S5468 Tripping Over Trypsin: How Coexistent Inflammatory States Can Trip up Healthcare Providers in the Diagnosis of Alpha-1 Antitrypsin Deficiency

Introduction: Alpha-1 antitrypsin deficiency (AATD) is an autosomal, codominant disorder characterized by decreased functionality of alpha-1 antitrypsin (AAT), a protein that inhibits human neutrophil elastase. AATD is typically associated with Pi*ZZ homozygotes but also occurs in Pi*MZ and the Pi*SZ heterozygotes, affecting both lung and liver function. Case Description/Methods: A 48-year-old man living with controlled HIV, chronic hepatitis B, and chronic cholestasis thought to be from antiretrovirals, presented with one month of recurrent right upper quadrant (RUQ) pain, fatigue, nausea, and vomiting. Initial evaluation was remarkable for scleral icterus and RUQ tenderness, as well as total bilirubin (Tbili) 7.7 mg/dL (from baseline 4.2 mg/dL), alkaline phosphatase 403 U/L, aspartate aminotransferase 201 U/L, and alanine aminotransferase 142 U/L. magnetic resonance imaging abdomen confirmed liver cirrhosis without biliary ductal dilatation, masses, or venous occlusions. By day 4, his symptoms improved. Tbili peaked at 10.9 mg/dL. He was discharged with plans for outpatient liver biopsy. He returned 5 days later with worsening RUQ pain, myalgias, chills, night sweats, dyspnea, and a Tbili of 13.1 mg/dL. A liver biopsy was performed, and he was discharged once Tbili stabilized at 11.9 mg/dL. Pathology revealed cholestatic hepatitis, stage III/IV fibrosis, chronic portal inflammation, and scattered Periodic Acid-Schiff (PAS)-positive globules. Stains for Epstein-Barr virus, cytomegalovirus, and herpes simplex viruses were negative. Autoimmune workup was negative. AAT level was mildly elevated to 216 mg/dL, decreasing initial concern for AATD. Drug-induced liver injury was favored, but due to PAS+ globules, AAT genotyping was ordered and revealed a Pi*MZ genotype. Over the next 5 months, the patient’s Tbili rose to 26.3. He ultimately was felt to have cirrhosis and severe cholestatic injury due to his AAT PI*MZ phenotype compounded by chronic HIV and HBV, despite viral suppression. Six months later, he received a liver transplant. His explant demonstrated an incidental <1 cm hepatocellular carcinoma. Discussion: AAT is an acute phase reactant that can be elevated, even in the setting of AATD. In patients with progressively worsening liver injury and proinflammatory states, AATD should remain on the differential despite an elevated AAT level, and genotyping should be pursued. Heterozygous Pi*MZ patients may be at increased risk for chronic liver disease progression if they have comorbid conditions, such as chronic viral infections. Disclosure: Generative artificial intelligence was used to condense this abstract.