Correspondence

Acute Hepatic Porphyrias and Primary Liver Cancer

N Engl J Med 1998; 338:1853-1854June 18, 1998

Article

To the Editor:

Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria) are inherited disorders caused by partial enzyme defects in heme biosynthesis.1 Two retrospective studies and one case–control study have suggested an association between primary liver cancer and acute hepatic porphyrias.2-4 We present data from a prospective cohort study that assessed the crude annual incidence rate of primary liver cancer in 650 French carriers of the gene for acute hepatic porphyria followed for seven years. We compared this incidence with the incidence of primary liver cancer in France using the standardized rate ratio after indirect standardization. National age- and sex-specific incidences of primary liver cancer were provided by the French network of cancer registries.5 Of the patients with acute hepatic porphyria, 71 were lost to follow-up and 18 died. None of the deaths were ascribed to primary liver cancer.

Primary liver cancer was found in seven patients (mean age, 50 years; range, 37 to 65); all had hepatocellular carcinoma. Five patients had acute intermittent porphyria, one had variegate porphyria, and one had hereditary coproporphyria. The carriers of the porphyria gene had a markedly increased risk of primary liver cancer as compared with the French population; this risk was particularly increased in women (Table 1Table 1Standardized Rate Ratio for the Incidence of Primary Liver Cancer in the Patients with Acute Hepatic Porphyrias Followed from January 1989 to January 1996.).

In the patients with acute intermittent porphyria, hepatocellular carcinoma was not related to a specific porphobilinogen-gene mutation. We investigated the etiologic factors of primary liver cancer in the seven cases: alcohol consumption, blood transfusion, hepatotoxic-drug intake, aflatoxin, and occupational exposure to organic solvents. We assessed serum ferritin; transferrin saturation; smooth-muscle, antinuclear, and antimitochondrial antibodies; hepatitis B virus antigen and DNA; and hepatitis C virus antibody and RNA. Two patients had chronic viral hepatitis (one hepatitis B and one hepatitis C) with cirrhosis. Otherwise, these etiologic factors were not found. In the five patients with no risk factors, histologic study of the nontumor liver tissue was normal (four patients) or showed fatty changes in hepatocytes (one patient); there was no fibrosis, inflammatory-cell infiltrate, necrosis, or iron overload. The overall standardized rate ratio, with the two patients with chronic viral hepatitis and cirrhosis excluded, was 26 (95 percent confidence interval, 8 to 59). Our findings are consistent with those of previous retrospective studies and the evidence that acute hepatic porphyria precedes hepatocellular carcinoma. We conclude that acute hepatic porphyria should be considered as a rare cause of hepatocellular carcinoma.

Christophe Andant, M.D.
Hervé Puy, M.D.
Hôpital Louis Mourier, 92701 Colombes, France

Jean Faivre, M.D.
INSERM CRI 9505, 21033 Dijon, France

Jean-Charles Deybach, M.D.
Hôpital Louis Mourier, 92701 Colombes, France

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Citing Articles (8)

Citing Articles

1. 1

   J.-C. Deybach, H. Puy. (2011) Hepatocellular carcinoma without cirrhosis: think acute hepatic porphyrias and vice versa. Journal of Internal Medicine 269:5, 521-524
   CrossRef

2. 2

   Joanna K Dowman, Bridget K Gunson, Darius F Mirza, Simon R Bramhall, Mike N Badminton, Philip N Newsome, . (2011) LT-11-056 liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis. Liver Transplantationn/a-n/a
   CrossRef

3. 3

   Philipp Lutz, Daniel Maring, Henriette J. Tschampa, Tilman Sauerbruch. (2010) Eine 25-jährige Patientin mit Pseudoobstruktion des Kolons, Hyponatriämie, hypertensiver Entgleisung und diffusem Schmerzsyndrom. Medizinische Klinik 105:4, 267-272
   CrossRef

4. 4

   Hervé Puy, Laurent Gouya, Jean-Charles Deybach. (2010) Porphyrias. The Lancet 375:9718, 924-937
   CrossRef

5. 5

   Avnish Kumar Seth, Michael N. Badminton, Darius Mirza, Scott Russell, Elwyn Elias. (2007) Liver transplantation for porphyria: Who, when, and how?. Liver Transplantation 13:9, 1219-1227
   CrossRef

6. 6

   Neville Roy Pimstone. (2005) Roles and pitfalls of transplantation in human porphyria. Liver Transplantation 11:12, 1460-1462
   CrossRef

7. 7

   Jürgen Fuchs, Stefan Weber, Roland Kaufmann. (2000) Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free Radical Biology and Medicine 28:4, 537-548
   CrossRef

8. 8

   AS Kashyap, Surekha Kashyap. (1999) Hepatocellular carcinoma. The Lancet 354:9174, 253
   CrossRef