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OBJECTIVES: During the summer of 2021, case reports began to emerge documenting a small number of individuals who developed autoimmune hepatitis (AIH) following COVID-19 vaccination. These cases are rare and novel, and very little is known. In our systematic review, we analyzed every published case of AIH and reviewed their characteristic findings, treatment, and outcomes. METHODS: We searched PubMed, Embase, and Web of Science from December 1, 2019, to November 1, 2021. Two researchers independently extracted information from the articles about vaccine type, patient history, laboratory values, histology results, treatment regimens, and disease course. RESULTS: Thirty-two patients developed AIH-like syndromes after receiving a COVID-19 vaccine. Jaundice was the most frequently reported symptom (81%), and 19% of patients were initially asymptomatic and presented with elevated liver enzymes found during routine bloodwork. Mean alanine transaminase, aspartate transaminase, and total bilirubin were 1231 U/L, 921 U/L, and 14 mg/dL, respectively. Anti-nuclear antibody was positive in 56%, and anti-smooth muscle antibody in 28% of patients. Steroids were used in 75% of patients. Improvement or complete resolution was seen in 97% of patients. One patient died despite aggressive steroid treatment. CONCLUSION: COVID-19 vaccine-induced AIH is an uncommon association with just 32 documented cases in the literature. Clinicians should be vigilant for AIH in patients who present with liver injury following vaccination. These new findings should under not deter individuals from getting vaccinated, as the benefits of vaccination far outweigh the risks. Fortunately, COVID-19 vaccine-induced AIH appears amendable to corticosteroid therapy and appears to have a favorable outcome.
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Vacunas contra la COVID-19 , COVID-19 , Hepatitis Autoinmune , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/etiología , Humanos , VacunaciónRESUMEN
BACKGROUND: Frailty is common and is associated with increased mortality, lower quality of life, and higher readmission rates in cirrhotic patients. Not only are these outcomes important, but further understanding the impact of frailty on a caregiver's life is crucial to better comprehend caregiver burden in cirrhotic patients and develop strategies to improve care for patients and their caregivers. METHODS: A single-center, prospective study was conducted of cirrhotic patients and their caregivers between 4/1/2019 and 11/1/2019. Frailty testing combined aspects from the Fried Frailty Instrument, Short Physical Performance Battery, and activities of daily living. Caregivers completed questionnaires to evaluate caregiver burden using the Zarit Burden Interview (ZBI-12), and perceived social support, using the Interpersonal Support Evaluation List. RESULTS: In total, 94 cirrhotic patients were included, 50% males with a median age of 63.1 years. The most common etiology of cirrhosis was nonalcoholic steatohepatitis. Frailty was prevalent (45.1%). In total, 12.8% of caregivers reported a high burden based on ZBI-12. There was no association between frailty and caregiver burden, hospitalization rates, or death. However, frailty was associated with a higher number of outpatient GI visits (p = 0.002). Lower perceived social support among caregivers was associated with a higher caregiver burden (p < 0.0001). CONCLUSION: Frailty is prevalent in cirrhotic patients but is not associated with higher rates of caregiver burden. Low perceived social support among caregivers, however, was associated with higher caregiver burden. It is important to recognize the impact of caregiver burden on caregivers of cirrhotic patients and ensure caregivers have the appropriate support to mitigate burden.
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Carga del Cuidador , Fragilidad/etiología , Cirrosis Hepática/complicaciones , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Background and Aims: Being a caregiver for a patient with chronic liver disease (CLD) can be burdensome mentally, emotionally financially, and physically. The aim of this study was to systemically review the available tools and propose tools that can comprehensively evaluate caregiver burden for individuals caring for patients with CLD. Methods: We searched the PubMed database for all studies on the impact of patients with CLD on caregiver burden without timeframe restriction. Eligible studies included cohort studies, review studies, or cross-sectional studies. The number of patients and caregivers was isolated from each paper. Studies in the same categories were isolated and statistically compared. Results: A total of 13 studies meeting our inclusion criteria as stated in the methods sections were included. In total, 2528 caregivers were taking care of 2003 patients with CLD. Women made up the majority of caregivers at 78.2%, 95.7% of whom identified as the patient's spouse. Caregiver strain index is one of the most comprehensive tools; however, the questions are very general and do not fully elucidate financial strain. Beck depression and anxiety were correlated (p=0.0001), and both depression and anxiety were correlated with perceived caregiver burden (PCB) and Zarit Burden Interview (ZBI) (p=0.002). Depression scale correlated with Interpersonal Support Evaluation - Short Form, and Model for End-Stage Liver Disease score correlated with ZBI and PCB (total and in most domains; p=0.001). Patient's poorer cognitive performance correlated with higher ZBI and PCB (employed patients had higher cognitive performance and lower ZBI and PCB). Conclusions: Caregiver burden remains poorly understood due to the lack of uniformity in the assessment tools used to evaluate caregiver burden. None of the tools used to evaluate caregiver burden are comprehensive; however, most tools correlate statistically in the ability to identify caregiver burden. A comprehensive tool is lacking for identifying caregiver burden in patients with CLD.
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Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype. The A197V substitution occurs in the crucial Ala-rich protein kinase-like motif I of yeast Coq8. Here we show that long-term cultures of mutants expressing Coq8-A197V produce spontaneous revertants with the ability to grow on medium containing a non-fermentable carbon source. Each revertant is shown to harbor a secondary intragenic suppressor mutation within the COQ8 gene. The intragenic suppressors restore the synthesis of coenzyme Q. One class of the suppressors fully restores the levels of coenzyme Q and key Coq polypeptides necessary for the maintenance and integrity of the high-molecular mass CoQ synthome (also termed complex Q), while the other class provides only a partial rescue. Mutants harboring the first class of suppressors grow robustly under respiratory conditions, while mutants containing the second class grow more slowly under these conditions. Our work provides insight into the function of this important yet still enigmatic Coq8 family.
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Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Supresión Genética , Ubiquinona/biosíntesis , Sustitución de Aminoácidos , Asparagina , Medios de Cultivo/química , Regulación Fúngica de la Expresión Génica , Conformación Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Ubiquinona/genéticaRESUMEN
Coenzyme Q (CoQ or ubiquinone) serves as an essential redox-active lipid in respiratory electron and proton transport during cellular energy metabolism. CoQ also functions as a membrane-localized antioxidant protecting cells against lipid peroxidation. CoQ deficiency is associated with multiple human diseases; CoQ10 supplementation in particular has noted cardioprotective benefits. In Saccharomyces cerevisiae, Coq10, a putative START domain protein, is believed to chaperone CoQ to sites where it functions. Yeast coq10 deletion mutants (coq10Δ) synthesize CoQ inefficiently during log phase growth and are respiratory defective and sensitive to oxidative stress. Humans have two orthologs of yeast COQ10, COQ10A and COQ10B Here, we tested the human co-orthologs for their ability to rescue the yeast mutant. We showed that expression of either human ortholog, COQ10A or COQ10B, rescues yeast coq10Δ mutant phenotypes, restoring the function of respiratory-dependent growth on a nonfermentable carbon source and sensitivity to oxidative stress induced by treatment with PUFAs. These effects indicate a strong functional conservation of Coq10 across different organisms. However, neither COQ10A nor COQ10B restored CoQ biosynthesis when expressed in the yeast coq10Δ mutant. The involvement of yeast Coq10 in CoQ biosynthesis may rely on its interactions with another protein, possibly Coq11, which is not found in humans. Coexpression analyses of yeast COQ10 and human COQ10A and COQ10B provide additional insights to functions of these START domain proteins and their potential roles in other biologic pathways.