Severe de novo liver injury after Moderna vaccination - not always autoimmune hepatitis.
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ABSTRACT:
SUBMITTER: Nyein CM
PROVIDER: S-EPMC9051901 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Severe de novo liver injury after Moderna vaccination - not always autoimmune hepatitis.
Nyein Chan Maung CM Liew Zi Hui Sherilyn ZHS Leow Wei-Qiang WQ Yeong Poh Sheng Joe PSJ Ho Gim Hin GH
Journal of hepatology 20220418 2
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Project description:A 60-year-old male patient presented to the emergency department with complaints of easy bruising and worsening epistaxis after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Moderna mRNA vaccination. He had no personal or family history of hematological conditions. He had bruises in various stages involving the upper and lower extremities. Laboratory data revealed white blood cell count of 1.2 ×103/mm3, hemoglobin of 8.0 g/dL, platelet count of 1 ×103/mm3, immature platelet fraction of 0.7%, absolute neutrophil count of 0 ×103/µL, lymphocytes of 1.1 ×103/µL, neutrophils of 3% and lymphocytes of 93%. He had normal liver and renal function tests. Bone marrow biopsy confirmed very severe aplastic anemia with severely hypocellular bone marrow. His platelets continued to downtrend despite platelet transfusions and steroids. He was treated with immunosuppressive therapy with cyclosporine, anti-thymocyte globulin, eltrombopag and prednisone. The patient was discharged but was readmitted to the hospital secondary to recurrent neutropenic fever and pneumonia. He had high-grade vancomycin-resistant enterococcal infection and Clostridium difficile infection leading to septic shock and succumbing to cardiac arrest. This case demonstrates the possibility of very severe aplastic anemia following SARS-CoV-2 mRNA vaccination and clinicians need to be aware of this rare but serious side effect.
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Project description:Background/aimsIn this observational study, we explored the humoral and cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune hepatitis (AIH) and patients with cholestatic autoimmune liver disease (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]).MethodsAnti-SARS-CoV-2 antibody titers were determined using the DiaSorin LIAISON and Roche immunoassays in 103 AIH, 64 PSC, and 61 PBC patients and 95 healthy controls >14 days after the second COVID-19 vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of individuals.ResultsPrevious SARS-CoV-2 infection was frequently detected in AIH but not in PBC/PSC (10/112 (9%), versus 4/144 (2.7%), p = 0.03). In the remaining patients, seroconversion was measurable in 97% of AIH and 99% of PBC/PSC patients, respectively. However, in 13/94 AIH patients antibody levels were lower than in any healthy control, which contributed to lower antibody levels of the total AIH cohort when compared to PBC/PSC or controls (641 vs. 1020 vs. 1200 BAU/ml, respectively). Notably, antibody levels were comparably low in AIH patients with (n = 85) and without immunosuppression (n = 9). Also, antibody titers significantly declined within 7 months after the second vaccination. In the AIM assay of 20 AIH patients, a spike-specific T-cell response was undetectable in 45% despite a positive serology, while 87% (13/15) of the PBC/PSC demonstrated a spike-specific T-cell response.ConclusionPatients with AIH show an increased SARS-CoV-2 infection rate as well as an impaired B- and T-cell response to SARS-CoV-2 vaccine compared to PBC and PSC patients, even in the absence of immunosuppression. Thus, antibody responses to vaccination in AIH patients need to be monitored and early booster immunizations considered in low responders.
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Project description:Background & aimsDrug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine.MethodsWe analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls).ResultsOf the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively).ConclusionsIn analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH.
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Project description:As hepatitis B virus is widely spread, WHO recommend vaccination from infancy to reduce acute infection and chronic carriers. However current subunit vaccines are not 100% efficacious and leaves 5-10% persistent non-responders unprotected. To handle large inter-individual variability in immune response after the first Engerix-B vaccination, we employed whole blood early gene expression signatures at day 3 and 7. Immune related pathways are differential expressed in the responders group mostly at day 3 and at day 7 in the non-responders. A notable difference between both groups are significant differential expressed genes at day 0, before vaccination, showing the inter-individual variation. The granulin precursor (GRN) was significant downregulated in responders while upregulated in non-responders. Further absolute granulocytes numbers were significant higher in non-responders. So there is a certain diversity in basic innate immune system.
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Project description:AimTo examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit.MethodsHepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction.ResultsFour cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases.ConclusionIn patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.
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Project description:Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD.
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Project description:BackgroundDonors positive for hepatitis B core antibody (HBcAb) are an important source of organs in hepatitis B virus (HBV) endemic areas despite the risk of occult infection. We analyzed the long-term outcomes of hepatitis B immunoglobulin in de novo HBV prevention following liver transplantation (LT) using HBcAb-positive grafts.MethodsThe prospectively collected data from 2,201 recipients at Seoul National University Hospital (SNUH) and Seoul National University Boramae Medical Center between 1988 and 2018 were retrospectively reviewed. A total of 1,458 patients were enrolled. Of the 1,458, 478 (32.8%) grafts were core-positive, 152 (10.4%) of which belonged to HBV surface antigen-negative recipients. During the anhepatic phase, hepatitis B immunoglobulin 4,000 IU was administered intravenously and daily until postoperative day 3.ResultsThe 152 patients with hepatitis B surface antigen-negative received HBcAb-positive graft. De novo HBV developed in 21 (13.8%) of these recipients. De novo HBV occurred in 1, 11, 0, and 9 of the 4 HBcAb- and hepatitis b surface antibody (anti-HB)-negative, 49 HBcAb-negative and anti-HB-positive, 1 HBcAb-positive and anti-HB-negative, and 98 HBcAb- and anti-HB-positive recipients, respectively. Patients with higher Model for End-stage Liver Disease (MELD) score (23.8±8.7 vs. 19.5±9.2) or HBcAb-negative recipients (22.6% vs. 9.1%) had a higher risk of de novo infection. The median follow-up and serum HBV surface antigen-positivity detection time was 69 and 18 months, respectively. The median HBV surface antibody titer was 65.0 IU/L at de novo infection. Nineteen patients of 21 were treated with nucleoside analogs (NAs), and seven of 19 achieved seroconversion. No patient died of de novo HBV infection.ConclusionsWith close monitoring of viral serum markers and appropriate initiation of NAs, de novo HBV infection can be prevented and treated appropriately with the hepatitis B immunoglobulin monoprophylaxis protocol.
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Project description:BackgroundData regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine.Patients and methodsWe performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression.ResultsWe included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35).ConclusionsSARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.
| S-EPMC9448709 | biostudies-literature