S-Adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury

Background: Liver toxicity can be observed during treatment with most chemotherapic agents, and represents one of the principal causes of dose reduction or chemotherapy delays. S-Adenosylmethionine (AdoMet) plays a critical role in the synthesis of polyamines and provides cysteine for the production of glutathione (GSH), the major endogenous hepatoprotective agent. Our study was aimed at assessing the protective effect of AdoMet supplementation in cancer chemotherapy-induced liver toxicity. Patients and Methods: Fifty cancer patients who developed, for the first time, anticancer chemotherapy-induced liver toxicity were studied. Enrolled patients received oral AdoMet supplementation. Results: AST, ALT and LDH levels recorded at the moment of the recognition of liver toxicity were significant reduced after one week of AdoMet therapy (respectively p: 0.009, 0.0005 and 0.012). AST, ALT and LDH decrease was confirmed after two weeks of treatment. Furthermore, the effect on these enzyme levels persisted in the following chemotherapy courses, permitting our patients to perform the scheduled chemotherapy courses with a minimal number of dose reductions or administration delays. The efficacy of AdoMet supplementation was not influenced by the presence of liver metastases, and no appreciable side-effects were recognized. Conclusion: The results of our study clearly demonstrate a protective effect of AdoMet in cancer chemotherapy-induced liver toxicity. Further large phase III studies are required to assess the real clinical benefit associated with AdoMet supplementation

A polygenic risk score for progressive non-alcoholic fatty liver disease risk stratification

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Increased burden of inherited IRF3 rare genetic variants in Europeans with severe Non-alcoholic fatty liver diease

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ATG7 genetic variants predispose to severe fatty liver disease

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Drug\u2013drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Societ\ue0 Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0\u20139.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients

Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from \u201cRegistro Politerapia Societ\ue0 Italiana di Medicina Interna (REPOSI)\u201d. Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m2 was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60\u20130.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients