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Introduction and Objectives: Acute autoimmune-like liver injury has been increasingly reported after vaccination against SARS-CoV-2. Pathogenesis, steroid requirement and long-term prognosis are unknown. This study aimed to evaluate clinical, serological and histological features, response to treatment and prognosis in patients with post-vaccination acute hepatitis. Material(s) and Method(s): We included patients without known pre-existing liver diseases with transaminase levels >= 2.5 upper limits of normal within 90 days after the SARS-CoV-2 vaccine with an available liver biopsy. Clinical data and outcomes after a six months follow-up were collected. Result(s): 17 patients were included,12 females, median age 60 (51,5/66) exposed to vectorial (Sputnik V n=7, AstraZeneca n=6), inactivated (Sinopharm n=3) or ARNm Vaccines (Moderna=1). In 8 patients, liver injury developed after the first dose and in 7 after the second dose and in 2 after the third dose. The median time to the development of injury was 33(23,50/53,50) days. Eight patients had a history of extrahepatic autoimmune disease and five patients had metabolic syndrome and used statins. Immune serology showed anti-antinuclear antibody in 10 (58,8%), anti-smooth muscle antibody in 5(29,4%). 14/17 patients presented with elevated IgG levels. Liver histology showed lobular hepatitis in 13/17, portal hepatitis in 17/17 with plasmocytic lymphocytic infiltrate and 4/17 had eosinophils, 6/17 with severe interface hepatitis, and one patient had fibrosis Ishak stage >=3. 12/17 (70,5%) were treated with steroids. Transaminases improved in 17 cases and normalized in 6/12 by month 6. Only 1/17 developed liver function deterioration, yet no patient required liver transplantation. Most patients tolerated the tapering of steroids and in 6 azathioprine was started before month 3. Conclusion(s): Long-term follow-up might help to differentiate between induced classical autoimmune hepatitis, autoinflammatory self-limited events, or drug-induced liver injury in these patients.Copyright © 2023
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Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)
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The pathogenesis of liver dysfunction that complicates coronavirus disease 2019 (COVID-19) remains unclear, especially in mild to moderate severity cases. In this case, a novel coronavirus infection was detected by polymerase chain reaction (PCR) in a 76-year-old woman hospitalized after presenting with fever. No other abnormal physical findings were observed, and oxygen administration was not required. Chest computed tomography (CT) showed a ground-glass-like and an infiltrative shadow in the right lung, and moderate COVID-19 was diagnosed. Initially, the fever resolved, and PCR turned negative; however, the fever reappeared on hospitalization day 14, and CT showed pneumonia exacerbation accompanied by new onset of fatty liver. Biochemical testing revealed marked liver dysfunction, accompanied by elevated serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α levels. Physical findings and all laboratory parameters improved after conservative treatment, and she was discharged on day 22. A liver biopsy performed 44 days post-discharge showed T-cell-dominant inflammatory cell infiltration, mainly in the portal region. Some hepatocytes showed fatty degeneration.We report a case of moderate COVID-19 in which histological hepatitis persisted after a substantial period had passed since the initial infection had cleared and associated transaminase elevations had resolved, with a comparison of serum cytokine dynamics.
Subject(s)
COVID-19 , Liver Diseases , Female , Humans , Aged , COVID-19/complications , Cytokines , Aftercare , Patient Discharge , Liver Diseases/etiologyABSTRACT
Background & Aims Liver injury with autoimmune features after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of patients with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Approach & Results Patients without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine and available liver biopsy are included. Fifty-nine patients were recruited;35 females;median age 54 years;they were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Liver histology showed predominantly lobular hepatitis in 45 (76%) cases, predominantly portal hepatitis in 10 (17%), and other patterns in four (7%);seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in 8 (26%), anti-liver kidney microsomal in 4 (13%), anti-mitochondrial antibody in 4 (13%). Ninety-one percent were treated with steroids, ± azathioprine. Serum transaminase levels improved in all cases, and were normal in 24/58 (41%) after three months, and in 30/46 (65%) after six months. One patient required liver transplantation. Re-exposure to SARS-CoV-2 vaccines of 15 patients resulted in three relapses. Conclusion Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcome of this condition. Lay summary Cases of liver injury after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of patients with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.
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Introduction: Weight management is currently the only established treatment of pediatric non-alcoholic fatty liver disease (NAFLD). Studies have shown improvements in liver histology, aminotransferase activity, and quality of life after weight loss in children with NAFLD.1 Recent studies demonstrate an accelerated rate of weight gain among children and adolescents during the COVID-19 pandemic that has been attributed to many factors, including the inability to be in a structured school setting and disruptions in family income.2,3 Objective: Our study aims to explore the effect of COVID-19 stay-at-home mandates and school closures on weight gain and liver function tests in children with NAFLD. Method(s): Following IRB approval (IRB 2021-4333), a retrospective chart review was performed on children aged 13-20 years who were seen at Lurie Children's Hospital (LCH) hepatology clinic for NAFLD and had two or more clinic visits at least three months apart during the pandemic period, defined as 3/1/20-9/1/21, and the pre-pandemic period, defined as before 3/1/20. The two most recent visits at least three months apart were the ones selected for the pre-pandemic period. Demographic and clinical data (race, ethnicity, age, BMI, height, weight, AST, ALT) were ed. Monthly BMI, AST, and ALT differences during the two periods were calculated for each patient. Paired-samples T-Tests were used to analyze differences between the two periods. Relative risks for an increase in BMI, AST, or ALT during the pandemic period compared to the pre-pandemic period were calculated. Result(s): Our cohort included 102 patients, with mean age of 14.5 (SD 1.6) during pre-pandemic period and 15.6 (SD 1.4) during pandemic period, 71 (70%) males, and 85 (83%) identifying as Hispanic or Latino. Mean BMI was 34.2 kg/m2 (SD 7.16) with mean Z-score of 2.16 (SD 0.56) during pre-pandemic period and mean BMI of 35.5 kg/m2 (SD 7.0) with mean Z-score of 2.21 (SD 0.56) during pandemic period. Seventy-seven (75%) children had a liver biopsy or other imaging consistent with their NAFLD diagnosis. There was a significant difference between monthly BMI differences during the pre-pandemic period (mean 0.0691 kg/m2/month, SD 0.271) and pandemic period (mean 0.161 kg/m2/month, SD 0.271);p=0.02. Of the 102 patients in our cohort, 75 had two or more ALT measurements at least three months apart during both time periods. There was a significant difference between monthly ALT differences during the pre-pandemic period (mean -2.39 IU/L, SD 8.67) and pandemic period (mean 1.70 IU/L, SD 11.3);p=0.01 (Figure 1). There was no significant difference between monthly AST differences during the two time periods. The relative risk of having an increase in BMI Z-score during the pandemic period compared to the pre-pandemic period was 1.37 (95% CI [1.09-1.72], p < 0.01, Figure 2). The relative risk of having an increase in ALT or AST during the pandemic period compared to the pre-pandemic period was not significant. Conclusion(s): Our cohort of children with NAFLD experienced an accelerated rate of BMI increases and ALT elevation during the COVID-19 pandemic. These findings underscore the importance of increasing access to resources for healthy behaviors during public health emergencies or extended school closures in facilitating the health and well-being of children with NAFLD.
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Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.
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Objectives: A 36-year-old Caucasian woman developed acute hepatitis and morbilliform eruption arising ten days after the first dose of the mRNA BNT162b2 SARS-CoV-2 vaccine. Materials and Methods: The patient was asymptomatic apart from the skin rash. Liver function tests showed predmoninantly severe transaminitis (AST 523 U/L, ALT 1550 U/L, GGT 151 U/L, ALP 128 U/L, bilirubin 12 umol/L). Only the ANA 1:160 was abnormal. Other serology for autoimmune and infectious diseases were negative. Multiphase computed tomography of the abdomen was unremarkable. The SARS-CoV-2 anti-spike IgG titre was 67.5 AU/mL (cut-off[15 AU/mL). The skin histology revealed spongiotic reaction pattern with focal interface lymphocytic inflammation. Multiple eosinophils and a few plasma cells were present. The epidermal lymphocytes were composed of CD2, CD3, C4, CD5, CD7 and CD8-positive T cells, with a CD4:CD8 ratio of 1:5. A small number stained positive with TIA1, PD1 and granzyme B. CD56 staining was negative. A liver biopsy was performed after 2 days of steroids. Liver histology showed mild steatosis and mild inflammatory portal infiltrate comprising mainly of small lymphocytes that were CD3 positive with retained staining for CD7 and CD8. Lobular architecture was preserved with inconspicuous interface hepatitis or piecemeal necrosis. Results: The patient was treated with intravenous hydrocortisone (400 mg/day) followed by prednisone (50 mg/day). There was rapid improvement in her liver function tests and cutaneous manifestations (Fig. 1). Conclusion: mRNA COVID-19 vaccine induced hepatitis is a rare phenomenon that is steroid-responsive and has associations with cutaneous eruptions. Our patient's lack of hepatic histological abnormalties is most likely due to early immunosuppression. She had epidermal lymphocytosis with predominance of CD8-positive T cells that were not of cytotoxic phenotype and we are uncertain as to their significance. There is limited guidance on the safety of SARS-CoV-2 vaccination in those who have had developed significant hepatic and cutaenous reactions. Further work is needed.