Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate "high-" and "low-benefit" patients. To do so, the innovative concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (MELD, alpha-fetoprotein, Milan-Criteria status and radiological response) displayed a high effect in terms of delta-benefit. According to these risk factors, four benefit groups were identified. Patients with three-four factors ("no-benefit group", n=405/2103; 19·2%) had no benefit of LT compared to alternative treatments. Inversely, patients without any risk factor ("large-benefit group", n=108; 5·1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The here presented innovative ITT transplant survival benefit allows to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equal way for organ allocation. Patients with no benefit should be de-listed, whilst patients with large benefit ratio should be prioritized for LT. This article is protected by copyright. All rights reserved

Wolfram syndrome: a clinical and molecular genetic analysis

In water management systems, accurate rainfall forecasting is indispensable for operation and management of reservoir, and flooding prevention because it can provide an extension of lead-time of the flow forecasting. In general, time series prediction has been widely applied to predict rainfall data. The conventional time series prediction models or artificial neural networks can be used to perform this task. However, such models are difficult to interpret by human analyst. From a hydrologist's point of view, the accuracy of the prediction and understanding the prediction model are equally important. This study proposes the use of a Modular Fuzzy Inference System (Mod FIS) to predict monthly rainfall data in the northeast region of Thailand. The experimental results show that the proposed model can be a good alternative method to provide both accurate results and human-understandable prediction mechanism

Altered hepatic BMP signaling pathway in human HFE hemochromatosis.

Human hemochromatosis (HC) has been associated with the common C282Y polymorphism of HFE or rare pathogenic mutations of TfR2, HJV, FPN and HAMP. All forms of human HC seem to be caused by low or inadequate levels of hepcidin, the iron hormone. We and others have recently shown that Hfe(-/-) mice exhibit an impairment in the bone morphogenetic protein (BMP) signaling pathway controlling hepcidin. However, all data indicating the central role of BMPs in hepcidin regulation and an impaired BMP/SMAD signaling in HC have been collected in mice. In this study we investigated whether also in humans the expression of BMP signaling targets, SMAD7 and Id1, are associated with liver iron concentration (LIC) and whether such regulation is disrupted in HFE-HC. We correlated the mRNA expression, assessed by RT-PCR, of HAMP, SMAD7 and Id1 with LIC in liver biopsies from patients with normal iron status. HFE-HC or non-HC hepatic iron overload. We found that in human liver, not only HAMP, but also SMAD7 and Id1 mRNA significantly correlate with the extent of hepatic iron burden. However, this correlation is lost in patients with HFE-HC, but maintained in subjects with non-hemochromatotic iron overload. These data indicate that in human HFE-HC a disrupted BMP/SMAD signaling in the liver is key in the pathogenesis of the disease

Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment. A multicenter European experience

During the last decades, several risk factors for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) have been investigated. However, the impact of two important drivers of oncogenesis, namely the immunosuppression and the treatment of acute cellular rejection (ACR) have been marginally addressed. This study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT population