Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which ...endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the recent years, there have been an increasing number of reports on favourable effects of statins in patients with advanced chronic liver disease. These include reduction in portal pressure, ...improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure, prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver diseases. The present article reviews the current knowledge on the potential applications of statins in chronic liver diseases, from its mechanistic background to objective evidence from clinical studies.
The Child-Pugh classification is one of the commonest and oldest bedside tools utilized in estimating prognosis in patients with cirrhosis. However, its usage as a risk prediction tool or indeed a ...decision-making tool should be revisited. In this review, we discuss some inherent issues with the Child-Pugh classification and present a few contexts in which the current usage of Child-Pugh warrants reassessment, elaborating on its utility in acute variceal bleeding, specifically its role in decision-making on early transjugular intrahepatic portosystemic shunt, as well as its use in the context of hepatocellular carcinoma and drug development and dose adjustment.
Whether preoperative clinically significant portal hypertension (CSPH) has or not an impact on the outcome of surgery for hepatocellular carcinoma (HCC) in patients with compensated cirrhosis is ...debated. This systematic review assesses the impact of CSPH on the outcome of HCC in patients with compensated cirrhosis treated with surgery. We performed a systematic search of the MEDLINE database (articles published in full in English language from 1996 to October 2013) and related bibliography for studies reporting on the postoperative outcomes (3‐ and 5‐year mortality and/or early clinical decompensation) of patients with HCC and compensated cirrhosis treated with surgery according to the presence or absence of CSPH. Independent extraction of articles by two authors using predefined data fields, including study quality indicators, was used; pooled analyses were based on random‐effects models. Eleven studies in total met our inclusion criteria (eight studies for 3‐ and 5‐year postoperative mortality and eight for postoperative clinical decompensation). Moderate heterogeneity among studies for both outcomes was observed, which disappeared after pooling studies using similar methods to assess CSPH. The presence of CSPH increased the risk of 3‐ and 5‐year mortality versus absence of CSPH (pooled odds ratio OR for 3‐year mortality: 2.09; 95% confidence interval CI: 1.52‐2.88; for 5‐year mortality: 2.07; 95% CI: 1.51‐2.84). CSPH also increased the risk of postoperative clinical decompensation (pooled OR: 3.04; 95% CI: 2.02‐4.59). Conclusions: CSPH (evaluated by any method) significantly increases the risk of 3‐ and 5‐year mortality and of clinical decompensation after surgery for HCC. (Hepatology 2015;61:526‐536)
Liver cirrhosis Ginès, Pere; Krag, Aleksander; Abraldes, Juan G ...
The Lancet (British edition),
10/2021, Letnik:
398, Številka:
10308
Journal Article
Recenzirano
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, ...autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
In patients with compensated advanced chronic liver disease (cACLD), the presence of clinically significant portal hypertension (CSPH) and varices needing treatment (VNT) bears prognostic and ...therapeutic implications. Our aim was to develop noninvasive tests‐based risk prediction models to provide a point‐of‐care risk assessment of cACLD patients. We analyzed 518 patients with cACLD from five centers in Europe/Canada with paired noninvasive tests (liver stiffness measurement LSM by transient elastography, platelet count, and spleen diameter with calculation of liver stiffness to spleen/platelet score LSPS score and platelet‐spleen ratio PSR) and endoscopy/hepatic venous pressure gradient measurement. Risk of CSPH, varices, and VNT was modeled with logistic regression. All noninvasive tests reliably identified patients with high risk of CSPH, and LSPS had the highest discrimination. LSPS values above 2.65 were associated with risks of CSPH above 80%. None of the tests identified patients with very low risk of all‐size varices, but both LSPS and a model combining TE and platelet count identified patients with very low risk (<5%) risk of VNT, suggesting that they could be used to triage patients requiring screening endoscopy. LSPS values of <1.33 were associated with a <5% risk of VNT, and 26% of patients had values below this threshold. LSM combined with platelet count predicted a risk <5% of VNT in 30% of the patients. Nomograms were developed to facilitate point‐of‐care risk assessment. Conclusion: A significant proportion of patients with a very high risk of CSPH, and a population with a very low risk of VNT can be identified with simple, noninvasive tests, suggesting that these can be used to individualize medical care. (Hepatology 2016;64:2173‐2184).
LINKED CONTENT
This article is linked to Vaishnav et al papers. To view these articles, visit https://doi.org/10.1111/apt.17868 and https://doi.org/10.1111/apt.17893
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