An unhappy triad: Hemochromatosis, porphyria cutanea tarda and hepatocellular carcinoma-A case report

Abstract

Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma (HCC). Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in hereditary hemochromatosis (HHC), is a risk factor for HCC and may also promote the symptoms of porphyria cutanea tarda (PCT). A 68-year old male patient presented to our clinic with a suspected HCC, elevated alpha-fetoprotein but normal liver function tests. He reported a 25 year-old history of vitiligo upon exposure to sunlight. The patient underwent an extended left hemihepatectomy, and the recovery was uneventful, with the exception of a persistent hyperbilirubinemia. Perfusion problems and extrahepatic cholestasis were ruled out by CT-scan with angiography and MR-cholangiopancreatography. However, MRI showed an iron overload. Histology confirmed the HCC (pT3, pN0, G3, R0) and revealed a portal fibrosis and hemosiderosis. Based on the skin lesions we suspected a PCT that was confirmed by laboratory tests showing elevated porphyrin, uroporphyrin, coproporphyrin and porphobilinogen. Concurrently, molecular diagnostics revealed homozygosity for the C282Y mutation within the hemochromatosis HFE gene. After phlebotomy and normalization of liver function tests the patient was discharged. This is the first case ever showing the unusual combination of HCC in a fibrotic liver with HHC and PCT. This diagnosis not only warrants oncological follow-up but also symptomatic therapy to normalize iron metabolism and thereby improve liver function and alleviate the symptoms of HHC and PCT. Thus progression of fibrosis may be prevented and liver regeneration supported.

Unravelling the debate on heme effects in COVID-19 infections

“…This seems to correlate with increased levels of the iron-storage protein ferritin. An increase in ferritin concentration is observed in diseases like hemochromatosis or porphyria (Mogl, 2007). Furthermore, it is upregulated during hemolytic diseases as a consequence of hemoglobin degradation and the associated increase of oxidative stress, e.g.…”

“…The blood and coagulation system is pronounced by the connecting proteins ferritin and albumin ( Figure 3D, Table S3). Both conditions lead to reduced levels of ferritin, a protein involved in iron uptake and release (Mogl, 2007). Same applies for albumin in COVID-19 patients Guan et al, 2020;Yang et al, 2020;Zhou et al, 2020a).…”

Hepatocarcinoma, porfiria y hemosiderosis. Una asociación no reportada en nuestro país: Caso clínico

“…El hepatocarcinoma es uno de los tumores con factores de riesgo mejor conocidos, entre otros, la fibrosis hepática y más aun la cirrosis 9 y la porfiria cutánea tarda [10][11][12] . La incidencia de hepatocarcinoma en pacientes con cirrosis es 10 veces mayor que en los que no tienen esa enfermedad 13 . La hemocromatosis hereditaria ha sido relacionada con la aparición de hepatocarcinoma, pero no hay consenso 14,15 si ello se debe al depósito de Fe per se o al hecho de haber comúnmente en ella fibrosis y aun cirrosis en el hígado.…”

“…La hemocromatosis hereditaria ha sido relacionada con la aparición de hepatocarcinoma, pero no hay consenso 14,15 si ello se debe al depósito de Fe per se o al hecho de haber comúnmente en ella fibrosis y aun cirrosis en el hígado. Sin embargo, Mogl describió el caso de un portador de PCT asociada a hemosiderosis y hepatocarcinoma en el que no había fibrosis hepática, lo que sugiere que tanto la acumulación de Fe, la PCT o ambos fueron factores de riesgo suficientes para ocasionar el tumor 13 . En 1994 se dio cuenta en Chile de un paciente en quien coexistió hepatocarcinoma e infección con virus de hepatitis C 2 .…”

Etiology and Pathogenesis of Hepatocellular Carcinoma: Hepatocellular Carcinoma Associated with Inborn Errors of Metabolism and Hepatobiliary Malformations

“…Relatively few patients develop HCC in porphyria cutanea tarda, with a yearly incidence of less than 1 % per patient year of follow-up (Kordac 1972;Packe and Clarke 1985;Gisbert et al 2004;Whittle et al 2010), and risk factors for HCC were the presence of liver cirrhosis, male sex, and age over 51 (Salata et al 1985). Porphyria cutanea tarda can occur in combination with hereditary hemochromatosis, the condition being complicated with HCC (Mogl et al 2007). On the other hand, HCC can induce pseudo-porphyria through production of large amounts of porphobilinogen (Pierach et al 1984;Ochiai et al 1997) or porphyrins, resulting in acquired cutaneous porphyria (Keczkes and Barker 1976).…”