Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies

Königshofer, Philipp; Hofer, Benedikt; Brusilovskaya, Ksenia; Simbrunner, Benedikt; Petrenko, Oleksandr; Wöran, Katharina; Herac, Merima; Stift, Judith; Lampichler, Katharina; Timelthaler, Gerald; Bauer, Dávid; Hartl, Lukas; Robl, Bernhard; Sibila, Maria; Podesser, Bruno K.; Oberhuber, Georg; Schwabl, Philipp; Mandorfer, Mattias; Trauner, Michael; Reiberger, Thomas

doi:10.1002/hep.32220

Cited by 27 publications

(23 citation statements)

References 51 publications

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“…( 11 ) In addition, SS might be a more dynamic marker, reflecting “acute” changes in HVPG that are not detected by LS (e.g., a decrease in portal pressure occurring immediately after and within 30 minutes of transjugular intrahepatic portosystemic shunt [TIPS] ( 79 ) ) or changes in HVPG that occur mainly due to pharmacologic inhibition of hyperdynamic circulation/splanchnic blood flow. ( 80 ) For example, in a single‐cohort, proof‐of‐concept study in patients with CSPH in cirrhosis and high‐risk varices, a change in SS predicted a hemodynamic response (≥20% decrease in HVPG or an HVPG <12 mmHg) to the NSBB carvedilol whereas LS and HVPG did not. ( 76 ) Another study investigated changes in SS measured by TE in 20 patients with cirrhosis and high‐risk varices undergoing sequential HVPG measurement before and during NSBB therapy.…”

Section: Noninvasive Assessments Of Portal Hypertension Of Prognostic...mentioning

confidence: 99%

The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis

Reiberger

2021

Hepatol Commun

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Patients with compensated advanced chronic liver disease who develop clinically significant portal hypertension (CSPH) are at high risk for hepatic decompensation and mortality if left untreated. Liver biopsy and hepatic venous pressure gradient (HVPG) measurements are the current gold standard procedures for determining fibrosis severity and diagnosing CSPH, respectively; however, both are invasive, limiting their use in clinical practice and larger trials of novel agents. As such, there is an unmet clinical need for reliable, validated, noninvasive measures to detect CSPH and to further assess portal hypertension (PH) severity. Alterations in the biomechanical properties of the liver or spleen in patients with cirrhosis can be quantified by tissue elastography, which examines the elastic behavior of tissue after a force has been applied. A variety of methods are available, including magnetic resonance elastography, shear‐wave elastography, and the most thoroughly investigated measure, vibration‐controlled transient elastography. Liver stiffness (LS) and spleen stiffness (SS) measurements offer valuable alternatives to detect and monitor CSPH. Both LS and SS correlate well with HVPG, with thresholds of LS >20‐25 kPa and SS >40‐45 kPa indicating a high likelihood of CSPH. Because SS is a direct and dynamic surrogate of portal pressure, it has the potential to monitor PH severity and assess PH improvement as a surrogate marker for clinical outcomes. Importantly, SS seems to be superior to LS for monitoring treatment response in clinical trials focusing on reducing PH.

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Section: Noninvasive Assessments Of Portal Hypertension Of Prognostic...mentioning

confidence: 99%

The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis

Reiberger

2021

Hepatol Commun

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“…Liver damage was also reported in animals infected for 6 months with fibrotic nodules (stage IV liver fibrosis or cirrhosis) in most of the lobes (Perez et al 1999). Collagen accumulation in liver fibrosis can increase vascular resistance and portal hypertension, both of which are critical factors for complicating in advanced fibrosis (Konigshofer et al 2021). Indart et al (2019) also reported that fluid accumulation in the abdominal cavity in calves was found due to widespread liver fibrosis.…”

Section: Discussionmentioning

confidence: 91%

“…Collagen accumulation in liver fibrosis can increase vascular resistance and portal hypertension, both of which are critical factors for complicating in advanced fibrosis (Konigshofer et al 2021). Clinical ascites in cattle with chronic fasciolosis are closely related to the presence of collagen fibril deposits and portal hypertension (Buob et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Fibrosis and Collagen-I Accumulation in Bali Cattle Liver Tissue Infected with Fasciola gigantica

2022

Int J Vet Sci

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This study aims to determine the histopathological changes of fibrosis and accumulation of collagen I in liver tissue of Bali cattle infected with Fasciola gigantica in the Badung district, Bali Indonesia. On examination of 100 Bali cattle livers at the traditional abattoir of Badung, 37 of them were found to contain F. gigantica worms in both the bladder and bile ducts. The liver tissue was then fixed with 10% formalin for processing and stained with hematoxylin-eosin dyes. The liver sample preparation in the coating slide was also reacted with rabbit anti-collagen-I antibody. On histopathological examination, it was found that the distribution of fibrosis varied in the portal, interlobular, and bridging fibrosis areas. Immunohistochemical examination showed an immunoreactive reaction using rabbit anti-collagen I in the portal area with strong and weak intensity in the interlobular area and in bridging fibrosis. Fibrosis and accumulation of collagen I in Bali cattle infected with F. gigantica at the traditional abattoir of Badung district, Bali Indonesia was found in the portal, interlobular, and bridging fibrosis areas.

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“…Along with other factors, the increased collagen content in the liver fibrogenesis contributed to an increase in intrahepatic vascular resistance, resulting in the development of portal hypertension, which is a critical factor for complications in advanced fibrosis [ 31 ]. Recently, it has been shown that the collagen measurement correlates to the portal pressure in animal models of fibrosis, whereas in patients, it correlates to the hepatic venous pressure gradient [ 31 ]. Thus, the collagen content is still one indirect method for monitoring the stage of liver fibrosis and can be used as a prognostic tool to manage the therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

et al. 2022

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During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.

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Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies

Cited by 27 publications

References 51 publications

The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis

The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis

Fibrosis and Collagen-I Accumulation in Bali Cattle Liver Tissue Infected with Fasciola gigantica

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

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