Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease

Baffy, György

doi:10.1007/s10620-017-4903-5

Cited by 45 publications

(48 citation statements)

References 141 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PHT is defined as HVPG >5 mm Hg and clinically significant PHT is defined as HVPG >10 mm Hg . The importance of mild PHT (HVPG ranging between 5 and 10 mm Hg) in the pathobiology of NAFLD remains incompletely understood . Sinusoidal shear stress in NAFLD is initially caused by steatosis and hepatocellular ballooning, compounded by impaired NO release from SECs, enhanced contractility of HSCs, extracellular matrix deposition, loss of fenestration (“capillarization”) and neovascularization …”

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

“…Changes in molecular pathways implicated in early PHT include impaired insulin‐mediated eNOS phosphorylation suggesting endothelial dysfunction, upregulation of vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, elevated levels of thromboxane A2 and oxidative stress, all potentially contributing to increased intrahepatic vascular resistance . Human observations in non‐cirrhotic liver disease also indicate that portal pressure may begin to rise in the early stages of NAFLD . A recent observational study of 354 patients with biopsy‐proven NAFLD found clinical evidence of PHT in 6% of cases with steatosis but only mild or no fibrosis .…”

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

“…Currently approved pharmaceutical management of clinically significant PHT is limited to the use of non‐selective beta‐blockers . In recent years, a number of molecular candidates have been studied for targeting increased hepatic vascular resistance or hyperdynamic splanchnic circulation with the intention to control PHT . With better understanding of host‐microbiome interactions, potential pharmacological strategies for the prevention and management of PHT may increasingly focus on molecular mechanisms that involve the gut microbiota.…”

Section: Gut Microbiota As a Therapeutic Target In Phtmentioning

confidence: 99%

“…59,60 Human observations in non-cirrhotic liver disease also indicate that portal pressure may begin to rise in the early stages of NAFLD. 53 A recent observational study of 354 patients with biopsy-proven NAFLD found clinical evidence of PHT in 6% of cases with steatosis but only mild or no fibrosis. 61 HVPG exceeded 5 mmHg in 20% of obese patients undergoing transjugular liver biopsy, which confirmed the absence of cirrhosis.…”

Section: Evidence For Increased Portal Pressure In Nafldmentioning

confidence: 99%

See 3 more Smart Citations

Potential mechanisms linking gut microbiota and portal hypertension

Baffy

2018

Liver International

Self Cite

View full text Add to dashboard Cite

Gut microbiota is the largest collection of commensal micro‐organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host‐microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute‐on‐chronic liver failure. Better understanding of the gut‐liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.

show abstract

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

Section: Host‐microbiota Interactions and The Beginnings Of Portal Hymentioning

confidence: 99%

Section: Gut Microbiota As a Therapeutic Target In Phtmentioning

confidence: 99%

Section: Evidence For Increased Portal Pressure In Nafldmentioning

confidence: 99%

See 2 more Smart Citations

Potential mechanisms linking gut microbiota and portal hypertension

Baffy

2018

Liver International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Accumulation of fatty acids and cholesterol within hepatocytes causes hepatocyte ballooning, which leads to sinusoidal compression, increased intrahepatic vascular resistance (IHVR) and increased shear stress, thereby acting as a mechanical stressor on LSEC to promote dysfunction and capillarization [34]. LSEC dysfunction, elicited by continuous vascular stress, is mainly characterized by decreased nitric oxide bioavailability either through impaired eNOS production, or through its reaction with superoxides [32].…”

Section: Liver Sinusoidal Endothelial Cellsmentioning

confidence: 99%

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

Peters¹,

Wilson²,

Borradaile³

2018

Current Opinion in Lipidology

View full text Add to dashboard Cite

Purpose of reviewNon-alcoholic fatty liver disease (NAFLD) appears to be independently associated with the development of atherosclerosis. The biological mechanisms underlying this association are complex, and likely involve liver-resident cell types other than hepatocytes. Thus, we review recent evidence that non-parenchymal hepatic cell responses to lipid excess contribute to the pathogenesis of both NAFLD and atherosclerosis.Recent findingsSignificant independent associations between NAFLD and atherosclerosis have been identified through cross-sectional studies and meta-analyses. Mechanistic studies in cell cultures and in rodent models suggest that liver-resident macrophages, activated hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) mount lipotoxic responses under NAFLD conditions which can contribute to the progression of both NAFLD and atherosclerosis.SummaryNon-parenchymal hepatic cell types exhibit some similarity in their responses to lipid excess, and in their pathogenic mechanisms, which likely contribute to the coordinated progression of NAFLD and atherosclerosis. In response to lipotoxic conditions, macrophages, Kupffer cells and HSC initiate robust inflammatory responses, whereas LSEC generate excess reactive oxygen species (ROS). The extent to which inflammatory cytokines and ROS produced by non-parenchymal cells contribute to the progression of both NAFLD and atherosclerosis warrants further investigation.

show abstract

NAFLD and Cardiovascular and Cardiac Disease: Clinical Implications

Scorletti

Byrne

2020

Non-Alcoholic Fatty Liver Disease

View full text Add to dashboard Cite

Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease

Cited by 45 publications

References 141 publications

Potential mechanisms linking gut microbiota and portal hypertension

Potential mechanisms linking gut microbiota and portal hypertension

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

NAFLD and Cardiovascular and Cardiac Disease: Clinical Implications

Contact Info

Product

Resources

About