Browsing by Subject "Autoimmune hepatitis"
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Item Autoimmune hepatitis: Current and future therapies(Wolters Kluwer, 2024-06-05) Reau, Nancy S.; Lammert, Craig S.; Weinberg, Ethan M.; Medicine, School of MedicineAutoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.Item Environmental risk factors are associated with autoimmune hepatitis(Wiley, 2021) Lammert, Craig; Chalasani, Sai N.; Atkinson, Elizabeth J.; McCauley, Bryan M.; Lazaridis, Konstantinos N.; Medicine, School of MedicineBackground: Failure of immunologic homeostasis and resultant hepatocyte destruction in autoimmune hepatitis (AIH) is likely the result of environmental triggers within a permissive genetic architecture. Aims: We aimed to identify risk factors associated with AIH in a well-phenotyped AIH cohort. Methods: We prospectively collected environmental questionnaires from 358 AIH cases and 563 healthy controls. Response frequencies were compared using logistic regression, adjusting for age at recruitment, sex and education. Results: AIH cases were more likely to ever have a urinary tract infection (UTI) (53.6% vs 33.9%, P < .001) and recurrent UTI (more than 1 per year) (23.5% vs 15.9%, P = .002) compared to controls. Female cases more frequently had ever used oral contraceptives (83.0% vs 73.7%, P = .006), fewer pregnancies (median = 1 vs 3, P < .001) and less often used hormone replacement therapy compared to controls (28.5% vs 60.1%, P < .001). Current smoking was more prevalent in cases (18.9% vs 7.4%, P = .022), yet no difference according to historical smoking behaviours was observed. Finally, cases were less likely to have history of mumps (32.4% vs 53.1%, P = .011) and rheumatic fever (1.1% vs 4.4%, P = .028), but reported higher vaccination frequency to chicken pox (38% vs 28.1%), measles (66.5% vs 39.3%), mumps (58.7% vs 34.6%), rubella (55.3% vs 32.7%), pertussis (59.8% vs 40.1%) and pneumococcus (47.2% VS 39.4%) (P < .002). Conclusions: Environmental factors are important in AIH pathogenesis. Replication of these findings and prospective examination may provide new insight into AIH onset and outcomes.Item Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome(Wolters Kluwer, 2022) Efe, Cumali; Kulkarni, Anand V.; Beretta-Piccoli, Benedetta Terziroli; Magro, Bianca; Stättermayer, Albert; Cengiz, Mustafa; Clayton-Chubb, Daniel; Lammert, Craig; Bernsmeier, Christine; Gül, Özlem; Higuera-de la Tijera, Fatima; Anders, Margarita; Lytvyak, Ellina; Akın, Mete; Purnak, Tugrul; Liberal, Rodrigo; Peralta, Mirta; Ebik, Berat; Duman, Serkan; Demir, Nurhan; Balaban, Yasemin; Urzua, Álvaro; Contreras, Fernando; Venturelli, Maria Grazia; Bilgiç, Yılmaz; Medina, Adriana; Girala, Marcos; Günşar, Fulya; Londoño, Maria-Carlota; Androutsakos, Theodoros; Kisch, Ayelen; Yurci, Alper; Güzelbulut, Fatih; Çağın, Yasir Furkan; Avcı, Enver; Akyıldız, Murat; Dindar-Demiray, Emine Kübra; Harputluoğlu, Murat; Kumar, Rahul; Satapathy, Sanjaya K.; Mendizabal, Manuel; Silva, Marcelo; Fagiuoli, Stefano; Roberts, Stuart K.; Soylu, Neşe Karadağ; Idilman, Ramazan; Yoshida, Eric M.; Montano-Loza, Aldo J.; Dalekos, George N.; Ridruejo, Ezequiel; Schiano, Thomas D.; Wahlin, Staffan; Medicine, School of MedicineBackground and aims: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.Item Overlooked Symptoms in Autoimmune Hepatitis Negatively Impact Many Facets of Life(Springer, 2023) Jones, Emma; Watkins, Margaret; Anderson, Erin; Gelow, Kayla; Green, Kelsey; Draucker, Claire; Lammert, Craig; Medicine, School of MedicineBackground: Significant reduction in quality of life among patients with autoimmune hepatitis (AIH) patients has been observed in several studies. While acute symptoms associated with AIH have been well described, little is known about the overall impact of living with AIH on patients' quality of life. The aim of this qualitative descriptive study was to describe the impact of AIH and associated symptoms on quality of life from the perspectives of patients living with AIH. Methods: Patients from Autoimmune Hepatitis Association support groups were recruited to participate in one of five online focus groups conducted between August and September 2020. After enrollment, patients were asked to complete a brief demographic and disease history questionnaire. A single moderator conducted interviews with each group guided by seven questions focused on the impact of AIH on the participants' quality of life. Each session was recorded, transcribed, and verified. Content analysis was used to summarize the participants' responses. Results: The participants' discussed three overarching topics: (a) symptoms of AIH and medication side effects, (b) the impact the disease and symptoms/side effects on five domains of quality of life (work life, relationships with friends and family, social life, leisure activities, and diet and exercise) and (c) interactions with healthcare providers and recommendations for future research. Conclusions: Living with AIH can have profound effects on patients' quality of life in several domains. Healthcare providers and the AIH research community should focus on developing further strategies that can improve the quality of life in persons suffering from AIH.Item Patients with Autoimmune Hepatitis Report Lower Lifetime Coffee Consumption(Springer, 2022) Lammert, Craig; Chalasani, Sai N.; Green, Kelsey; Atkinson, Elizabeth; McCauley, Bryan; Lazaridis, Konstantinos N.; Medicine, School of MedicineBackground: Coffee drinking has been associated with decreased risk of some autoimmune diseases as well liver disease and outcomes. Environmental factors, such as coffee consumption, are yet to be assessed among patients with autoimmune hepatitis (AIH). Aim: We sought to investigate the relationship between coffee consumption and risk of AIH utilizing the Genetic Repository of Autoimmune Liver Disease and Contributing Exposures (GRACE) database. Methods: Lifetime coffee drinking was collected from 358 AIH patients (cases) and 564 volunteers (controls) from primary care visits. Groups were compared utilizing the Wilcoxon rank sum test for continuous variables and the Chi-square test for discrete variables. Logistic regression was used to analyze the effects of different coffee parameters (time, frequency, and cups) after adjusting for age, sex, education, smoking status, BMI, and daily activity. Results: 24.6% of AIH patients never drank coffee compared to 15.7% of controls (p < 0.001), and only 65.6% were current drinkers compared with 77% of controls (p < 0.001). Among "ever" coffee drinkers, AIH patients consumed fewer lifetime cups of coffee per month (45 vs. 47 for controls, p < 0.001) and spent less percentage of life drinking coffee (62.5% vs. 69.1% for controls, p < 0.001). Concurrent inflammatory bowel disease was higher among AIH patients than controls (5.7% vs. 1.2%, p < 0.001), yet did not significantly contribute to "never" coffee drinking status. The relationship between lower coffee consumption and AIH persisted even after controlling for covariates. Conclusions: Coffee consumption is lower among patients with AIH compared to controls.Item Primary Sclerosing Cholangitis-Autoimmune Hepatitis Overlap Syndrome: Significant Barriers in Liver Disease Diagnosis and Treatment Experienced by the Latino Community(Springer, 2023-03-14) Guifarro, Daniel A.; De Oliveira-Gomes, Diana; Beas, Renato; Yibirin-Wakim, Marcel J.; Montalvan-Sanchez, Eleazar E.; Medicine, School of MedicineOverlap syndrome (OS) is a term that comprises the presentation of multiple hepatic disease characteristics in the same patient, such as the presence of autoimmune hepatitis (AIH) features in addition to primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC). Standard therapy for AIH is immunosuppression, while ursodeoxycholic acid is the preferred treatment for PBC. Additionally, liver transplantation (LT) may be considered in severe cases. Hispanics have been found to have a higher prevalence of chronic liver disease and develop more complications associated with portal hypertension at the time of listing for LT. Despite being the fastest-growing population in the USA, Hispanics have a higher probability of not receiving an LT due to issues with social determinants of health (SDOH). It has been reported that Hispanics are more likely to be removed from the transplant list. We report a case of a 25-year-old female immigrant from a Latin American developing country who presented with symptoms consistent with worsening liver disease after years of inappropriate workup and late diagnosis due to barriers within the healthcare system. The patient had a history of unresolved jaundice and pruritus and presented with worsening of her previous symptoms and new onset abdominal distention, bilateral leg edema, and telangiectasias. Laboratory and imaging studies confirmed the diagnosis of AIH and primary sclerosing cholangitis (PSC-AIH syndrome). The patient was started on steroids, azathioprine, and ursodeoxycholic acid, showing improvement. Due to her migratory status, she could not receive an appropriate diagnosis and follow up with a single provider or healthcare institution, putting her at increased risk for life-threatening complications. Although medical management is the first step, the probability of future liver transplants exists. The patient is still undergoing liver transplant evaluation and completing a workup since she was found to have an elevated model for end-stage liver disease (MELD) score. Even with the introduction of new scores and policies that aim to reduce disparities in LT, Hispanic patients are still at higher risk of being removed from the waitlist because of death or clinical deterioration compared to non-Hispanics. To this day, Hispanics have the highest percentage of waitlist deaths (20.8%) of all ethnicities and the lowest overall rate for undergoing LT. Understanding and addressing the causes that could contribute to and explain this phenomenon is essential. Increasing awareness of this problem is vital to promote more research on LT disparities.Item Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management(Public Library of Science, 2022-03-21) Tana, Michele May-Sien; Klepper, Arielle; Lyden, Amy; Pisco, Angela Oliveira; Phelps, Maira; McGee, Breann; Green, Kelsey; Feng, Sandy; DeRisi, Joseph; Crawford, Emily Dawn; Lammert, Craig S.; Medicine, School of MedicineAutoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.Item Utilization and Impact of Complementary and Alternative Medicines in Symptomatic Autoimmune Hepatitis Patients(Springer, 2022) Gelow, Kayla; Chalasani, Sai; Green, Kelsey; Lammert, Craig; Medicine, School of MedicineBackground: Complementary and alternative medicine (CAM) use has become increasingly common. It is also prevalent in patients with chronic liver disease, but the scope, depth, and safety of use is not well known. Aims: This study aimed to evaluate the prevalence and patterns of CAM use in autoimmune hepatitis (AIH) patients. Methods: Electronic invitation to complete a 22 item CAM-specific questionnaire was posted weekly to well-established AIH Facebook communities (combined membership of 4700 individuals) during a 6-week study period. Age ≥ 18 years and AIH diagnosis made by a treating physician were the eligibility criteria. Results: The prevalence of ever CAM use among participants was 56.4%, and nearly 42% used CAM after AIH diagnosis. Among those reporting CAM use after diagnosis, 53.7% (51/95) indicated CAM was used to mitigate AIH-related phenomenon, most often targeting liver inflammation/fibrosis (67.7%), fatigue (51%), joint pain (47.1%), and sleep issues (45.1%). Most frequent physical CAM strategies were exercise (49.5%) and yoga (34%), whereas most frequent consumable CAM included healthier eating (45.3%), cannabidiol preparations (45.3%), and probiotics (44.3%). Seventy-five percent reported that CAM improved AIH symptoms and no severe adverse events were reported. Conclusions: CAM use in AIH patients is prevalent, yet providers have historically failed to document their patient's CAM strategies. Beyond inherent drug-induced liver injury risk, drug-drug interactions remain a concern and could alter baseline immunosuppression levels in AIH. Despite a majority found CAM approaches that improved targeted symptoms, all were unable to alter the course of chronically prescribed medications by physicians.