S1424 Porphyrias Are Linked to Primary Liver Cancer, Particularly Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis

Abstract

Introduction: Porphyrias are in-born defects in the heme biosynthesis pathway resulting in neurovisceral manifestations, cutaneous photosensitivity, and multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common which carries a risk of malignancy. To this end, we aim to determine the risk of primary liver cancer and hepatocellular carcinoma (HCC) in patients with porphyria. Methods: We conducted a comprehensive search of several databases, including PubMed, EMBASE, and Web of Science.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Keywords used in the literature search included “porphyria,” “hepatic porphyria,” “delta-aminolevulinate-dehydratase deficiency porphyria,” “acute intermittent porphyria,” “porphyria cutanea tarda,” “cirrhosis,” “hepatocellular carcinoma,” “cancer,” “transplant,” to identify relevant articles. Results: In total, 19 studies, which included 7,381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/ml. Elevated urinary delta-aminolevulinic acid dehydratase, prophobilinogen, and other uroporphyrins were observed. Median follow-up time ranged from 3 to 24 years. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A small subset of patients was found to have cholangiocarcinoma (n=18; 0.3% of the total). Interestingly, progression to HCC was seen despite the development of advanced liver disease or cirrhosis. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Compared to those who did not undergo periodic screening, only four patients (28.6%) underwent tumor resection with a recurrence rate of 75% (n=3/4). (Figure) Conclusion: Our study revealed that patients with porphyria are at increased risk for the development of primary liver cancer and HCC. Furthermore, we showed that malignancy can occur even in the absence of cirrhosis, supporting the need for appropriate screening. To this end, AFP should be used in conjunction with imaging modalities to screen for liver malignancy as frequently as every 6–12 months. Further studies should aim to develop diagnostic and prognostic models aimed at its early detection.Figure 1.: Flow chart of included studies