Acute Intermittent Porphyria: a risk factor for development of hepatocellular carcinoma. First case in Argentina

MELITO, VA; VARELA, L; ANTINUCCI, F; BRUTTI, J; MAURETTE, R; TOMASSI, L; BUZALEH, AM; ANDERS, M; PARERA, VE

Bethesda

Simposio; International Porphyrias Sympossium; 2023

United Porphyrias Association

The risk of hepatocellu la r carcinoma {HCC) is sign ifi cantly increased in patients with Acute lntermitten tPorphyria (AIP), comp ared t o the gene ral p opulation. Most HCCs are asymptomatic and up to one-third evelop in non-cirrhotic pa tie nt s. The aim was to report the first case of an AIP patient and a giant HCC. This is a 57-year-old female diagnosed with AIP in 1986: urinary porphobilinogen (PBG) (49.1 mg/24h, normal value=S2) and 5-aminolevulinic acid (10.3 mg/24h, normal value=S4), Hydroxymethylbilane synthetase (30.03 U/mlGR,) normal value=81.51±11.96) at diagnosis; genetic study detected c.612G>T mutation. The patient has been asymptomatic for more than 20 years, and in August 2022 biochemical parameters remained normal.She was negative for HCV, HBV and HIV and no alcoholic. In June 2022, she consulted the emergency room for abdominal pain and, an ultrasound was performed showing a large liver mass. An abdominal triphasic MRI showed a focal lesion of 105x79mm that was enhanced with intravenous contrast compatible with a primary liver tumour (alpha-fetoprotein: 4400 ng/ml). Extension studies (chest tomography and bone scintigraphy)excluded secondary disease and there was no evidence of vascular invasion. The patient had a performancestatus of O and presented no weight loss. She had hyponatremia with inadequate secretion of antidiuretichormone. She was diagnosed with an early-stage HCC of the BCLC classification, and surgical resection wassuggested. After performing liver volumetry, it was decided to do a two-stage surgery to hypertrophy the leftlobe (ALPPS surgery). Postoperative complications were ascites with parameters of portal hypertensionsecondary to a small size syndrome and sponta~eous bacteraemia dueto E. Coli. The pathological anatomyconfirmed the diagnosis of HCC. Early recurrence of hepatic carcinoma and metastasis in the lung wasobserved two months later. ALA has been identified as a key mediator in cancer development in non-cirrhoticliver of AHP patients. Oxidative stress and DNA damage could be due to ALA accumulation in hepatocytes,although in this patient, probably HCC would not be related to ALA. This case highlights the relevance of anHCC screening program in all AIP patients from the age of 50 years independently of their biochemical andclinical evolution.