Low density lipoproteins (LDL) reduction remains the key goal for reducing the risk of atherosclerotic cardiovascular diseases (CVD) in people with high residual risk and metabolic complications including liver disease. Notwithstanding, epidemiological projections support a key role of liver-derived apolipoprotein B (ApoB) containing lipoproteins, namely very low density lipoproteins (VLDL) and their “remnants” (TG), undergoing the activity of lipases, in eliciting atherosclerotic inflammatory sequelae of a comparable order of magnitude to that of LDL. Disparate experimental evidence supports that triglycerides (TG), residual cholesterol content, or the large apolipoprotein set on the surface of these lipoproteins can elicit a number of plausible immune-inflammatory mechanisms that foster the vascular atherosclerotic process. Therapeutic options that convincingly lowered the plasma levels of liver-derived ApoB containing lipoproteins, either by reducing the hepatic synthesis or by improving the peripheral lipolysis of the lipid content, did not exert robust CVD risk reduction, and the effect on inflammation was questionable. Understanding the mechanisms linking liver-derived lipoproteins with chronic inflammation will provide pathophysiological insights for the identification of new therapeutic targets for people at high CVD risk and with metabolic complications. In this perspective, this topic is of immediate interest for the prevention of CVD in patients affected by non-alcoholic fatty liver disease (NAFLD) and, even more, for NAFLD patients with diabetes, insulin resistance, or other comorbidities (metabolic-associated fatty liver disease). This review resumes the principal physio-pathological insights regarding the metabolism of liver-derived lipoproteins and provides an update on the current pharmacological options that can be considered for improving CVD prevention in metabolic liver diseases.
Aim: The optimal screening strategy for advanced liver fibrosis in overweight and obese patients is unknown. The aim of this study is to compare the performance of different strategies to select patients at high risk of advanced liver fibrosis for screening using non-invasive tools.
Methods: All patients underwent: liver 1H-MRS and percutaneous liver biopsy (in those with nonalcoholic fatty liver disease [NAFLD]). Unique selection strategies were compared to determine the best screening algorithm: (A) A "metabolic approach": selecting patients based on HOMA-IR ≥ 3; (B) A "diabetes approach": selecting only patients with type 2 diabetes; (C) An "imaging approach": selecting patients with hepatic steatosis based on 1H-MRS; (D) A "liver biochemistry approach": selecting patients with elevated ALT (i.e., ≥ 30 IU/L for males and ≥ 19 IU/L for females); and (E) Universal screening of overweight and obese patients. FIB-4 index, NAFLD fibrosis score, and APRI were applied as screening strategies.
Results: A total of 275 patients were included in the study. Patients with advanced fibrosis (n = 29) were matched for age, gender, ethnicity, and BMI. Selecting patients by ALT elevation provided the most effective strategy, limiting the false positive rate while maintaining the sensitivity compared to universal screening. Selecting patients by any other strategy did not contribute to increasing the sensitivity of the approach and resulted in more false positive results.
Conclusion: Universal screening of overweight/obese patients for advanced fibrosis with non-invasive tools is unwarranted, as selection strategies based on elevated ALT levels lead to the same sensitivity with a lower false positive rate (i.e., fewer patients that would require a liver biopsy or referral to hepatology).
Primary nonalcoholic fatty liver disease (NAFLD) is bi-directionally associated with the metabolic syndrome and its constitutive features (“factors”: impaired glucose disposal, visceral obesity, arterial hypertension, and dyslipidemia). Secondary NAFLD occurs due to endocrinologic disturbances or other cofactors. This nosography tends to be outdated by the novel definition of metabolic associated fatty liver disease (MAFLD). Irrespective of nomenclature, this condition exhibits a remarkable pathogenic heterogeneity with unpredictable clinical outcomes which are heavily influenced by liver histology changes. Genetics and epigenetics, lifestyle habits [including diet and physical (in)activity] and immunity/infection appear to be major cofactors that modulate NAFLD/MAFLD outcomes, including organ dysfunction owing to liver cirrhosis and hepatocellular carcinoma, type 2 diabetes, chronic kidney disease, heart failure, and sarcopenia. The identification of cofactors for organ dysfunction that may help understand disease heterogeneity and reliably support inherently personalized medicine approaches is a research priority, thus paving the way for innovative treatment strategies.
People with diabetes mellitus (DM) undergo more elective surgery than those without DM; however, up to half of the patients are undiagnosed when referred for surgery. This is an opportunity to intervene and instigate a management plan. Preoperative strategies may vary based on coexisting medical diseases such as obesity and the availability of resources with the aim of achieving glycaemic control while also treating coexisting conditions. In the context of obesity, there is substantial overlap in some of the treatment strategies. Guidelines, such as those from the UK Centre for Perioperative Medicine, suggest target glycated haemoglobin levels, preoperative fasting blood glucose levels, and when to defer an elective operation or instigate treatment to proceed if deemed safe. Preoperatively glycaemic control is often achieved pharmacologically, and newer agents, including glucagon-like peptide one receptor agonists (GLP1-RA) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, are emphasised in the preoperative management of diabetes mellitus, particularly if obesity is also present. A very low-energy diet is an underutilised but well-evidenced method of achieving both glycaemic control and weight loss with a particularly dominant effect on liver fat which is helpful for people who are due to undergo abdominal surgery. Bariatric-metabolic procedures are of growing interest as bridging interventions to surgery and are more commonly used for obesity, but they also have a well-recognized impact on the improvement and remission of DM. This review gives an overview of the necessity of preoperative identification of DM and strategies for management. Intra-operative glycaemic control is also discussed, and the role of stress hyperglycaemia perioperatively.