Rafael Martín-Vivaldi

Bio: Rafael Martín-Vivaldi is an academic researcher from Services Hospital. The author has contributed to research in topics: Liver injury & Liver disease. The author has an hindex of 7, co-authored 10 publications receiving 1063 citations.

Model for end-stage liver disease score-based allocation of donors for liver transplantation: a spanish multicenter experience.

Abstract: BACKGROUND Prioritizing the liver transplant waiting list (WL) is subject to great variability. We present the experience of four transplant centers in Andalusia (Southern Spain) with a new consensus model of WL management based on the Model for End-Stage Liver Disease (MELD) score. METHODS The initial criteria for local prioritizing were: a) cirrhosis with MELD score > or =24, and b) all hepatocellular carcinoma (HCC) admitted to the WL. Fourteen months later new criteria were established: a) cirrhosis with MELD score > or =18, and b) uninodular HCC between 3-5 cm or multinodular HCC (2-3 nodules <3 cm). Access to regional priority was scheduled after three months for patients with cirrhosis or six months for patients with HCC. We analyzed the WL mortality rate, posttransplant survival rate, and overall survival rate over three 14-month periods: A (before implementation of priority criteria), B (initial criteria), and C (current criteria). RESULTS Priority was given to 36% of recipients in period B and 47% in period C. The WL mortality rate (including removals from WL) was 12.9%, 12.9%, and 10.7% in periods A, B, and C, respectively. One-year graft survival was 79.7%, 72.6%, and 81.2% in the same periods. The overall one-year survival rate for new cases on the WL was 74.9% in period A, 68.6% in period B, and 82.2% in period C. CONCLUSIONS The allocation system and WL management with the current criteria resulted in lower waiting list mortality without reducing posttransplant survival, leading to better survival for all patients listed.

Flutamide-induced hepatotoxicity: report of a case series.

Abstract: OBJECTIVE To evaluate the characteristics of flutamide induced hepatotoxicity. MATERIAL AND METHODS In this retrospective study we have analyzed all cases of flutamide hepatotoxicity submitted to the Andalucian Registry of drug-induced liver disease. Data were collected using a structured reporting form. Causality assessment was performed using two clinical scales: the standard CIOMS scale and the recently developed Maria and Victorino scale. RESULTS Nine of 185 patients (4.9%) were identified. In 8 male patients, mean age 75 years (range 65-83), flutamide was indicated for palliative therapy of disseminated prostatic carcinoma, and in one young female (14 years) was given for the treatment of facial hirsutism. The mean duration of the flutamide therapy was 151 days (range 4-443). All patients presented with overt liver injury, the most frequent features being asthenia, anorexia, weight loss, nausea, vomiting and jaundice. No patient showed hypersensitivity features. In two patients (22%) the hepatic damage evolved to fulminant liver failure, one of them undergoing a liver transplantation and the other subsequently died. An additional patient died of a non-hepatic related cause when his liver function was improving. Causality assessment by the two clinical scales did not exclude any case, but the two patients who died where classified as unlikely by the Maria and Victorino scale. CONCLUSIONS Flutamide can induce severe acute hepatitis, probably due to an idiosyncratic metabolic mechanism. Liver tests monitoring should probably be mandatory during the first months of flutamide therapy and the drug withdrawn if transaminases began to increase.

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

Abstract: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

Drug-Related Hepatotoxicity

Abstract: Given its rarity, drug-related hepatotoxicity may not be seen during the initial clinical trials of a new medication. After approval, when many more patients are exposed, toxic effects that are very infrequent may emerge. This review explains the difficulties in identifying the cause of hepatotoxic effects in such situations and provides clinical guidance with regard to the detection, evaluation, and possible prevention of drug-related hepatotoxicity.

Guidelines of care for the management of acne vulgaris

Abstract: Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.