Objective: To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP).
Design: A retrospective population-based mortality study.
Subjects: All inhabitants who died between 1978-1990 (2122) including 33 with AIP, in two municipalities in northern Sweden with a high prevalence of AIP.
Interventions: Death certificates and hospital records were examined. Histological re-examination of paraffin-embedded specimens from patients with HCC was performed and hepatitis B virus content analysed.
Results: HCC was found in 27% of patients with AIP versus 0.2% of the deceased non-AIP subjects, P < 0.0001. HCC was more common in women (men:women 1:2) and in manifest AIP (manifest: latent 2:1). Liver cirrhosis was more common in AIP patients (12%), especially in women, compared with controls (0.5%), P < 0.0001.
Conclusions: AIP patients seem to have an increased risk of developing HCC. This tumour is more common in patients with manifest AIP and in women, a reversal of the usually reported gender ratio for HCC. No cause for developing HCC other than AIP was found. The pathogenesis may be explained by abnormalities in porphyrin metabolism and by intrinsic production of mutagenic substances, resulting in a condition of systemic overload of oxidative stress, enhancing mutation rate and liver cell injury. Liver cirrhosis appears to be more common in AIP patients and may be a preliminary stage to HCC. All AIP gene carriers aged > or = 55 should be screened for HCC.