Porphyries are caused by several defects in the biosynthesis of haem. Porphyria cutanea tarda (PCT) is the most common and it is usually latent. The sporadic form (type I) accounts for the 80% of the patients and the other cases are attributed to the familial form (type II).1 Exposure to alcohol or different drugs can precipitate the clinical expression of this disease and hepatitis C virus can also play a role,2 furthermore, iron overload and hepatic siderosis seem necessary for PCT to become clinically manifest.3 In ultrasonography (US) exam, the liver can be normal, hyperechogenic or exhibit signs of chronic liver disease or cirrhosis. Several cases of patients with chronic hepatic porphyria with multiple hepatic nodules firstly assessed by liver US and confirmed by magnetic resonance (MR) or computed tomography (CT) have been described.4–6 We report two cases of such unusual finding in patients not previously diagnosed with PCT, one with excessive alcohol consumption and the other with previously treated chronic hepatitis C.
CASE 1A 49 year old man was referred in 2006 because of abnormal liver tests. He had a history of alcohol abuse for two years. The liver US showed the presence of multiple nodular lesions throughout the parenchyma. These nodules were hyperechoic, homogeneous and well-defined, the vessels were not displaced and portal and hepatic veins went right through the nodules, as confirmed by colour Doppler. A percutaneous liver biopsy showed minimal hemosiderosis, inflammatory infiltrate, and occasional steatosis without porphyrin crystals. Ultraviolet light autofluorescence was positive. Urine analysis showed total porphyrins of 3112mcg/24hours (ULN 150 mcg/24hours). Serology for hepatitis B and C viruses and the C282Y HFE gene mutation were negative. The MRI confirmed multiple nodules with decrease of the signal intensity in T2 sequences. The fat suppression images showed a loss of signal. He was diagnosed as multifocal fatty liver (Fig. 1). The patient was advised to abstain from alcohol and was treated with phlebotomies. After 12months, the clinical manifestations had resolved and repeat US showed diffuse steatosis. The clinical disease did not recur after five years of follow-up.
CASE 2
A 41 year old man with chronic hepatitis C, genotype 1b, was treated with pegylated interferon alpha-2b plus ribavirin in 2005. Treatment was stopped due to lack of virological response. In May 2007 a routine liver US, showed multiple hyperechoic regular nodules with a maximum diameter of 1.5cm each, scattered throughout the liver. The initial diagnosis was multinodular focal fatty liver. A MRI scan with gadolinium was performed. The lesions did not show any significant enhancement with the contrast medium in T1 and T2, and in the delayed phase they were isointense compared with the liver parenchyma. The lesions showed an intense loss of signal in opposed phase, confirming deposition of fat. The final MRI diagnosis was multifocal nodular fatty infiltration (Fig. 1). In August 2008 he presented a bullous rash on the fingers and hands and malar hypertrichosis. An elevation in total urine porphyrins of nearly 50 fold, 7068mcg/24hours was found. He refused a liver biopsy. The C282Y mutation was negative. Phlebotomies were indicated as treatment and the US performed 18 months later, demonstrated diffuse steatosis without nodules. No recurrence of the disease or the US alterations were seen after four years of follow up.
Porphyria cutanea tarda is the most common form of porphyria in western countries. The deficiency of uroporphyrinogen decarboxylase is present in all tissues in the congenital form and is limited to the liver in the acquired form. Alcohol ingestion, hepatitis C, or abnormal iron metabolism, act as precipitating or aggravating factors. In a meta-analysis including 2167patients the mean HCV prevalence was 50%.2 One study in Spain found anti-HCV (+) in 79% of 100 consecutive patients, the frequency increasing with the severity of the liver disease.7 In contrast, in one report from Germany the prevalence of HCV infection was 8% only.8 In our second patient, a previous chronic hepatitis C had been previously diagnosed and treated. Clinical PCT appeared 28 months after stopping the treatment, but liver nodules were found 15 months earlier. There are some reports of development of clinical PCT during treatment with interferon and ribavirin. It has been suggested that the iron overload due to the ribavirin associated hemolysis, could act as a trigger.9 Liver steatosis usually appears as diffuse hyperechogenic parenchyma in US, but sometimes focal, geographic or nodular infiltration can be seen.10 In PCT, a hyperechoic liver can also been found, suggesting diffuse steatosis. It is believed that increase of fat, rather than accumulation of porphyrins or iron, most likely causes this appearance.5 We have found only fourteen cases of multinodular liver foci reported in patients with PCT.
MRI and TC have been considered good techniques for the detection of steatotic nodules of the liver. In MRI diffuse hyperintense areas seen on T2-weighted sequences are related with inflammatory reaction or fat deposition in over half the cases with PCT.5 In our experience, MRI gadolinium scan is an excellent tool for the diagnosis of hepatic multinodular focal fatty liver, when previously found in a US exam. Chemical shift in MRI imaging is a very effective method to identify and characterize these nodules. CT scan has also demonstrated to be useful. In summary, the finding of multiple hyperechoic nodules in the liver in patients without clinical or biochemical signs of malignancy, must lead to have in mind the possibility of other entities. PCT must always be considered and it has to be included in the differential diagnosis. In such a case, a MRI or CT is required.
Conflicts of interestNothing to disclose.
We are indebted to Dr. Rafael Menéndez de Llano and to Dr. Faustino G. Arias, from de Department of Radiology for advisement in the selection and interpretation of the images. We also thank Prof. Javier F. Gago for technical assistance.
