Hepatocellular Carcinoma in Patients with Acute Intermittent Porphyria

Abstract

Hepatocellular carcinoma in patients with acute intermittent porphyria. Acta Med Scand 1984; 215: 2714. In a retrospective study over a 20-year period we found in the Umel region in Sweden I 1 patients (7 women and 4 men, mean age 67 years) with both hepatocellular carcinoma and acute intermittent porphyria. This coincidence was highly significant. Concomitant existence of portal cirrhosis of the liver was demonstrated in those 5 patients in whom it could be examined. Key words: hepatocellular carcinoma, acute intermittent porphyria.Apart from a reported high mortality in acute porphyric attack, the long-term prognosis of acute intermittent porphyria (AIP) is generally reported to be good (1, 2). The most frequent long-term problem in a report from Great Britain was a high prevalence of chronic hypertension (I).Within a short time span we treated two patients with AIP and primary liver cancer. To test whether this was a random finding we performed a retrospective study of the occurrence of primary liver cancer in patients with AIP and found 9 more cases. PATIENTS AND METHODSInformation on patients with AIP, living in the counties of Norrbotten and Vasterbotten, was provided for the years 1%0-81 by The Swedish Association to Combat the Porphyrias.Three groups of patients were studied, comprising a total of 206 carriers of the AIP gene 15 years of age and older. Group 1. The diagnosis of AIP was verified by an identity card signed by a physician (n=ll). The mean age was 47 years (range 36-71). Group 11. The diagnosis was based on a clearly reduced activity of uroporphyrinogen-I-synthetase (U-I-S) in red blood cells (3) (n=58). The mean age was 40 years (range 15-88). Group 111. The diagnosis was based on increased levels of porphobilinogen in the urine (n=137). The mean age was 63 years (range 29-90).The mean population per year in the two counties in 1960-81 was 496626 (about 80 % of them were I5 years of age and older). During this period, 342 patients (193 males, 149 females) with primary liver cancer were registered. Both hepatocellular carcinoma (HCC) and intrahepatic bile duct carcinoma were included and also those which were unspecified as to whether primary or not (4).The liver tissues examined were from biopsy and/or autopsy materials. The biopsy or autopsy specimens had been examined by several pathologists and were reexamined for the present study by one and the same experienced liver pathologist (Sune Eriksson). RESULTSThere were 11 patients (7 females) with primary liver cancer ( Table I). All of them belonged to group 111. Histologically, the type of cancer was HCC in all patients. Noncarcinomatic parts of the livers were available for examination from only 5 patients, all female, and all showed histological signs of portal cirrhosis.Abbreviations: AIP = acute intermittent porphyria, HCC = hepatocellular carcinoma, U-I-S = uroporphyrinogen-I-synthetase.

Occurrence of Malignant Tumours in the Acute Hepatic Porphyrias

“…Since the first report on the concomitant occurrence of HCC and AIP in 1984, several studies have shown an association between this type of primary liver cancer and the AHPs in Europe (Lithner and Wetterberg 1984;Hardell et al 1984;Bengtsson and Hardell 1986;Tidman et al 1989;Grabczynska et al 1996;Andersson et al 1996;Linet et al 1999;Andant et al 2000;Schneider-Yin et al 2009;Innala and Andersson 2011;Elder et al 2013;Sardh et al 2013). However, some of the aforementioned studies linking HCC to AHP certainly include cases in which there were further risk factors.…”

“…Well-known risk factors for the development of HCC include alcohol ingestion, hepatitis B and C virus infection and liver cirrhosis (Hardell et al 1984;Fattovich et al 2004). Several mortality and case-control studies have demonstrated an association between this type of liver cancer and the AHPs in Europe (Lithner and Wetterberg 1984;Bengtsson and Hardell 1986;Kauppinen and Mustajoki 1988;Andersson et al 1996;Linet et al 1999;Andant et al 2000;Schneider-Yin et al 2009;Innala and Andersson 2011;Elder et al 2013;Sardh et al 2013). Concerning other malignant tumour entities, however, systematic studies on their occurrence in AHP patients have not yet been conducted.…”

The acute hepatic porphyrias: Current status and future challenges

“…Well known risk factors comprise alcohol over-consumption, chronic infection with hepatitis B and C viruses, and cirrhosis [28,29]. Recently, the autosomal dominantly inherited acute hepatic porphyrias AIP, VP, and HCP have also been implicated as risk factors in the development of HCC [30][31][32]. Since the first report on the concomitant occurrence of HCC and AIP in 1984 [30], several mortality studies and case-control studies have demonstrated an association between this type of primary liver cancer and the acute hepatic porphyrias in Europe [30][31][32].…”

“…Recently, the autosomal dominantly inherited acute hepatic porphyrias AIP, VP, and HCP have also been implicated as risk factors in the development of HCC [30][31][32]. Since the first report on the concomitant occurrence of HCC and AIP in 1984 [30], several mortality studies and case-control studies have demonstrated an association between this type of primary liver cancer and the acute hepatic porphyrias in Europe [30][31][32]. Because HCC is associated with a considerable and rising mortality in Europe and its prognosis depends on an early therapeutic intervention, we suggest that more attention should be given to regular screening in patients with acute hepatic porphyrias.…”

The Porphyrias: Clinic, Diagnostics, Novel Investigative Tools and Evolving Molecular Therapeutic Strategies

“…Like VP, HCP is a neurocutaneous porphyria and the clinical symptoms resemble those of VP. In HCP, VP, and AIP, an increased risk for the development of hepatocellular carcinoma has been reported [1][2][3][14][15][16][17] .…”