Galad Score as a Prognostic Marker for Patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for more than 75% of primary liver cancers, which are the second leading cause of cancer-related deaths. The GALAD (gender, age, AFP-L3, AFP, and des-carboxy-prothrombin) score is a diagnostic tool developed based on gender, age, alpha-fetoprotein, alpha-fetoprotein L3, and des-gamma-carboxy prothrombin, originally designed as a diagnostic tool for HCC in high-risk patients. METHODS: We analyzed 212 patients with and without cirrhosis. The population study was divided into patients with liver cirrhosis without evidence of HCC at the time of serum sample collection for GALAD score determination and patients with liver cirrhosis and a confirmed diagnosis of HCC at the time of serum sample collection for GALAD score determination. Patients were followed up until death or liver transplantation. The association between variables and HCC mortality risk was performed, and the results were presented as hazard ratio (HR). The receiver operating characteristic (ROC) curve was used to assess the performance of the GALAD HCC diagnosis. The survival probability was explored using the non-parametric test, and the equality of survival amongst categories was assessed with the log-rank test. RESULTS: Biomarkers were higher in the HCC group compared to cirrhosis. Kaplan-Meier survival probability analysis for individual GALAD categories revealed that a high GALAD level was associated with decreased survival during follow-up, and the difference between the curves was statistically significant (p = 0.01). CONCLUSIONS: Our findings suggest that the GALAD score has promise as a prognostic tool, with implications for improving patient management and treatment strategies for HCC.

Liver Matrix in Benign and Malignant Biliary Tract Disease.

The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the "desmoplastic matrix" of cholangiocarcinoma along with their pro-oncogenic effects.

Electronic sanitary database: a new potential tool to identify occult chronic liver disease in general population.

Chronic liver disease (CLD) is a leading global cause of mortality, morbidity, and healthcare resource utilization. However, the burden of CLD is underestimated because the course of the disease is often asymptomatic until clinical decompensation and the development of life-threatening complications. In this study, we assessed the use of available blood tests from electronic medical records for identifying individuals with undiagnosed CLD in the general population. We analyzed a total of 202,529 blood tests obtained from 99,848 adults recorded in the Electronic Health Records of the Padova Teaching Hospital. Transaminases levels > 1.5 times the normal value indicated occult CLD, while platelet counts < 120,000/µL identified occult cirrhosis. We characterized patients using Italian Medical Exemptions (IME), excluding oncologic cases. Overt and occult cirrhosis prevalence was 1% and 4.18%, respectively, while overt and occult CLD affected 2.85% and 4.61% of the population. The epidemiology of patients with overt and occult cirrhosis was similar but significantly different from that of the controls. Among subjects aged 60-70 years, working disability was twofold higher in those with occult cirrhosis compared to those with overt cirrhosis. Occult CLD and cirrhosis had higher prevalence rates than diagnosed cases in the general population. Electronic medical record data may serve as a valuable tool for CLD identification, potentially reducing cirrhosis development and clinical decompensation. This, in turn, may lead to a decrease in the economic impact on the healthcare system.

The ATRA-dependent overexpression of the glutamate transporter EAAC1 requires RARbeta induction.

The mechanisms underlying trafficking and membrane targeting of EAAC1, the rodent counterpart of the human EAAT3 carrier for anionic amino acids, are well characterized. In contrast, much less is known on the regulation of Slc1a1, the gene that encodes for the transporter. We have recently found that all-trans retinoic acid (ATRA) stimulates EAAC1 expression and anionic amino acid transport in C6 rat glioma cells. We report here that the ATRA effect on EAAC1 activity was inhibited by the specific RAR antagonist LE540 and mimicked by Am80, a RAR agonist, but not by the RXR agonist HX630. Moreover, the ATRA-dependent induction of Slc1a1 mRNA required the synthesis of a protein intermediate and was not associated with changes in the messenger half-life. ATRA treatment induced the expression of both Rarb mRNA and RARbeta protein several hours before the induction of Slc1a1, while the mRNA for RFX1, a transcription factor recently involved in Slc1a1 transcription, was unchanged. In addition, Rarb silencing markedly inhibited the ATRA-dependent increase of both Rarb and Slc1a1 mRNAs. We conclude that in C6 glioma cells the induction of Slc1a1 by ATRA requires the synthesis of RARbeta, suggesting that the receptor is involved in the regulation of the transporter gene.