steatosis and liver transplantation

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy...

BACKGROUND: Quantification of macrosteatosis (MS) in the liver is important given that it has shown to directly correlate with adverse post-liver transplant (LT) outcomes. With advances in medical technology and an implicit understanding of pathology, noninvasive methods of quantitatively assessing MS are in various stages of development. Each of these methods is based on the physical principles of differences between a fat-laden hepatocyte and a normal one. METHODS: In this regard, after a proof-of-concept study on a prototype for a simple, real-time, handheld device using the principle of diffuse reflectance spectroscopy, this study presents an upgraded point-of-care (POC) device for the noninvasive assessment of hepatic MS in liver donors...

Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic liver disorders, with a high prevalence but no approved treatment. Therefore, it is indispensable to find a trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) is strongly associated with NAFLD. SIRT1 activation or overexpression attenuate NAFLD, while SIRT1 deficiency aggravates NAFLD...

IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. OBJECTIVE: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD...

The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended criteria donors (ECDs). Using the UNOS/OPTN STAR dataset we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a Differences-in-Differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization...

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD, has ascended to prominence as the predominant chronic liver disease in Western countries and now stands as a leading cause of liver transplantations. In the more advanced stage, Metabolic Dysfunction-Associated Steatohepatitis (MASH), may lead to fibrosis, a gateway to cirrhosis, liver cancer, and liver failure. Despite extensive research and exploration of various drug mechanisms, the anticipation for the inaugural approved drug to materialize by 2024 is palpable, marking a significant milestone...

BACKGROUND: Fatty livers are widely accepted as marginal donors for liver transplantation but are more susceptible to liver ischemia and reperfusion (IR) injury. Increased macrophage-related inflammation plays an important role in the aggravation of fatty liver IR injury. Here, we investigate the precise mechanism by which endoplasmic reticulum (ER) stress activates macrophage NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling by regulating mitochondrial calcium overload in fatty liver IR...

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery...

BACKGROUND: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. METHODS: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020...

In the realm of liver transplantation, accurately determining hepatic steatosis levels is crucial. Recognizing the essential need for improved diagnostic precision, particularly for optimizing diagnosis time by swiftly handling easy-to-solve cases and allowing the expert time to focus on more complex cases, this study aims to develop cutting-edge algorithms that enhance the classification of liver biopsy images. Additionally, the challenge of maintaining data privacy arises when creating automated algorithmic solutions, as sharing patient data between hospitals is restricted, further complicating the development and validation process...

BACKGROUND: Primary dysfunction and rejection are more common in donor liver tissues with steatosis. AMP-activated protein kinase (AMPK) assumes organ-protective functions during ischemia. Metformin was used for the activation of AMPK in hepatocytes. The aim of this study is to investigate the effectiveness of metformin administration for the reversal of cold-ischemia-induced damage in hepatosteatosis. MATERIAL AND METHODS: Seven-week-old C7BL56 male-mice (n = 109) were separated into four groups depending on diet type and metformin use...

Non-alcoholic fatty liver disease (NAFLD) is a complex disease characterized by a massive accumulation of lipids in the liver, with a continuous progression of simple steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is associated with obesity, insulin resistance, and metabolic syndrome; it is a severe public health risk and is currently the most common liver disease of the world. In addition to the fatty infiltration of the liver in non-alcoholic fatty liver disease patients, the field of liver transplantation faces similar obstacles...

It has been established that more than mild large-droplet macrovesicular steatosis (LD-MAS) is associated with increased risk of graft non-function. In contrast, even severe small-droplet macrovesicular steatosis (SD-MAS) has been found to be less prognostically significant. It remains unclear if a donor liver with diffuse microvesicular steatosis is associated with an increased risk of graft dysfunction. A 56-year-old male with alcoholic cirrhosis was transplanted with a liver from a 42-year-old overweight male donor after brain death...

AIM: To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH). METHODS: We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+ -LSECs were determined using coculture and bone marrow transplantation (BMT) methods. RESULTS: Three special clusters of single-LSEC were differentiated. C-Kit+ -LSECs of cluster 0, Msr1+ -LSECs of cluster 1 and Bmp4+ Selp+ -VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH...

BACKGROUND: Fluorescence-based confocal microscopy (FCM) can be used to create virtual H&E sections in real time. So far, FCM has been used in dermato-, uro-, and gynecopathology. FCM allows the creation of a completely digitized frozen section, which could potentially replace conventional frozen sections in the future. OBJECTIVE: The aim of the current work is to implement FCM technology as a component of fully digitized processes in the pathological workflow...

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0...

Background Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis. It is the leading cause of liver-related mortality, end-stage liver disease, and the need for liver transplantation. This study aimed to assess the level of awareness regarding NAFLD among the adult population in Jazan, Saudi Arabia, and to explore the determinants of the awareness level. Method This descriptive cross-sectional study was conducted among the general population of Jazan, Saudi Arabia, under the supervision of Jazan University, excluding those with end-stage liver failure...

Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. No approved effective therapeutic medicine is available to date for NAFLD. Helminth therapy is believed to be a novel direction and therapeutic strategy for NAFLD. Our previous study showed that Trichinella spiralis -derived antigens ( TsAg ) had the potential for partially alleviating obesity via regulating gut microbiota. However, the effect of TsAg on NAFLD remains unclear...

Patients post liver transplant (LT) with progressive familial intrahepatic cholestasis type 1 (PFIC-1) often develop progressive graft steatohepatitis, intractable diarrhea, and growth failure. A total internal biliary diversion (TIBD) during an LT may prevent or reverse these adverse events. Children with PFIC-1 who underwent an LT at our institute were divided into 2 groups, A and B based on the timeline where we started offering a TIBD in association with LT. Pre-LT parameters, intraoperative details, and posttransplant complications like graft steatosis and diarrhea were also analyzed between the 2 groups, and their growth velocity was measured in the follow-up period...

Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of MASLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IRI because the mechanisms by which steatosis leads to increased injury are unclear...