Background: Wilson’s disease (WD) is a genetic disorder of copper metabolism with over 600 disease-causing mutations, leading to variable hepatic and neurological symptoms. Early diagnosis and treatment are crucial. To evaluate hepatic involvement, serum scores and non-invasive imaging techniques complement histology. Methods: This pilot study assessed the utility of ultrasound-based tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI), and shear-wave elastography (SWE) for quantifying steatosis and fibrosis in WD. Results: Among 131 treated patients, 53 (mean age 40.5 ± 13.1 years, M/F = 35/18) underwent measurements. Based on literature-validated thresholds, 41 patients did not have significant liver fibrosis, 5 patients had moderate (F2) and 4 advanced (F3) fibrosis, while 3 patients had cirrhosis. The LS (liver stiffness) was in moderate correlation with FIB-4 (r = 0.306, p < 0.03), NAFLD fibrosis index (r = 0.336, p < 0.02), and APRI (r = 0.31, p = 0.0857). Among the WD patients, 37 had no steatosis (S0), 14 had mild steatosis (S1), and 2 had intermediate steatosis (S2); none of them had severe steatosis (S3) based on UEFF calculation. LS correlated positively with calculated free copper and negatively with serum ceruloplasmin. Normal-BMI patients exhibited no significant steatosis (R2 = 0. 0065, p = 0.966) by ultrasound-estimated fat fraction (UEFF), while those with BMI > 25 kg/m2 had increased UEFF correlating with BMI (R2 = 0.288, p < 0.015). Over a five-year follow-up using liver elastography, the fibrosis score did not progress significantly in adequately treated patients. Conclusions: Ultrasound with artificial intelligence-derived parameters supports the non-invasive evaluation of hepatic steatosis and fibrosis in WD, complementing clinical and laboratory data. However, population-specific liver stiffness thresholds are still needed.

INTRODUCTION:Wilson's disease may lead to cirrhosis, but timely medical treatment could slow down its progression. Clinical markers helping early diagnosis are essential. Decreased fetuin-A concentration has been reported in cirrhosis of different etiologies. The aim of this study was to investigate whether decreased serum fetuin-A concentration could identify patients with Wilson's disease who developed cirrhosis.MATERIALS AND METHODS:In this cross-sectional study we determined the serum fetuin-A concentration of 50 patients with Wilson's disease. We analyzed the data of patients with liver involvement, comparing cirrhotic and non-cirrhotic patients.RESULTS:Among patients with liver involvement those with cirrhosis had significantly lower fetuin-A and albumin level, white blood cell and platelet count. Fetuin-A negatively correlated with disease duration, bilirubin level, positively with total protein and albumin concentration, but not with copper and ceruloplasmin concentrations or markers of systemic inflammation. In multivariate analysis with fetuin-A and the Nazer score or its parameters only fetuin-A was a significant determinant of having cirrhosis. In receiver operator curve analysis among patients with liver involvement the fetuin-A level of 523 μg/ml was associated with cirrhosis with 82% sensitivity and 87% specificity. The presence of the H1069Q mutation was not associated with alteration in fetuin-A concentration.CONCLUSIONS:The serum concentration of fetuin-A is a sensitive marker of liver cirrhosis in Wilson's disease, independently of the H1069Q mutation, ceruloplasmin concentration or systemic inflammation.

Absztrakt: Bevezetés: A hepatitis C-vírus (HCV) krónikus májgyulladáshoz, májcirrhosishoz, májrákhoz vezethet. A Flaviviridae csoportba tartozó RNS vírus nemcsak hepatotrop, de lymphotrop tulajdonsággal is rendelkezik. Számos extrahepatikus manifesztációja között jelentős a lymphoproliferatív eltérés. A főként B-sejtes betegségek közül leggyakoribb az alacsony malignitású marginalis zóna lymphoma, a diffúz nagy B-sejtes lymphoma, valamint a follicularis lymphoma. Beteg: A hypertoniás, visszérműtéten átesett 54 éves férfi beteg thrombopeniájának, indirekt, Coombs-pozitív hyperbilirubunaemiájának és hepatosplenomegaliájának hátterében HCV-infekció talaján kialakult Child B stádiumú májcirrhosis igazolódott. Az inhomogén szerkezetű, megnagyobbodott, lobulált felszínű májban körülírt eltérés nem látszott. A portalis keringés megtartott volt. A máj fokozott keménysége (26 kPa, IQR/med. 18%) F4 cirrhosisra utalt. A homogén szerkezetű lépet jelentősen nagyobbnak (20×9 cm) mértük. A perifériás vérkenet alapján lymphoma gyanúja merült fel, amit a crista-biopsia eredménye megerősített, CD5/CD10-negatív marginális zóna lymphomát (MZL) diagnosztizáltunk. A fenti májbetegségnek és a HCV 1b genotípusnak megfelelően, sofosbuvir/ledipasvir direkt antivirális kezelést indítottunk. A 12 hetes kezelés tartós vírusmentességet eredményezett. Mind a májbetegség, mind a lymphoma tünetei mérséklődtek, a beteg testsúlya nőtt, fáradékonysága megszűnt. Megbeszélés: Az irodalomból is ismert, hogy a krónikus C hepatitisben a B-sejtes lymphomák előfordulása gyakoribb. Az antiviralis kezelés hatására lymphoma javulását is leírták, esetünkben a társuló immunhaemolysis mértékének csökkenését észleltük. Lymphomaspecifikus kezelés jelenleg nem szükséges, a beteg tünetmentes és stabil, progresszió esetén rituximab monoterápia jön szóba. Következtetés: A fenti eset példa a HCV-pozitív betegekben előforduló B-sejtes lymphomára. Bár az irodalomból ismert, hogy a hepatitis C-vírus eradikációjával a B-sejtes non-Hodgkin-lymphoma regrediálhat, esetünkben az eddig eltelt vírusmentes időszakban ezt még nem észleltük, igaz, hogy progressziót sem.

Bevezetés: A hepatitis C-vírus (HCV) krónikus májgyulladáshoz, májcirrhosishoz, májrákhoz vezethet. A Flaviviridae csoportba tartozó RNS vírus nemcsak hepatotrop, de lymphotrop tulajdonsággal is rendelkezik. Számos extrahepatikus manifesztációja között jelentős a lymphoproliferatív eltérés. A főként B-sejtes betegségek közül leggyakoribb az alacsony malignitású marginalis zóna lymphoma, a diff úz nagy B-sejtes lymphoma, valamint a follicularis lymphoma. Beteg: A hypertoniás, visszérműtéten átesett 54 éves férfi beteg thrombopeniájának, indirekt, Coombs-pozitív hyperbilirubunaemiájának és hepatosplenomegaliájának hátterében HCV-infekció talaján kialakult Child B stádiumú májcirrhosis igazolódott. Az inhomogén szerkezetű, megnagyobbodott, lobulált felszínű májban körülírt eltérés nem látszott. A portalis keringés megtartott volt. A máj fokozott keménysége (26 kPa, IQR/med. 18%) F4 cirrhosisra utalt. A homogén szerkezetű lépet jelentősen nagyobbnak (20×9 cm) mértük. A perifériás vérkenet alapján lymphoma gyanúja merült fel, amit a crista-biopsia eredménye megerősített, CD5/CD10-negatív marginális zóna lymphomát (MZL) diagnosztizáltunk. A fenti májbetegségnek és a HCV 1b genotípusnak megfelelően, sofosbuvir/ledipasvir direkt antivirális kezelést indítottunk. A 12 hetes kezelés tartós vírusmentességet eredményezett. Mind a májbetegség, mind a lymphoma tünetei mérséklődtek, a beteg testsúlya nőtt, fáradékonysága megszűnt. Megbeszélés: Az irodalomból is ismert, hogy a krónikus C hepatitisben a B-sejtes lymphomák előfordulása gyakoribb. Az antiviralis kezelés hatására lymphoma javulását is leírták, esetünkben a társuló immunhaemolysis mértékének csökkenését észleltük. Lymphomaspecifi kus kezelés jelenleg nem szükséges, a beteg tünetmentes és stabil, progresszió esetén rituximab monoterápia jön szóba. Következtetés: A fenti eset példa a HCV-pozitív betegekben előforduló B-sejtes lymphomára. Bár az irodalomból ismert, hogy a hepatitis C-vírus eradikációjával a B-sejtes non-Hodgkin-lymphoma regrediálhat, esetünkben az eddig eltelt vírusmentes időszakban ezt még nem észleltük, igaz, hogy progressziót sem.

Absztrakt: Bevezetés: A Wilson-kór a rézanyagcsere ritka, kezelés nélkül fatális, öröklődő megbetegedése. Bár a diagnosztika és a kezelés jelentős fejlődésen ment át az elmúlt években, számos beteg esetében ma is májátültetésre van szükség. Célkitűzés: A vizsgálat célja a Magyarországon Wilson-kór miatt májátültetésen átesett betegek adatainak összegyűjtése és feldolgozása volt. Módszer: Retrospektív módon vizsgáltuk a Semmelweis Egyetemen 1996 és 2017 között Wilson-kór miatt májátültetésen átesett 24 beteg adatait. A Wilson-kór diagnózisa minden esetben a nemzetközi, lipcsei pontrendszeren alapult. A heveny májelégtelenség felállításához a King’s College-kritériumrendszert használtuk. A májátültetések a Semmelweis Egyetem Transzplantációs és Sebészeti Klinikáján történtek, első alkalommal 1996-ban. Eredmények: Az átlagéletkor 26 év volt, a nő/férfi arány 13/11. 12 beteg heveny májelégtelenség miatt, 12 beteg dekompenzált cirrhosis miatt esett át májátültetésen. Egy beteg krónikus rejekció miatt retranszplantációra került. Három heveny májelégtelen beteg az Eurotransplant segítségével kapott új májat. A várólistán eltöltött átlagos idő 3 nap volt a heveny májelégtelen betegek, míg 320 nap a dekompenzált májbetegek esetében. Az ötéves túlélés 66% volt, azonban a 2002 után transzplantáltak esetében 80%, ami a tanulási folyamatot és a májátültetés elérhetőségének javulását jelezheti. A diagnosztika nehézségei ellenére a betegek többségében (21/24 beteg) már a műtét előtt ismert volt a Wilson-kór. Következtetések: Bár a Wilson-kór diagnosztikája és kezelése jelentős fejlődésen ment át az elmúlt évek során, ma is számos esetben van szükség májátültetésre. A betegek megfelelő kiválasztása és a transzplantáció időzítése jelentősen javítja a betegek túlélését. Orv Hetil. 2019; 160(51): 2021–2025.

Introduction: Wilson's disease is a lethal-without-treatment inherited disorder of copper metabolism. Despite the increased focus on the diagnosis and treatment, liver transplantation is needed in a number of cases even nowadays. Aim: To collect and analyze the data of the Hungarian Wilson's disease patients who underwent liver transplantation. Method: Data of 24 Wilson's disease patients who underwent liver transplantation at the Semmelweis University have been analyzed retrospectively. The diagnosis of Wilson's disease was based on the international score system. The diagnosis of acute liver failure corresponded to the King's College criteria. All liver transplantations had been performed at the Department of Transplantation and Surgery of Semmelweis University, in 1996 for the first time. Results: The mean age was 26 years, F/M = 13/11. Twelve patients needed urgent liver transplantation for acute liver failure, and 12 underwent transplantation for decompensated liver cirrhosis. One patient had been retransplanted because of chronic rejection. Three patients with acute on chronic liver failure were transplanted via the Eurotransplant program. The mean time on the waiting list was 3 vs 320 days in acute liver failure and chronic liver disease groups, respectively. The overall 5-year survival was 66%, but it was 80% after 2002 indicating both the learning curve effect and the improvement of vigilance in Hungary. Despite difficulties of the diagnostic process, Wilson's disease was identified in 21/24 patients prior to the transplantation. Conclusion: Liver transplantation is needed in a number of cases of Wilson's disease. The ideal indication and timing of transplantation may improve the survival of the patients. Orv Hetil. 2019; 160(51): 2021-2025.

It has been suggested that hepatobiliary carcinomas are less frequent in Wilson's disease (WD) than in liver diseases of other etiology. However, the protective role of copper against malignancies is debated. Only a few cases of cholangiocarcinoma (CCC) in WD have been published. Here we report on a case of a 47-year-old male H1069Q homozygous, Kayser-Fleischer ring positive WD patient with a low ceruloplasmin level who was followed up and treated with chelating agents throughout nine years. The patient presented with neurological symptoms and liver cirrhosis at diagnosis. Clinical symptoms regressed after the treatment initiation. Rapidly developed tumour metastases were found in the bones, lung and liver (without jaundice). Autopsy revealed cholangiocarcinoma as the primary tumour confirmed by strong CK7 positivity and glypican-3 negativity. The curiosity of the presented case is the very rapid development of CCC despite continuous chelating agent therapy.

Objective. Wilson's disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost-effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilson's disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile) was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time-saving, and cost-effective method for diagnosing Wilson's disease in selected cases.

Absztrakt Bevezetes: Az 1,25-dihidroxi-D3-vitamin tumorellenes hatasa hepatocellularis carcinomaban mar reszben ismert. Celkitűzes: Az 1,25-dihidroxi-D3-vitamint inaktivalo CYP24A1-mRNS- es feherjeexpresszio, az aktivalo CYP27B1- es a VDR-mRNS-expresszio mertekenek osszehasonlitasa human hepatocellularis carcinomaban es az azt korulvevő tumormentes majszovetben. Modszer: 13 beteg friss fagyasztott majszovetmintajat a CYP24A1-mRNS- es feherje-, 36 beteg paraffinba agyazott majszovetmintajat hasznaltuk a VDR- es a CYP27B1-mRNS-expresszio kimutatasara. Az mRNS-expressziot RT-PCR-rel, a feherjet immunhisztokemiai vizsgalatokkal mertuk. Eredmenyek: A hepatocellularis carcinomamintak tobbsegeben kimutathato volt a CYP24A1-mRNS-expresszio, mig a nem tumoros majszovetmintak egyikeben sem. A CYP27B1- es VDR-expresszio szignifikansan alacsonyabb hepatocellularis carcinomaban a tumormentes majszovethez kepest (p<0,05). A CYP24A1-mRNS-expressziot feherjeszintezis koveti. Kovetkeztetesek: A CYP24A1 inaktivalo enzim jelenlete, az aktivalo CYP27B1 es a VDR csokkent expresszioja human hepatocellularis carcinomaban a D-vitamin csokkent helyi aktivitasara enged kovetkeztetni, mint egy menekulő mechanizmus a tumor reszeről a D-vitamin antitumorhatasa ellen. Orv. Hetil., 2016, 157(48), 1910–1918. | Abstract Introduction: 1,25-Dihydroxy vitamin D3 mediates antitumor effects in hepatocellular carcinoma. Aim: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Methods: Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Results: Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. Conclusions: The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910–1918.

Introduction: 1,25-Dihydroxy vitamin D3 mediates antitumor effects in hepatocellular carcinoma. Aim: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Methods: Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Results: Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. Conclusions: The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910–1918.

INTRODUCTION:1,25-Dihydroxy vitamin D3 mediates antitumor effects in hepatocellular carcinoma.AIM:We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver.METHODS:Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry.RESULTS:Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis.CONCLUSIONS:The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

Introduction: Wilson's disease (WD) is a rare autosomal recessive disease caused by the toxic accumulation of copper due to ATP7B gene mutations. Neurological symptoms develop in about half of the patients. We present two cases of WD diagnosed only more than 10 years after onset of neurological/psychiatric symptoms. Case report: In the 25-year-old male patient thalamotomy was performed because of head and hand tremor thought to be consequence of a 3 year earlier car accident. The symptoms worsened, gait disorder and partial spastic hemiparesis developed. Head MRI was negative. WD was diagnosed only 12 years later. Low ceruloplasmin level (0.02 g/l), Kayser-Fleischer ring (KFR) positivity and the genetic testing (H1069Q homozygous mutations) confirmed the diagnosis. D-penicillamine treatment resulted in improvement of the tremor, speech disorder and writing skills but he did not become symptomless. 35-year-old male has been treated because of anxiety, depression and sleep disorder since his age of 18 years. He was treated with several psychiatric medicines without any beneficial effect. High transaminase levels were detected. However, the cause was not identified at that time. 14 years later neurological symptoms developed such as tremor, blurred speech, ataxia, dystonia, muscle spasm. He needed wheelchair because of the movement disorders. Wilson's disease has been diagnosed by KFR, the low ceruloplasmin level (0.03 g/l), the liver abnormalities and by genetic testing (H1069Q homozygous). Despite the long history of the psychiatric, neurological and liver symptoms, significant improvement was followed after the introduction of D-penicillamine. He does not need wheelchair anymore, liver tests returned to the normal. Conclusion: Although the vide variety of symptoms in Wilson's disease is well known, the diagnosis in the real life is often established very late after the initial symptoms. In our two presented cases more than ten years passed until the correct diagnosis. We call attention that WD should be considered not only in case of neurological, but that of psychiatric symptoms of unknown origin. The treatment could be effective even in advanced disease.

Introduction: Wilson's disease (WD) is a rare autosomal recessive disease caused by mutation of the ATP7B gene. The toxic accumulation of copper in many organs is fatal without treatment. The diagnosis may be difficult because of vide variability of symptoms. Only few papers are available on identical twins with WD. Here we report on identical twins with different clinical presentation. Case report: 21-year-old female university student went to see the doctor because of abdominal discomfort, nausea and vomiting. Liver cirrhosis was diagnosed. The cause of the liver disease was not identified that time. Symptoms of vascular decompensation and liver failure developed within six months. The low prothrombin value (16%), high bilirubin (157/63µmol/L) and symptoms of hepatic encephalopathy (ammonia: 186µmol/L) indicated the progression. Liver transplantation has been performed at her age of 22 years. Ten years passed and the patient is well. WD was diagnosed only after the transplantation by detection of high copper content in the liver and by genetic testing. ATP7B mutations were detected on both alleles (H1069Q/A874V). Her identical twin sister with same mutations was symptomless despite low ceruloplasmin and Kayser-Fleischer ring positivity at her age of 22 years. Liver function tests were negative. She is treated with D-penicillamine. No symptoms or abnormal findings appeared in the last ten years meanwhile she delivered three healthy children. Discussion: Although Wilson's disease is caused by the mutations of ATP7B gene, looking at the fully different clinical presentation in our twins it seems that there is no direct genotype-phenotype correlation. There is no explanation for the differences. Epigenetic and/or environmental factors might play a role. The twins lived in the same family and environment until their age of 19. Thereafter they visited different universities for one semester only. Later they joined again and graduated at the same university. It could be of interest that the first sister had a longer new-born jaundice and underwent medical treatments because of epistaxis repeatedly. Conclusion: The genetic testing is mandatory in siblings of the index patient. The presented two siblings are examples for a totally different manifestation of WD despite the identical gene mutations. The investigation for possible role of both epigenetic and/or environmental factors is in progress.

P0320 TARGETING TGF-BETA I WITH THE TRANSFORMING GROWTH FACTOR RECEPTOR TYPE I KINASE INHIBITOR, LY2157299, MODULATES STEMNESS-RELATED BIOMARKERS IN HEPATOCELLULAR CARCINOMA B. Rani, F. Dituri, Y. Cao, U. Engstrom, L. Lupo, S. Dooley, A. Moustakas, G. Giannelli. Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy; Biomedical Center, Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy; Molecular Hepatology-Alcohol associated diseases, Department of medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Medical Biochemistry and Microbiology, and Ludwig Institute for Cancer Research, Science for Life Laboratory, Box 581 Biomedical Center, Uppsala, Sweden E-mail: bhavna.rani@uniba.it

Introduction: Acute on chronic liver failure is a rare but high mortality form of Wilson disease. We present a case of acute liver failure of WD proved by a new ATP7B gene mutation detected by Ion Torrent. Urgent liver transplantation was accomplished via Eurotransplant.

Introduction: Wilson disease (WD) is a rare genetic disorder of copper metabolism. It is suggested that in WD malignancies are less frequent than in other cirrhotic patients. However, there is no data on the frequency of cholangiocarcinoma (CCC) in WD patients. Only four cases have been published according to our knowledge. Here we present a case.

Aim: 1,25-DihydroxyvitaminD3 (1,25(OH)2D3), the active form of vitamin D, mediates antitumor effects mostly by the vitamin D nuclear receptor (VDR) in various cancers. We aimed to examine mRNA and protein expression differences of 1,25(OH)2D3-inactivating CYP24A1 and mRNA expression of the activating CYP27B1 enzymes, as well as that of VDR between human non-tumorous liver and hepatocellular carcinoma (HCC) tissue samples, and to study the correlation with clinicopathological characteristics.

Background and Aims: Acute liver failure (ALF) is a rare form of Wilson disease (WD) developing mostly in young female patients. Use of chelating agents and supportive therapies including MARS (Molecular Adsorbent Recirculating System) in time may result in a remission in some cases making liver transplantation unnecessary.