Can nonalcoholic steatohepatitis trigger porphyria cutanea tarda clinical manifestations?

Porphyria cutanea tarda (PCT), the most common form of porphyria, is characterized by cutaneous lesions that appear after exposure to sunlight that are caused by uroporphyrin deposits. Reduced activity of hepatic urophorphyrinogen decarboxylase (URO-D) underlies the disease whose clinical manifestations are triggered by chronic HCV (hepatitis C virus) infection, alcoholic liver disease (ALD), drugs such as estrogens, and exposure to toxic compounds. Excess hepatic iron seems to be able to trigger PCT clinical manifestation in susceptible individuals, and it is still debated whether alcohol and HCV induce PCT by themselves or through their known effect on iron metabolism. Mild iron overload is detected in the majority of patients with PCT, and iron depletion by phlebotomy induces disease remission and normalizes uroporphyrin levels in the majority of cases [1]. A high prevalence of mutations in the HFE gene of hereditary hemochromatosis has been reported in patients with PCT, with the C282Y being prevalent in USA, Australia and Northern Europe, and the H63D in Southern Europe. Thus, a complex interaction between acquired and host factors seems necessary to develop PCT. Nonalcoholic fatty liver disease (NAFLD), associated with obesity and the metabolic syndrome, has recently emerged as the leading liver disease, affecting 34% of the general population. In roughly one-third of cases, and especially in subjects carrying HFE mutations, NAFLD is characterized by mild hepatic iron overload, which is determined by decreased hepatocellular iron export [2] and may worsen the progression of the disease [3, 4]. However, partly in view of a potential referral bias to specialized tertiary centers, evidence concerning the fibrogenic effect of mild iron accumulation is still controversial [5]. Despite the fact that NAFLD cannot be distinguished from alcoholic liver disease (ALD) based on histologic findings, and both are frequently associated with altered iron metabolism and mitochondrial oxidative damage, possibly implicated in URO-D inactivation, as far as we know an association of NASH with PCT has never been reported. However, the role of NAFLD in determining hepatic iron accumulation in patients with PCT and HFE mutations without HCV or alcohol abuse has not been evaluated in the past. Indeed, it is now clear that only a small minority of HFE mutation carriers develop iron overload in the absence of cofactors [6]. We describe the case of a 61-year-old woman, referred by the dermatology service because of cutaneous lesions typical of PCT localized to the face and sun-exposed areas, and increased urinary porphyrins (7,254 lg/24 h, n.v. \150). Liver enzymes had been altered since 10 years before, following menopause. She drank 30 g alcohol/week, as confirmed by her husband, and was negative for HBV and HCV infection, as confirmed by HBsAg, HBcAb, and HCVRNA determinations. The BMI was 27.4 kg/m, abdominal circumference 99 cm. She did not take any drugs, including hormonal replacement therapy. At presentation, laboratory findings were ALT 47 IU/ml, AST 35 IU/ml, GGT 34 IU/ml, ferritin 274 ng/ml and transferrin saturation 45%. Glucose tolerance, as assessed by oral glucose tolerance test, lipid levels, Cu and ceruloplasmin, and carboxydesialylated L. Valenti A. L. Fracanzani P. Dongiovanni S. Fargion (&) Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli Universita’ degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Università di Milano, Via F Sforza 35, 20122 Milan, Italy e-mail: [email protected]