The Role of Lipophagy in the Development and Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction) associated liver disease (MAFLD), is, with a global prevalence of 25%, the most common liver disorder worldwide. NAFLD comprises a spectrum of liver disorders ranging from simple steatosis to steatohepatitis, fibrosis, cirrhosis and eventually end-stage liver disease. The cause of NAFLD is multifactorial with genetic susceptibility and an unhealthy lifestyle playing a crucial role in its development. Disrupted hepatic lipid homeostasis resulting in hepatic triglyceride accumulation is an hallmark of NAFLD. This disruption is commonly described based on four pathways concerning 1) increased fatty acid influx, 2) increased de novo lipogenesis, 3) reduced triglyceride secretion, and 4) reduced fatty acid oxidation. More recently, lipophagy has also emerged as pathway affecting NAFLD development and progression. Lipophagy is a form of autophagy (i.e. controlled autolysosomal degradation and recycling of cellular components), that controls the breakdown of lipid droplets in the liver. Here we address the role of hepatic lipid homeostasis in NAFLD and specifically review the current literature on lipophagy, describing its underlying mechanism, its role in pathophysiology and its potential as a therapeutic target

Referral care paths for non-alcoholic fatty liver disease-Gearing up for an ever more prevalent and severe liver disease

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent and potentially severe liver disease, emphasizing the need for implementation of widely supported care paths for patients at risk for advanced stages of NAFLD. In particular, the distinction of patients with a progressive and/or advanced, fibrotic NAFLD from those with simple steatosis requires improvement, as well as the awareness for NAFLD among health care professionals. Broad acceptance and implementation of interdisciplinary care paths in the near future will bring enhanced identification of those patients that benefit from surveillance, intensive lifestyle management, and empirical or investigational pharmacotherapy and enhance our epidemiological grasp of NAFLD in relation to lifestyle, genetic background, and cardiometabolic comorbidities related to NAFLD.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Non-alcoholic fatty liver disease: a multidisciplinary approach towards a cardiometabolic liver disease

Non-alcoholic fatty liver disease (NAFLD) is a growing health p roblem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is co nsidered the hepatic component of the metabolic syndrome and is associated with an increased risk of the develo pment of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated com orbidities and complications, treatment requires interventions from a variety of different healthcare specialties . However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associate d comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which pati ents suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiova scular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are amb ivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidiscipl inary care path development could move forward. Nephrolog

Cystic hygroma in a female suckling pig, a case report

Background: Cystic hygromas (lymphangiomas) are rarely reported in various animal species, humans included. A hygroma is a benign congenital malformation of the lymphatic drainage system, presenting itself as a mass consisting of multiple cysts of various sizes with a watery content. Case presentation: This report describes clinical, ultrasonographic, and post-mortem findings of a cystic hygroma in a suckling pig. The mass was characterized by a few thin-walled cysts, containing clear yellow serous fluid. Histologically, the central cavity was lined by a single layer of squamous cells, supported by a thick fibrous stroma. On immunohistochemistry, scattered lining cells were weakly positive for Factor-VIII, suggesting their possible endothelial origin. Conclusions: This case report contributes to raising awareness on this condition in pigs allowing early identification in life so that appropriate care can be provided. The case report attributes to science on hygromas in general, as better understanding of pathologic features, the aetiology and appropriate treatment are needed

A global survey of health care workers' awareness of non-alcoholic fatty liver disease:The AwareNASH survey

Background: The estimated global prevalence and burden of non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), is increasing. Yet, NAFLD remains largely underdiagnosed. In addition to hepatic morbidity and mortality, NAFLD is associated with increased cardiovascular complications, warranting a multidisciplinary approach. Despite its rapidly increasing prevalence, knowledge of NAFLD among healthcare workers is limited, especially with specialists outside the field of hepatology and gastroenterology. Objectives: To investigate knowledge, practice and opinions/attitudes of healthcare workers towards diagnosis and management of NAFLD/NASH. Methods: The survey was designed in collaboration with a multidisciplinary scientific committee established especially for this study. The survey was disseminated to healthcare workers from seven different disciplines through four collaborating societies, social media and at a cardiology-themed conference from February to June 2022. Median and interquartile range were mentioned for numeric responses and proportions for categorical responses or responses on a Likert scale. Likert scale responses were treated as ordinal data and analysed with the appropriate tests. Results: The full dataset included 613 respondents from 88 different countries (including 488 physicians). 64% of the surveyed physicians underestimated the prevalence of NAFLD. General practitioners and cardiologists underestimated the prevalence most often (74% and 77%, respectively). Compared to the other disciplines, cardiologists were least familiar with the symptoms and diagnostic criteria and felt least confident in diagnosing and managing NAFLD. Overall, 65% of physicians reported regularly using evidence-based guidelines for managing NAFLD, yet 72% reported challenges in providing lifestyle recommendations. A lack of awareness was the most common reported reason for the lack of screening for NAFLD (68% respectively). Conclusions: Despite the growing burden of NAFLD, there is a significant gap in awareness, knowledge, and management among physicians treating patients with cardiometabolic comorbidities, particularly cardiologists. Hepatologists and gastroenterologists could play a role in educating their fellow physicians.</p

Segmental volvulus of the ileum without malrotation in an infant: A case report

AbstractIntestinal volvulus usually occur secondary to malrotation, and primary segmental volvulus has rarely been reported. A 12-month-old female infant presented with a 3-day history of excessive vomiting. An ultrasonography revealed a “whirlpool sign” in the right upper abdomen, suggesting small bowel volvulus with obstruction. Laparotomy revealed a twisted, viable loop of small bowel in the right upper abdomen, and abnormal adhesions were noted between the distal and mid ileum, with resulting mesenteric narrowing. Attempted mesenteric widening by dissection of the peritoneum overlying the adhesions failed, because of abnormal, taut mesenteric vessels. Subsequent resection of the involved segment cured the patient. Recurrent obstructive symptoms in an infant can be an atypical presentation of segmental volvulus, and segmental volvulus should be included in the differential diagnosis of such cases

Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations

The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls. B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP