Apolipoprotein C-III (apo C-III) is an important regulator of metabolism of triglyceride-rich lipoproteins that include hepatically-derived very low-density lipoproteins, intestinally derived chylomicrons, and remnant lipoproteins. Apo C-III is carried on triglyceride-rich lipoproteins, but exchanges bidirectionally with high-density lipoprotein particles. Apo C-III inhibits lipoprotein lipase (LPL), a key mediator of clearance of triglycerides from plasma, thereby contributing to hypertriglyceridemia. Apo C-III is also involved in hepatic VLDL synthesis and secretion, interferes with apo E-mediated clearance of triglyceride-rich lipoproteins, has proinflammatory properties, and has a causative role in development of atherosclerotic cardiovascular disease. Familial chylomicronemia syndrome (FCS) is a rare recessive condition caused by defects in LPL, or four associated proteins, and is associated with severe hypertriglyceridemia and recurrent pancreatitis. Standard triglyceride-lowering interventions lack efficacy in patients with FCS, so there has been a quest to develop efficacious and safe medications for treatment of FCS. In December 2024, olezarsen, an antisense oligonucleotide medication targeting apo C-III, was FDA approved for treatment of patients with FCS. It substantially lowered levels of apo C-III and triglycerides in plasma and reduced the incidence of pancreatitis by 88%. Plozasiran, an experimental small interfering RNA compound targeting apo C-III that may be approved in late 2025, also substantially lowered levels of apo C-III and triglycerides in plasma and reduced pancreatitis risk by 83%. The availability of olezarsen, and possible availability of plozasiran later this year, has ushered in a new era of highly efficacious treatments for FCS that can prevent pancreatitis and improve quality of life.

Chronic liver disease (CLD), a significant ailment, contributes to nearly two million deaths annually. CLD can be caused by alcohol consumption, fat, viral infections, and genetic disorders. Accurate diagnosis and application of therapeutics are crucial strategies for enhancing the management of CLD. The CRISPR-Cas system, originally a prokaryotic innate immunity mechanism, has evolved into a current-generation tool for therapeutic and diagnostic applications. The cis-cleavage feature of the CRISPR-Cas system involves crRNA-guided specific target cleavage. This mechanism is utilized for the development of therapeutics. Few CRISPR-Cas systems possess the additional feature of trans-cleavage, which is non-specific cleavage, also known as collateral cleavage. This unique feature can be exploited to generate diagnostics. In viral hepatitis, CRIPSR-Cas systems have been concurrently applied and reported for viral genome-targeted therapeutics and detection systems. Research on alcoholic and non-alcoholic fatty diseases mainly focuses on CRISPR-Cas therapeutics targeting disease progression factors. Also, CRISPR-Cas-based gene editing can be used to manage genetic disorders. In hepatocellular carcinoma, CRISPR-Cas systems are used for oncogene-targeted therapies and biomarker diagnostics. Various viral and non-viral delivery systems for CRISPR-Cas are been proposed for developing therapeutic applications. Despite limited progress, CRISPR-Cas systems have significant potential for broader application in CLD. This review describes the comprehensive use of the CRISPR-Cas system in experimental therapeutic and diagnostic approaches for CLD.

Background: Artificial intelligence (AI) technologies have the potential to transform many aspects of patient care and is playing an increasing role in health care in diagnostics and patient management. Several studies have already demonstrated that AI can perform as well as or better than humans at key healthcare tasks. The aim of this study was to evaluate and compare the utility of the AI chatbots ChatGPT and Deepseek to answer everyday chemical pathology queries as handled by the registrars in the Chemical Pathology Department at Inkosi Albert Luthuli Central Hospital in Durban, South Africa. Method: All queries received by the registrars over a month period were documented and answers from traditional sources such as laboratory procedures and sample handbooks were documented. The queries were later asked to ChatGPT and Deepseek and further evaluated and the answers evaluated by two blinded senior pathologists in terms of suitability and accuracy of responses and key word recognition. Results: A total of 37 queries were asked to the chatbots. Based on average scoring of the two reviewers 97% (n = 36/37) of queries for ChatGPT responses and 73% (n = 27) for Deepseek were ranked 3 and above for suitability and accuracy. The poorly scoring responses from both Deepseek and ChatGPT related to questions that were very specific to the local laboratory or testing in the laboratory. Conclusion: A longer-term evaluation and verification of ChatGPT as a resource to assist with lab related queries is required. It may be a useful resource not only to the trainee chemical pathology registrar but to under-resourced health care settings where pathologist support may not be present.

The triglyceride-glucose (TyG) index, is a promising biomarker of Metabolic Syndrome (MetS), Type-2 Diabetes (T2DM) and premature atherosclerotic cardiovascular diseases (ASCVD). Whilst increased inflammation is a crucial mechanism in the pathogenesis of these disorders there is a general paucity of data on the association of the TyG index and inflammation. Accordingly, in the present report we investigated the relationship between tertiles of TyG index and accepted measures of inflammation, the ratios of Neutrophil (PMN):HDL-C and Monocyte(Mono):HDL-C in a cohort of 99 individuals (41 controls and 58 patients with MetS). Both PMN:HDL-C and Mono:HDL-C ratios increased significantly with increasing tertiles of the TyG index and both ratios correlated significantly with the TyG index. Also there was a significant correlation with certain biomarkers of inflammation which also increased over tertiles of PMN:HDL-C and Mono:HDL-C. In conclusion, in this cross-sectional study, we provide further support for a pro-inflammatory phenotype with an increase in the TyG index as manifest by increases in the ratio of the professional phagocytes (neutrophils and monocytes) to HDL-C, as a potential mechanism to explain the increase risk for cardio-metabolic syndromes.

POEMS is a rare paraneoplastic syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Castleman disease (angiofollicular lymph node hyperplasia) and elevation of serum vascular endothelial growth factor (VEGF) are associated features as well. Pathogenesis of POEMS syndrome is still unclear, although a loss of balance between proinflammatory and anti-inflammatory cytokines is considered the underlying pathophysiology. Hypogonadism is the most common endocrinopathy encountered in POEMS syndrome. We report the case of a 45-yearold man with history of hypogonadism who developed Castleman disease. He was eventually diagnosed with POEMS syndrome upon developing polyneuropathy, his VEGF levels were elevated, and additionally, he was found to have subclinical hypothyroidism. Clinical and biochemical response to therapy and the course of his disease are presented. With treatment and normalization of his VEGF levels, his repeat thyroid function testing showed a decrease in his thyroid stimulating hormone levels to normal range. His hypogonadism continued to require testosterone replacement therapy. A potential role of cytokines and angiogenic factors in the development of the disease including the endocrinopathy component, is discussed. It is unclear whether VEGF has a role in the etiopathogenesis of the endocrinopathies or perhaps it is simply a marker of disease activity, with a low disease activity correlating with the recovery of the thyroid function. Further studies are needed to elucidate the underlying mechanisms, although we suspect it likely involves, at least in part, inflammatory cytokines and angiogenic factors.