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Résumé: Selon les estimations au niveau mondial, 5 % des patients porteurs d'une infection chronique virale B (VHB) sont co-infectés par le virus de l'hépatite Delta (VHD) qui est considéré comme l'hépatite virale la plus sévère. Cette co-infection augmente le risque de mortalité hépatique et globale ainsi que le risque de développer un carcinome hépatocellulaire (CHC). Le VHD est un virus défectif qui nécessite l'antigène HBs (AgHBs) pour entrer et sortir des hépatocytes, mais sa réplication et son cycle viral sont indépendants du VHB. Le VHD diminue la réplication du VHB chez la majorité des patients. La connaissance des mécanismes virologiques du VHD permet de comprendre l'histoire naturelle de cette co-infection ainsi que les stratégies de dépistage et de diagnostic. Il existe deux modes de présentation du VHD : soit une infection aiguë VHB/VHD caractérisée par une cytolyse biphasique ; soit une super-infection par le VHD d'un patient porteur d'une infection chronique VHB (traité ou non). Le dépistage de l'ensemble des porteurs d'un AgHBs positif reste primordial et surtout si les patients présentent des facteurs de risque de co-infection : population issue de l'immigration, usagers de drogues intraveineuses, pratiques sexuelles à risque ou co-infection avec le VIH et/ou le VHC. Tout patient porteur d'un AgHBs positif doit avoir une sérologie VHD qui doit être répétée en cas de facteur de risque. En cas de cytolyse aiguë chez un porteur d'une infection chronique VHB, une sérologie VHD doit être réalisée. Toute sérologie positive doit être complétée par une charge virale sérique VHD pour identifier les porteurs d'une infection chronique et discuter un éventuel traitement. Des stratégies de dépistage doivent être mise en place pour dépister l'ensemble des porteurs d'une co-infection. It is estimated that 5% of patients with chronic viral B infection (HBV) are co-infected with hepatitis Delta virus (HDV) worldwide. HDV is considered as the most severe viral hepatitis. This co-infection increases the risk of liver and overall mortality as well as the risk of hepatocellular carcinoma (HCC). HDV is a defective virus that requires HBsAg to enter and exit hepatocytes, but its replication and viral cycle are independent of HBV. HDV decreases HBV replication in most patients. Understanding the virological mechanisms of HDV provides insight into the natural history of this co-infection as well as screening and diagnostic strategies. There are two modes of presentation of HDV infection: either an acute HBV/HDV infection characterized by biphasic cytolysis; or an HDV superinfection of a patient with chronic HBV infection (treated or not). Screening of all HBsAg-positive patients remains essential, especially those with risk factors for co-infection: migrants, intravenous drug users, risky sexual practices, or co-infection with HIV and/or HCV. All patients with positive HBsAg should have an HDV serology test, which should be repeated in case of risk factors. In case of acute cytolysis in a patient with positive HBsAg, an HDV serology must be performed. Any positive serology should be completed by a serum HDV viral load to identify chronically infected patients and discuss possible treatment. Screening strategies should be implemented to identify all co-infected individuals. [ABSTRACT FROM AUTHOR]

La prescription de la dose en radiothérapie est actuellement basée sur des abaques qui ne prennent pas en compte la complexité de la relation patient/dose/effet. Leurs performances prédictives tant sur l'efficacité anti-tumorale que sur la toxicité peuvent être améliorées par l'utilisation de modèles radiobiologiques. C'est dans cette optique qu'ont été développés les modèles de calculs TCP (Tumor Control Probability) et NTCP (Normal Tissue Complication Probability). Leur construction comporte plusieurs étapes importantes utiles à comprendre. La première étape est basée sur les modèles radiobiologiques permettant de définir de manière plus ou moins complexe des taux de cellules survivantes après irradiation. Deux étapes supplémentaires sont nécessaires pour convertir la dose physique en dose biologique équivalente, notamment en dose biologique équivalente à 2 Gy (EQD 2) ; d'une part, pour prendre en compte l'effet du fractionnement de la dose, tant pour le volume cible que les organes à risque, et d'autre part, pour réaliser sa conversion en une dose uniforme qui permet de modéliser l'effet produit par une dose hétérogène sur un organe (dose uniforme équivalente généralisée (gEUD) de Niemierko). Enfin, les modèles radiobiologiques de prédiction des effets cliniques transforment les doses en probabilités de contrôle tumoral (TCP) ou de toxicité (NTCP) en recourant aux paramètres qui rendent compte des caractéristiques radiobiologiques des tissus en question. L'utilisation de ces modèles est encore limitée en pratique courante mais comme les logiciels de radiothérapie en propose l'utilisation, il est important d'en connaître les conditions d'application. In radiotherapy, the dose prescription is currently based on discretized dose-effects records that do not take into fully account for the complexity of the patient-dose-response relationship. Their predictive performance on both anti-tumour efficacy and toxicity can be optimized by integrating radiobiological models. It is with this in mind that the calculation models TCP (Tumor Control Probability) and NTCP (Normal Tissue Complication Probability) have been developed. Their construction involves several important steps that are necessary and important to understand. The first step is based on radiobiological models allowing to calculate according to more or less complexity the rate of surviving cells after irradiation. Two additional steps are required to convert the physical dose into an equivalent biological dose, in particular a 2 Gy equivalent biological dose (EQD2): first to take into account the effect of the fractionation of the dose for both the target volume and the organs at risk; second to convert an heterogeneous dose to an organ into an homogeneous dose having the same effect (Niemierko generalized equivalent uniform dose (gEUD)). Finally, the process of predicting clinical effects based on radiobiological models transform doses into tumour control (TCP) or toxicity (NTCP) probabilities using parameters that reflect the radiobiological characteristics of the tissues in question. The use of these models in current practice is still limited, but since the radiotherapy softwares increasingly integrate them, it is important to know the principle and limits of application of these models. [ABSTRACT FROM AUTHOR]

Liver chronic infections by hepatotropic viruses remain a major health problemworldwide. Hepatitis B, C, andDviruses (HBV,HCV,HDV) are responsible for severe liver damages. In spite of different viral structures and life cycles, they all exclusively infect the liver, suggesting the presence of hepatocyte-specific factors allowing viral infection. If viral life cycles are already well described, the molecular interactions between liver host factors and viral structures remain elusive. Host factors represent promising targets for the development of newantiviral strategies. Recently, the bile acid transporter NTCP, mainly expressed at the cell surface of hepatocytes, was described as the first bona-fide receptor for both HBV and HDV. Moreover, this solute carrier was shown to be involved in the modulation of HCV entry, confirming its importance in liver infection by hepatic viruses. This review summarizes the interactions between NTCP and these three major viruses. [ABSTRACT FROM AUTHOR]

Abstract: Liver metastases are frequently found in oncologic patients. Chemotherapy is the standard treatment in plurimetastatic patients, with the possibility to obtain a clear improvement of their prognosis. Local treatment (surgery, radiofrequency, cryotherapy, radiotherapy, etc.) could be proposed for oligometastatic patients, particularly for those with a good prognosis. Historically, radiation therapy has had a limited role in the treatment of liver metastases because of its toxicity when whole liver irradiation was delivered. Improvements in the knowledge of liver radiobiology and radiopathology as well as technical innovations in delivering radiation therapy are the basis of the modern partial liver irradiation concept. In this historical and therapeutic landscape, extracranial stereotactic radiation therapy is particularly interesting for the treatment of liver metastases. This review summarises published data on stereotactic radiotherapy for the treatment of liver metastases. [Copyright &y& Elsevier]

Abstract: The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radiobiologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation. [ABSTRACT FROM AUTHOR]

Abstract: The a priori evaluation of normal tissue complication probability is an important issue for the radiation oncologist looking for the best therapeutic index. The advances in radiobiological and technological knowledge provide a better understanding of the determinants of radiation effects. The amount of information required to optimize the treatment modalities justifies the use of mathematical models linking the treatment characteristics (dose, volume, treatment time…) to the likelihood of complications. The radiation oncologist needs a minimal understanding of the mathematical models and their limits to justify his prescriptions. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Comparative study between a classical conformational prostate radiotherapy (3DRTC) and two arctherapy techniques, a coplanar (AT-C) and the other non-coplanar (AT-NC). Patients and Methods: The comparison has been made retrospectively on 30 patients with localized prostate cancer (T2-T3a, PSA<20ng/ml, Gleason<7). The objective criteria for comparison were the NTCP, EUD, and dose volume (on DVH), for the volumes of bladder wall, rectal wall, femoral heads, small bowel, prostate (P) and seminal vesicles (VS). The treatment was 46Gy on PTV1 (VS+P+margins), and then an overdose of 30Gy on PTV1 (P+margins). Results: For prostate volumes exceeding 75cm3, arctherapy leads to a decrease in uniformity in the target volume and an increase in the dose received by the femoral heads, this method does not seem appropriate. For prostate volumes less than 75cm3, in addition to the coverage almost tumor, and radiation toxicity equivalent to the bladder and the small intestine, there is a significant increase in the dose to the femoral heads, while the remaining is still within limits, such as clinically tolerable. The contribution of arctherapy is mainly observed at the level of rectal doses. The dose received by 30% of the rectum is reduced by –12% for AT-C and –11.7% for AT-NC, and EUD rectum –5.2% and –4.8%. Conclusion: In this virtual study, the arctherapy seems to generate a true dose reduction in the rectum wall. These results encourage us to continue the investigation for a possible integration in a dynamic clinical routine. [Copyright &y& Elsevier]

Radiotherapy is aimed at getting the best possible therapeutic ratio (tumor local control versus morbidity). Physicists and radiation oncologists have to evaluate explicitly or implicitly the probability of induced complications to normal surrounding tissues. This is based on published data and clinician’s experience. Quantitative methods have been introduced with different models in order to predict the impact of partial or global irradiation on a normal organ. These models correspond to the Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP). These biological models may be useful to evaluate the quality of a treatment planning or for the optimization process. The methodologies used and the clinical data are developed and discussed. [Copyright &y& Elsevier]

Liver chronic infections by hepatotropic viruses remain a major health problem worldwide. Hepatitis B, C, and D viruses (HBV, HCV, HDV) are responsible for severe liver damages. In spite of different viral structures and life cycles, they all exclusively infect the liver, suggesting the presence of hepatocyte-specific factors allowing viral infection. If viral life cycles are already well described, the molecular interactions between liver host factors and viral structures remain elusive. Host factors represent promising targets for the development of new antiviral strategies. Recently, the bile acid transporter NTCP, mainly expressed at the cell surface of hepatocytes, was described as the first bona-fide receptor for both HBV and HDV. Moreover, this solute carrier was shown to be involved in the modulation of HCV entry, confirming its importance in liver infection by hepatic viruses. This review summarizes the interactions between NTCP and these three major viruses.