Risk of Severe Infection in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease – A Population-based Cohort Study

Clinical Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 21(13), P. 3346 - 3355.e19

Published: May 27, 2023

Background & AimsIt has been suggested that patients with nonalcoholic fatty liver disease (NAFLD) might be at increased risk of severe infections, but large-scale data from cohorts biopsy-proven NAFLD are lacking.MethodsPopulation-based cohort study including all Swedish adults histologically confirmed (n = 12,133) 1969 to 2017. was defined as simple steatosis 8232), nonfibrotic steatohepatitis 1378), noncirrhotic fibrosis 1845), and cirrhosis 678). Patients were matched ≤5 population comparators 57,516) by age, sex, calendar year, county. national registers used ascertain incident infections requiring hospital admission. Multivariable adjusted Cox regression estimate hazard ratios in histopathological subgroups.ResultsOver a median 14.1 years, 4517 (37.2%) vs 15,075 (26.2%) hospitalized for infections. had higher incidence than (32.3 vs. 17.0/1000 person-years; ratio [aHR], 1.71; 95% confidence interval, 1.63−1.79). The most frequent respiratory (13.8/1000 person-years) urinary tract (11.4/1000 person-years). absolute difference 20 years after diagnosis 17.3%, equal one extra infection every 6 NAFLD. Risk worsening histological severity (simple [aHR, 1.64], 1.84], 1.77], 2.32]. Also compared their full siblings, (aHR, 1.54; 1.40–1.70).ConclusionsPatients significantly hospitalization both the general siblings. Excess evident across stages severity. It lacking. Population-based subgroups. Over 1.40–1.70).

Language: Английский

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Inflammatory processes involved in NASH-related hepatocellular carcinoma

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(1)

Published: Jan. 1, 2023

Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. In recent years nonalcoholic fatty liver disease (NAFLD) becoming a growing HCCs and incidence NAFLD-related expected to further dramatically increase by next decade. Chronic inflammation regarded as driving force NAFLD progression key factor in hepatic carcinogenesis. Hepatic results from persistent stimulation innate immunity response hepatocellular injury gut dysbiosis well activation adaptive immunity. However, relative roles processes HCC are still incompletely characterized. This due complex interplay between different cell populations, which also strongly influenced gut-derived bacterial products, metabolic/nutritional signals. Furthermore, carcinogenic mechanisms NAFLD/NASH appear involve signals mediated hypoxia inducible factors. review discusses data regarding contribution inflammatory cells their possible impact on patient current treatments.

Language: Английский

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Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr−/−.Leiden mice with manifest obesity‐associated NASH

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(8)

Published: July 13, 2022

Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however, it remains unclear whether individual BCAAs can attenuate already established NASH oxidative-inflammatory stress. After 26 weeks run-in on fast food diet (FFD), obese Ldlr-/-.Leiden mice were treated for another 12 either valine or isoleucine (3% FFD) then compared to FFD controls. Valine did not affect obesity, dyslipidemia, gut permeability, fecal fatty acid excretion, but significantly reduced hyperinsulinemia. ALT, CK18-M30, liver steatosis particularly pronounced suppression the microvesicular component (-61% by -71% isoleucine). Both decreased intrahepatic diacylglycerols 4-hydroxynonenal immunoreactivity, marker oxidative stress-induced lipid peroxidation. Functional genomics analysis demonstrated that affected BCAA genes, deactivated master regulators anabolic pathways related (e.g., SREBPF1), activated mitochondrial biogenesis PPARGC1A) catabolism ACOX1, AMPK). This correction critical metabolic gene expression level was accompanied significant decrease histological inflammation, FFD-stimulated cytokine chemokine proteins KC/CXCL1, MCP-1/CCL2, MIP-2/CXCL2 their pathways. In conclusion, dietary intervention corrected diacylglycerols, multiple processes, histology profound hepatoprotective effects stress inflammatory proteins.

Language: Английский

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The Crosstalk Between Liver Sinusoidal Endothelial Cells and Hepatic Microenvironment in NASH Related Liver Fibrosis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 28, 2022

Chronic liver injury can be caused by many factors, including virus infection, alcohol intake, cholestasis and abnormal fat accumulation. Nonalcoholic steatohepatitis (NASH) has become the main cause of fibrosis worldwide. Recently, more evidences show that hepatic microenvironment is involved in pathophysiological process induced NASH. Hepatic consists various types cells intercellular crosstalk among different sinusoids. Liver sinusoidal endothelial (LSECs), as gatekeeper microenvironment, play an irreplaceable role homeostasis alterations microenvironment. Many recent studies have reported during progression NASH to fibrosis, LSECs are stages mediated a series mechanisms. Therefore, here we review key between (steatosis, inflammation, fibrosis), well promising therapeutic strategies targeting LSECs.

Language: Английский

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Immune cells and their derived microRNA-enriched extracellular vesicles in nonalcoholic fatty liver diseases: Novel therapeutic targets

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 243, P. 108353 - 108353

Published: Feb. 2, 2023

Language: Английский

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NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis

Science Immunology, Journal Year: 2023, Volume and Issue: 8(87)

Published: Sept. 29, 2023

Metabolic-associated fatty liver disease (MAFLD) is a spectrum of clinical manifestations ranging from benign steatosis to cirrhosis. A key event in the pathophysiology MAFLD development nonalcoholic steatohepatitis (NASH), which can potentially lead fibrosis and hepatocellular carcinoma, but triggers MAFLD-associated inflammation are not well understood. We have observed that lipid accumulation hepatocytes induces expression ligands specific activating immune receptor NKG2D. Tissue-resident innate-like T cells, most notably γδ activated through NKG2D secrete IL-17A. IL-17A licenses produce chemokines recruit proinflammatory cells into liver, causes NASH fibrosis. NKG2D-deficient mice did develop dietary models had decreased incidence hepatic tumors. The frequency + blood patients with correlated directly pathology. Our findings identify molecular mechanism stressed trigger context MAFLD.

Language: Английский

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Anti-Angiogenic Effects of Natural Compounds in Diet-Associated Hepatic Inflammation

Nutrients, Journal Year: 2023, Volume and Issue: 15(12), P. 2748 - 2748

Published: June 14, 2023

Alcoholic liver disease (ALD) and non-alcoholic fatty (NAFLD) are the most common causes of chronic increasingly emerging as a global health problem. Such disorders can lead to damage, resulting in release pro-inflammatory cytokines activation infiltrating immune cells. These some features ALD progression ASH (alcoholic steatohepatitis) NAFLD NASH (non-alcoholic steatohepatitis). Hepatic steatosis, followed by fibrosis, continuous accompanied angiogenesis. This process creates hypoxia, which activates vascular factors, initiating pathological angiogenesis further fibrosis. forms vicious cycle ongoing damage progression. condition exacerbates injury may contribute development comorbidities, such metabolic syndrome well hepatocellular carcinoma. Increasing evidence suggests that anti-angiogenic therapy have beneficial effects on these hepatic their exacerbation. Therefore, there is great interest deepen knowledge molecular mechanisms natural products could both prevent control diseases. In this review, we focus role major compounds against steatohepatitis determine potential therapeutic benefits treatment inflammation caused an imbalanced diet.

Language: Английский

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Antiangiogenic Effects of Natural Compounds in Hepatic Inflammation

Published: May 18, 2023

Alcoholic Liver Disease (ALD) and Non-Alcoholic Fatty (NAFLD) are the most common causes of chronic liver disease increasingly emerging as a global health problem. Such disorders can lead to damage, resulting in release pro-inflammatory cytokines activation infiltrating immune cells. These some features ALD progression ASH (alcoholic steatohepatitis) NAFLD NASH (non-alcoholic steatohepa-titis). Hepatic steatosis subsequent fibrosis, whose continuous is accompanied by angiogenesis, hypoxia, inducing vascular factors, which turn triggers pathological angiogenesis vicious cycle. This condition further exacerbates injury may contribute development comorbidities, such metabolic syndrome well hepatocellular carcinoma. Increasing evidence suggests that antiangiogenic therapy have beneficial effects on these hepatic their exacerbation. Therefore, there great interest deepen knowledge molecular mechanisms natural products could both prevent control diseases. In this review, we focus role major antian-giogenic compounds against steatohepatitis determine potential therapeutic benefits treatment inflammation.

Language: Английский

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Implications of innate immune sexual dimorphism for MASLD pathogenesis and treatment

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(7), P. 614 - 627

Published: June 12, 2024

Language: Английский

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Association between neutrophil-to-high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease: evidence from NHANES 2017–2020

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 15, 2025

Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic (MASLD) is closely associated with chronic inflammation and lipid metabolism disorders. The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) an integrative marker reflecting inflammatory responses disorders various diseases. This cross-sectional study aimed to determine the association between NHR NAFLD, MASLD, fibrosis. Data for this were obtained from 2017-2020 National Health Nutrition Examination Survey (NHANES), we employed weighted multiple regression restricted cubic spline (RCS) analysis assess relationship Additionally, performed stratified analyses based on gender, age, body mass index, diabetes, hypertension, smoking status, history of cardiovascular evaluate consistency these associations across different subgroups. A total 6,526 participants included in study. 2,839 (weighted 44.1%) diagnosed NAFLD 2,813 43.7%) MASLD. After adjusting confounders, was positively risk NAFLD/MASLD, correlation particularly significant subgroups females, those without diabetes (p < 0.05). By quartile, NAFLD/MASLD increased progressively higher levels (P trend <0.001). In addition, RCS showed a nonlinear fibrosis (P-non-linear <0.05). may serve as potential fibrosis, lowering could help reduce incidence conditions.

Language: Английский

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