Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies

Background and aims: Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC.

Methods: Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI).

Results: 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2-0.5) in AHP, 0.4 (0.2-0.6) in AIP, 0.3 (0-0.4) in VP, and 0.2 (0.1-0.6) in HCP. The risk was 0.4 (0.2-0.6) in females, 0.3 (0.1-0.5) in males, 0.9 (0.1-1.7) in symptomatic, and 0.5 (0-1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis.

Conclusions: The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP.