Diseases related to fatty liver, independently of alcohol consumption («non-alcoholic fatty liver disease» or NAFLD), are increasing because of the epidemics of obesity and type 2 diabetes. These disorders reflect a continuum that comprises isolated steatosis, steatohepatitis (NASH) and fibrosis, with, at the end, an increased risk of cirrhosis and hepatocarcinoma. It has been recently proposed to replace the term NAFLD by MAFLD, i.e. «Metabolic (dysfunction) Associated Fatty Liver Disease», which better reflects the pathogenesis of the disease. Inflammation plays a crucial role in the aggravation of the disorder and profoundly influences the prognostic evolution. This article illustrates the natural history of this underestimated metabolic disorder, recall the diagnostic criteria used in clinical practice, emphasizes the deleterious role of inflammation and discusses some therapeutic perspectives.

Introduction. - The toxicity associated with hepatic radioembolization (RE) by microspheres labeled with Yttrium 90 (Y-90) has a very variable incidence between studies and depends on a multitude of parameters. The objective of this study is to assess the various predictive factors of this toxicity, inherent of the patient or the type of procedure. Patients and methods. - Single-center retrospective study including 85 patients with hepatocarcinoma treated by hepatic RE. The medico-technical and clinical-biological parameters were studied over a defined time interval and the toxicity of the latter graded according to the Common Terminology Criteria for Adverse Events. Dosimetry was carried out on the basis of the Y-90 PET/CT using the "Simplicit90Y" software and the statistical analysis using the "SAS" software. Results. - Post-RE hepatotoxicity observed in 77.7% of our population with maximum grade 3 toxicity in 10.6% of cases. The presence post-RE of hyperbilirubinemia and ascites were detected in 32.1% (only grade 1-2) and 27.1% (4.7% grade 3) of patients, respectively. The pre-therapeutic presence of cirrhosis and/or hyperbilirubin are predictive of post-RE toxicity. Other biological elements studied are less relevant in practice. Radioembolization-induced liver disease (REILD) was observed in 15.3% of cases, mainly of moderate form (13.0%). No impact of the dosimetric approach was observed. Conclusion. - A personalized dosimetric approach does not generate additional side effects, while maximizing the tumor dose and therefore the therapeutic effect. The presence of cirrhosis and hyperbilirubinemia pre-RE seem to be the two predominant in the appearance of REILD. (C) 2021 Elsevier Masson SAS. All rights reserved.

In Belgium and around the world, the incidence of primary malignant liver tumours is increasing, both for hepatocarcinoma and cholangiocarcinoma. Their curative treatment is based on multidisciplinary and specialized care, of which surgery (including liver transplantation) remains the cornerstone, often associated with other logoregional treatments, as radioembolisation, radiofrequency ablation, and chemoembolisation. For advanced cases, the prognosis remains poor, in particular due to a certain chemoresistance of these tumours. New treatments include targeted therapies (including various tyrosine kinase inhibitors) and immunotherapy. A specialized multidisciplinary discussion is therefore necessary to define the best therapeutic management, individualized to each patient. In this article, the authors review the most recent data relating to the treatment of hepatocarcinoma and cholangiocarcinoma.

Alcoholic hepatitis is a syndrome defined primarily by the clinical onset of jaundice in patients with a concomitant heavy consumption of alcoholic beverages. This pathology is managed by alcohol withdrawal with a 30-day survival rate of 90 %. For patients with severe alcoholic hepatitis, with a Maddrey score greater than 32 (taking into account bilirubin and prothrombin time), treatment with corticosteroids is discussed provided that a possible infection can be sufficiently excluded or adequately managed. The administration of corticosteroids is continued for 28 days if the Lille score, calculated after 7 days of treatment, is favourable (inferior to 0.45), leading to a survival rate of 80-90 %. However, if the Lille score is unfavourable (superior to 0.45), the prognosis is bad, with a survival of only 25-30 % at 6 months. Special attention needs to be paid to assure a sufficient caloric intake during the treatment period for a successful management. Liver transplantation, previously prohibited for this indication, can be discussed under certain circumstances. However, the success of treatment is contingent upon the alcohol withdrawal. Innovative drugs are currently under investigation to improve the prognosis of this condition.

Ever since the initial description of the Milan criteria, used for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT), there has been a clear need to go further than solely morphological criteria. Tumours exceeding the Milan criteria, but presenting favourable biological behaviour, might still allow for comparable overall- and disease-free survivals after LT. As it is well established that the presence of microvascular invasion is a major factor that influences HCC recurrence after LT, several serum and tissue biomarkers in addition to imaging studies are attracting wider attention as more refined tools for selecting HCC patients for LT. A thorough review of the recent literature on the subject was conducted. In the future a combination of systemic inflammation markers, biomarkers and morphological criteria may be key to more accurate prediction of HCC recurrence after LT. This may allow LT in patients whose HCC tumours exceed the Milan criteria but have favourable biological behaviour. Further prospective studies are required in order to improve patient selection for transplantation in HCC and these could help a move towards more transparent and improved management.

In Belgium as in many other countries, alcohol is one of the leading causes of adult liver transplantation. Liver transplantation for terminal liver failure due to excessive alcohol intake raises clear ethical issues concerning the use of grafts to save patients suffering from a self-inflecting affection. Alcoholic liver disease is one of the best indications for liver transplantation, with excellent results in terms of length of survival and post transplantation quality of life, if this transplantation is proposed by a multidisciplinary team in a patient able to and helped by a supporting family and social environment.

Rarely encountered in the Western countries, membranous occlusion of the inferior vena cava results from a fibrous thickening of the intima and is commonly located at the orifices of the hepatic veins. To date, two etiopathogenic hypotheses have been formulated: the first, dealing with the embryological aspect, the second, arguing for a thrombotic origin. Nevertheless, several studies are still underway to understand the exact physiopathological mechanism of this obstruction. Among these studies, some suspect the predisposing role of anatomical and infectious factors. On average, it takes 6 years between the beginning of the symptoms and the diagnosis. The later the diagnosis is settled, the higher is the risk of encountering a hepatocellular carcinoma. The most relevant additional examinations to visualize the membrane are the abdominal ultrasound and the cavography. Computed tomography allows to highlight the effects of obstruction on the hepatic parenchyma. Concerning the treatment, many studies showed that angioplasty has an excellent immediate and late efficacy. A few surgical techniques also exist but those are less exploited because of the non invasive aspect and lower morbidity-mortality of the endovascular treatment.

There is a long-recognized association between cancer and venous thromboembolism. Venous thrombosis is the most common paraneoplastic complication. We describe a case of rupture of esophageal varices in a patient with a paraneoplastic portal thrombosis. We highlight the links between venous thromboembolism and cancer and also discuss treatment and prognostic factors.

Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reactivation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft re-infection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignancies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good.

The cation-exchange capture step of a monoclonal antibody (mAb) purification process using single column batch and multicolumn continuous chromatography (MCSGP) was modeled with a lumped kinetic model. Model parameters were experimentally determined under analytical and preparative conditions: porosities, retention factors and mass transfer parameters of purified mAb were obtained through a systematic procedure based on retention time measurements. The saturation capacity was determined through peak fitting assuming a Langmuir-type adsorption isotherm. The model was validated using linear batch gradient elutions. In addition, the model was used to simulate the start-up, cyclic steady state and shut down behavior of the continuous capture process (MCSGP) and to predict performance parameters. The obtained results were validated by comparison with suitable experiments using an industrial cell culture supernatant. Although the model was not capable of delivering quantitative information of the product purity, it proved high accuracy in the prediction of product concentrations and yield with an error of less than 6%, making it a very useful tool in process development.

Current therapies with pegylated interferon and ribavirin are effective to eradicate the virus C. Improvements are foreseen in the near future with combination of the current treatment with antiviral therapies (antiproteases, antipolymerases). Eradication of the virus, when obtained, has a favorable impact on an individual basis. However, to reduce the mortality related to the virus C at a population level, an important point is the accessibility to therapy. It has been calculated that the impact of current management to reduce mortality is minimal, as compared to the absence of treatment, due to a poor accessibility to therapy. To obtain a significant additional reduction of mortality, a better screening, a better access to the threatment are crucial.

A two-step chromatography process for monoclonal antibody (mAb) purification from clarified cell culture supernatant (cCCS) was developed using cation exchange Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) as a capture step. After an initial characterization of the cell culture supernatant the capture step was designed from a batch gradient elution chromatogram. A variety of chromatographic materials was screened for polishing of the MCSGP-captured material in batch mode. Using multi-modal anion exchange in bind-elute mode, mAb was produced consistently within the purity specification. The benchmark was a state-of-the-art 3-step chromatographic process based on protein A, anion and cation exchange stationary phases. The performance of the developed 2-step process was compared to this process in terms of purity, yield, productivity and buffer consumption. Finally, the potential of the MCSGP process was investigated by comparing its performance to that of a classical batch process that used the same stationary phase.

Objective. Donation after cardiac death (DCD) has been proposed to overcome in part the organ donor shortage. In liver transplantation, the additional warm ischemia time associated with DCD procurement may promote higher rates of primary nonfunction and ischemic biliary lesions. We reviewed the results of liver transplantation from DCD.Patients and Methods. From 2003 to 2007, we consecutively performed 13 controlled DCD liver transplantations. The medical records of all donors and recipients were retrospectively reviewed, evaluating in particular the outcome and occurrence of biliary complications. Mean follow-up was 25 months.Results. Mean donor age was 51 years, and mean intensive care unit stay was 5.4 days. Mean time between ventilation arrest and cardiac arrest was 9.3 minutes. Mean time between cardiac arrest and arterial flushing was 7.7 minutes. No-touch period was 2 to 5 minutes. Mean graft cold ischemia time was 295 minutes, and mean suture warm ischemia time was 38 minutes. Postoperatively, there was no primary nonfunction. Mean peak transaminase level was 2546 UI/mL. Patient and graft survival was 100% at I year. Two of 13 patients (15%) developed main bile duct stenosis and underwent endoscopic management of the graft. No patient developed symptomatic intrahepatic bile duct strictures or needed a second transplantation.Conclusions. Our experience confirms that controlled DCD donors may be a valuable source of transplantable liver grafts in cases of short warm ischemia at procurement and minimal cold ischemia time.

Curative management of early-stage hepatocarcinoma may include partial hepatic resection, liver transplantation or tumoral necrosis using radiofrequency ablation or alcoholisation. Until recently, no efficient therapeutic mean was available for advanced hepatocarcinoma. Sorafenib (Nexavar, Bayer) is a multikinase inhibitor that decreases tumoral proliferation and angiogenesis, and increases apoptosis in many cancer models. The results of a phase 3 randomized, multicentric, study, entitled SHARP, have now demonstrated that sorafenib increases survival in patients with advanced hepatocarcinoma developed in Child A cirrhosis. Mean survival gain was a little less than 3 months, without any radiologic response or improvement in the delay before symptomatic progression of the disease. The monthly cost of sorafenib is a little more than 5,000 euros. It is now crucial to evaluate the potential role of sorafenib in adjuvant therapy after liver resection or radiofrequency ablation of hepatocarcinoma. The CHU of Liège is taking part to a randomized, multicentric study evaluating the use of sorafenib after liver resection or radiofrequency ablation for hepatocarcinoma. Another future evaluation could be the association of sorafenib with other antitumoral agents.

The FibroScan is a device allowing a non invasive diagnosis and quantification of liver fibrosis. The procedure is based on transient elastography and allows to record liver stiffness by measuring the velocity of shear wave across liver parenchyma. The elasticity is directly correlated to velocity of the wave. In chronic hepatitis C, there is a good correlation between liver elasticity and stage of fibrosis. The FibroScan has also been studied in other chronic liver diseases, such as hepatitis B, primary biliary cirrhosis, sclerosing cholangitis, auto-immune hepatitis, alcohol, steatosis, hemachromatosis with reproductible results. In a cirrhotic patient, it also allows to assess the severity of cirrhosis and to evaluate the risk of complication. It is a painless procedure, with a good acceptability by the patients. Therefore, the FibroScan can be regularly performed, allowing the follow up of fibrosis evolution over time.

Over the last 20 years, significant improvements in hepatic surgery and transplantation have allowed better results. Better patients selection, new preoperative modalities aiming at modifying the volume of the liver or the tumour, new surgical techniques, and better postoperative management are the keys to improved outcome. These progresses are reviewed in this article. In hepatic surgery, the latest surgical improvements are the possibility of laparoscopic hepatic resection and of radiofrequency ablation. Modern neoadjuvant chemotherapy may in some cases allow a reduction of large liver colorectal metastases and render them resectable. Improved radiological techniques allow better planning of the surgical resections, reduction of the risks by calculation of the residual liver mass, and induction of liver hypertrophy by preoperative portal embolisation. In liver transplantation, the most significant changes were the use of living related liver donors and of non-heart beating donors to overcome the cadaveric organ donor shortage.

Hemochromatosis is the most common genetic disorder in persons of northern European descent, and the majority of cases are caused by a mutation in the gene HFE. Genetic testing for hemochromatosis is therefore indicated in all patients with increases in transferrine saturation and ferritin levels. When this genetic testing does not demonstrate a hemochromatosis, other diseases responsible for elevated ferritin levels have to be ruled out, mainly hemolytic anemia, chronic inflammatory disorders, liver diseases such as hepatitis B or C, alcohol abuse, and non alcoholic fatty liver disease. In demonstrated iron overload with absence of classic causes, second-line genetic testing should be considered.

BackgroundImmunological and functional bronchopulmonary abnormalities may be present in up to two‐thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma.MethodsEighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, α2‐macroglobulin, interleukin‐8 (IL‐8), IgA and IL‐8/immunoglobulin A complexes.ResultsWhen compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0–79.9%] vs 0.2% [0–2.3%]; P < 0.001) and ECP levels (26.2 μg/L [4–124.2 μg/L] vs 9.8 μg/L [0–94.2 μg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and α2‐macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL‐8, IgA and IL‐8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels.ConclusionsCrohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability.