Livers, Volume 1, Issue 2 (June 2021) – 4 articles

Physalin B belongs to a family of Physalins that can be isolated from the genus Physalis (Solanaceae). In traditional Chinese Medicine, Physalis angulata L. is frequently used to treat a variety of illnesses such as dermatitis, trachitis, rheumatism, and hepatitis. Physalin B promotes cellular apoptosis and has antitumor, antimalarial, and antimycobacterial activities. Two recent studies evaluated the therapeutic activities of Physalin B in pre-clinical hepatic disease models. In this comment, a brief summary of the most important findings of these two studies is given and discussed. Full article

Pyruvate metabolism is critical for all mammalian cells. The pyruvate dehydrogenase complex couples the pyruvate formed as the primary product of glycolysis to the formation of acetyl-CoA required as the primary substrate of the citric acid cycle. Dysregulation of this coupling contributes to alterations in metabolic flexibility in obesity, diabetes, cancer, and more. The pyruvate dehydrogenase kinase family of isozymes phosphorylate and inactive the pyruvate dehydrogenase complex in the mitochondria. This function makes them critical mediators of mitochondrial metabolism and drug targets in a number of disease states. The liver expresses multiple PDKs, predominantly PDK1 and PDK2 in the fed state and PDK1, PDK2, and PDK4 in the starved and diabetic states. PDK4 undergoes substantial transcriptional regulation in response to a diverse array of stimuli in most tissues. PDK2 has received less attention than PDK4 potentially due to the dramatic changes in transcriptional gene regulation. However, PDK2 is more responsive than the other PDKs to feedforward and feedback regulation by substrates and products of the pyruvate dehydrogenase complex. Although underappreciated, this makes PDK2 particularly important for the minute-to-minute fine control of the pyruvate dehydrogenase complex and a major contributor to metabolic flexibility. The purpose of this review is to characterize the underappreciated role of PDK2 in liver metabolism. We will focus on known biological actions and physiological roles as well as what roles PDK2 may play in disease states. We will also define current inhibitors and address their potential as therapeutic agents in the future. Full article

The presence of hepatic steatosis and inflammation is increasingly associated with both metabolic and alcohol-related liver conditions. Both are on the increase globally and, apart from liver transplantation, there are no licensed therapies that target the full complement of disease features. The presence of some shared pathogenic mechanisms and histological features in NAFLD and ALD suggests that it may be possible to develop markers for prognostication or staging, or indeed new therapeutic tools to treat both conditions. One such example of an approach exists in the form of the NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway. Activation of the NLRP3 inflammasome results in hepatocyte pyroptosis, persistence, and amplification of liver inflammation and activation of profibrogenic signaling cascades. Thus, targeting elements of the pathway in NAFLD and ALD may provide a tractable route to pharmacological therapy. In this review, we summarize the contribution of this inflammasome to disease and review the current options for therapy. Full article

Background: Esophageal varices occur at middle to advanced stages of cirrhosis and are associated with increased mortality due to their potential for rupture and bleeding. The aim of this study is to examine the accuracy of a surrogate marker, Mac-2 binding protein glycosylation isomer (M2BPGi), for screening high-risk esophageal varices in cirrhotic patients. Methods: Ninety-four cirrhotic patients who underwent endoscopy screening at Cipto Mangunkusumo Hospital, Jakarta, Indonesia were included. Patients with a history of ligation, portal vein thrombosis, or hepatocellular carcinoma were excluded. All enrolled patients underwent ultrasonography, transient elastography, and laboratory tests. The HISCL-5000 Sysmex analyzer was used to measure M2BPGi levels. Results: Of these 94 patients, 27 had high-risk esophageal varices and 67 had non-high-risk esophageal varices. M2BPGi levels were higher in patients with high-risk esophageal varices compared with those with non-high-risk esophageal varices (cutoff index (COI) of 11.4 vs. 3.7, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of M2BPGi with a cutoff value of 5 COI was 92.6%, 70.1%, 55.6%, and 95.9%, respectively. Conclusions: M2BPGi could be used as a non-invasive surrogate marker for ruling out high-risk esophageal varices in cirrhotic patients. This method is cheap and non-invasive and could be used as a screening tool in resource-limited settings. Full article