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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.
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Objective: To examine whether established patient-reported outcome measures are suitable for capturing the impact of ARPKD in children and their families. Method(s): We assessed 44 children with ARPKD (40 families) with respect to patients' health-related quality of life ((hr- QOL) using PedsQLTM ESRD module) and mental health (strength and difficulties questionnaire (SDQ)) as well as family and caregiver burden (Impact on family score (IFS) und Ulm inventory of parental caregiver QOL (ULQIE)) and compared them to published data and 36 healthy control children matched for age and time. Result(s): Patients were aged 9.5 +/- 5.9 years (vs. controls 8.8 +/- 5.0, p = ns) and 21 (48%) were female (vs. 19 controls (53%), p = ns). Mean eGFR was 81 ml/min*1.73m2 (range 4 - 165);7 received dialysis and 11 had functioning kidney transplants (KTX, 2 combined with liver transplants). Eight patients had developmental delay secondary to medical complications, while chronic illness was an exclusion criterion for healthy controls. 61 caregivers of affected children had same gender-distribution (61% vs. 60% mothers) and age (both 42 +/- 7 years) and number of dependent children (1.8 +/- 0.9 vs. 2.0 +/- 0.8) as 57 caregivers of healthy children. The mean proxy reported PedsQL Total score was 77.5 +/- 10.6 (range 59 - 96). It correlated significantly to eGFR (r = 0.5, p < 0.01, (also within the subpopulations pre- and post-KTX)). Parents reported greater mental health problems in affected than in control children with a higher SDQ total score mainly due to higher scores in the hyperactivity and peerinteraction subscales. ULQIE revealed that parents of affected children had significantly lower levels of physical functioning, self-fulfillment and general QOL, but despite higher emotional burden scores they indicated similar satisfaction with family life. Impact on family scores were in a similar range to those of children with moderate to severe disabilities. Conclusion(s): The good spread of PedsQLTM ESRD-scores and their correlation to renal function indicates that it captures significant aspects of ARPKD, however, it may need further adjustment to include liver complications. All four chosen instruments revealed significant impact of ARPKD on hrQOL and mental health of affected children as well as family life and parental wellbeing in comparison to healthy controls. More problems with peer-interactions may also be due to more stringent shielding of chronically ill children from social contacts during the COVID pandemic compared to healthy children.
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Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.
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Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.
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Introduction: The Acuity Circles (AC) allocation policy was implemented on February 4, 2020, with the primary intent of reducing disparities in access to deceased donor liver transplants (DDLTs). Overall, it has been successful at achieving this goal. However, changes in end-stage liver disease etiology following the policy change have not been well-characterized. Our goal was to understand how primary etiology of disease in DDLTs has changed since implementation of AC. Method(s): Data from the Organ Procurement Transplantation Network (OPTN) and United Network of Organ Sharing (UNOS) were analyzed to compare the primary classified etiologies of liver disease for DDLTs overall and based on allocation Model-for-end-stage-liver-disease (aMELD) categories used for AC sharing: aMELD>=37, aMELD 33-36, aMELD 29-32, aMELD 15-28, and aMELD<=14 DDLTs. Time was divided into four equivalent "eras" of 256 days duration by date of transplantation: 1) 9/10/18-5/23/19 (Era 1);2) 5/24/19-2/3/20 (Era 2);3) 2/4/20-10/16/20 (Era 3);and 4) 10/17/20-6/29/21 (Era 4). Result(s): The percentage of all DDLTs for alcohol-related liver disease (ARLD) increased from 32.3% pre-AC to 38.7% of DDLTs post AC. This was met with a corresponding decrease in the relative percentage of DDLTs related to Hepatitis C Virus (from 17.0% of DDLTs pre-AC to 12.2% post-AC), with the relative differences of other etiologies being a less than 1% difference pre- vs post- AC. There is a consistent increase in the share of DDLTs due to ARLD across each Era. The rise in adult DDLTs for ARLD was most pronounced among aMELD >=37 recipients, although similar trends were seen among aMELD 33-36 and aMELD 29-32 groups, but not aMELD 15-28 and aMELD <=14 groups. The median age of adult DDLTs for ARLD decreased consistently over time for the aMELD >=37 group, but not for the aMELD 33-36 and aMELD 29-32 groups. (Figure) (Table) Conclusion(s): Following implementation of AC, there was a relative increase in DDLTs due to ARLD. The younger age and high aMELD scores of these patients suggests these may be largely among patients with acute alcoholic hepatitis. This would align with published data on the overall increase in liver transplantation due to ARLD during the COVID-19 pandemic. (Figure Presented).
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Purpose: The COVID-19 pandemic led to nationwide postponement of outpatient preventative health services. The purpose of our study was to determine the effect of the COVID-19 pandemic on hepatocellular carcinoma ultrasound (HCC US) surveillance volumes at a liver transplant center. Material(s) and Method(s): This retrospective study examined ultrasound volumes across the first two years of the pandemic (March 1, 2020, to February 28, 2022) compared to a baseline year (March 1, 2019, to February 28, 2020). Monthly and annual surveillance volumes, cumulative number of positive ultrasound examinations, and rate of follow-up CT or MRI on an US-3 observation were compared using paired t-tests. Result(s): A total of 6765 ultrasound examinations for HCC at our institution were performed over the three-year study period: 2507 in the baseline year, 1943 in the first year, and 2345 in the second year, representing a 24% (p = 0.036) and 6% (p = 0.144) decline in volume, respectively, compared to baseline. The first pandemic year had the greatest decline (mean 159/month, range 8-217, versus baseline year mean 209/month, range 182-241/month;p = .0363). The most dramatic reductions were in March, April, and May, in which 111, 8, and 126 surveillance ultrasound examinations were performed, respectively. In the baseline year, 95 (4%) had an US-3 observation (1 cm or larger nodule at ultrasound) and 63 (66%) underwent followup CT or MRI. In the first pandemic year, 64 (3%, p = 0.016) patients had an US-3 observation and 48 (75.00%, p = 0.0584) underwent follow-up CT or MRI. In the second pandemic year, 65 (3%, p = 0.001) patients had an US-3 observation and 48 (74%, p = 0.040) underwent follow-up CT or MRI. Conclusion(s): The significantly decreased surveillance ultrasound volume during the pandemic led to fewer positive surveillance studies and therefore fewer recommendations for follow-up imaging. As frequent surveillance is critical to HCC management, the pandemic is expected to have a significant impact on HCC epidemiology in the future.
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Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.
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Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).
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Introduction: Altered mental status (AMS) is a common symptom in patients with liver disease with a wide list of differential diagnoses. Knowledge of etiologies of AMS unique to patients with hepatic dysfunction is vital in order to help recognize, diagnose, and treat the underlying cause in a timely manner. Case Description/Methods: A 46-year-old man with a history of recent COVID infection was transferred to our hospital for further evaluation of acute liver injury and AMS. On arrival, his labs were notable for AST of 408 U/L, ALT of 620 U/L, ALP of 5942 U/L, TB of 11.0 mg/dL, and an INR of 1.1. His work-up included an MRCP that showed segmental biliary ductal dilation with associated restricted diffusion and peribiliary enhancement concerning for sclerosing cholangitis. ERCP revealed a 3cm biliary cast that was removed and noted diffuse rarefaction of ducts throughout the entire biliary tree. A liver biopsy revealed centrizonal cholestasis with portal-based bile ductular reaction and mild bile duct injury. Despite adequate treatment of suspected infection and hepatic encephalopathy, his AMS persisted. His basic metabolic panel (BMP) was notable for Na of 143 mEq/L. A send-out lipid panel that was obtained to work-up his dyslipidemia revealed a total cholesterol of 1018 mg/dL, triglycerides of 420mg/dL, and the presence of lipoprotein X. A venous blood gas (VBG) was obtained showing a Na of 157 mEq/L and serum osmolality was 322 mmol/kg, confirming true hypernatremia. He was slowly treated with hypotonic solutions with significant improvement in his mentation. On follow-up one year later, he has persistent cholestasis and is currently being considered for liver transplant. Discussion(s): The final diagnosis was COVID-related ischemic cholangitis and disappearing bile ducts with persistent cholangiopathy, presenting with severe cholestasis, accumulation of lipoprotein X, and pseudonormonatremia. When faced with severe cholestatic liver disease, clinicians should keep in mind the possibility of accumulation of lipoprotein X and its association with hyperviscosity and spurious electrolyte abnormalities. Clinicians should rely on obtaining blood gas analyses for accurate electrolyte measurement in such cholestatic patients as blood gas analyses utilize direct ion-sensitive electrodes (ISE) to measure electrolytes, whereas routine basic metabolic panels utilize indirect ISE that are liable to spurious results in the presence of hyperlipoproteinemia/lipoprotein X.
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A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors
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Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.Copyright © 2021 The Authors
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Background: As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ''organ utilisation'' in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years. Method(s): Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported. Result(s): The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638;55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%. Conclusion(s): The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.Copyright © 2022
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Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients;(2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.Copyright © 2021 The Authors
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Organ transplant recipients show weaker immune responses to vaccines than immunocompetent individuals, which may be related to the repertoire of HLAbound vaccine antigens presented to T lymphocytes. The HLA evolutionary divergence (HED) metric, which quantifies pairwise allele divergence at each HLA locus, provides a primary measure of the breadth of the immunopeptidome. We recently showed that high class I HED of the donor is a strong and independent driver of allograft rejection in a large cohort of liver transplant recipients. Here, in the same cohort, we explored the relation between HED, the size of the predicted immunopeptidome derived from vaccine antigens, and the quality of vaccine responses. We analyzed humoral response to the SARS-CoV-2 BNT162b2 vaccine (n = 310 patients;undetectable anti-spike IgG titers considered as no response, <=250 BAU/mL as moderate and >250 BAU/mL as strong response) and Hepatitis B virus (HBV) vaccine (n = 424 patients;anti-HBs IgG <10 mIU/mL considered as no response, 10-100 mIU/mL as moderate and >=100 mIU/mL as strong response). HED at HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 loci were measured using the Grantham distance. NetMHCIIpan-4.0 was used to predict the binding to HLA-DQ molecules of all possible 15mer peptides derived from the Spike and HBS sequences. For each vaccine, HED at the DQB1 locus, but not at the other loci, was significantly higher in responders than in non-responders (p = 0.0003), independent of response-associated covariates (age, time since transplant, immunosuppression). Moreover, for both vaccines, there was a strong relationship between DQB1 HED, the diversity of the immunopeptidome and the quality of the vaccine response. In conclusion, DQB1 HED is a critical determinant of humoral response to vaccines in liver transplant recipients. This metric could guide the design of future vaccines as it predicts the magnitude of the repertoire of vaccine-derived peptides presented to CD4 helper T cells.
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Background We present a case of a young male with new severe cardiomyopathy requiring critical care within 24 hours. Case A Latino male with alcoholism was admitted for COVID and severe liver injury due to alcohol-induced hepatitis. Within hours, he developed hypoxia, worsening metabolic acidosis with undetectable bicarbonate level and partial respiratory compensation, coagulopathy, acute kidney injury, right lower lobe infiltrates without pulmonary embolism. Reduced ejection fraction heart failure at 15-20% with a large left ventricle apical thrombus was also found. Worsening signs of cariogenic shock despite sustaining normal blood pressure was identified on a physical exam. The patient was transferred to ICU with confirmation of cardiogenic shock with right ventricular failure with Swan-Ganz Catheter. With Concern for impending fulminant liver failure, transfer to a tertiary care center for emergent liver transplant was initiated. Decision-making The dichotomy of requirement for anti-coagulation for LV thrombus with cardiogenic shock and worsening coagulopathy due to liver failure was a challenge. Decision was made to transfuse blood products as needed with goal fibrinogen of 150 mg/dl, later changed to 100-120 mg/dl with heparin. Liver enzymes were down-trending, but it was difficult to determine if this was due to recovery or worsening of liver failure with stabilization of hemodynamics. While awaiting transfer, he developed acute cerebrovascular accident requiring emergent mechanical thrombectomy of a left MCA occlusion with suspension of heparin complicated by acute large intraventricular and intraparenchymal hemorrhage with rapid decline in neurological function. The family declined decompressive craniotomy with evacuation of parenchymal hemorrhage and the patient was transitioned to comfort care measures. Conclusion There are no clear guidelines for transfusion of plasma-based blood products in the setting of cardiogenic shock and liver disease. Expert opinion recommends maintaining fibrinogen levels above 100-200 mg/dl, however, this is in the setting of acute blood loss and is not studied in patients with liver disease. Further studies are needed.Copyright © 2023 American College of Cardiology Foundation
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The COVID-19 pandemic has had a remarkable impact on the field of liver transplantation. Increasing evidence demonstrates a minimal risk of transmission of SARS-CoV-2 from non-lung donors who test positive for SARS-CoV-2;however, the risks of donor-derived SARS-CoV-2 from liver donors are unknown. We present our experience with two cases in which a liver was transplanted successfully from a brain-dead donor with incidental SARS-CoV-2 infection. Both donors were asymptomatic SARS-CoV-2-positive with negative bronchoalveolar lavage polymerase chain reaction (BAL PCR) and mechanism of death unrelated to COVID-19. Both the recipients did well after transplant and went home with a well-functioning liver. One patient did get readmitted and was found to be SARS-CoV-2-positive;however, it was probably related to hospital exposure rather than donor-derived. SARS-CoV-2-positive donors in select cases may be used for organ donation and liver transplant is safe for recipients.Copyright © 2023 The Author(s)
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Background and aims Liver transplant recipients (LTR) are threatened by a lower immunogenicity of SARS-CoV-2 mRNA vaccines. However, the interplay between the different branches of the adaptive immune system especially after a third (and fourth) vaccine dose is still poorly understood. Methods Our study longitudinally compares the humoral as well as the cellular response between age-matched LTR (n = 24) and healthy controls (HC, n = 19) after three to four vaccine doses. Therefore, we assessed antibody titers, analyzed the spike-specific T cell epitope repertoire, performed an in-depth characterization of spike-specific CD8 + T cells on a single-epitope level and examined the distribution of different virus-specific CD4 + T cell subpopulations. Results Compared to HC, the development of high antibody titers depended on a third vaccine dose in most LTR. In contrast, spike-specific CD8 + T cells reached a stable level already after the second vaccine dose, albeit with a lower frequency and a narrower epitope repertoire compared to HC. Concerning the CD4 + T cells, the total number of detectable responses as well as the repertoire of targeted epitopes within the spike protein did not signifcantly difer in both cohorts. However, we observed a link between the overall attenuated vaccine response and a reduced frequency of spike-reactive follicular T helper cells (TFH) in LTR. Conclusion Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTR. Evaluations of additional booster doses may thus consider the individual vaccine responsiveness as well as the evolution of novel variants of concern.