30, 2021. We evaluated all recipients of liver transplantfrom deceased donors during this period in the COVID-19 pandemic. RESULTS: There were 14 patients with decompensated liver cirrhosis who had recovered from COVID-19 as documented by reverse transcription-polymerase chain reaction test for SARS-CoV-2. Mean duration from COVID-19 to transplant surgery was 56.14 ± 29.96 days. Mortality occurred in 3 patients, and of whom 2 had been hospitalized and received medications for COVID-19 before transplant. Five patients had positive reverse transcription-polymerase chain reaction results for SARS-CoV-2 after liver transplant. CONCLUSIONS: This is a large reported series of patients with liver cirrhosis who have received liver transplant after recovery from COVID-19. We provided evidence that liver transplant from deceased donors should be considered in patients recovered from COVID-19, especially in those with deterioration of clinical status.