The Calculation and Evaluation of an Ultrasound-Estimated Fat Fraction in Non-Alcoholic Fatty Liver Disease and Metabolic-Associated Fatty Liver Disease.

We aimed to develop a non-linear regression model that could predict the fat fraction of the liver (UEFF), similar to magnetic resonance imaging proton density fat fraction (MRI-PDFF), based on quantitative ultrasound (QUS) parameters. We measured and retrospectively collected the ultrasound attenuation coefficient (AC), backscatter-distribution coefficient (BSC-D), and liver stiffness (LS) using shear wave elastography (SWE) in 90 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD), and 51 patients with clinically suspected metabolic-associated fatty liver disease (MAFLD). The MRI-PDFF was also measured in all patients within a month of the ultrasound scan. In the linear regression analysis, only AC and BSC-D showed a significant association with MRI-PDFF. Therefore, we developed prediction models using non-linear least squares analysis to estimate MRI-PDFF based on the AC and BSC-D parameters. We fitted the models on the NAFLD dataset and evaluated their performance in three-fold cross-validation repeated five times. We decided to use the model based on both parameters to calculate UEFF. The correlation between UEFF and MRI-PDFF was strong in NAFLD and very strong in MAFLD. According to a receiver operating characteristics (ROC) analysis, UEFF could differentiate between <5% vs. ≥5% and <10% vs. ≥10% MRI-PDFF steatosis with excellent, 0.97 and 0.91 area under the curve (AUC), accuracy in the NAFLD and with AUCs of 0.99 and 0.96 in the MAFLD groups. In conclusion, UEFF calculated from QUS parameters is an accurate method to quantify liver fat fraction and to diagnose ≥5% and ≥10% steatosis in both NAFLD and MAFLD. Therefore, UEFF can be an ideal non-invasive screening tool for patients with NAFLD and MAFLD risk factors.

Evaluation of Artificial Intelligence-Calculated Hepatorenal Index for Diagnosing Mild and Moderate Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease.

Background and Objectives: This study aims to evaluate artificial intelligence-calculated hepatorenal index (AI-HRI) as a diagnostic method for hepatic steatosis. Materials and Methods: We prospectively enrolled 102 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD). All patients had a quantitative ultrasound (QUS), including AI-HRI, ultrasound attenuation coefficient (AC,) and ultrasound backscatter-distribution coefficient (SC) measurements. The ultrasonographic fatty liver indicator (US-FLI) score was also calculated. The magnetic resonance imaging fat fraction (MRI-PDFF) was the reference to classify patients into four grades of steatosis: none < 5%, mild 5-10%, moderate 10-20%, and severe ≥ 20%. We compared AI-HRI between steatosis grades and calculated Spearman's correlation (rs) between the methods. We determined the agreement between AI-HRI by two examiners using the intraclass correlation coefficient (ICC) of 68 cases. We performed a receiver operating characteristics (ROC) analysis to estimate the area under the curve (AUC) for AI-HRI. Results: The mean AI-HRI was 2.27 (standard deviation, ±0.96) in the patient cohort. The AI-HRI was significantly different between groups without (1.480 ± 0.607, p < 0.003) and with mild steatosis (2.155 ± 0.776), as well as between mild and moderate steatosis (2.777 ± 0.923, p < 0.018). AI-HRI showed moderate correlation with AC (rs = 0.597), SC (rs = 0.473), US-FLI (rs = 0.5), and MRI-PDFF (rs = 0.528). The agreement in AI-HRI was good between the two examiners (ICC = 0.635, 95% confidence interval (CI) = 0.411-0.774, p < 0.001). The AI-HRI could detect mild steatosis (AUC = 0.758, 95% CI = 0.621-0.894) with fair and moderate/severe steatosis (AUC = 0.803, 95% CI = 0.721-0.885) with good accuracy. However, the performance of AI-HRI was not significantly different (p < 0.578) between the two diagnostic tasks. Conclusions: AI-HRI is an easy-to-use, reproducible, and accurate QUS method for diagnosing mild and moderate hepatic steatosis.

Malignant solid tumor associated with hypereosinophilic syndrome / Malignus solid tumorhoz társuló hypereosinophil szindróma

Hypereosinophilic syndrome is characterized by chronic eosinophil overproduction, resulting in multiple organ damages due to eosinophil infiltration and mediator release. According to the etiology, we distinguish between myeloproliferative disorders, parasitic infections, solid tumors, T-cell lymphomas and idiopathic forms. In our case report, the 49-year-old man was hospitalized with weight loss, leg edema and tachycardia. In his laboratory tests increased biliary obstructive parameters as well as extreme leukocytosis and eosinophilia had been highlighted. We started our evaluation with a strong suspicion of hematologic malignancy. The CT scan of the thorax, abdomen and pelvis described hepatosplenomegaly, multiple intrahepatic lesions and an uncertain solitary cystic lesion in the tail of the pancreas with abnormal lymph nodes and pleural fluid. The described CT image and the other clinical parameters were primarily consistent with the manifestation of chronic myeloid leukemia. However, the diagnosis was not confirmed by peripheral blood smear, flow cytometry, bone marrow biopsy or genetic tests. After these results, we continued the assessment towards solid tumor associated leukemoid reaction, core biopsy was performed to verify the liver lesions. The biopsy confirmed the infiltration of a poorly differentiated epithelial tumor as a metastasis of pancreatobiliary carcinoma. To the best of our knowledge, this is the first case report on hypereosinophilic syndrome associated with gastrointestinal solid tumors in the Hungarian medical literature. It draws attention to the differential diagnosis of extreme leukocytosis and eosinophil ratios and by the absence of confirmed hematological disease the importance of early biopsy sampling of solid lesions.

Tissue attenuation imaging and tissue scatter imaging for quantitative ultrasound evaluation of hepatic steatosis.

We aimed to assess the feasibility of ultrasound-based tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) for quantification of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We prospectively enrolled 101 participants with suspected NAFLD. The TAI and TSI measurements of the liver were performed with a Samsung RS85 Prestige ultrasound system. Based on the magnetic resonance imaging proton density fat fraction (MRI-PDFF), patients were divided into ≤5%, 5-10%, and ≥10% of MRI-PDFF groups. We determined the correlation between TAI, TSI, and MRI-PDFF and used multiple linear regression analysis to identify any association with clinical variables. The diagnostic performance of TAI, TSI was determined based on the area under the receiver operating characteristic curve (AUC). The intraclass correlation coefficient (ICC) was calculated to assess interobserver reliability. Both TAI (rs = 0.78, P < .001) and TSI (rs = 0.68, P < .001) showed significant correlation with MRI-PDFF. TAI overperformed TSI in the detection of both ≥5% MRI-PDFF (AUC = 0.89 vs 0.87) and ≥10% (AUC = 0.93 vs 0.86). MRI-PDFF proved to be an independent predictor of TAI (ß = 1.03; P < .001), while both MRI-PDFF (ß = 50.9; P < .001) and liver stiffness (ß = -0.86; P < .001) were independent predictors of TSI. Interobserver analysis showed excellent reproducibility of TAI (ICC = 0.95) and moderate reproducibility of TSI (ICC = 0.73). TAI and TSI could be used successfully to diagnose and estimate the severity of hepatic steatosis in routine clinical practice.

Delayed contrast enhancement of hepatic parenchyma after intravenous sonographic contrast agent: unusual phenomenon. Case report and review of literature.

AIM: A case of heterogeneous late-phase hepatic enhancement (HLHE) using contrast-enhanced ultrasound (CEUS) with SonoVue is presented, where HLHE lasted after 50 min of injection. METHODS: This study aims to review prior literature on this topic, to characterize the features of HLHE in the liver, and to find possible and reliable explanations for this phenomenon. RESULTS: From literature, thus far five publications discuss this phenomenon with a total of 21 patients. CONCLUSION: We suggest that phagocytosis of contrast agent microbubbles by macrophages, and lymphocytosis of peripheral blood due to stress conditions of the patients might be in the background of HLHE.

Three-dimensional CT texture analysis of anatomic liver segments can differentiate between low-grade and high-grade fibrosis.

BACKGROUND: CT texture analysis (CTTA) has been successfully used to assess tissue heterogeneity in multiple diseases. The purpose of this work is to demonstrate the value of three-dimensional CTTA in the evaluation of diffuse liver disease. We aimed to develop CTTA based prediction models, which can be used for staging of fibrosis in different anatomic liver segments irrespective of variations in scanning parameters. METHODS: We retrospectively collected CT scans of thirty-two chronic hepatitis patients with liver fibrosis. The CT examinations were performed on either a 16- or a 64-slice scanner. Altogether 354 anatomic liver segments were manually highlighted on portal venous phase images, and 1117 three-dimensional texture parameters were calculated from each segment. The segments were divided between groups of low-grade and high-grade fibrosis using shear-wave elastography. The highly-correlated features (Pearson r > 0.95) were filtered out, and the remaining 453 features were normalized and used in a classification with k-means and hierarchical cluster analysis. The segments were split between the train and test sets in equal proportion (analysis I) or based on the scanner type (analysis II) into 64-slice train 16-slice validation cohorts for machine learning classification, and a subset of highly prognostic features was selected with recursive feature elimination. RESULTS: A classification with k-means and hierarchical cluster analysis divided segments into four main clusters. The average CT density was significantly higher in cluster-4 (110 HU ± SD = 10.1HU) compared to the other clusters (c1: 96.1 HU ± SD = 11.3HU; p < 0.0001; c2: 90.8 HU ± SD = 16.8HU; p < 0.0001; c3: 93.1 HU ± SD = 17.5HU; p < 0.0001); but there was no difference in liver stiffness or scanner type among the clusters. The optimized random forest classifier was able to distinguish between low-grade and high-grade fibrosis with excellent cross-validated accuracy in both the first and second analysis (AUC = 0.90, CI = 0.85-0.95 vs. AUC = 0.88, CI = 0.84-0.91). The final support vector machine model achieved an excellent prediction rate in the second analysis (AUC = 0.91, CI = 0.88-0.94) and an acceptable prediction rate in the first analysis (AUC = 0.76, CI = 0.67-0.84). CONCLUSIONS: In conclusion, CTTA-based models can be successfully applied to differentiate high-grade from low-grade fibrosis irrespective of the imaging platform. Thus, CTTA may be useful in the non-invasive prognostication of patients with chronic liver disease.

Interobserver agreement and diagnostic accuracy of shearwave elastography for the staging of hepatitis C virus-associated liver fibrosis.

PURPOSE: Our study aimed to evaluate the technical success rate, interobserver reproducibility, and accuracy of shearwave elastography (SWE) in the staging of hepatitis C virus (HCV)-associated liver fibrosis. METHODS: A total of 10 healthy controls and 49 patients with chronic liver disease were enrolled prospectively. Two examiners performed point shearwave elastography (pSWE) and two-dimensional shearwave elastography (2D-SWE) measurements with an RS85A ultrasound scanner using the S-Shearwave application (Samsung Medison, Hongcheon, Korea). The performance of S-Shearwave in the staging (METAVIR F0-F4) of liver fibrosis was compared with prior transient elastography (TE) with receiver operating characteristic (ROC) curve analysis. RESULTS: The interobserver reproducibility was excellent with pSWE (ICC = 0.92, 95% CI: 0.86-0.95, P < .001). A very good agreement was found between pSWE and TE measurements (ICC =0.85, 95% CI: 0.78-0.89, P < .001). The ROC analysis determined the optimal cut-off values of pSWE for the staging of chronic hepatitis C-associated fibrosis (F2, 1.46 m/s; F3, 1.63 m/s; F4, 1.95 m/s). Both observers achieved excellent diagnostic accuracy (AUROC: 94% vs 97%) in the detection of significant (≥F2) liver fibrosis. CONCLUSION: The interobserver agreement is excellent with S-Shearwave pSWE, and observers can diagnose significant liver fibrosis with a comparable accuracy to TE.

[Liver transplantation in Wilson's disease patients, 1996-2017]. / Májátültetés Wilson-kóros betegekben, 1996­2017.

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.

Cholangiocarcinoma in Wilson's Disease - a Case Report.

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.

Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson's Disease.

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.

Disturbed post-movement beta synchronization in Wilson's disease with neurological manifestation.

We analyzed the changes of post-movement beta synchronization (PMBS) of the electroencephalogram (EEG) in Wilson's disease with neurological manifestation. Our aim was to determine if PMBS in Wilson's disease is altered in a different way than in Parkinson's disease or in essential tremor. Our purpose was to find out whether the analysis of PMBS could help the diagnosis in ambiguous cases. Ten patients with neurological manifestation of Wilson's disease and ten controls performed self-paced movements with the dominant hand during EEG acquisition. Five electrodes above the sensorimotor cortex were selected for evaluation (C3, C1, Cz, C2, C4) as contralateral (C); contralateral medial (CM); medial (M); ipsilateral medial (IM); ipsilateral (I) relative to the dominant hand. Power and latency of PMBS were calculated by time resolved power spectral analysis with multitaper method. PMBS power in the C electrode position was significantly lower in patients than in controls, its contralateral preponderance disappeared in the patient group. In every location, latency of PMBS was significantly longer in the Wilson group compared to controls. More altered PMBS could be measured in patients with both basal ganglia and cerebellar involvements. Since decreased power of PMBS was observed in Parkinson's disease and increased latency in essential tremor, the combined change of PMBS can indicate pathology of different neural circuits and may help the diagnosis in challenging cases.

Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease.

BACKGROUND/AIMS: Diagnosis of Wilson's disease may be difficult in patients presenting with liver disease and in asymptomatic siblings. The aim of the present study was to assess the impact of genetic testing for diagnosis of the disease in a large cohort (n=109) from Hungary. PATIENTS/METHODS: One hundred and nine patients with Wilson's disease were studied (65 men and 44 women; mean age at onset of symptoms: 20+/-9 years). Diagnosis of the disease was based on typical clinical and laboratory features (all had a Wilson's disease score of >or=4). H1069Q was assessed by the semi-nested polymerase chain reaction-based restriction fragment length polymorphism assay. H1069Q heterozygotes and H1069Q negative samples were then screened for mutations (on exons 6 to 20) by denaturating high-performance liquid chromatography and than sequenced on a genetic analyser. RESULTS: Twenty-three different mutations were found. H1069Q was the most frequent mutation in Hungary, detected in 77 patients (71%). Fourteen further known mutations were found by sequencing. We identified eight new mis-sense mutations not described before: N676I, S693Y, Y715H, M769L, W939C, P1273S, G1281D and G1341V. In 36/109 patients (33%) the diagnosis of Wilson's disease was established by adding mutational analysis. The Kayser-Fleischer ring was more frequent in H1069Q homozygous patients and their mean age at the time of diagnosis was higher than in patients heterozygous or negative for H1069Q. CONCLUSION: Eight novel mutations in addition to the 15 that are already known were found in Hungarian patients with Wilson's disease. Our results underline the importance and usefulness of genetic testing for patients presenting with liver disease and for family screening.

Myocardial infarction is associated with Spl binding site polymorphism of collagen type 1A1 gene.

OBJECTIVE: Human atherosclerotic lesions contain collagen type I, which plays a pivotal role in atherosclerotic plaque stability. In contrast, the normal coronary arteries do not express this type of collagen. Data have shown that the collagen type 1A1 (COL1A1) gene Sp1 binding site (-1245 G/T) polymorphism is associated with disturbed collagen protein production. METHODS: In our study, COL1A1 gene Sp1 polymorphism was investigated in 136 patients with myocardial infarction (MI) 5 months after the acute phase, and 212 age-matched control subjects in association with any cardiovascular risk factors (such as serum adiponectin levels, hyperinsulinaemic status, hyperlipaemia). RESULTS: The "SS" genotype of the COL1A1 gene was found to occur significantly more frequently in patients surviving a MI, as compared to the control group and the "Ss" and "ss" genotype frequencies (the presence of the s allele) were lower in our patients, than in control group. However, the occurrence of cardiovascular risk factors was significantly higher among the "s" allelic carriers as compared to patients carrying the "S" allele of the COL1A1 gene. CONCLUSION: Our results raise the possibility that COL1A1 gene Sp1 polymorphism might have an impact on the development of MI.

[Xanthomatosis and extreme hypercholesterolemia after laparoscopic cholecystectomy. Total reversibility following surgical treatment of iatrogenous stenosis of the common bile duct]. / Extrém hypercholesterinaemia es xanthomatosis laparoszkópos cholecystectomia után. Teljes reverzibilitás az iatrogén szukület mutéti megoldását követoen.

INTRODUCTION: Hypercholesterolemia and xanthomatosis are known complications of chronic cholestasis. This is the first report on xanthomatosis and severe hypercholesterolemia caused by common bile duct stenosis following laparoscopic cholecystectomy. CASE REPORT: Laparoscopic cholecystectomy was performed in a 32-year old woman because of numerous tiny gallstones. Bile leakage was observed in the early postoperative period which stopped spontaneously. Six months later itching, progressively increasing serum bilirubin level, cholestasis syndrome, xanthelasma and widespread eruptive xanthomatosis developed in a few months. The cholesterol level was extremely high (92.3 mmol/l), while the triglyceride level was normal. Though the ultrasound and the cholangio-MR did not showed any dilatation of bile ducts, the ERCP verified a 2 mm long, hair's-breadth thin stenosis of choledochus in the level of cystic duct. Primary biliary cirrhosis and primary sclerosing cholangitis were excluded, no evidence for familial hypercholesterolemia was found. Choledochojejunostomy was performed and the patient became complaint- and symptom-free within two months. All xanthomas disappeared, the extremely high cholesterol level gradually decreased to the normal level, and all the laboratory data became normal. The anticholesterol antibody level was undetectable at presentation, but later reached the level of the healthy controls. CONCLUSION: The presented case is an example for laparoscopic cholecystectomy caused bile duct stenosis and for extra-hepatic cholestasis induced xanthomatosis and severe hypercholesterolemia. The bile leakage as early complication of bile duct damage may predict the later developed stenosis. Even severe xanthomatosis and extreme hypercholesterolemia can be totally reversible following elimination of biliary obstacle.

Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: a case report.

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia,enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma.Simultaneously, celiac disease was diagnosed.Gluten-free diet resulted in a significant improvement of celiac disease,but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis.

BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. CONCLUSIONS: We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.

Bone disorders in experimentally induced liver disease in growing rats.

AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats. METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl(4)), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (F(max)) of the femora were determined. The results in animals treated with DEN+PB+CCl(4) (DPC, n = 21) were compared to those in untreated animals (UNT, n = 14) and in control group treated only with DEN+PB (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and F(max) values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

[Combined antiviral treatment in a patient with recurrent chronic hepatitis C after liver transplantation]. / Májtranszplantáció utáni krónikus C-hepatitis recidívájának kombinált antivirális kezelése.

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of the patients. We report a case of orthotopic liver transplantation with more than five years survival despite the early recurrence of hepatitis C virus. CASE REPORT: A 49-year old woman underwent orthotopic liver transplantation because of liver cirrhosis following chronic hepatitis C virus infection. Twelve years before she received blood-transfusion. The chronic liver disease was diagnosed four years later. However, then it was thought to be a drug induced liver damage. After the liver transplantation hepatitis C chronic hepatitis recurred within one year. The serotype analysis (1b) proved the autoreinfection. The combined antiviral treatment (interferon plus ribavirin) resulted significant improvement. She was asymptomatic nearly for two years. The liver biopsy showed a significant histological improvement. However the virologic response and remission was transient. Four years after the transplantation recurrence occurred again. The liver biopsy proved cirrhosis. Antiviral therapy with pegylated interferon plus ribavirin was started but it had been stopped because of severe cytopenia. Lack of adequate antiviral treatment her condition became progressively worse. Finally, five years after the transplantation she died because of bilateral haemorrhagic ovarian necrosis and severe circulatory insufficiency thanks to the low albumin level. CONCLUSIONS: In the case of liver cirrhosis caused by hepatitis C virus the liver transplantation could prolongs the life with years. The presented case illustrate that the hepatitis C virus injures the transplanted liver by autoreinfection. However, the combined antiviral therapy could result sustained virologic response in these cases as well. Our patient survived five years thanks to the transplantation and the following antiviral therapy.

[Wilson disease]. / Wilson-betegség.

Wilson disease is an autosomal, recessive inherited disorder of copper metabolism, characterized by the accumulation of copper in the body due to defective biliary copper excretion of hepatocytes. Recently, novel components involved in copper metabolism, Wilson disease protein (ATP7B) and copper chaperones, have been identified. It has been demonstrated that ATP7B functions in copper secretion into the plasma, coupled with coeruloplasmin synthesis and biliary copper excretion. Genetic testing may help early diagnosis and with the beginning of therapy the development of symptoms can be prevented. Various mutations of ATP7B have been identified, the most common is in Hungary, the H1069Q mutation. Genetic screening should only be advised if there is a predominant mutation characteristic for the geographic area. The authors discuss the modern diagnostic and therapeutic possibilities of Wilson disease.