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Purpose: 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., Patients and 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)., Conclusion: 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., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

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.

Ischemia-reperfusion injury (IRI) induces an inflammatory response and production of reactive oxygen species, which affects the organs remote to the sites of renal IR. However, remote effects of renal IRI on the liver need further investigations. Renal injury associated with liver disease is a common clinical problem. Colchicine is an established drug for microtubule stabilization that may reduce tissue injury and has antioxidant and antiinflammatory effects. The aim of the present study was ( i ) to assess the hepatic changes after induction of renal IRI, ( ii ) to explore the possible protective effect of colchicine on liver injury following renal IRI, and ( iii ) to investigate the possible mechanisms underlying the potential effect. Forty rats were randomly divided into four groups: sham operation group, colchicine-treated group, IR group, and colchicine-treated IR group. Colchicine treatment improved liver function (ALT/AST) after renal IRI, decreased hepatic oxidative stress and cell apoptosis by reducing hepatic MDA, upregulating hepatic total antioxidant capacity, Nrf2, and HO-1. Furthermore, colchicine inhibited inflammatory responses by downregulating hepatic NLRP3 inflammasome, IL-1β, and caspase-1. Colchicine attenuates renal IRI-induced liver injury in rats. This effect may be due to reducing inflammation and oxidative stress markers.

Ketogenic diets (KDs) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise is unknown. We investigated the effects of a KD versus a "western" diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to 3 groups ( n = 8-14 per group): standard chow (SC; 17% fat), WD (42% fat), or KD (90.5% fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD versus SC, although KD females displayed lower BF% versus WD ( p ≤ 0.05). Liver triglycerides were higher in KD and WD versus SC but were attenuated in KD females versus WD ( p ≤ 0.05). KD suppressed hepatic markers of de novo lipogenesis (fatty acid synthase, acetyl coenzyme A carboxylase) and increased markers of mitochondrial biogenesis/content (peroxisome proliferator activated receptor-1α, mitochondrial transcription factor A (TFAM), and citrate synthase activity). KD also increased hepatic glutathione peroxidase 1 and lowered oxidized glutathione. Female rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (light chain 3 II/I ratio, autophagy-related protein 12:5), and cellular energy homeostasis (phosphorylated 5'AMP-activated protein kinase/5'AMP-activated protein kinase) versus males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation. Novelty KD feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, and increased markers of mitochondrial content versus WD feeding. Males and females responded similarly to combined KD feeding and exercise. Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats.

Fibroblast growth factor 21 (FGF21), follistatin and leukocyte cell-derived chemotaxin 2 (LECT2) are novel hepatokines that are modulated by metabolic stresses. This study investigated whether exercise intensity modulates the hepatokine response to acute exercise. Ten young, healthy men undertook three 8-h experimental trials: moderate-intensity exercise (MOD; 55% peak oxygen uptake), high-intensity exercise (HIGH; 75% peak oxygen uptake), and control (CON; rest), in a randomised, counterbalanced order. Exercise trials commenced with a treadmill run of varied duration to match gross exercise energy expenditure between trials (MOD vs HIGH; 2475 ± 70 vs 2488 ± 58 kJ). Circulating FGF21, follistatin, LECT2, glucagon, insulin, glucose and nonesterified fatty acids (NEFA) were measured before exercise and at 0, 1, 2, 4, and 7 h postexercise. Plasma FGF21 concentrations were increased up to 4 h postexercise compared with CON ( P ≤ 0.022) with greater increases observed at 1, 2, and 4 h postexercise during HIGH versus MOD ( P ≤ 0.025). Irrespective of intensity ( P ≥ 0.606), plasma follistatin concentrations were elevated at 4 and 7 h postexercise ( P ≤ 0.053). Plasma LECT2 concentrations were increased immediately postexercise ( P ≤ 0.046) but were not significant after correcting for plasma volume shifts. Plasma glucagon (1 h; P = 0.032) and NEFA (4 and 7 h; P ≤ 0.029) responses to exercise were accentuated in HIGH versus MOD. These findings demonstrate that acute exercise augments circulating FGF21 and follistatin. Exercise-induced changes in FGF21 are intensity-dependent and may support the greater metabolic benefit of high-intensity exercise.

Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 μU/mg vs. control groups, 3.6 ± 0.6 μU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines' concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.

This study examined the effects of vanadyl sulfate (VOSO 4 ) on the livers of nondiabetic and streptozotocin-induced diabetic rats. Rats were divided into 6 groups. Groups 1, 2, and 3 consisted of nondiabetic rats that were, respectively, control animals or those receiving an intraperitoneal (i.p.) injection of either 5 or 10 mg·kg -1 (i.p.) VOSO 4 for 30 days. Groups 4, 5, and 6 consisted of diabetic animals that were, respectively, control animals or those treated with 5 or 10 mg·kg -1 (i.p.) VOSO 4 for 30 days. Results showed that VOSO 4 reduced body mass in nondiabetic rats, whereas it increased body mass in diabetic groups. Plasma transaminases (aspartate aminotransferase, alanine aminotransferase), lactate dehydrogenase, and alkaline phosphatase activities and malondialdehyde levels were increased, while liver catalase and superoxide dismutase activities were profoundly decreased in diabetic animals in comparison with enzyme activities in the nondiabetic group. Rats in the diabetic group also showed notable oxidative damage to the liver. Treatment of diabetic rats with VOSO 4 decreased the hepatotoxic markers, significantly restored the activities of antioxidant enzymes, and attenuated histopathological changes in liver tissue. In nondiabetic rats, VOSO 4 treatment increased most of the hepatotoxic markers, reduced antioxidant enzyme activities, and induced pronounced oxidative damage in liver tissue. These data suggest that treatment with VOSO 4 exerts toxic effects in healthy animals and significantly prevents liver oxidative damage in streptozotocin-induced diabetic rats, but without total safety. Further studies are needed to clarify its mechanism of action.

Oxidative stress is involved in the development of various cancers. In the present study, the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive and curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) considered as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP; aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin also decreased TBARS content. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination.

Objectives: Consumption of Vitis vinifera seed has been reported to ameliorate liver pathology in diabetes mellitus; however, the mechanisms underlying its effects remain unknown. In this study, the anti-inflammatory, anti-apoptotic and pro-proliferative effects of the ethanolic seed extract of V. vinifera (VVSEE) in the liver in cases of diabetes were identified., Methods: Adult male rats with streptozotocin-nicotinamide-induced diabetes were given 50, 100 or 200 mg/kg body weight VVSEE orally for 28 days. At the end of the treatment, body weights were determined, and the blood was collected for analyses of fasting blood glucose, insulin and liver enzyme levels. Following sacrifice, livers were harvested and their wet weights and glycogen contents were measured. Histologic appearances of the livers were observed under light microscopy, and the expression and distribution of inflammatory, apoptosis and proliferative markers in the livers were identified by molecular biologic techniques., Results: Treatment of rats with diabetes by VVSEE attenuates decreased body weight, liver weight and liver glycogen content. Additionally, increases in fasting blood glucose levels and liver enzyme levels and decreases in serum insulin levels were ameliorated. Lesser histopathologic changes were also observed: decreased inflammation and apoptosis, as indicated by decreased levels of inflammatory markers (TNF-α, NF-Kβ, IKK-β, IL-6, IL-1β) and apoptosis markers (caspase-3, caspase-9 and Bax). VVSEE treatment induces increase in hepatocyte regeneration, as indicated by increased PCNA and Ki-67 distribution in the livers of rats with diabetes. Several molecules identified in VVSEE via gas chromatography mass spectrometry might contribute to these effects., Conclusions: The anti-inflammatory, anti-apoptotic and pro-proliferative effects of VVSEE could account for its hepatoprotective actions in diabetes., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Liver ischemia-reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary nonfunction after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to 1 h of partial warm ischemia (70%) followed by 6 h of reperfusion. Before ischemia, rats were treated with saline (IR group), Olp (Olp group), or Olp with Akt inhibitor LY294002 (Olp plus LY group). After reperfusion, hepatic injury (transaminase activities), mitochondrial damage (glutamate dehydrogenase activity), oxidative stress (malondialdehyde and glutathione concentrations and catalase and superoxide dismutase activities), and protein kinase Akt activation were evaluated. Rat treatment with Olp reduced liver injury, prevented mitochondrial damage, decreased lipid peroxidation, and enhanced antioxidant enzymes. Also, Olp induced a significant activation in protein kinase Akt. Inhibition of Akt with LY294002 abolished all of the protective effects of Olp. In conclusion, Olp treatment may be an effective strategy in reducing liver IR injury through oxidative stress prevention and Akt activation.

Atorvastatin (ATO) was commonly used to lower blood cholesterol, but it caused harmful effects to organs, including the liver. Thymoquinone (TQ), a prominent constituent of Nigella sativa, has antioxidant, antiinflammatory, antiapoptotic, antimicrobial, and anticancer activity. The current study investigated the mechanism of ATO-induced hepatotoxicity, whether posttreatment TQ could reverse ATO-induced hepatic injury, and the mechanism of action of TQ as a hepatoprotective agent. Forty adult male Sprague Dawley rats were divided into four equal groups: control, TQ-treated, ATO-treated, and combined ATO/TQ-treated. Rats were treated for 8 weeks and 10 days and euthanized by cervical dislocation 3 days after the last treatment. Blood samples and livers were tested for liver enzymes, oxidative stress, and apoptosis markers and used for histopathological and ultrastructural examination. The ATO-treated group showed an increase in liver enzymes, decreases in reduced glutathione and catalase, and increases in the malondialdehyde lipid peroxidation marker, protein carbonylation, and caspase 3 activity. Posttreatment TQ in the ATO/TQ-treated group seemed to reverse these changes. Histopathological and ultrastructural examination supported these data. Results from the current study suggested that posttreatment TQ may reverse oxidative stress injury in rat liver produced by ATO, suggesting a potential clinical application of using TQ to prevent ATO-induced hepatic injury.

The aim of this study was to investigate the protective effect of Mentha spicata supplementation against nicotine-induced oxidative damage in the liver and erythrocytes of Wistar rats. Bioactive substances were determined by liquid chromatography - electrospray ionization - tandem mass spectrometry analysis. Animals were divided into 4 groups of 6 rats each: a normal control group, a nicotine-treated group (1 mg/kg), a group receiving M. spicata extract (100 mg/kg), and a group receiving both M. spicata extract (100 mg/kg) and nicotine (1 mg/kg). Many phenolic acids were identified in the M. spicata aqueous extract. After 2 months of treatment, nicotine induced an increase in the level of white blood cells and a marked decrease in erythrocytes, hemoglobin, and haematocrit. Aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities were also found to be higher in nicotine-treated group than those of the control group. Furthermore, nicotine-treated rats exhibited oxidative stress, as evidenced by a decrease in antioxidant enzymes activities and an increase in lipid peroxidation level in liver and erythrocytes. Interestingly, the oral administration of M. spicata extract by nicotine-treated rats alleviated such disturbances. M. spicata contained bioactive compounds that possess important antioxidant potential and protected liver and erythrocytes against nicotine-induced damage.

The use of dietary supplements to enhance the benefit of exercise training is a common practice. The liver is the organ where all substances are metabolized, and certain supplements have been associated with liver injury. Vitamin A (VA), a liposoluble vitamin stored in the liver, is commonly used as an antioxidant supplement. Here, we evaluated the effect of chronic VA supplementation on oxidative damage and stress parameters in trained rats. Animals were divided into the following groups: sedentary (SE), sedentary/VA (SE+VA), exercise training (ET), and exercise training/VA (ET+VA). During 8 weeks, animals were subjected to swimming (0%, 2%, 4%, 6% body weight) for 5 days/week and a VA daily intake of 450 retinol equivalents/day. Parameters were evaluated by enzymatic activity analysis, ELISA, and Western blotting. VA caused liver lipid peroxidation and protein damage in exercised rats and inhibited the increase in HSP70 expression acquired with exercise alone. The ET group showed higher levels of antioxidant enzyme activity, and VA inhibited this adaptation. Expression of the pro-inflammatory cytokines, interleukin (IL)-1β, and tumor necrosis factor-α was reduced in the ET+VA group, while the anti-inflammatory cytokine, IL-10, was increased. Western blotting showed that both exercised groups had lower levels of the receptor for advanced glycation end products, suggesting that VA did not affect this receptor. Our study demonstrated that, although VA caused oxidative damage, a controlled administration might exert anti-inflammatory effects. Further studies with higher VA doses and longer ET interventions would elucidate more the effects of the supplementation and exercise on liver parameters.

The liver is an essential organ that ensures many vital functions such as metabolism of bilirubin, glucose, lipids, synthesis of coagulation factors, destruction of many toxins, etc. The hepatic parenchyma can be irradiated during the management of digestive tumors, right basithoracic, esophagus, abdomen in toto or TBI. In addition, radiotherapy of the hepatic area, which is mainly stereotactic, now occupies a central place in the management of primary or secondary hepatic tumors. Irradiation of the whole liver, or part of it, may be complicated by radiation-induced hepatitis. It is therefore necessary to respect strict dosimetric constraints both in stereotactic and in conformational irradiation in order to limit the undesired irradiation of the hepatic parenchyma which may vary according to the treatment techniques, the basic hepatic function or the lesion size. The liver is an organ with a parallel architecture, so the average tolerable dose in the whole liver should be considered rather than the maximum tolerable dose at one point. The purpose of this article is to propose a development of dose recommendations during conformation or stereotactic radiotherapy of the liver., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The aim of this study was to investigate whether (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) protects against hepatotoxicity induced by thioacetamide (TAA). On the first day of treatment, male adult Wistar rats received BPD (10 or 50 mg·kg -1 ). On the second day, the rats received a single intraperitoneal injection of TAA (400 mg·kg -1 ). Twenty-four hours after TAA administration, biochemical determinations and liver histological analysis were carried out. BPD (50 mg·kg -1 ) reduced plasma aspartate and alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities increased by TAA exposure. Treatment with BPD was effective against increased lipid peroxidation levels and attenuated a decrease in hepatic reduced glutathione and ascorbic acid levels as well as an inhibition of glutathione peroxidase activity caused by TAA exposure. The higher dose of BPD protected against the inhibition of hepatic δ-aminolevulinic dehydratase activity induced by TAA. Finally, histopathological examination of the liver showed that BPD markedly ameliorated TAA-induced hepatic injury. In conclusion, BPD protected against hepatotoxicity and oxidative stress caused by TAA exposure in rats.

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

Stress affects many organs in addition to the brain, including the liver. We assessed the effects on the liver of blocking N-methyl-d-aspartate (NMDA) glutamate receptors with memantine in acute and repeated restraint stress. Forty-two male albino rats were divided into 7 groups; control, acute restraint stress (ARS), ARS + memantine, repeated restraint stress, repeated restraint + memantine, and positive control groups. We measured serum iron, zinc, alanine transferase and aspartame transferase, hepatic malondialdehyde, tumor necrosis factor-α (TNF-α), glutathione peroxidase, superoxide dismutase, metallothionein content, zinc transporter ZRT/IRT-like protein 14 mRNA expression, and hepcidin expression. We conducted a histopathological evaluation via histological staining and immunostaining for glial fibrillary acidic protein and synaptophysin expression, both of which are markers of hepatic stellate cell (HSC) activation. Both ARS and repeated stress increased markers of hepatic cell injury, oxidative stress, and HSC activation. Blocking NMDA with memantine provided a hepatoprotective effect in acute and repeated restraint stress and decreased hepatic cell injury, oxidative stress, and HSC activation.

Olanzapine, an antipsychotic drug, is used to treat depressive disorder, but its effects on the liver, the main site of drug metabolism, still remain elusive. We studied the effects of 3 weeks of olanzapine treatment (7.5 mg/kg per day) on the malondialdehyde (MDA) and protein carbonyl (PCO) contents, protein expression of copper/zinc superoxide dismutase (CuZnSOD), and activity of total superoxide dismutase (SOD), as well as catalase (CAT) protein expression and activity levels in the liver cytosol of rats exposed to 6 weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behaviors. Increased cytosolic MDA in CSIS rats (vehicle- or olanzapine-treated) indicated hepatic oxidative stress. Increase in PCO and CAT activity associated with unchanged total SOD activity following CSIS also confirm the presence of oxidative stress. Chronic olanzapine treatment in CSIS prevented increase in PCO without an effect on MDA content. Increased SOD activity in olanzapine-treated (controls and CSIS) groups compared with corresponding vehicle-treated groups and decreased CAT activity in olanzapine-treated CSIS rats compared with vehicle-treated CSIS group was found. The data suggest that chronic olanzapine treatment has a protective effect on hepatic protein oxidation and improves antioxidant defense. The beneficial effects of olanzapine may be due to its free radical scavenging properties and antioxidant activity.

Sirtuins (SIRT1-SIRT7) are a family of NAD + -dependent protein deacetylases that are linked to post-translational regulation of many metabolic processes. There are few reports available for chicken sirtuins (designated cSIRT1-cSIRT7), whose expression and regulation in the liver have yet to be explored. In the present study, we characterized the expression and regulation of sirtuin family members in chicken liver. The results showed that the sirtuin family members in chicken share the same conserved functional SIR2 domains. All the sirtuin family members were expressed extensively in all tissues examined, and the expression levels of cSIRT1, cSIRT2, cSIRT4, cSIRT6, and cSIRT7 in the liver increased significantly with sexual maturity. However, all sirtuin family members were downregulated (P < 0.05) in chicken livers and cultured primary hepatocytes treated with 17β-estradiol. We concluded that the expression levels of some chicken sirtuin family members in the liver were upregulated with sexual maturation, but might not be regulated directly by estrogen. Whereas estrogen could be used as an inhibitor of all sirtuins, both in vivo and in vitro.

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

The inflammation induced by obesogenic diets is associated with deposition of fat in the liver. On the other hand, anti-inflammatory and immunosuppressive therapies may impact in body fat storage and in liver lipid dynamics. It is important to study specific inflammatory mediators in this context, since their role on hepatic damage is not fully clarified. This study aimed to evaluate the role of interleukin (IL)-18 and tumor necrosis factor (TNF) receptor in liver dysfunction induced by diet. Male C57BL/6 wild-type (WT), IL-18, and TNF receptor 1 knockout mice (IL-18 -/- and TNFR1 -/- ) were divided according to the experimental diets: chow diet or a high-refined carbohydrate-containing diet. Alanine aminotransferase was quantified by colorimetric analysis. Total fat content in the liver was determined by Folch methods. Levels of TNF, IL-6, IL-4, and IL-13 in liver samples were measured by ELISA assay. IL-18 and TNFR knockout mice fed with chow diet showed higher liver triglycerides deposition than WT mice fed with the same diet (WT: 131.9 ± 24.5; IL-18 -/- : 239.4 ± 38.12*; TNF -/- : 179.6 ± 50.45*; *P < 0.01). Furthermore, these animals also showed a worse liver histopathological score and lower levels of TNF, IL-6, IL-4, and IL-13 in the liver. Interestingly, treatment with a high-carbohydrate diet did not exacerbate liver damage in IL-18 -/- and TNFR1 -/- mice. Our data suggest that IL-18 and TNF may be involved on hepatic homeostasis mainly in a context of a healthy diet.

It has been known for centuries that regularly performed exercise has beneficial effects on metabolic health. Owing to its central role in locomotion and the fact that it accounts for a large majority of whole-body glucose disposal and fatty acid oxidation, the effects of exercise on skeletal muscle has been a central focus in exercise physiology research. With this being said it is becoming increasingly well recognized that both adipose tissue and liver metabolism are robustly modified by exercise, especially in conditions of obesity and insulin resistance. One of the difficult questions to address is if the effects of exercise are direct or occur secondary to exercise-induced weight loss. The purpose of this review is to highlight recent work that has attempted to tease out the protective effects of exercise, or intrinsic aerobic capacity, against metabolic and inflammatory challenges as it relates to the treatment and prevention of obesity and insulin resistance. Recent studies reporting improvements in liver and adipose tissue insulin action following a single bout of exercise will also be discussed. The research highlighted in this review sheds new insight into protective, anti-inflammatory effects of exercise that occur largely independent of changes in adiposity and body weight.

The objective of this study was to investigate the protective effects of pomegranate (Punica granatum) juice (PGJ) on oxidative damages in liver tissue and erythrocytes of rats intoxicated by sodium fluoride (NaF). Rats were randomly divided into two groups: group I received standard diet and group II received orally 1 mL of PGJ. After 5 weeks of pretreatment, each group was divided again into two subgroups and treated for another 3 weeks as follows: group I was subdivided into a control group and a group that was treated with 100 ppm of NaF (in drinking water); group II was subdivided into one group that was treated daily with both 100 ppm NaF and PGJ (1 mL orally) and one that received daily 1 mL of pomegranate juice. Exposure to NaF decreased hematological parameters, changed the total protein, albumin, bilirubin levels, and increased the activities of hepatic marker enzymes. We also noted an increase in lipid peroxidation contents, accompanied by a decrease of reduced glutathione levels. Antioxidant enzyme activities in both tissues were modified in the NaF group compared with the control group. However, the administration of PGJ juice caused an amelioration of the previous parameters. Our results indicated the potential effects of NaF to induce oxidative damage in tissues and the ability of PGJ to attenuate NaF-induced oxidative injury.

The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg·kg(-1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves)·kg(-1)·day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide-induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis.

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

The aim of the present study was to investigate whether hydrocortisone induces oxidative stress in hepatocytes and to evaluate the possible ameliorative effect of thymol against such hepatic injury. Twenty-four adult male rats were divided into control, thymol, hydrocortisone, and hydrocortisone+thymol groups. The 4 groups were treated daily for 15 days. Hydrocortisone significantly induced oxidative stress in the liver tissues, marked by increased serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total oxidative capacity (TOC), and tumor necrosis factor-alpha (TNF-α) accompanied by marked decline of serum levels of total protein, albumin, and total antioxidant capacity (TAC). Also, marked elevation in the levels of the thiobarbituric acid reactive substances (TBARS) and TNF-α, beside significant decrease in the level of glutathione (GSH) in hepatic tissues were recorded. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal hepatic architecture, in addition to ultrastructural alterations represented by degenerative features covering almost all the cytoplasmic organelles of the hepatocytes. Supplementation of hydrocortisone-treated rats with thymol reversed most of the biochemical, histological, and ultrastructural alterations. The results of our study confirm that thymol has strong ameliorative effect against hydrocortisone-induced oxidative stress injury in hepatic tissues.

Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated. To further clarify the underlying mechanism, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the 5-HT depleting agent parachlorophenylalanine (pCPA) were applied to adjust serum levels of 5-HT. Serum levels of 5-HT were measured using LC-MS/MS; the expression of hepatic transporters, DMEs, and nuclear receptors were examined by Western-blot technique. Our results showed that in PI-IBS rats the expression of multidrug resistance protein 2 (Mrp2) was significantly decreased, while colonic enterochromaffin cell density and serum levels of 5-HT were all significantly increased. Moreover, 5-HTP treatment significantly increased serum levels of 5-HT and decreased the expression of Mrp2 and glycoprotein P (P-gp), whereas treatment with pCPA markedly decreased serum levels of 5-HT and increased the expression of Mrp2 and P-gp. Our results indicated that serum 5-HT regulates the expression of Mrp2 and P-gp, and the underlying mechanism may be related to the altered expression of the nuclear receptor constitutive androstane receptor (CAR).

The purpose of this study was to examine the effects of whey protein supplementation on homocysteine (Hcy) metabolism and liver oxidative stress in rats. Twenty-four rats were divided into 3 groups (n = 8) to receive one of the following diets for 4 weeks: control diet (C), whey protein-composed diet (WP), and whey protein-supplemented diet (WPS). The C and WP diets consisted of AIN-93 with 20% casein and 20% whey protein as protein source, respectively. WPS was AIN-93 (20% casein) supplemented by the addition of 20% (w/w) whey protein. Four weeks of ingesting a WPS diet resulted in a significantly higher (P < 0.05) total protein and methionine intakes. Although a significant increase (P < 0.05) in the hepatic S-adenosylmethionine and S-adenosylhomocysteine levels occurred in WPS group compared with C and WP, no significant change was observed in plasma Hcy concentration between groups. Furthermore, the levels of lipid hydroperoxides and advanced oxidation protein products, known liver oxidative stress markers, were increased in the WPS group compared with the C group. In addition, no change in glutathione liver concentration was observed in any of the groups studied. In conclusion, whey protein supplementation increases methionine intake substantially; however, it does not change plasma Hcy concentrations. On the other hand, increased hepatic oxidative stress markers were observed in whey protein supplemented rats were probably due to high protein intake.

Objectives: This study aimed to determine whether antenatal ultrasound measurements of fetal soft-tissues and liver can predict macrosomia in women with pregestational diabetes., Methods: Fetal biometry, soft-tissue thickness (anterior abdominal wall [STAW], thigh [STT], upper arm [STA], scapular [STS]) and liver size were measured sonographically at 23, 28, 31 and 34 weeks of gestation. Large for gestational age (LGA) was defined as a birth weight greater than 90th percentile for gestational age on standard curves adjusted for maternal height and weight, parity and fetal gender. The area (±standard error) under receiver operating characteristic (AUROC) curves were also calculated., Results: A total of 29 pregnant women with pregestational diabetes were included, and a total of 663 measurements taken. Fifteen neonates were LGA. There was no significant difference in fetal soft-tissue thickness at 23, 28 and 31 weeks between the LGA and non-LGA neonates. In contrast, at 34 weeks, fetal soft-tissues were significantly thicker in LGA neonates (P<0.05), but with no difference in liver surface area between the two groups. The specificity and sensitivity of 34-week ultrasonography to detect macrosomia was 78.6% and 66.7%, respectively, for abdominal circumference (AC), 71.4% and 93.3% for STT, 85.7% and 80.0% for STA, and 71.4% and 86.7% for STAW. No parameter was more powerful than the others. The best AUROC curves were found for AC (0.807), STT (0.821), STA (0.855) and STAW (0.821)., Conclusion: Third-trimester sonographic measurements of fetal soft-tissue may help to detect macrosomia in pregnancies complicated by pregestational diabetes., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

During several decades, patients with haemophilia have been treated using FVIII and FIX concentrates by haematologists working in specialized comprehensive haemophilia care centres. In the last fifteen years haemophilia treatments have been tremendously improved and novel treatment options have been developed. Gene therapy is one of these innovative approaches and will soon be available on the market. The European Association for Haemophilia and Allied Disorders and the European Haemophilia Consortium recently described a new healthcare setting for the management of patients who will receive gene therapy. This hub-and-spoke model aims to ensure the safe administration and monitoring of gene therapy by expert comprehensive haemophilia care centres, in close collaboration with the proximity haemophilia treatment centres where the patient is followed up. Any adverse events should be managed by both the expert "hubs" in collaboration with the spoke centre to provide the timeliest state-of-the-art treatment and management options to patients receiving gene therapy. All adverse events and efficacy data should be reported lifelong to a centralised registry. French reference centre for haemophilia and the patient's organization AFH worked together to adapt the European Hub and spoke model to the existing infrastructures and organization for rare bleeding disorders in France. This review describes the haemophilia patient's journey for gene therapy in France. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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 5 cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5 cm. [ABSTRACT FROM AUTHOR]

Résumé: L'échinococcose kystique hépatique (EKH), dénomination remplaçant désormais celle de kyste hydatique, est une zoonose parasitaire cosmopolite. Elle sévit principalement dans les pays où l'élevage de moutons constitue une ressource importante, expliquant qu'en France la majorité des patients soient des migrants. L'homme est un hôte intermédiaire accidentel. Le foie est l'organe préférentiel pour le développement du stade larvaire d' Echinococcus granulosus (E. g) sensu lato. La progression d'une lésion d'EKH est extrêmement lente, comparable à celle d'un processus tumoral bénin. La présentation clinique est d'une grande diversité, souvent totalement asymptomatique et de découverte fortuite mais parfois révélée par un tableau clinique aigu pouvant mettre en jeu le pronostic vital, témoin d'une complication évolutive dont la plus fréquente expression est la fissuration du kyste dans les voies biliaires. Le diagnostic repose sur l'examen échographique de la lésion en se référant à la classification de l'OMS permettant d'en apprécier le stade évolutif qui guidera la réflexion de prise en charge. Selon la situation, pourront être proposés une simple surveillance ou un traitement combinant, selon le cas, prise médicamenteuse, sous la forme d'albendazole à activité parasitostatique, techniques instrumentales et chirurgie. L'hépato-gastroentérologue est en première ligne à chacune de ces étapes à l'issue desquelles les décisions bénéficient grandement d'une réflexion pluridisciplinaire permettant aussi d'éviter un sur-traitement. Des études prospectives sont en effet indispensables pour progresser sur les aspects thérapeutiques qui, à ce jour, reposent essentiellement sur avis d'experts. L'observatoire national de l'EK, OFREKYS initié depuis 2018 par le CNR Échinococcoses au CHU de Besançon devrait contribuer à la meilleure connaissance de cette parasitose dans notre pays. Cystic echinococcosis (CE), a denomination now replacing that of hydatid cyst, is a cosmopolitan parasitic zoonosis. It is present mainly in countries where sheep farming constitutes an important resource explaining that in France, the majority of patients are migrants. Humans is an accidental intermediate host. The liver is the organ of choice for the development of the larval stage of Echinococcus granulosus (E. g) sensu lato. The progression of the cyst is extremely slow, comparable to that of a benign tumor. The clinical presentation is of great diversity, often completely asymptomatic and of fortuitous discovery but sometimes revealed by an acute clinical picture which can be life-threatening, related to complications. The most frequent one is the cyst rupture within the bile ducts. The diagnosis is based on the ultrasound examination using the WHO classification. It also allows to assess the evolutionary stage that is crucial to make treatment decisions. Depending on the situation, simple monitoring or a treatment combining, as the case may be, medication in the form of a parasitostatic, albendazole, instrumental techniques and surgery may be offered. The hepato-gastroenterologist is on the front line at each of these steps, at the end of which decisions benefit greatly from a multidisciplinary discussion. This also makes it possible to avoid over-treatment. Prospective studies are needed to progress on the therapeutic aspects which, to date, are essentially based on expert opinion. The French observatory of CE, OFREKYS, initiated in 2018 by the National Reference Center on Echinococcosis at Besançon University Hospital should contribute to better knowledge of this disease in our country. [ABSTRACT FROM AUTHOR]

Malignant melanoma is a disease with high metastatic potential which starts in melanocytes. The liver is the organ most often targeted for metastatic spread. Nonetheless, primary liver melanoma is very rare. Few cases have been described. We here report the case of a female patient with primary liver melanoma diagnosed based on liver biopsy results and confirmed by histological and immunohistochemical analyses as well as by providing a comprehensive assessment excluding other localizations. [ABSTRACT FROM AUTHOR]

Sucrose drink induced obesity and metabolic syndrome in human and animal models. However, age-specific metabolic effects of sucrose beverages are not clear yet. The purpose of this study was then to investigate changes in plasma biochemical parameters, oxidative stress markers, as well as lipid and redox contents and lipolytic activities in insulin target organs (liver, adipose tissue) in sucrose drinking rats at 10% and 30% during one month (day 30) and three months (day 90). Our results emphasized that sucrose drink induced obesity, adipose tissue accumulation with hyperinsulinemia, hyperglycemia, hyperlipidemia, liver steatosis, alterations in lipases activities and oxidative stress. These metabolic alterations were worsened by the amount of sucrose in the drink (30% versus 10%). The changes were apparent in young rats at day 30 and persisted until adulthood at day 90. Adult rats presented more sucrose-induced-metabolic abnormalities. In conclusion, sucrose drink induced an early increase in metabolic syndrome components. These data indicate the need of corrective nutritional intervention for young people and also for adults. [ABSTRACT FROM AUTHOR]

Résumé: Les parasitoses hépatiques restent très fréquentes en Afrique où le niveau d'hygiène est précaire. Elles relèvent d'un problème de santé publique, associées à une mortalité considérable avec des expressions cliniques polymorphes. Deux grands groupes de parasitoses sont identifiés : les parasitoses dues aux protozoaires et celles dues aux métazoaires. L'amœbose hépatique, la schistosomose, l'échinococcose kystique, le paludisme et la leishmaniose viscérale sont les plus fréquentes. Le foie par son rôle de carrefour vasculaire, métabolique et immunitaire est atteint par les parasites. Pour les parasites ingérés, mais aussi pour ceux dont la migration implique un passage dans les vaisseaux drainés par le système porte, le foie est un site anatomique privilégié. Hepatic parasitosis remains very frequent in Africa where the level of hygiene is precarious. They are part of a public health problem, associated with considerable mortality with polymorphic clinical expressions. Two groups of parasitosis are identified: parasitosis caused by protozoa and those caused by metazoa. Liver amoebosis, schistosomiasis, cystic echinococcosis, malaria and visceral leishmaniasis are the most common. The liver, through its role as a vascular, metabolic and immune crossroads, is affected by parasites. For ingested parasites, but also for those whose migration involves passage through vessels drained by the portal system, the liver is an anatomical site of choice. [ABSTRACT FROM AUTHOR]

Introduction: the treatment of large biliocystic fistulas is not unanimous among authors in the absence of consensus or a high level of evidence. There is a controversy over the use of a radical approach which allows the fistula to be sutured in a healthy area or conservative treatment that poses repair issues. The purpose of this study is to compare different conservative techniques to treat large biliocystic fistulas. Methods: we conducted a retrospective study of 54 patients with large fistulas in the Department of General Surgery at the Habib Bourguiba University Hospital in Sfax over a period of 9 years (2010 - 2018). Results: fourty-four patients were enrolled in the study. Abdominal ultrasound suggested opening of the bile ducts in 18 cases (47.4%) while computed tomography (CT) scan suggested opening in 28 patients (68.3%). The treatment of fistulas was based on DITFO (internal trans-fistulary drainage) in 18 cases (33.3%), cystobiliary disconnection (PERDROMO) in 11 cases (20.4%) and bipolar drainage in 25 cases. Specific surgical morbidity rate was 31.5% and it was dominated by postoperative biliary fistula in 18.5% of cases. DITFO technique was associated with shorter hospital stay (p=0.028) and lower morbidity rates (22.2%) with no statistically significant difference. Conclusion: DITFO technique is the gold standard technique in the treatment of biliocystic fistula because it is associated with lower morbidity rates and the shortest hospital stay. [ABSTRACT FROM AUTHOR]

La stéatohépatite non-alcoolique (NASH) est une maladie du foie responsable de complications et de mortalité de causes hépatique (fibrose, cirrhose, hépatocarcinome) et extra-hépatique (insulinorésistance, maladies cardiovasculaires). Actuellement, il n'existe pas de traitement approuvé dans cette indication. Toutefois, une perte de poids de 5 à 10 % du poids initial permet d'améliorer l'histologie hépatique. Cet objectif est cependant, soit difficile à atteindre chez tous les patients, soit peu efficace ou pas indiqué en cas de diagnostic de la maladie à un stade de cirrhose irréversible. Différents médicaments, à notre disposition dans le contexte dysmétabolique, sont présentés (statines, metformine...) avec leur impact sur la maladie hépatique. Récemment, de nombreux traitements à l'étude ont donné des résultats modestes mais encourageants. Plusieurs composés testés en phase 2 sont expliqués dans cet article, dont les agonistes FXR et TGR5, agonistes PPARα/δ/γ, le FGF21 recombinant, l'analogue du FGF19, l'agoniste du récepteur thyroïdien β1, les agonistes GLP-1, les inhibiteurs de la lipogenèse, l'antagoniste CCR2/5... Les résultats les plus avancés concernent l'évaluation intermédiaire de l'étude de phase 3 de l'acide obéticholique (agoniste FXR) qui a notamment confirmé une régression de la fibrose hépatique avec ce traitement. Quatre autres composés sont actuellement également testés en phase 3. L'article fait également le point sur le bénéfice potentiel d'une combinaison de traitements. D'autres pistes thérapeutiques, comme la chirurgie de l'obésité, la modulation du microbiote et l'endoscopie bariatrique, sont exposés. Non-alcoholic steatohepatitis (NASH) is a liver disease responsible for complications and mortality from hepatic (fibrosis, cirrhosis, hepatocellular carcinoma) and extrahepatic (insulin resistance, cardiovascular diseases) causes. Currently, there is no approved treatment for this indication. However, a weight loss of 5 to 10 % of the initial body weight is able to improve liver histology. However, it is difficult to achieve in all patients or ineffective/not indicated if the disease is diagnosed at an irreversible cirrhosis stage. Different drugs available in the dysmetabolic context are presented (statins, metformin, etc.) with their impact on liver disease. Recently, numerous agents have shown modest but positive results. Several compounds tested in phase 2 trials are explained in this article, including FXR or TGR5 agonists, PPARα/δ/γ agonists, recombinant FGF21, FGF19 analog, thyroid receptor agonist β1, GLP-1 agonists, inhibitors of lipogenesis, CCR2/5 antagonist... The most advanced results concern the interim analysis of the phase 3 study on obeticholic acid (FXR agonist) which notably confirmed a regression of hepatic fibrosis with this treatment. Four other compounds are also currently tested in phase 3 trials. The multi-mechanistic strategy of a combination therapy is also discussed. Other therapeutic approaches such as obesity surgery, microbiota modulation and bariatric endoscopy are exposed. [ABSTRACT FROM AUTHOR]

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Résumé: Les hépatopathies gravidiques sont les atteintes hépatiques les plus fréquentes au cours de la grossesse et peuvent être classées en fonction de leur survenue précoce (hyperemesis gravidarum) ou plus tardive (cholestase gravidique, foie toxémique incluant le HELLP syndrome et stéatose hépatique aiguë gravidique) au cours de la grossesse. Les anomalies du bilan hépatique associées aux vomissements sévères de la grossesse se corrigent après arrêt des vomissements. La cholestase gravidique est l'affection la plus fréquente et se caractérise par un prurit associé ou non à une augmentation des transaminases. L'acide ursodésoxycholique doit être débuté précocement et poursuivi jusqu'à l'accouchement. Le taux des acides biliaires est utile au diagnostic en cas de prurit sans anomalie du bilan hépatique et a une bonne valeur pronostique pour prédire le risque de mort fœtale in utero et la nécessité d'un accouchement prématuré. Les anomalies du bilan hépatique avec ou sans HELLP, associées à une pré-éclampsie se caractérisent par une cytolyse avec un risque d'hématome sous-capsulaire du foie. La stéatose hépatique aiguë gravidique est une maladie rare et grave qui se caractérise par des anomalies initialement modérées du bilan hépatique puis rapidement un ictère et une insuffisance hépatocellulaire. Le diagnostic se fait essentiellement par les critères composites de Swansea et par l'évolution de la stéatose à l'IRM en post-partum. Le traitement dans les formes graves repose sur l'évacuation utérine. En cas de retard de diagnostic et de prise en charge, le pronostic de la mère et de l'enfant est engagé. Pregnancy-related liver diseases are the most common cause of liver dysfunction in pregnancy. They can be classified as early (hyperemesis gravidarum) and later (intrahepatic cholestasis of pregnancy, pre-eclampsia with hepatic involvement including HELLP syndrome and acute fatty liver of pregnancy) specific liver diseases. Abnormal liver blood tests associated with severe vomiting of pregnancy resolve on cessation of vomiting. Intrahepatic cholestasis of pregnancy is the commonest pregnancy-specific liver disease and characterized by pruritus associated or not with elevated transaminases. Ursodeoxycholic acid should be prescribed early and continued until delivery. Serum bile acids level is useful for diagnosis in the event of pruritus without abnormal liver blood tests and has a good prognostic value for predicting stillbirth and the need of preterm delivery. Abnormal liver blood tests with or without HELLP syndrome, associated with pre-eclampsia are characterized by high transaminases levels with a risk of sub-capsular liver hematoma. Acute fatty liver of pregnancy is a rare and severe complication characterized by initially moderate liver tests abnormalities, rapidly evolving towards jaundice and hepatocellular insufficiency. The diagnosis is based on the Swansea composite criteria and by the resolution of steatosis on MRI during post-partum. The treatment in the severe forms is based on the rapid uterine evacuation. In the event of delayed diagnosis and/or need of supportive care, the prognosis is poor for the mother and the foetus. [ABSTRACT FROM AUTHOR]

Le foie est un organe filtre majeur et, de fait, peut héberger un certain nombre de parasites. Il peut s'agir aussi bien de protozoaires, c'est-à-dire de parasites unicellulaires, que d'helminthes beaucoup plus volumineux. Certains de ces parasites induisent une maladie essentiellement hépatique, tandis que d'autres sont impliqués dans un tableau multi-organes. Leur diagnostic n'est pas toujours aisé car il peut s'agir d'une localisation hépatique avec peu de répercussions sur le fonctionnement de l'organe, ou même d'une impasse parasitaire. Dans d'autres situations, la symptomatologie sera beaucoup plus bruyante à l'image d'un abcès amibien hépatique. C'est pourquoi, le diagnostic associe des techniques de mise en évidence directe du parasite à la sérologie et à l'imagerie. De manière intéressante, d'un point de vue tissulaire, le foie est capable de répondre très différemment à ces infections, avec une réponse qui peut être nécrotique, granulomateuse ou fibrotique. Les différents protozoaires pouvant être responsables d'atteintes hépatiques sont détaillés dans cet article. The liver is an organ assuming an important role in blood filtering, and because of that it can be in contact with numerous parasites. Protozoa i.e. unicellular eukaryotes, but also helminths that are much more voluminous can be responsible for hepatic localization. Some of them induce a disease mostly with hepatic symptoms, while others are involved in multi-organ manifestations. Diagnosis is sometimes difficult because of few functionnal consequences, or the parasite can even stop its development. Clinical manifestations can also be severe, as for the amoebic abscess of the liver. For these reasons, diagnosis combines direct exam with serology and imagery. Interestingly, the liver tissues are able to respond variously to these infections, with an immune reaction that can be necrotic, granulomatous or fibrotic. The different protozoan infecting liver are detailed in this article regarding their impact on liver functions. [ABSTRACT FROM AUTHOR]

La radiothérapie stéréotaxique hépatique est une technique de traitement en développement pour le traitement des tumeurs primitives et secondaires. Sa mise en œuvre est complexe du fait des particularités de l'organe traité et des comorbidités des patients. Elle représente cependant une opportunité de traitement efficace pour beaucoup de patients en impasse thérapeutique. Son niveau de preuve est jugé insuffisant par la Haute Autorité de Santé (HAS) pour une large diffusion en dehors des centres expérimentés. Il existe pourtant un nombre conséquent et grandissant d'études rétrospectives ou prospectives, mais peu de données comparatives. Cet article résume les particularités de la radiothérapie stéréotaxique pour cette localisation et reprend les résultats des études publiées pour les machines dédiées et non dédiées. Liver stereotactic body radiotherapy is a developing technique for the treatment of primary tumours and metastases. Its implementation is complex because of the particularities of the treated organ and the comorbidities of the patients. However, this technique is a treatment opportunity for patients otherwise in therapeutic impasse. The scientific evidence of liver stereotactic body radiotherapy has been considered by the French health authority as insufficient for its widespread use outside specialized and experienced centers, despite a growing and important number of retrospective and prospective studies, but few comparative data. This article focuses on the specific features of stereotactic body radiotherapy for liver treatments and the results of published studies of liver stereotactic body radiotherapy performed with classic linear accelerators and dedicated radiosurgery units. [ABSTRACT FROM AUTHOR]

Résumé: Les kystes simples ou biliaires sont très fréquents et le plus souvent asymptomatiques. Ce travail présente les éléments permettant de faire le diagnostic de cette lésion fréquente mais également des autres causes de lésions kystiques du foie. Cet article décrit l'aspect des kystes simples, de leurs formes compliquées et des autres lésions d'allure kystique telles que les lésions kystiques néoplasiques, inflammatoires et d'origine congénitale. En tenant compte du contexte clinique, le diagnostic repose sur le nombre de lésions, leur dissémination et leur aspect après injection d'un produit de contraste. Une approche systématique est nécessaire pour diagnostiquer les différentes lésions kystiques du foie. Un arbre décisionnel est proposé pour aider le clinicien. Benign and asymptomatic liver cysts are very frequent. This work presents the imaging features of these lesions but also other mimicking lesions. This article describes imaging features of uncomplicated and complicated liver cysts, cystic mass of various origins, such as developmental, neoplastic or inflammatory. The diagnostic approach should take in account the clinical context, the lesion number, their dissemination and their patterns before and after contrast media injection. A systematic approach is required to diagnose the large amont of liver cyst and a diagnostic tree is proposed to help the clinician. [ABSTRACT FROM AUTHOR]

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Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)