Isomeri urinari della Coproporfirina in pazienti con Epatopatie Colestatiche Acquisite e sindrome di Dubin-Johnson

Argomento della nostra comunicazione è la valutazione dell’escrezione urinaria degli isomeri della coprorporfirina in pazienti affetti da diverse forme di epatopatia colestatica o da sindrome di Dubin-Johnson. Esistono diverse dimostrazioni (basate su studi di cinetica combinata di escrezione biliare, su modelli animali e umani) che suggeriscono che l’MRP2, l’unico trasportatore di membrana della famiglia dei trasportatori delle Multidrug Resistance Protein presente sul polo biliare dell’epatocita (gli altri sono normalmente ben rappresentai sul versante baso-laterale dell’epatocita) sia il trasportatore biliare più specifico per gli isomeri della CP. Tale trasportatore condivide la sua specificità anche con altre sostanze, come la BSF e la bilirubina coniugata. E’ oggi ben dimostrato che il suo deficit congenito è alla base della sindrome di Dubin-Johnson. Va inoltre ricordato che tutti gli MRPs hanno una notevole omologia strutturale pertanto non è sorprendente come in condizioni particolari ciò possa riflettere anche un certo grado di analogia funzionale (possono cioè condividere stessi substrati).Ci siamo chiesti se questi dati possano avere un utilizzo nella pratica clinica. Basandoci sulla dimostrazione delle reversibilità dell’espressione dell’espressione bilare dell’MRP2 in caso di eliminazione della causa scatenante, ci siamo focalizzati (XXIII) sui pazienti affetti da Epatite cronica attiva in terapia con IFN. Si tratta di dati preliminari e su pochi casi ma potete vedere che i soggetti con HCV-RNA negativizzato a tre mesi di terapia (e con alta probabilità di essere”responders”) vanno incontro a una progressiva normalizzazione nel tempo del rapporto CPI / CPIII urinario, cosa che non abbiamo osservato in coloro che a tre mesi sono risltati HCV RNA negativi (non repsonders).(XXIV) In conclusioneLa diversa regolazione sia a livello intracellulare che intraorgano dei sistemi di trasporto (MRP) può spiegare le caratteristiche alterazioni del profilo urinario della CP osservabili in corso di DJS a di epatopatie colestatiche acquisiteConsiderando il relativo basso costo e la semplicità della determinazioni quali-quantitativa degli isomeri delle CP nelle urine , unitamente alla dimostrazione della precoce alterazione (o normalizzazione) in seguito a induzione (o risoluzione) di colestasi, tale determinazione potrebbe avere un significato nella diagnosi, prognosi e monitoraggio di diverse forme di epatopatia colestatica

Sarcoma primitivo del cuore. Descrizione di un caso

Primary cardiac tumors are rare events. We describe here a case of undifferentiated pleomorphic sarcoma (so-called pleomorphic malignant fibrous histiocytoma) obliterating mostly the left side and the anterior wall of pericardium in a 84-year-old man admitted for mild dyspnea at rest. The diagnosis was suspected after excluding the lung origin of the mass (observed by plain chest radiography) by thorax computed tomography but it was confirmed only by cardiac-gated magnetic resonance imaging and transthoracic biopsy. Considering both patient's age and comorbidity, and local extension of the lesion, after counseling with cardiac surgeons and oncologists, the patient was treated only by conservative medical therapy. The patient died 6 months after the diagnosis due to a superior vena cava syndrome as an effect of infiltration and obstruction of superior vena cava by the tumor at the site of vein entry in the right atrium. This case is an example of a primary cardiac tumor that causes relative myocardial sufferance both by infiltration and by limitation of normal heart diastolic function

Urinary coproporhyrin isomers during therapy with IFn-RIBA in patients with chronic hepatitis due to HCV infection

Background : MRP2 transporter has a proven role in biliary export of many different products of hepatocytic metabolism. Particularly, human and animal models have demonstrated MRP2 role in biliary excretion of coproporhyrins: its preference for isomer I (CPI) export with respect to isomer III (CPIII) is responsable for the biliary CPI/CPIII ratio about 2-3:1 and the plasma and urinary CPI/CPIII ratio about 1:2-3. A significant reduction of MRP2 expression has been described in many different acquired cholestatic liver diseases and in patients with chronic hepatitis (CH) due to HCV infection. Aim of our study was to evaluate quantitative and qualitative (CPI/CPIII ratio) urinary CP excretion in patients with CH due to HCV before (T0), at 3 months (T3) and at the end of antiviral therapy (ET) (peg-IFN + Ribavirin)Materials and Methods: 60 patients (18 females, aged 46±11 years, genotype: 1 (31); 2(10); 3(15); 4(4); 51 naive) with istologically proven HCV-inducted CH were consecutively enrolled; 5 (8.4%) did not conclude the study. 10 healthy subjects sex- and age-matched were also considered for comparing the basal values. None of considered subjects had overt laboratory [i.e. serum alkaline phosphatase (AP) over the normal range] or clinical signs of cholestasis. All patients underwent a urinary evaluation (HPLC) of CPI excretion at T0, T3 and ET. SVR (n=34) was defined as serum HCV-RNA undetectable after 6 months of follow-up. Results: Basal serum FA levels resulted significantly related both to basal urinary total CPI (r=.405, p=.001), and basal CPI/CPIII ratio (r=.692, p=.000). Table I show Total urinary CPI e urinary CPI/CPIII ratio in controls and in HCV patients with respect to serum PA percentile.Table IPA ≥ 75°percentile(≥ 232 u/L) (n=16)(group A)PA 60% at T3 showed a 88% PPV for SVR, reaching 95% if considering only patients in group A.Our data indirectly confirm the effect of liver chronic infection due to HCV on MRP2 expression, whose alteration may be considered as the main responsible for the observed urinary CPI modifications (greater excretion with CPI/CPIII ratio inversion). Even if more confirmative data are needed, monitoring of urinary CPI excretion (especially CPI/CPIII ratio) may be a useful, cheap and simple tool in early prediction of the response to antiviral therapy in subjects affected by HCV CH, especially in the presence of mild laboratory signs of cholestasis

Hyperhomocysteinaemia in chronic liver diseases: role of disease stage, vitamin status and methylenetetrahydrofolate reductase genetics

Background/Aims: The liver plays a key role in sulphur aminoacid metabolism hence, homocysteine metabolism may be impaired in chronic liver diseases. The aim of this study was to investigate, in patients affected by chronic liver diseases, (1) the prevalence of hyperhomocysteinaemia and (2) the role of its determinants such as the stage and the aetiology of disease, vitamin status, genetic documented alterations (methylenetetrahydrofolate reductase deficiency) and presence/absence of documented malignant evolution (hepatocellular carcinoma). Materials and methods: One hundred and thirty patients with chronic liver disease (34 with chronic active hepatitis, 12 with fatty liver and 88 with liver cirrhosis) and 50 healthy age-matched control subjects were included into the study. Results: Hyperhomocysteinaemia was defined as homocysteine plasma levels greater than 12.6 mumol/l. Hyperhomocysteinaemia prevalence in liver cirrhosis group was 40.9%, significantly higher (all PT mutation (both as CT and as TT) and hyperhomocysteinaemia results in significantly higher levels with respect to controls. Methylenetetrahydrofolate reductase C677-->T mutation and disease stage showed to be the most important predictive factors of hyperhomocysteinaemia in liver cirrhosis whereas the influence of homocysteine-related vitamin status seems to have a secondary role. Conclusions: In conclusion hyperhomocysteinaemia is highly prevalent in liver cirrhosis but not in other chronic liver diseases; it may contribute to fibrogenesis and vascular complication of liver cirrhosis

Radiofrequency ablation combined with transcatheter arterial chemioembolization in the treatment of advanced hepatocellular carcinoma

Background : Treatment of HCC complicating liver cirrhosis still remains a controversial issue, due to both the characteristics of the malignant disease per se and to the problems of underlying associated chronic liver disease. In particular, for patients with HCC not elegible for “curative” options (advanced HCC) (who, despite of surveillance programs, still remain a relevant amount in the clinical practice) there is no standard therapy. Aim: to evaluate efficacy of combined treatment with radiofrequency ablation (RFA) and transcatether arterial chemio-embolization (TACE) in the treatment of advanced hepatocellular carcinoma.Materials and Methods: We compared the treatment efficacy (cumulative survival rate after treatment) in 30 HCC-confirmed (imaging and/or histological proven) patients treated with combined therapy (simultaneous application of TACE and RFA; RFA was performed on to the greatest node in case of multiple nodes) [RFA-TACE group] with HCC-confirmed patients treated only by TACE [TACE group] or by conservative option [Control group]. Patients in TACE and Control groups were chosen as matching more as possible with patients in RFA-TACE group with regard to all possible factors influencing survival. Patients in TACE group could not undergo RFA due to technical (site of tumour, lesion undetectable at ultrasound, etc) and/or refuse of treatment. Control group could not undergo TACE due to portal complete or partial thrombosis or site of tumour. All patients were monitored at one-three months after treatment and every six months by imaging to control for treatment success and neoplasm relapse.Results: Characteristics of the considered groups are resumed in the table below. No patients were lost at follow-up. Survival rates were better in TACE-RFA group than TACE and control group. The median survival time was 16.1 months for TACE-RFA, 12.1 for TACE and 8.4 for Controls. The 6-month, 1-year and 2-years survival rate was 78%, 71% and 47% TACE-RFA group vs. 72%, 66% and 40% and 65%, 55% and 39% in TACE and Control group (p=.025 and p=.002 with respect to TACE-RFA group, i.e significant after Bonferroni correction for multiple comparisons).RFA-TACE (n=30)TACE (n=34)Controls (n=35)Age67±764±868±10Sex (males)22 (73.3%)25 (73.5%)26 (74.3%)Child score6.8±1.56.8±1.37.1±1.9Child group A/B11/1911/2310/25Nodes (mean)3.1±1.23.2 ±1.13.4±1.6Major node dimension3.9±1.53.8±1.63.9±1.8Single / Multiple node8/209/269/26BCLC stage ( B/C)16/1416/1815/20Milan criteria1 2/ 3 17/1315/1915/20Duration of Liver Disease (years) 8.4±4.48.7±3.58.6±3.5Etiology : Viral vs. Nonviral22/828/628/71 2= Single node > 3 and 5 cm or multiple nodes (more than 3 or up to 3 with the greatest > 3 cm)Conclusion: The combination of RFA and TACE is a promising approach for the treatment of advanced HCC complicating liver cirrhosis, nevertheless a better definition of patient’s characteristics and technical approaches are needed together with large scale-randomized trial for confirmation of results