Background and Aim
Metabolic dysfunction‐associated steatotic liver disease (MASLD) has been proposed as an alternative for the validated definition of metabolic dysfunction‐associated fatty liver ...disease (MAFLD). We compared the abilities of MAFLD and MASLD to predict the risk of atherosclerotic cardiovascular disease (ASCVD).
Methods
Six thousand and ninety six participants from the 2017 to 2020 National Health and Nutrition Examination Survey cohort who received a thorough medical health check‐up were chosen for the study. The associations between fatty liver status and coronary risk surrogates, such as 10‐year ASCVD risk and self‐reported cardiovascular events, were analysed.
Results
MAFLD and MASLD were identified in 2911 (47.7%) and 2758 (45.2%) patients, respectively. MAFLD (odds ratio OR: 2.14, 95% confidence interval CI, 1.78–2.57, p < .001) was more strongly independently associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI, 1.52–2.18, p < .001) was in comparison with the absence of each condition. However, compared with MAFLD, MASLD alone was not associated with increased ASCVD risk. Multiple logistic regression revealed that MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82; 95% CI: 1.13–7.01; p < .03) than MASLD alone.
Conclusions
Although both MAFLD and MASLD were associated with different ASCVD risks, MAFLD predicted the ASCVD risk better than MASLD. The higher predictive ability of MAFLD compared to MASLD was attributed to metabolic dysfunction rather than moderate alcohol use.
Summary
Background
Patients with liver diseases have complicated haemostatic alternations, resulting in both bleeding and thromboembolic complications, which cannot be sufficiently evaluated by ...conventional coagulation tests (CCTs), such as platelet count or prothrombin time. Thromboelastography (TEG) is a whole blood viscoelastic test which globally reflects changes in the haemostatic system, and its utility in evaluating patients with liver disease is increasingly recognised.
Aims
To review the current evidence and clinical significance of TEG in liver diseases.
Methods
Literature regarding TEG and liver diseases was comprehensively searched.
Results
TEG is associated closely with the severity and aetiology of liver disease, the course of infection and the risk of bleeding and death, but not the risk of portal venous system thrombosis. Additionally, TEG‐guided transfusion protocols can significantly decrease the requirement for blood products compared to those guided by CCTs.
Conclusion
TEG can reflect the haemostatic status of liver diseases more comprehensively than CCTs. It has the potential to assess the severity of liver diseases, predict the risk of bleeding and death in patients with liver disease and guide blood product transfusion. Future studies should standardise the use of TEG for assessing disease severity and development of clinical events and guiding blood product transfusion in patients with liver diseases.
Physiological haemostasis includes primary haemostasis, coagulation cascade, and fibrinolysis, which can be comprehensively reflected by thromboelastography (TEG) test, but not conventional coagulation tests (CCTs). Hypercoagulable and hypocoagulable state can be evaluated by the results of various TEG parameters. There are several factors associated with hypercoagulable and hypocoagulable TEG profile based on the current evidence. Currently, the management of hypercoagulable state indicated by TEG profile is not clear, and TEG guided transfusion protocol has been proposed for the management of hypocoagulable state reflected by the results of various TEG parameters.
Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched ...for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.
AbstractThe gut microbiota has been considered a cornerstone of maintaining the health status of its human host because it not only facilitates harvesting of nutrients and energy from ingested food, ...but also produces numerous metabolites that can regulate host metabolism. One such class of metabolites, the bile acids, are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. These bioconversions modulate the signaling properties of bile acids through the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate diverse metabolic pathways in the host. In addition, bile acids can regulate gut microbial composition both directly and indirectly by activation of innate immune response genes in the small intestine. Therefore, host metabolism can be affected by both microbial modifications of bile acids, which leads to altered signaling via bile acid receptors, and by alterations in the composition of the microbiota. In this review, we mainly describe the interactions between bile acids and intestinal microbiota and their roles in regulating host metabolism, but we also examine the impact of bile acid composition in the gut on the intestinal microbiome and on host physiology.
AbstractLiver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibro-sis, viral infection is most common (hepatitis B and ...C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.
Metabolic (dysfunction)‐associated fatty liver disease has taken importance during the last two years, given the new criteria for diagnosis compared to the previous criteria used to define ...non‐alcoholic fatty liver disease. Multiple studies have also shown that this definition better adjusts to the pathogenesis and patient characteristics with fatty liver.
Fibrosis is a response to chronic liver disease that results in excessive accumulation of extracellular matrix proteins and formation of scar tissue. Fibrosis represents a clinical challenge of ...worldwide significance. Several studies have demonstrated that many natural products and herbal medicines have activity against liver fibrosis, and extracts of milk thistle such as silymarin and silybin are the natural compounds most commonly prescribed for liver diseases. Therefore, we sought to assess and compare the pharmacokinetic properties and bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules and conventional silymarin tablets in healthy Mexican volunteers.
We enrolled 23 healthy volunteers to participate in a prospective, balanced, blind, single-dose, two-way crossover study with a one-week washout period. Fasting participants received either 45 mg silybin-phosphatidylcholine complex or 70 mg silymarin to assess which formulation provided better bioavailability of silybin. Plasma was obtained and analysed for silybin concentration using a validated ultra-performance liquid chromatography-tandem mass spectroscopy method. Pharmacokinetic parameters were obtained by non-compartmental analysis and values were compared by analysis of variance for a crossover design. Ratios of maximum plasma drug concentration and area under the curve (AUC) were obtained and 90% confidence intervals were calculated.
The 23 healthy subjects (11 women, 12 men) who participated in the study were aged 22-31 years old (average: 28), average weight 64.8 kg, height 1.65 m and body mass index 23.5 kg/m
. Plasma levels of silybin were higher after the administration of silybin-phosphatidylcholine complex capsules compared with that after conventional silymarin tablets (P < 0.0001).
The silybin-phosphatidylcholine complex in oily-medium soft-gel capsules seems to provide superior bioavailability. However, clinical studies must be performed to demonstrate its clinical relevance in the treatment of liver diseases.
NCT03440164 ; registered on November 11, 2016.
We report the genetic analysis of a “humanized” hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human apolipoprotein ...E*3‐Leiden and cholesteryl ester transfer protein and fed a “Western” diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci, and pericellular collagen deposition. Time course experiments indicated that while hepatic triglyceride levels increased steadily on the diet, hepatic fibrosis occurred at about 12 weeks. We found that the genetic variation predisposing to NASH and fibrosis differs markedly from that predisposing to simple steatosis, consistent with a multistep model in which distinct genetic factors are involved. Moreover, genome‐wide association identified distinct genetic loci contributing to steatosis and NASH. Finally, we used hepatic expression data from the mouse panel and from 68 bariatric surgery patients with normal liver, steatosis, or NASH to identify enriched biological pathways. Conclusion: The pathways showed substantial overlap between our mouse model and the human disease.
Screening for MAFLD: who, when and how? Pal, Shreya C.; Méndez-Sánchez, Nahum
Therapeutic Advances in Endocrinology and Metabolism,
01/2023, Letnik:
14
Book Review, Journal Article
Recenzirano
Odprti dostop
Metabolic-associated fatty liver disease (MAFLD) is a highly prevalent disease with increasing prevalence worldwide. Currently, no universal screening methods have been standardized, even when this ...disease poses a major health burden. MAFLD as a spectrum of diseases can range from simple steatosis, and steatohepatitis to fibrosis and hepatocellular carcinoma. Its extra-hepatic manifestations are vast and include cardiovascular diseases, extra-hepatic malignancies, cognitive and respiratory alterations. Given its extensive damage targets as well as its high prevalence, timely identification of the high-risk population presenting metabolic dysfunction should undergo universal non-invasive screening methods, which can be carried out through blood tests, easy and effective imaging techniques, such as ultrasound, score calculation and general clinical information brought together from primary patient–physician contact.
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