COVID-19 in an international European liver transplant recipient cohort.

Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome

Irritable bowel syndrome: the role of the intestinal microbiota, pathogenesis and therapeutic targets

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that predominantly affects women and accounts for up to 40% of the gastroenterology unit outpatient visits. The pathophysiology is complex and multifactorial. In the present review we will focus on the role of intestinal dysbiosis in its pathogenesis and treatment. Post-infectious IBS (PI-IBS) can put light on the mechanisms underlying IBS. Modified commensal gut flora may lead to mucosal inflammation. Several changes such as an increase in mucosal cellularity (enterochromaffin cells, lamina propria T lymphocytes and mast cells), modified pro-inflammatory/anti-inflammatory cytokine balance and disordered neurotransmission have been observed. The normal microbiota is an essential factor in health. A modification of the flora, such as small intestinal bacterial overgrowth (SIBO) is thought to play a pathogenic role in IBS. Changes in the composition of the luminal and mucosal colonic flora have been linked to IBS. It is not clear however, whether these changes are a cause or a consequence of the syndrome. The comprehension of the interaction between the dysbiotic microbiota and the host will probably lead to the development of focused therapies. Based on these assumptions, treatments modulating the microbiota have been investigated. On the one hand several probiotics have shown a reduction in IBS symptoms by an immunomodulatory and analgesic effects. On the other hand antibiotic treatment has proven efficacy in treating IBS with or without associated SIBO. Due to its complex pathophysiology, treating IBS nowadays implies multiple approaches, one of which may be modulation of the intestinal flora

Liver fibrosis post SVR

Hepatitis C (HCV) recurrence after liver transplantation (LT) is universal if HCV-RNA persists at time of LT and progression to fibrosis can occur rapidly. Nowadays, sustained virological response (SVR) is obtained in 97% of HCV-infected patients treated with direct acting antivirals (DAA) after LT. Fibrosis diminishes in HCV patients after SVR but there is paucity of data on fibrosis regression occurring after SVR following LT. In addition, most studies evaluate fibrosis with non-invasive techniques while these are not validated after LT because of LT-specific complications. There are no data evaluating long-term evolution of fibrosis after SVR since the introduction of DAA treatments (> 5 - 10 years). The aim of this study is to histologically evaluate liver fibrosis evolution in short and long term follow-up biopsies after HCV-elimination in LT-patients

Hepatic tuberculoma: A challenging diagnosis.

Clinical case presentation : We present the case of a 32-year-old Tunisian woman living in Belgium with a 5-year history of liver lesions. Her medical history is marked by two pregnancies, and pleural tuberculosis at the age of 23, treated by antitubercular agents. The lesions were incidentally discovered in 2013 on a CT scan during a workout because of postpartum fever. They measured 8, 28, and 11 mm, respectively, at segments 7, 5, and 6; based on both MRI and ultrasound, they were considered atypical. She was asymptomatic and put under surveillance with no precise diagnosis

Fibrosis and steatosis of the liver graft: are non-invasive tests useful? A short review.

As life expectancy of liver transplanted patients improves, new questions are arising to avoid progressive graft loss. The spectrum of chronic inflammation and fibrosis are known to be important triggers in the alteration of graft function. Liver biopsy remains the gold standard to better understand progressive, normal, and abnormal histological modifications of the graft. In parallel, the interest for metabolic steatosis development in post-transplantation is also growing. Long-term survival of these patients involves the management of comorbidities including metabolic syndrome and cardiovascular diseases. Early detection of altered graft parenchyma, and monitoring of its evolution are undoubtedly essential. Non-invasive methods including transient elastography and fibrosis biomarkers are attractive tools to avoid drawbacks and complications of liver biopsy. Accuracy of these methods are well-known in a pre-transplantation setting, but evidence is lacking in post-transplantation setting. We review current knowledge of progressive liver fibrosis and steatosis development after transplantation and non-invasive methods of their assessment

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

Muscle mass depletion in chronic liver diseases: An accelerated model of aging or a distinct entity?

Sarcopenia was initially defined as loss of muscle mass, strength and function related to aging. This phenomenon is a multifactorial process. The evaluation of the geriatric population in which sarcopenia has extensively been studied opens the field for other chronic diseases. Cirrhosis is one of them and the term ‘‘sarcopenia’’ is now also used in this pathological situation. It must be emphasized that the pathophysiology of sarcopenia in cirrhosis is likely different from the pathogenesis in geriatric patients. Furthermore, cirrhosis has heterogeneous causes. Therefore, we need a better understanding of the changes in muscle physiology specifically in chronic liver diseases as well as easy, accurate, reproducible and validated tools, taking into consideration etiology specific aspects to identify sarcopenia in every cirrhotic patient

Frailty, sarcopenia and mortality in cirrhosis: what is the best assessment, how to interpret the data correctly and what interventions are possible?

Cirrhosis-induced sarcopenia plays a deleterious role in patients on the waiting list of transplantation. Liver frailty index (LFI) calculation based on easy measurable clinical parameters (muscle strength and balance data) seems therefore accurate for identifying patients at risk for waiting list mortality. However, some questions remain open such as the difficult clinical testing of patients with encephalopathy, the comparison of these clinical data with the radiological evaluation of muscle quantity and quality, the attitude to adopt towards these patients identified as fragile (emergency versus futile transplantation?) and the possible benefit of interventions (nutrition and/or exercise). Finally, recent data show that the deterioration of the muscle condition occurs early prior to the development of advanced fibrosis (specifically in fatty liver disease). This underlines the interest of evaluating the muscle compartment during the pathogenesis of liver diseases, also before the emergence of cirrhosis