Are elevated systemic bile acids involved in the pathophysiology of sarcopenia and liver injury following gastric bypass?

Bariatric surgery is currently the most effective treatment for sustained weight loss in severe obesity. However, recent data describe the development of liver damage and in particular massive steatosis and cholangitis in some patients, for which certain pathophysiological mechanisms are suggested such as bacterial overgrowth, malabsorption or sarcopenia. We describe the case of a patient presenting with a new liver dysfunction 6 years after a gastric bypass. The work-up revealed sarcopenic obesity characterised by low muscle mass and low muscle function as well as elevated fasting bile acids, severe liver steatosis and cholangitis. The pathophysiology of this disease is complex and multifactorial but could include bile acid toxicity. Bile acids are increased in cases of liver steatosis, but also in cases of gastric bypass and malnutrition. In our opinion, they may contribute to the loss of muscle mass and the vicious circle observed in this situation. Treatment with enteral feeding, intravenous albumin supplementation and diuretics reversed the liver dysfunction and the patient was discharged from hospital.

[Alcoholic steatohepatitis: what's new in 2012?]. / Stéatohépatite alcoolique: nouveautés 2012.

Alcoholic liver disease is a spectrum of lesions, of which the most severe is alcoholic steatohepatitis (ASH). Recent European guidelines define alcoholic hepatitis as a clinical syndrome: the recent onset of jaundice and/or ascites in a patient with ongoing alcohol misuse. Next to infection, the most frequent aetiology is ASH, a histological diagnosis. In case of severe ASH, as defined by prognostic scores, a biopsy is needed to confirm the diagnosis. Non-severe forms of ASH may improve with interruption of alcohol abuse only; however survival of severe forms of ASH is improved by the association of corticosteroids and N-acetylcysteine. In case of uncontrolled infection, pentoxifylline may be administered. The Lille score, measured at the 7th day of corticosteroid therapy, measures response to therapy and guides the total duration of treatment.

Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target?

Liver diseases and in particular end stage liver diseases are frequently complicated by muscle modifications that are linked to worse clinical outcome. In addition, recent studies have demonstrated the negative impact of these muscle changes on liver function leading to the hypothesis of a bidirectional relationship referred in the literature as "muscle-liver axis". In a context of evolution towards a more holistic and less organocentric vision of medicine, studying frailty, myosteatosis and sarcopenia and their underlying pathophysiological mechanisms has led to many publications in the last five years. These studies are describing several pathophysiological mechanisms, highlighting the extremely complex character of this relationship. This review aims to summarize these mechanisms as well as potential therapeutic targets, independently of liver disease etiology.

Malnutrition is highly prevalent in hospitalized cirrhotic patients and associates with a poor outcome.

Background and study aims: The role of malnutrition on the prognosis of hospitalized cirrhotic patients is incompletely studied. Our aim was to determine the prevalence of malnutrition, functional scores and their impact on prognosis of hospitalized cirrhotic patients. Patients and methods: This retrospective study included all patients with cirrhosis hospitalized in the gastroenterology unit at Saint-Luc university hospital, Brussels between April 2014 and September 2014. Nutritional status was evaluated according to minimum clinical summary diagnostic criteria. Cirrhosis-related complications or death occurrence were analysed in a one-year follow-up. Results: 95 cirrhotic patients were assessed for nutritional status and outcomes. Malnutrition affected 45.3% of patients and was more frequent with the severity of cirrhosis: 29% in Child-Pugh A, 48.8% in Child-Pugh B and 72.2% in Child-Pugh C patients. 58.9% of patients developed cirrhosis-related complications (60.7% in the malnutrition group vs. 39.3%, p<0.001, OR 5.06, IC95 1.90-14.58) and 33.7% of patients died (68.75% vs. 31.25%, p=0.002, OR 4.33, IC95 1.62-12.28). Adjusting for age, sodium, MELD, Charlson index, hepatocellular carcinoma, platelets, diabetes, prognostic nutritional index and Braden scale, malnutrition was significantly associated with higher mortality and morbidity rates with an OR of 3.56 (CI95 1.55-8.16) and 2.09 (CI95 1.16-3.77) respectively. Braden scale was significantly associated with higher mortality (p=0.027, OR 1.25, CI95 1.03-1.52) whereas prognostic nutritional index was associated with higher morbidity (p=0.001, OR 0.94, CI95 0.90-0.98). Conclusion: Malnutrition is highly prevalent in hospitalized cirrhotic patients. Malnutrition, low prognostic nutritional index and low Braden scale are associated with poor outcomes in cirrhosis.

Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.

Risk of hepatocellular carcinoma and fibrosis evolution in hepatitis C patients with severe fibrosis or cirrhosis treated with direct acting antiviral agents.

Background and study aims: Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods: We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results: 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions: DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.

The history of Acta Gastro-Enterologica Belgica.

The history of Acta Gastro-Enterologica Belgica is long, rich… and cloudy. There is no centralised archive available. However, all currently active gastroenterologists in Belgium have been trained with the journal, have published abstracts or manuscripts in it, or at least know of its existence. Whereas it started as a national society's journal in 1933, it has grown to a competitive international journal with Impact Factor. We felt the need to reconstruct the journal's long history, since this was never done before. This review tried to highlight some of the important milestones, without claiming to be complete. Looking back helps to better foresee and anticipate the future.

Impact of liver inflammation on whole body insulin resistance : a case report on primary biliary cholangitis.

Chronic liver diseases such as hepatitis C or non-alcoholic fatty liver disease could be associated with insulin resistance, even in the absence of cirrhosis or significant fibrosis. In this report, we present the case of a patient who was diagnosed with primary biliary cholangitis and metabolic syndrome. Initial evaluation also revealed diabetes with elevated fasting plasma glucose and glycated hemoglobin. After eight weeks of treatment with ursodeoxycholic acid, a complete normalization of the hepatic biological tests was observed. A few months later, while body weight and abdominal perimeter remained stable, fasting blood glucose and glycated hemoglobin decreased significantly, compatible with diabetes disappearance. This finding supports the concept that the inflamed liver plays a major role in the pathogenesis of insulin resistance and diabetes occurrence in chronic liver diseases, including primary biliary cholangitis.

Hepatitis C virus (HCV) prevalence estimation in the adult general population in Belgium : a meta-analysis.

BACKGROUND AND STUDY AIMS: Although multiple HCV prevalence studies were recently performed in the general population from Belgium, they suffer from a lack of geographical representativeness, an insufficient number of participants or a lack of inclusion of high prevalence groups. The aim of this study is to provide robust information on the HCV burden. METHODS: Recently performed HCV prevalence studies in the general, adult population were included in this study, based on well-defined selection criteria. A meta-analysis was performed to estimate the seroprevalence, the prevalence of participants with viremia and the prevalence estimation for people with viremia which were unaware of their status. RESULTS: Eight studies fulfilled the criteria for inclusion of the quantitative prevalence estimation. Based on the meta-analysis on these 8 studies, we estimated an HCV seroprevalence of 1.01% [95% CI : 0.66-1.42%], representing a total of 90,722 adult, HCV seropositives of which 64,412 individuals (0.71%) were confirmed seropositive. Based on the RNA presence, an estimated viremic prevalence of 0.33% [95% CI : 0.21-0.47 %] was determined, corresponding with 29,642 individuals. This is 46,0% of the true HCV seropositive residents. Further, based on the availability of patient information in 5 out of the 8 studies, a prevalence of 0.18% [95% CI : 0.07-0.33] representing 16,168 individuals from the adult Belgian population are unaware of their HCV status. CONCLUSIONS: We believe that the quantitative measurement by the meta-analysis will be more reliable for their use in the design of a screening strategy or in the development of prevention campaigns as compared to the prevalence estimations performed at local level.

The Belgian Association for Study of the Liver Guidance Document on the Management of Adult and Paediatric Non-Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and associated with considerable liver-related and non-liverrelated morbidity and mortality. There is, however, a lot of uncertainty on how to handle NAFLD in clinical practice. The current guidance document, compiled under the aegis of the Belgian Association for the Study of the Liver by a panel of experts in NAFLD, from a broad range of different specialties, covers many questions encountered in daily clinical practice regarding diagnosis, screening, therapy and follow-up in adult and paediatric patients. Guidance statements in this document are based on the available evidence whenever possible. In case of absence of evidence or inconsistency of the data, guidance statements were formulated based on consensus of the expert panel. This guidance document is intended as a help for clinicians (general practitioners and all involved specialties) to implement the most recent evidence and insights in the field of NAFLD within a Belgian perspective.