S5432 Hepatic and Gastrointestinal Complications in Acute Intermittent Porphyria: Investigating the Role of Iron Metabolism and Disease Progression Factors

Introduction: Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder characterized by a deficiency of porphobilinogen deaminase (PBGD), leading to the accumulation of neurotoxic porphyrin precursors. While AIP is primarily considered a neurovisceral disease, emerging evidence suggests an association with hepatic dysfunction, including cirrhosis and hepatocellular carcinoma (HCC). Case Description/Methods: We present a 63-year-old man with a history of AIP, cryptogenic liver cirrhosis, and H63D mutation carrier status, who was admitted for recurrent gastrointestinal (GI) bleeding. Serial esophagogastroduodenoscopies (EGDs) demonstrated a progressive worsening of vascular lesions, including gastric antral vascular ectasia (GAVE) and duodenal angioectasias, despite stable cirrhosis. The patient underwent endoscopic interventions, including argon plasma coagulation (APC) and clip placement, with successful hemostasis. The progressive nature of the patient's GI vascular abnormalities raises questions regarding the interplay between AIP, chronic oxidative stress, hepatic dysfunction, and vascular fragility. Discussion: While portal hypertension remains a primary contributor to GI bleeding in cirrhosis, additional mechanisms such as endothelial dysfunction and porphyrin-related oxidative damage may play a role in vascular ectasia development. Furthermore, the patient’s H63D mutation status, though typically a low-penetrance variant, could contribute to hepatic dysfunction in the presence of other risk factors. This case underscores the need for heightened surveillance in patients with AIP and cirrhosis, particularly regarding progressive vascular pathology and GI bleeding. Future research should investigate the pathophysiologic mechanisms linking AIP to hepatic and vascular complications to optimize long-term management strategies.