Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium.

BACKGROUND AND AIM The risk for hepatocellular carcinoma (HCC) is increased in the acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States. METHODS Cross-sectional analysis evaluating patients with HCC in a multi-center, Longitudinal Study of AHPs. RESULTS Among 327 AHP patients, five (1.5%) were diagnosed with HCC. Of the five HCC cases, four had acute intermittent porphyria and one had variegate porphyria, confirmed by biochemical and/or genetic testing. All patients were white females, with a median age at AHP diagnosis of 27 years (range 21-75). The median age at HCC diagnosis was 69 years (range 61-74). AHP was asymptomatic in two patients, two reported sporadic attacks, and one reported recurrent attacks (>4 attacks/year). All patients had a single HCC lesion on liver imaging that was 1.8 to 6.5 centimeters in diameter. Serum alpha fetoprotein levels were below <10 ng/mL in all four patients with available results. Four patients underwent liver resection and one was treated with radioembolization. No significant inflammation or fibrosis was found in adjacent liver tissues of three patients who underwent liver resection. Two patients developed recurrence of HCC at 22 and 26 months following liver resection. All patients are alive with survival times from HCC diagnosis ranging from 26-153 months. CONCLUSION In this US study, 1.5% of AHP patients had HCC. HCC in AHP occurred in the absence of cirrhosis, which contrasts to other chronic liver diseases. Patients with AHP, regardless of clinical attacks, should be screened for HCC, beginning at age 50. The pathogenesis of hepatocarcinogenesis in AHP is unknown and needs further investigation.