Langerhans cell histiocytosis (LCH) is a disease whose physiopathology remains unclear, involving both inflammatory processes and clonal proliferation. It is observable at any given age, although about ten times more frequent in children than adults. Hepatic involvement is not rare, mostly part of a systemic disease, and linked to a poor prognosis. We report here a case of LCH with solitary hepatic involvement in a 74 year-old patient. This case demonstrated molecular anomaly of the MAPK pathway, BRAF N486_P490del. Through this observation, we precise the epidemiological and histological aspects and diagnostic criteria of this rare disease.

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OBJECTIVE: Semaglutide and liraglutide are glucagon-like peptide-1 (GLP-1)-based diabetes drugs. Semaglutide possesses a longer half-life. Utilizing relatively lower doses, we compared the beneficial metabolic effects of these 2 drugs in mice fed a high-fat diet (HFD), aiming to deepen our mechanistic understanding on their energy homeostatic functions.
METHODS: Male C57BL/6J mice were fed an HFD for 10 weeks, followed by daily phosphate-buffered saline (PBS, as control); liraglutide (150 μg/kg body weight); or semaglutide (12 μg/kg body weight, low dose [LD]; or 60 μg/kg body weight, high dose [HD]) injection for 4 weeks. Metabolic tolerance and other tests were conducted within the 4-week period. Expression of metabolism-related genes, including Fgf21 in the liver and adipose tissues, was assessed after mice were euthanized.
RESULTS: HFD-induced body weight gain, increasing inguinal fat tissue mass, glucose defects and insulin intolerance were effectively and comparably attenuated in the 3 experimental groups. HD semaglutide showed an even better effect on attenuating hyperleptinemia. Liraglutide but not semaglutide treatment enhanced hepatic fibroblast growth factor 21 (FGF21) protein level. All 3 experimental groups showed elevated expression of genes that encode pyruvate dehydrogenase kinase 4 and enoyl-CoA hydratase and 3-hydroxyacyl-coenzyme A dehydrogenase, associated with reduced plasma triglyceride levels. Finally, the plasma \"GLP-1\" level in HD semaglutide-treated mice was 14-fold higher than in HFD-fed control mice.
CONCLUSIONS: Liraglutide, but not semaglutide, increased hepatic FGF21 protein level, whereas semaglutide had a greater effect on attenuating hyperleptinemia. Thus, these 2 GLP-1-based diabetes drugs may target metabolic organs, including liver and adipose tissue, with differing levels of efficacy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy \"under stereotaxic conditions\". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

Ischemia-reperfusion injury (IRI) is typically associated with a vigorous inflammatory and oxidative stress response to hypoxia and reperfusion that disturbs the function of the organ. The remote effects of renal IRI on the liver, however, require further study. Renal damage associated with liver disease is a common clinical problem. Colchicine, a polymerization inhibitor of microtubules, has been used as an anti-inflammatory and anti-fibrotic drug for liver diseases. The goal of the current study was to investigate the possible protective mechanisms of colchicine on liver injury following renal IRI. Forty rats were divided randomly into four groups: sham group, colchicine-treated group, IRI group, and colchicine-treated + IRI group. Treatment with colchicine significantly reduced hepatic toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) transcription factor, myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-alpha (TNF-α) contents; downregulated BCL2 associated X apoptosis regulator (BAX) gene expression, transforming growth factor-β (TGF-β) content, and upregulated hepatic B cell lymphoma 2 (Bcl-2) gene expression as compared with the IRI group. Finally, hepatic histopathological examinations have confirmed the biochemical results. Renal IRI-induced liver damage in rats was alleviated by colchicine through its anti-inflammatory, anti-apoptotic, and anti-fibrotic actions.

BACKGROUND: This case report describes a 12-year-old female spayed mixed-breed dog referred for treatment of a large, inoperable hepatocellular carcinoma. A computed tomography (CT) scan confirmed the previous ultrasonographic and laparoscopic findings of a large, lobulated, poorly defined mass on the left and central aspect of the liver. Multiple biopsies confirmed the diagnosis of hepatocellular carcinoma. Due to the large extent of the tumor, the vascular association to the Vena cava caudalis and the associated high risk of intraoperative bleeding, a resection of the mass was refrained from and a radiotherapeutic treatment was chosen. The dog underwent radiation therapy (RT) with a 6MV linear accelerator with 5×6 Gy, total dose 30 Gy. In the follow up examinations three months and one year after therapy, the dog presented in normal condition and had normal Alanine-amino-transferase (ALT) and alkaline phosphatase (AP). The tumor size measured in the CT-examinations decreased by 61% and 90%, respectively. Two years after radiation therapy the dog has a normal general condition and liver enzymes are within the normal limits.
BACKGROUND: Dieser Fallbericht beschreibt eine 12-jährige weiblich-kastrierte Mischlingshündin, die aufgrund eines grossen, inoperablen hepatozellulären Karzinoms überwiesen wurde. Eine Computertomographie (CT) bestätigte die bereits zuvor ultrasonographisch und laparoskopisch erhobenen Befunde einer grossen, lobulierten, unscharf begrenzten Masse links und zentral in der Leber. Durch mehrere Biopsien konnte die Diagnose eines hepatozellulären Karzinoms gestellt werden. Aufgrund der Lokalisation in mehreren Leberlappen sowie der Nähe zur Vena cava caudalis war eine chirurgische Exzision nicht möglich. Der Hund wurde mittels Strahlentherapie mit einem 6MV Linearbeschleuniger mit 5×6 Gy, Totaldosis 30 Gy, behandelt. Bei den Nachuntersuchungen drei und zwölf Monate nach Ende der Strahlentherapie zeigten die CT-Bilder des Abdomens eine partielle Remission des Tumors mit einer Reduktion des Tumorvolumens um 61% bzw. 90%. Die Hündin hat heute, zwei Jahre nach Ende der Bestrahlung, ein normales Allgemeinbefinden und die Leberwerte liegen im Normalbereich.
BACKGROUND: Ce rapport décrit le cas d’une chienne de race mixte, stérilisée, âgée de 12 ans et référée pour traitement d’un important carcinome hépatocellulaire inopérable. Une tomodensitométrie (TDM) a confirmé les résultats échographiques et laparoscopiques antérieurs, à savoir une grande masse mal définie sur la partie gauche et centrale du foie. De multiples biopsies ont confirmé le diagnostic de carcinome hépatocellulaire. En raison de l’étendue de la tumeur, de l’association à la veine cave caudale et du risque élevé associé d’hémorragies peropératoires, on a renoncé à une résection de la masse et un traitement radiothérapeutique a été choisi. Le chien a subi une radiothérapie (RT) avec un accélérateur linéaire de 6 MV avec 5 × 6 Gy, dose totale 30 Gy. Lors des examens de suivi, trois mois et un an après le traitement, le chien présentait un état normal et avait une alanine-amino­-transférase (ALT) et une phosphatase alcaline (PA) normales. La taille de la tumeur mesurée lors des examens tomodensitométriques avait diminué de 61% respectivement de 90%. Deux ans après la radiothérapie, le chien présente un état général normal et les enzymes hépatiques sont dans la norme.
BACKGROUND: Questo caso clinico descrive un cane di razza mista femmina sterilizzato di 12 anni che è stato riferito per un grande carcinoma epatocellulare inoperabile. La tomografia computerizzata (TC) ha confermato i precedenti reperti ecografici e laparoscopici di una grande massa lobulata e indistinta a sinistra e al centro del fegato. La diagnosi di carcinoma epatocellulare è stata fatta attraverso diverse biopsie. L’asportazione chirurgica non è stata possibile a causa della sua posizione in diversi lobi del fegato e della sua vicinanza alla vena cava caudale. Il cane è stato trattato con radioterapia con acceleratore lineare 6 MV con 5 × 6 Gy, dose totale 30 Gy. Agli esami di follow-up a tre mesi e un anno dopo la terapia, il cane presentava condizioni normali e aveva dei valori normali di alanina-amino-transferasi (ALT) e di fosfatasi alcalina (AP). La dimensione del tumore, misurata durante gli esami TAC, era diminuita del 61% e risp. del 90%. Oggi, a due anni dalla fine della radioterapia, la cagna ha una condizione generale normale e i valori del fegato sono nella norma.

OBJECTIVE: In patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact.
METHODS: We enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5Gy in 16 fx) or standard fractionated (50Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10-16Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment.
RESULTS: A significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P=0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count\'s evolution was observed (P<0.025).
CONCLUSIONS: With the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.

Haemangioma is the most frequent benign hepatic tumour. Haemangioma is generally asymptomatic but it can sometimes cause disabling symptoms depending on its size and location. Surgery and interventional radiology are the cornerstone of the treatment in this situation. Radiation therapy, already used with good efficacy and safety to treat hepatic malignant lesions as hepatocarcinoma and metastases, is a relevant option in case of contraindication to surgery because of multiple or very large lesions. In this context, we report the case of a patient presenting with multiple symptomatic hepatic haemangiomas, successfully treated by radiation therapy in our department. These good results justified a review of the literature to report series of patients treated in this indication and to describe the main treatment regimens used.

BACKGROUND: Clinical symptoms are mostly unspecific in hepatic diseases, thus most clinical examinations are of limited benefit in the diagnosis of hepatic diseases and often only general statements can be made about parenchymal damage or loss of function. In contrast, sonography of the liver can provide information about the type of lesion and thus also about the prognosis for the animal. A systematic assessment of organ size, parenchymal, vascular and bile duct system structures can facilitate to make possible findings. Sonography is also used in further diagnostics such as liver biopsy or chole-cystocentesis. This review describes the basic procedure for the sonographic examination in ruminants and camelids on the basis of selected findings relevant to the clinical veterinarian. In addition, potential and limits of additional diagnostics are discussed.
BACKGROUND: Aufgrund meist unspezifischer Symptomatik der meisten Lebererkrankungen ist der diagnostische Wert vieler klinischer Untersuchungen limitiert, wobei in der Regel nur allgemeine Aussagen zu Parenchymschädigungen oder Funktionsverlust getroffen werden können. Demgegenüber kann die Sonographie der Leber Aufschluss über die Art der Läsion und damit auch über die Prognose des Tieres geben. Durch eine systematische Beurteilung von Organgrösse, parenchymaler Struktur und von Strukturen des Gefäss- und Gallengangsystems kann dabei die Ableitung möglicher Befunde erleichtert werden. Zudem findet die Sonographie Anwendung bei weiterführender Diagnostik wie Leberbiopsie oder Cholezystozentese. Diese narrative Übersichtsarbeit erläutert die grundsätzliche Vorgehensweise bei der sonographischen Untersuchung anhand ausgewählter Befunde beim Wiederkäuer und Kameliden, die für den praktizierenden Tierarzt relevant erscheinen. Zudem wird auf Möglichkeiten und Limitationen ergänzender Diagnostik eingegangen.
BACKGROUND: Dans les maladies hépatiques, les symptômes cliniques sont pour la plupart non spécifiques et la plupart des examens cliniques sont d’un bénéfice limité pour le diagnostic; souvent seules des considérations générales peuvent être faites sur les lésions parenchymateuses ou la perte de fonction. En revanche, l’échographie du foie peut fournir des informations sur le type de lésion et donc également sur le pronostic pour l’animal. Une évaluation systématique de la taille de l’organes, des structures des systèmes parenchymateux, vasculaire et biliaire peut faciliter le ciblage des résultats possibles. L’échographie est également utilisée dans d’autres diagnostics tels que la biopsie hépatique ou la cholécystocentèse. Cette revue explique la procédure de base de l’examen échographique chez les ruminants et les camélidés sur la base de résultats sélectionnés, pertinents pour le vétérinaire praticien. De plus, le potentiel et les limites des méthodes de diagnostic supplémentaires sont discutés.
BACKGROUND: Il significato diagnostico di molti esami clinici è limitato a causa di sintomi non specifici nella maggior parte delle malattie epatiche. Per questo motivo si possono solo fare delle constatazioni di ordine generale sui danni parenchimali o sulla perdita della funzione. Al contrario l’ecografia del fegato offre delle informazioni sul tipo della lesione e quindi sulla prognosi per l’animale. Via una valutazione sistematica delle dimensioni dell’organo, della struttura parenchimale e delle strutture dei sistemi vascolare e biliare si possono facilmente determinare i possibili risultati. L’ecografia viene pure utilizzata per ulteriori procedure diagnostiche come la biopsia del fegato o la colecistocentesi. Questa panoramica illustra la procedura di base dell’esame ecografico sulla base di risultati selezionati nei ruminanti e nei camelidi che possono risultare rilevanti per il veterinario. Inoltre, si sono discusse le possibilità e i limiti di una diagnostica complementare.

Chronic endurance exercise is a therapeutic strategy in the treatment of many chronic diseases in humans, including the prevention and treatment of metabolic diseases such as diabetes mellitus. Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified. In the liver, however, the cellular and molecular pathways that are modified by exercise and have preventive or therapeutic relevance to metabolic disease need to be elucidated. The mouse model used in the current study allows for the quantification of a human-relevant exercise \"dosage\". In this study we show hepatic gene expression differences between sedentary female and sedentary male mice and that chronic exercise modifies the transcription of hepatic genes related to metabolic disease and steatosis in both male and female mice. Chronic exercise induces molecular pathways involved in glucose tolerance, glycolysis, and gluconeogenesis while producing a decrease in pathways related to insulin resistance, steatosis, fibrosis, and inflammation. Given these findings, this mouse exercise model has potential to dissect the cellular and molecular hepatic changes following chronic exercise with application to understanding the role that chronic exercise plays in preventing human diseases. Novelty: Exercise modifies the hepatic gene expression and hepatic pathways related to metabolic disease in male and female mice. Sex differences were seen in hepatic gene expression between sedentary and exercised mice. The mouse exercise model used in this study allows for application and evaluation of exercise effects in human disease.