Hepatocellular Carcinoma in Variegate Porphyria: A Serious Complication

Abstract

Variegate porphyria is an acute hepatic porphyria resulting from a partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in haem biosynthesis. Cutaneous symptoms and acute neurovisceral attacks are well-known clinical characteristics of the disease. Less studied, however, is the risk of developing hepatocellular carcinoma, an aggressive type of liver cancer. We describe here two Swiss patients with variegate porphyria and this serious complication. Common risk factors, including alcohol over-consumption or chronic hepatitis, were absent in both patients. Interestingly, one patient carried mutation 1082-1083insC in the PPOX gene, a prevalent sequence deviation in the Swiss variegate porphyria population, which was also found in a French patient with variegate porphyria and hepatocellular carcinoma. Recent studies indicate that individuals with acute hepatic porphyria have a 36- to 61-fold increased risk of manifesting hepatocellular carcinoma. The incidence rate ratio in the Swiss population was estimated to be 34, comparable with those found in the French and Finnish populations. Because this tumour is associated with a rising mortality, we suggest regular screening for hepatocellular carcinoma in all patients with variegate porphyria.

Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case–control study of 188 patients

“…other forms of acute porphyria, have also been associated with PLC based on sporadic reported cases. 3,4,33,34 Both are known to have lower ALA and PBG levels compared to AIP and although robust estimates are lacking, PLC risks are low compared to AIP. In tyrosinemia type 1, another rare disease with very high ALA levels compared to AIP, >30% of the affected children developed PLC before effective treatments were available.…”

“…ALA has been implicated as a key carcinogenic mediator based on findings of oxidative stress, cytotoxicity and DNA damage in preclinical studies 10,31,32 . Variegate porphyria (VP) and hereditary coproporphyria (HCP), two other forms of acute porphyria, have also been associated with PLC based on sporadic reported cases 3,4,33,34 . Both are known to have lower ALA and PBG levels compared to AIP and although robust estimates are lacking, PLC risks are low compared to AIP.…”

Understanding Hepatic Porphyrias: Symptoms, Treatments, and Unmet Needs

“…VP is an important risk factor for development of HCC. 63,68 Liver surveillance twice a year beginning after age 50 is recommended in patients who have persistent elevation in porphyrin accumulation as this may aid in early detection of HCC.…”

The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease

“…90 Primary Liver Cancer in AHP AIP, VP, and HCP, which are autosomal dominantly inherited acute porphyrias, have been implicated as risk factors for the development of hepatocellular carcinoma (HCC). 94 Primary liver cancer is the most frequently reported tumor in patients with acute porphyria. Individuals with AHP possess a 36-to 61-fold increased risk of developing HCC compared to the general population.…”

“…Schneider-Yin et al reported that as of 2010, no VP patients with HCC have been reported in countries with a large VP population such as South Africa, as many of these cases are of patients with European origins. 94 PCT has been associated with hematological malignancies including acute lymphoblastic, nonlymphoblastic leukemia, chronic lymphatic, myelomonocytic, myeloid leukemia, idiopathic myelofibrosis, lymphosarcoma, hairy cell leukemia, multiple myeloma, and Hodgkin's and non-Hodgkin's lymphoma. 96 One study utilized the Norwegian Cancer Registry consisting of about 4 million adults to investigate the incidence and risk of primary liver cancer and other malignant neoplasms in individuals with AIP, in addition to examining whether there are differences in risk between men and women.…”