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Background: Primary sclerosing cholangitis (PSC) is an immune-mediated disease that has an unfavorable prognosis and needs a liver transplant (LT). The aim of this paper was to show the usefulness of the Majoie classification on magnetic resonance cholangiopancreatography (MRCP) images in assessing the prognosis in adult patients with PSC. Methods: Our work presents a retrospective monocentric study performed on 64 adult patients with PSC of the large bile ducts. Two radiologists evaluated the MRCP of diagnosis and calculated MRCP scores using the Majoie classification. Liver-related outcome (LT or liver-related death) was marked as a primary endpoint. Results: Univariate analysis showed that patients with more severe lesions (sum score of intrahepatic and extrahepatic ducts > 3) had a lower age at diagnosis, of 37.2 years, complicated with liver cirrhosis (53.1% of patients) and recurrent cholangitis (28.1%) p < 0.05, without significant differences in mortality, association with IBD or LT. Concordance analysis between MRCP prognostic scores and progression to a PSC-related event showed a moderate relationship (c-statistic 0.662), and a good AUROC was observed for the UKPSC score (0.893) and the MRS (0.936). Conclusions: In the study, we observed a good correlation between the imaging scores based on the Majoie classification and the evolution of the patients. These scores were outperformed by the UKPSC, MRS, and PREsTo clinical models. Their utility was best in predicting recurrent cholangitis. [ABSTRACT FROM AUTHOR]

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMFbased regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis. [ABSTRACT FROM AUTHOR]

Background. Wilson disease (WD) is an autosomal-recessive disorder of copper metabolism, caused by mutations in the ATP7B gene, which codes for a membrane-bound copper-binding ATPase. This leads to progressive copper accumulation in the liver, with hepatic injury and subsequent copper release into the blood. Aim. To analyze the efficacy and side-effects of the current copper chelating agents used in treatment of Wilson disease. Material and methods. Retrospective study of 37 adult patients diagnosed with Wilson disease at the Gastroenterology and Neurology Departments of Fundeni Clinical Institute between 2012 and 2017. Patients were grouped into three categories: (a) those with isolated liver disease, (b) those with isolated neurologic (or psychiatric) involvement and (c) those with both liver and neurologic involvement. Results. There were 54% females (n=20). Mean age at diagnosis was 23 ± 10 years-old. Liver cirrhosis was diagnosed in 54% of cases. Neurologic involvement was described in 65% of patients. Dysarthria was the most common neurologic feature (43%), followed by Parkinsonism (41%). D-Penicillamine was used as initial treatment in 89% of patients, but was interrupted in 27% of them (n=9) due to its adverse reactions. Keyser-Fleischer rings were absent in a significant proportion (40%) of patients with neurologic involvement. Both Trientine and D-Penicillamine were associated with improved or stationary liver fibrosis, however results were slightly better for Trientine. D-Penicillamine appeared to be a better option than Trientine in patients with neurologic involvement. Conclusions. Based on our study, we recommend treatment with D-Penicillamine as first-line therapy in patients with neurologic involvement. However, due to the frequent side-effects of D-Penicillamine, Trientine could be considered firstline treatment in patients with isolated hepatic involvement. [ABSTRACT FROM AUTHOR]