A case of possible drug-induced liver injury due to COVID-19 vaccine.

The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

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.

Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.

BACKGROUND AND AIMS: Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. METHODS: Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n=6) and from patients with an initial diagnosis of AIH (n=9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence and immune repertoire sequencing. RESULTS: Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8+ effector T cells, similar to drug-induced autoimmune like hepatitis (DI-AILH). In contrast, AIH showed a dominance of CD4+ effector T cells and CD79a+ B and plasma cells. T-cell receptor (TCR) and B-cell receptor (BCR) sequencing showed that T- and B-cell clones were more dominant in VILI than in AIH. In addition, many T-cell clones detected in the liver were also found in the blood. Interestingly, analysis of TCR beta chain and Ig heavy chain variable-joining gene usage further showed that TRBV6-1, TRBV5-1, TRBV7-6 and IgHV1-24 genes are used differently in VILI than in AIH. CONCLUSIONS: Our analyses support that SARS-CoV-2 vaccination-induced liver injury is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. VILI may be a separate entity, which is distinct from AIH and more closely related to DI-AILH. IMPACT AND IMPLICATIONS: Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury. Our analysis shows that COVID-19 vaccine-induced liver injury shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that vaccine-induced liver injury is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 vaccine-induced liver injury will recover completely and do not develop long-term autoimmune hepatitis.

SARS-CoV-2-Induced Autoimmune Hepatitis.

Few case reports discuss the incidences of autoimmune hepatitis (AIH) in patients after SARS-CoV-2 infection. Here, we present a case of SARS-CoV-2-induced AIH in a male patient who came into the emergency department with complaints of weight loss, poor oral intake, nausea, dark-colored urine, clay-colored stools, and scleral icterus, which began two weeks after he tested positive for SARS-CoV-2 PCR. Liver biopsy and subsequent histology confirmed the diagnosis of AIH with the most probable etiology being SARS-CoV-2 infection. The patient was treated with N-acetylcysteine (NAC) and steroids with clinical improvement and eventual discharge home. Our goal is to provide a clinical presentation, treatment, and outcome in a patient with SARS-CoV-2-induced AIH.

Clinicopathological Characteristics of Autoimmune-Like Hepatitis Induced by COVID-19 mRNA Vaccine (Pfizer-BioNTech, BNT162b2): A Case Report and Literature Review.

Widespread use of vaccinations worldwide in the coronavirus disease (COVID-19) pandemic has resulted in various side effects. Here, we presented a 27-year-old man with autoimmune-like hepatitis after the first dose of the BNT162b2 (mRNA) COVID-19 vaccine and reviewed previous reports. He presented with sweating, febrile sensations, and general weakness. He did not have any medical histories. Although he was treated with biphenyl dimethyl dicarboxylate and ursodeoxycholic acid, the elevated liver enzyme levels persisted for 2 months. Liver biopsy demonstrated portal inflammation with rosette formation, interface hepatitis, and infiltration of lymphocytes, histiocytes, plasma cells, and eosinophils. Especially, centrilobular edema and necrosis were found. The symptoms and liver enzymes improved with prednisolone treatment. If persistently elevated liver enzymes are found after COVID-19 mRNA vaccination, the possibility of autoimmune-like hepatitis induced by the vaccine should be considered and a careful pathologic evaluation is required.

Safety and effectiveness of SARS-CoV-2 vaccination in patients with autoimmune liver diseases-a multi-center, questionnairesbased study

Purpose: The efficacy and safety of SARS-CoV-2 vaccination have been confirmed in several clinical trials. However, patients with autoimmune liver disease were not subject to clinical trials, and data on the efficacy and safety of vaccines have been not available in these population. Therefore, we retrospectively investigated the safety and effectiveness of SARS-CoV-2 vaccination by questionnaire survey targeting Japanese patients with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Method(s): This is a multi-center, retrospective, cross-sectional, questionnaires-based study. Patients with AIH and PBC who are outpatients at participating facilities, 18 years of age or older, and have given consent to participate in this study are included. We distributed questionnaires asking about sex, date of birth, number and type of vaccinations, the presence and degree of adverse effects (AEs), and the presence or absence of SARS-CoV-2 infection before and after vaccination, and asked them to fill in the questionnaire. In addition, we collected the result of liver tests before and after vaccinations of participating patients from each facility. Result(s): The survey was conducted from September 2021 to May 2022. A total of 471 questionnaires were collected from 220 AIH patients (male/female = 33/187, average age 63.5 +/- 13.1 years old) and 251 PBC patients (38/213, 65.8 +/- 10.1). The number of vaccinations was 0/1/2/unknown = 4/0/210/6 for AIH and 4/2/244/1 for PBC. The median time from the second dose to the completion of the questionnaire was 156 days for AIH and 148 days for PBC. By vaccine type, 193 Pfizer, 11 Moderna, and 16 unknown in AIH, and 223/12/16 in PBC. As for AEs, pain and swelling at the injection site were the most common in both AIH and PBC (75% in the first and 64% in the second in AIH, 64%/61% in PBC), followed by general malaise (19%/21% in AIH, 19%/31% in PBC), and myalgia (16%/ 19% in AIH, 19%/14% in PBC). Fever above 38.5 degreeC was observed in 11%/11% of AIH and 11%/24% of PBC, indicating that more patients with PBC experiencing fever that AIH. Only 1 case of PBC had an anaphylactic reaction. By comparing liver tests before and after vaccinations, 4 (1.8%) and 16 (6.4%) patients with AIH and PBC, respectively, demonstrated elevation to 1.5 times the pre-vaccination value and exceeding the upper normal limit. No patients experienced severe deterioration of liver function. SARS-CoV-2 infection was reported in 4 cases (1.8%) in AIH and 3 cases (1.3%) in PBC. Conclusion(s): The safety and effectiveness of SARS-CoV-2 vaccination is comparable to those in the general population.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Autoimmune hepatitis after vaccination against COVID-19.

In this case report, we present a 61-year-old patient admitted to the hospital because of tiredness and jaundice less than three weeks after vaccination against SARS-CoV-2 with the first dose of the Comirnaty vaccine (Pfizer/ BioNTech). Based on the patient s medical history, laboratory data, imaging methods and liver biopsy, we diagnosed autoimmune hepatitis. The patient developed acute liver failure, and his liver function did not improve after corticosteroid administration. Therefore, the patient was enrolled in the waiting list and underwent a successful orthotopic liver transplantation.Copyright © 2023 Galen s.r.o.. All rights reserved.

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A: A Case Report

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Autoimmune Hepatitis Following mRNA COVID-19 Vaccination in a Very Old Patient With Preexisting Sjögren's Syndrome: A Case Report.

A case of autoimmune hepatitis (AIH) following COVID-19 vaccination in a very old patient is presented. An 85-year-old woman who had preexisting Sjögren's syndrome (SS) but had never shown evidence of liver disease was admitted to our hospital due to jaundice and liver dysfunction. Further laboratory tests, imaging studies, and liver histology proved this to be a case of definite AIH. Eight weeks before the disease onset, she had received the second dose of mRNA COVID-19 vaccination. To our knowledge, this is the first case of AIH following COVID-19 vaccination in a patient with a history of SS.

Postvaccination immune-mediated hepatitis: what do we really know?

Tweetable abstract The percentage of patients with immune-mediated vaccine-associated hepatitis is minimal compared with the number of patients vaccinated worldwide.

Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.

Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.

Autoimmune liver diseases and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.

Concurrence of Guillain-Barré syndrome and primary biliary cholangitis not related to SARS-CoV-2: Case report. / Concurrencia de síndrome de Guillain-Barré y colangitis biliar primaria no vinculado a SARS-CoV-2: reporte de caso.

Introduction: Guillain-Barré syndrome is a polyradiculoneuropathy of autoimmune origin, considered the most frequent cause of acute flaccid paralysis. Various associations of Guillain-Barré syndrome with other non-neurological autoimmune diseases have been reported, some of them extremely rare, such as that which occurs with primary biliary cholangitis, a chronic disease of autoimmune etiology whose diagnosis is also supported by the clinical picture. , in the alteration of liver enzymes and the presence of anti-mitochondrial antibodies. Clinical case: A 38-year-old male patient, with no history of previous comorbidities, who, after presenting with diarrheal disease two weeks prior, developed subacute onset ascending weakness associated with paresthesias in four extremities that progressed to quadriplegia and respiratory distress. Cerebrospinal fluid cytochemistry was performed, which showed albuminocytological dissociation and electromyography, which showed findings compatible with acute motor axonal neuropathy, for which he received treatment with intravenous immunoglobulin at 0.4g/kg/day, achieving improvement in the neurological condition. Since admission and during hospitalization, he presented persistent changes in liver enzymes which followed a cholestatic pattern, in addition to mild abdominal pain and generalized itching, for which he was evaluated by gastroenterology, who requested anti-mitochondrial antibodies that were positive. Concluding in the diagnosis of primary biliary cholangitis. Conclusion: The present case shows an extremely rare association of two autoimmune diseases Guillain-Barré syndrome and primary biliary cholangitis, so much so that it represents the first case reported, not linked to SARS-CoV-2.

Introducción: El síndrome de Guillain-Barré es una polirradiculoneuropatia de origen autoinmune, considerada la causa más frecuente de parálisis flácida aguda. Se han reportado diversas asociaciones del síndrome de Guillain-Barré con otras enfermedades autoinmunes no neurológicas, algunas de ellas extremadamente raras, como la que ocurre con la colangitis biliar primaria, una enfermedad crónica de etiología autoinmune cuyo diagnóstico se sustenta, además del cuadro clínico, en la alteración de las enzimas hepáticas y la presencia de anticuerpos anti-mitocondriales. Caso clínico: Paciente varón de 38 años, sin antecedente de comorbilidades previas, quien luego de presentar enfermedad diarreica dos semanas antes, desarrolló debilidad ascendente de inicio subagudo asociado a parestesias en cuatro extremidades que progresó hasta generar cuadriplejia y dificultad respiratoria. Se le realizó examen citoquímico de líquido cefalorraquídeo que evidenció disociación albumino-citológica y electromiografía que mostró hallazgos compatibles con neuropatía axonal motora aguda. Recibió tratamiento con inmunoglobulina intravenosa a dosis de 0,4 gramos por kilogramo al día, logrando mejoría del cuadro neurológico. Desde su ingreso y durante la hospitalización, presentó alteración persistente de las enzimas hepáticas que seguía un patrón colestásico. Además, se agregó dolor abdominal de leve intensidad y prurito generalizado, por lo cual fue evaluado por gastroenterología, quienes solicitaron anticuerpos anti-mitocondriales que resultaron positivos. Con esta prueba, se comprobó el diagnóstico de colangitis biliar primaria. Conclusión: El presente caso muestra una asociación extremadamente rara de dos enfermedades autoinmunes; síndrome de Guillain-Barré y colangitis biliar primaria, tanto así que representa el primer caso reportado, no vinculado a SARS-CoV-2.

Immune-mediated liver injury following COVID-19 vaccination.

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

The Threat of Weight-Loss Over the Counter Supplements: A Case of Camellia Sinensis Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) arises as a result of environmental and immunological interactions. Herbal and dietary supplements (HDS) are known triggers, and approximately half of the U.S. adult population consumes them, even though they are restricted. Therefore, the importance of recognizing potential triggers of AIH is considered relevant. The mechanism behind HDS Camellia Sinensis inducing AIH is related to its compounds, catechins, which induce reactive oxygen species leading to a liver immune-mediated response. We present here a challenging case of a middle-aged woman with AIH following the consumption of a weight-loss Mexican green tea containing Camellia Sinensis.

Clinical, Histological and Serological Features of Autoimmune-Like Acute Liver Injury after Sars-Cov-2 Vaccination

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

Liver and COVID-19 - A Review and Clinical Approach

Liver enzyme abnormalities occur frequently in patients diagnosed with Coronavirus disease 2019 (COVID-19). It has been suggested that patients with severe acute liver injury are more likely to be admitted to intensive care, require intubation or renal replacement therapy and their mortality rate is higher than patients without severe acute liver injury. This review article explores the possible aetiologies of liver dysfunction seen in patients with COVID-19 and also the effect of COVID-19 on patients with pre-existing liver disease. Finally, we suggest clinical approaches to treating a patient with liver enzyme disturbance and COVID-19 and also caring for patients who require liver transplantation in the COVID-19 era.Copyright © 2022 Bentham Science Publishers.

Autoimmune Hepatitis-Primary Biliary Cholangitis Overlap Syndrome Triggered by COVID-19.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 infection, has caused the ongoing global pandemic. Initially considered a respiratory disease, it can manifest with a wide range of complications (gastrointestinal, neurological, thromboembolic and cardiovascular) leading to multiple organ dysfunction. A range of immune complications have also been described. We report the case of a 57-year-old man with a medical history of hypertension, prediabetes and beta thalassemia minor, who was diagnosed with COVID-19 and subsequently developed fatigue and arthralgias, and whose blood work showed hyperferritinemia, elevated liver enzymes (AST/ALT/GGT), hypergammaglobulinemia, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-double-stranded DNA antibodies. The patient was diagnosed with autoimmune hepatitis-primary biliary cholangitis overlap syndrome triggered by COVID-19. To our knowledge, this is the first such case reported. LEARNING POINTS: COVID-19 can precipitate a wide range of immune complications; we report a case of autoimmune hepatitis-primary biliary cholangitis overlap syndrome triggered by COVID-19.Clinicians should be aware of this unusual manifestation of COVID-19 so that prompt and appropriate diagnostic and therapeutic interventions can be initiated if the syndrome is suspected or confirmed.Our case further suggests the necessity for continued and regular follow-up of patients who have recovered from COVID-19 in order to uncover the long-term effects of the novel virus.