Drug-induced Autoimmune Hepatitis Research Articles

Clinical and Pathological Features of Immune Checkpoint Inhibitor-induced Liver Injury in Comparison with Drug-induced Liver Injury and Autoimmune Hepatitis.

Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis. We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15). Liver biopsies were performed in 10 of the 15 cases. We also selected cases in which a liver biopsy was performed and drug-induced liver injury (n=7) or autoimmune hepatitis [n=21: acute exacerbation (n=13) was diagnosed and cases of acute onset (n=8), in which liver function test results corresponded to ≥ grade 3]. Portal fibrosis and periportal activity scores were significantly higher in the acute exacerbation autoimmune hepatitis group than in the other groups. Portal and lobular activity were not different between the groups. Plasma cell infiltration showed a higher trend in the autoimmune hepatitis group than in the other groups. Granuloma formations were seen in 90% of immune checkpoint inhibitor-related liver injury cases. The CD4/8 ratio was significantly lower in the immune checkpoint inhibitor-related liver injury group than in the other groups. Patients with bile duct injury had poorer response to corticosteroid therapy than those without. There are some obvious differences among immune checkpoint inhibitor-related liver injury, drug-induced liver injury, and autoimmune hepatitis in liver histology. Liver biopsy is helpful for the diagnosis and severity evaluation of liver injury.

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs.

WED-311 - Drug-induced autoimmune hepatitis or drug-induced liver injury with autoimmune features: two faces of the same coin?

WED-311 - Drug-induced autoimmune hepatitis or drug-induced liver injury with autoimmune features: two faces of the same coin?

DRUG-INDUCED AUTOIMMUNE HEPATITIS: SYSTEMATIC REVIEW AND CASE STUDY

Drug-induced liver injury (DILI) is one of the types of adverse reactions to drugs that occur as a result of their hepatotoxic effect. The pathogenesis of drug-induced autoimmune hepatitis (LIAH) is based on the production of autoantibodies to neoantigens, which are proteins of the cytochrome P450 system, which are the result of the reaction of drug metabolites. A clinically relevant problem, such as drug-induced liver damage, affects 1-1.5 million patients almost every year. The annual incidence of DILI ranges from 2.3-13.9 per 100,000 population in population studies from Europe. The Icelandic population study recorded the highest rates of 19.1 per 100,000 population per year. And in the only study based on the US population, it was found that DILI is approximately 3 per 100,000 population. Acute hepatitis is currently a well-known manifestation, and accounts for more than 90% of liver damage caused by medications. According to studies, 2.9 - 8.8% of DILI and 2 - 18% of AIH are associated with drug-induced autoimmune hepatitis. The incidence of drug-induced liver damage with the presence of antibodies (antibodies to nuclear antigen, smooth muscle and soluble liver antigen) to AIH is 83% for nitrofurantoin, 74% for minocycline, 60% for methyldopa and 43% for hydralazine.

TOP-092 - Distinctive cytokine profiles in checkpoint inhibitor-induced liver injury, idiosyncratic drug-induced liver injury and autoimmune hepatitis: a potential mechanistic biomarker panel

TOP-092 - Distinctive cytokine profiles in checkpoint inhibitor-induced liver injury, idiosyncratic drug-induced liver injury and autoimmune hepatitis: a potential mechanistic biomarker panel

SAT-381 - Intermediate monocytes and associated chemokines allow differentiation of idiosyncratic drug-induced liver injury (DILI) and autoimmune hepatitis (AIH)

SAT-381 - Intermediate monocytes and associated chemokines allow differentiation of idiosyncratic drug-induced liver injury (DILI) and autoimmune hepatitis (AIH)

Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM.

Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations

Drug induced liver injury (DILI) occurs in patients exposed to drugs at recommended doses that leads to idiosyncratic DILI and provides an excellent human model with well described clinical features, liver injury pattern, and diagnostic criteria, based on patients assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) as original method of 1993 or its update of 2016. Overall, 81,856 RUCAM based DILI cases have been published until mid of 2020, allowing now for an analysis of mechanistic issues of the disease. From selected DILI cases with verified diagnosis by using RUCAM, direct evidence was provided for the involvement of the innate and adapted immune system as well as genetic HLA (Human Leucocyte Antigen) genotypes. Direct evidence for a role of hepatic immune systems was substantiated by (1) the detection of anti-CYP (Cytochrome P450) isoforms in the plasma of affected patients, in line with the observation that 65% of the drugs most implicated in DILI are metabolized by a range of CYP isoforms, (2) the DIAIH (drug induced autoimmune hepatitis), a subgroup of idiosyncratic DILI, which is characterized by high RUCAM causality gradings and the detection of plasma antibodies such as positive serum anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), rarely also anti-mitochondrial antibodies (AMA), (3) the effective treatment with glucocorticoids in part of an unselected RUCAM based DILI group, and (4) its rare association with the immune-triggered Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) caused by a small group of drugs. Direct evidence of a genetic basis of idiosyncratic DILI was shown by the association of several HLA genotypes for DILI caused by selected drugs. Finally, animal models of idiosyncratic DILI mimicking human immune and genetic features are not available and further search likely will be unsuccessful. In essence and based on cases of DILI with verified diagnosis using RUCAM for causality evaluation, there is now substantial direct evidence that immune mechanisms and genetics can account for idiosyncratic DILI by many but not all implicated drugs, which may help understand the mechanistic background of the disease and contribute to new approaches of therapy and prevention.

Levetiracetam Liver Injury: A Benign Antiepileptic Agent?

Levetiracetam is a commonly prescribed antiepileptic agent and has rarely been linked to hepatotoxicity. This case describes a patient with drug-induced autoimmune hepatitis secondary to levetiracetam.

S3142 Rare Case of Drug-Induced Autoimmune Hepatitis

Introduction: Our case represents rare hepatotoxic effects of Norvasq and Lipitior, more specifically Drug Induced Autoimmune Hepatitis with mixed hepatitis and cholestatic pattern and positive autoimmune hepatitis markers. Case Description/Methods: 65 year old female, with history of hypertension, alcohol use, quit in October 2021 and sigmoid diverticulosis, presented to the office clinic with dark urine, unintentional 10lb weight loss as of 2 months ago, pale colored loose stools and new abnormal lab findings as seen in Figure 1. Patient’s abdominal ultrasound showed cholelithiasis and hepatic hemangioma. Patient’s home medications included Lipitor, which had a dose increase from 10 mg to 40 mg in August 2021. Additionally, the patient was started on Norvasc 5 mg in August 2021. Both medications were discontinued on 12/10/2021. Patient had resolution of liver enzymes after discontinuation of medications as seen in Figure 1. Discussion: Drug-induced autoimmune hepatitis can have a wide array of clinical presentations and therefore is included as a differential for abnormal liver biochemical tests, acute hepatitis, cirrhosis, or acute liver failure. Symptoms can range from being asymptomatic to anorexia, fatigue, abdominal pain, itching, and weight loss. Clinical studies have shown adverse hepatic function with statins, representing 0.5 to 3% of patients taking them.1 More specifically, statins do cause hepatitis in a dose-dependent manner. Rarely, there are reports of severe symptoms associated which include the hepatocellular, cholestatic and autoimmune injury. Additionally, amlodipine’s adverse drug reactions do not include hepatic injury; but post-marketing cases were reported showing amlodipine causing cholestatic hepatitis and hepatotoxicity. Similar to our case report, there was a resolution of liver enzymes after discontinuation of amlodipine. Our case is unique as the patient had drug-induced autoimmune hepatitis with a cholestatic pattern. It is important to consider Lipitor’s dose increase as a result of hepatitis, cholestatic and autoimmune injury. Additionally, Norvasq causing cholestatic hepatitis and hepatotoxicity. This case demonstrates the rare hepatotoxic effects of amlodipine and Lipitor, further studies are needed to document the incidences. Table 1. - 12/14/2021 12/23/2021 12/14/2021 AST 699 379 IgG 1885 ALT 657 519 IgM 298 ALP 1079 731 ANA Positive Total Bilirubin 7.3 2.1 Anti-Smooth Muscle Antibody 53 Direct Bilirubin 6.04 1.4 Anti-Mitochondrial Antibody 115

S3000 Ezetimibe-Induced Autoimmune Hepatitis: An Uncommon Offender

Introduction: Drug-induced autoimmune hepatitis (DIAIH) is a subset of autoimmune hepatitis (AIH) leading to a seropositive hepatitis caused by an inciting drug. Ezetimibe is a cholesterol absorption inhibitor within the intestinal tract that very rarely causes DIAIH. The proposed mechanism of Ezetimibe-induced DIAIH is thought to be due to interactions between drug metabolites and CYP450 within hepatic cells. Statins are another class of medication known to cause hepatotoxicity that are commonly used in combination with ezetimibe for hyperlipidemia. Highlighting cases of drug-related autoimmune hepatitis can be useful as routine liver function testing for statin-induced hepatitis is currently not recommended. Case Description/Methods: This case describes a 67 year old man with hyperlipidemia and Hashimoto’s thyroiditis admitted for abdominal pain and biochemical evidence of hepatitis after starting ezetimibe 6 weeks prior. He had also been on atorvastatin but had been on a stable dose for the previous 7 years. He did not have a history of alcohol, herbal medication or Tylenol use and had entirely normal liver function tests 6 months prior to admission. Admission labs were pertinent for AST of 2159, ALT of 3011, Alkaline phosphatase of 245, total bilirubin of 2.7 (direct bilirubin 1.3), INR of 1.3, and a creatinine kinase of 497. Autoimmune serologies were notable for a positive ANA (1:320) and anti-smooth muscle antibody (1:320). An ultrasound was negative for hepatic lesions or evidence of advanced cirrhosis. Ezetimibe and atorvastatin therapy were discontinued on admission and the patient was eventually discharged after his liver function tests improved. Discussion: Ezetimibe is a common 2nd line agent used for patients with statin-refractory hyperlipidemia which has also been known to cause hepatic injury typically with a latency period of 1-2 months into treatment. When used in combination with a statin the risk of hepatic injury increases. Current guidelines recommend against regular surveillance of liver function tests during statin treatment given that significant hepatotoxicity is exceedingly rare and routine testing did not prevent these events. However, in patients taking both a statin and ezetimibe it may be beneficial to obtain pre-treatment and in-treatment liver function testing towards the end of the latency period, especially if the incidence of ezetimibe-induced autoimmune hepatitis continues to rise.

S2981 Drug-Induced Autoimmune-Like Hepatitis Due to HemoHIM in a 28-Year Old Pregnant Woman

Introduction: Drug-induced autoimmune-like hepatitis (DIAIH) is a pathologic immune response against proteins in the liver that can be triggered in susceptible individuals by drugs or herbal remedies. While any supplement can cause idiosyncratic hepatotoxicity, up to 16% of drug-induced liver injuries are attributable to herbal supplements. To date, there are still limited data on herbal medicine-related hepatotoxicity. This topic is particularly understudied in pregnant patients, with most current clinical information coming from case reports. While use of supplements is common during pregnancy, there is still limited information regarding their safety. Case Description/Methods: A previously healthy G4P2A1 28-year-old presented at 5 weeks of pregnancy with right upper quadrant pain and fevers, and was presumed to have acute cholecystitis resulting in a laparoscopic cholecystectomy. Despite this, her liver enzymes continued to worsen (AST 2893, ALT 2664, TBili 2.6, Alk Phos 460, INR 1.3). The patient also had laboratory evidence of AIH including Anti-Mi+ 34.5, U1-RNP/RNA-A68 2.4, Chromatin Abs 1.6. She underwent liver biopsy showing drug-induced liver injury and autoimmune hepatitis (AIH). Given that AIH often presents during pregnancy, it was unclear if this presentation represented DIAIH or AIH. Notably, the patient had recently started taking an herbal supplement with purported immune support called HemoHIM that was thought to be a possible driver of DIAIH, The supplement was discontinued and she was started on a 60mg prednisolone with subsequent clinical and laboratory improvement. Despite improvement, the patient suffered spontaneous abortion early in the treatment course and in retrospect underwent unnecessary cholecystectomy. Given concern for possible AIH and slow normalization of LFTs, she was started on azathioprine, but self-discontinued after 7 months. Her liver enzymes remained stable 6 months later; supporting a diagnosis of DIAIH due to HemoHIM rather than AIH which would have likely rebounded with such early treatment withdrawal. Discussion: While DIAILH is an underreported disease in pregnant women this case demonstrates the importance of early diagnosis and treatment. Additionally, it illustrates he challenges in distinguishing between DAILH and AIH especially in patients taking herbal supplements.

S2967 Drug-Induced Autoimmune Hepatitis Post Acute Liver Injury From Skullcap Supplements: An Unfortunate Case of Herbal Toxicity

S2967 Drug-Induced Autoimmune Hepatitis Post Acute Liver Injury From Skullcap Supplements: An Unfortunate Case of Herbal Toxicity

S3272 A Potential New Use for Tocilizumab: A Case of Refractory Checkpoint Inhibitor Hepatitis

Introduction: Immune checkpoint inhibitors (CPI) are becoming increasingly common treatment options for several types of cancers. While their use in cancer treatment is very promising, these medications are not without side effects. Specifically, these drugs are commonly associated with hepatic adverse events, including auto-immune hepatitis (AIH). In fact, in one study, AIH was found in approximately 5% of people treated with a CPI. While we know that CPI hepatitis is a potential outcome of treatment with CPIs, we have yet to establish the best treatment options for this adverse event. Based on expert opinion, the recommended course of treatment involves high dose steroids and immunomodulators if needed. There is not, however, much literature on management of CPI hepatitis that is refractory to the typical treatments, though use of tocilizumab has shown some success previously in treatment of immune-related adverse events secondary to CPIs . Case Description/Methods: A 35 y.o. female with recurrent right renal cell carcinoma, status-post resection with nephrectomy, on palliative treatment with nivolumab/ipilimumab, presented to the hospital for further evaluation of elevated liver function tests (LFT) and an abdominal MRI concerning for hepatitis. At time of admission, she was on her 3rd week of steroids, started with concern for drug-induced autoimmune hepatitis due to her checkpoint inhibitor (CPI) treatment. At admission, she was started on IV steroids and mycophenolic acid. LFTs and bilirubin continued to rise despite several days of this treatment and she was given a dose of rituximab. Liver biopsy was obtained which was consistent with CPI induced hepatitis. LFTs and bilirubin continued to rise and tocilizumab was given. 4 days after that treatment, AST and ALT were nearly half their pretreatment values and bilirubin began downtrending. At this point, the patient was stable enough for discharge with very close follow up (Figure). Discussion: Studies from 2019 reveal that 43.68% of all people with cancer in the United States are eligible for CPI therapy. This number translates to 7.9 million patients who are potentially eligible for CPI therapy. With the incidence of severe CPI hepatitis suspected to be up to 20% of all people taking CPIs, this equates to 1.58 million people of whom could be affected. More studies need to be done to address treatment for refractory auto-immune CPI hepatitis, and to better understand the underlying pathogenesis in this rapidly growing population.Figure 1.: Liver biopsy with significant lobular hepatitis, loss of zone 3 hepatocytes, acidophil bodies, and Kupffer cell hyperplasia consistant with checkpoint inhibitor auto-immune hepatitis.

Drug-induced autoimmune hepatitis: A minireview.

Drug-induced autoimmune hepatitis (DIAIH) is a specific phenotype of drug-induced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation. Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins as well as anti-tumor necrosis agents. The clinical features of drug-induced liver injury are indistinguishable from idiopathic autoimmune hepatitis (AIH) as both may have positive AIH-related autoantibodies, elevated immunoglobulin G, as well as similar histopathological findings. In patients who show no clinical improvement, or there is progressive liver injury despite cessation of the suspected drug, a liver biopsy should be considered, whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH. Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury. A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper. In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature. Early identification and treatment often lead to a favorable outcome in DIAIH.

Challenges and Future of Drug-Induced Liver Injury Research—Laboratory Tests

Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which is also a major cause of study cessation and market withdrawal during drug development. Since no acknowledged diagnostic tests are available, DILI diagnosis poses a major challenge both in clinical practice as well as in pharmacovigilance. Differentiation from other liver diseases and the identification of the causative agent in the case of polymedication are the main issues that clinicians and drug developers face in this regard. Thus, efforts have been made to establish diagnostic testing methods and biomarkers in order to safely diagnose DILI and ensure a distinguishment from alternative liver pathologies. This review provides an overview of the diagnostic methods used in differential diagnosis, especially with regards to autoimmune hepatitis (AIH) and drug-induced autoimmune hepatitis (DI-AIH), in vitro causality methods using individual blood samples, biomarkers for diagnosis and severity prediction, as well as experimental predictive models utilized in pre-clinical settings during drug development regimes.

Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review.

Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: “corticosteroids” and “drug-induced liver injury”. Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33–50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33–100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI.

Hepatotoxicity Induced by Biological Agents: Clinical Features and Current Controversies.

Novel biological agents including cytokines and recombinant fusion proteins are increasingly prescribed for cancer, rheumatologic, autoimmune, and inflammatory diseases, and are currently being evaluated in hepatocellular carcinoma (HCC). They are classified by their mechanism of action and include tumor necrosis factor-alpha (TNF-α) antagonists, T cell mediated antitumor inhibitors, interleukin receptor antagonists, and immune checkpoint inhibitors (ICIs). Some ICIs cause frequent hepatotoxicity with a variable clinical, biochemical, and serological presentation, especially in patients receiving another immunomodulatory agent. Half of the cases of liver damage induced by biological agents spontaneously regress after drug withdrawal, but the others require steroid therapy. Unfortunately, there are no widely accepted recommendation for the use of corticosteroids in these patients, even though international cancer societies have their own guidelines. Differentiating drug-induced autoimmune hepatitis (DIAIH) from classic AIH is challenging for pathologists, but liver biopsy is valuable, particularly in cases with unclear clinical presentation. Interesting, novel histological patterns have been described in liver damage induced by these agents (i.e., endothelitis, ring granuloma and secundary sclerosing cholangitis associated with lymphocytic infiltration of cytotoxic CD8+T cells). Here, we describe the clinical and biochemical characteristics of patients with hepatotoxicity induced by TNF-α antagonists and ICIs. Controversial issues involved in the administration of corticosteroid therapy, and hepatitis B virus (HBV) reactivation induced by immunosuppressive therapy are also discussed.

From the Editor’s Desk...

From the Editor’s Desk...

S2841 Autoimmune Hepatitis: Possible Relation to the Pfizer-BioNTech COVID-19 Vaccine?

Introduction: Autoimmune Hepatitis (AIH) is a rare liver injury known to cause approximately 13% of acute liver failure cases in the United States. Drug-induced AIH has similar clinical, serological and histological features of AIH but is less likely to require long term immunosuppression or to relapse after discontinuation of immunosuppressants. It is mostly associated with nitrofurantoin, minocycline, hydralazine, and methyldopa, however other medications may be culprits. Herein, we present a patient with drug-induced AIH with possible relation to Pfizer-BioNTech COVID-19 vaccine. Case Description/Methods: A 38-year-old female with a history of Helicobacter pylori treated with amoxicillin and pantoprazole three months ago and recent COVID-19 vaccination presented with two weeks of right upper quadrant pain and diarrhea. Patient received second dose of vaccination two weeks prior to symptom onset. Five days post-symptom onset, she developed a pruritic rash with vomiting and yellowing of her skin. Physical examination was notable for normal mentation, scleral icterus, jaundice, and a maculopapular rash. Initial blood workup showed international normalized ratio 2.4, alkaline phosphatase 212 U/L, ALT 3769 U/L, AST 1572 U/L and total bilirubin of 23.8 mg/dL. Viral hepatitis serologies, chronic liver disease workup and autoimmune serologies were normal. Imaging demonstrated no intra- or extra-hepatic biliary ductal dilation. Liver biopsy showed portal inflammation with interface activity, diffuse lobular inflammation, and perivenulitis with abundant lymphocytes and plasma cells consistent with seronegative AIH or drug induced AIH. The patient developed altered mental status meeting the criteria of acute liver failure, she was started on corticosteroids as well as supportive care with resolution of encephalopathy and was discharged home on prednisone. Discussion: Several etiologies of drug-induced AIH are well-established, however cases secondary to COVID-19 vaccination have been minimally reported. Common adverse events for COVID-19 vaccination have been noted such as fever, chills, fatigue, headache, and muscle pain. Several rare side effects have occurred including immune thrombocytopenia and one other suspected case of Pfizer-BioNTech COVID-19 vaccination-induced AIH reported in the literature. In that case the patient developed symptoms within one week of the first dose. This case serves to report a potential association and not necessarily causation between the Pfizer-BioNTech COVID-19 vaccination and AIH.Figure 1.: Severely active lymphoplasmacytic hepatitis with frequent apoptotic hepatocytes with confluent necrosis.