Portal hypertension (PH) is the most common complication ofcirrhosis and represents the main driver of hepatic decompensation. The overarching goal of PH treatments in patients with compensated ...cirrhosis is to reduce the risk of hepatic decompensation (i.e development of ascites, variceal bleeding and/or hepatic encephalopathy). In decompensated patients, PH‐directed therapies aim at avoiding further decompensation (i.e. recurrent/refractory ascites, variceal rebleeding, recurrent encephalopathy, spontaneous bacterial peritonitis or hepatorenal syndrome) and at improving survival. Carvedilol is a non‐selective beta‐blocker (NSBB) acting on hyperdynamic circulation/splanchnic vasodilation and on intrahepatic resistance. It has shown superior efficacy than traditional NSBBs in lowering PH in patients with cirrhosis and may be, therefore, the NSBB of choice for the treatment of clinically significant portal hypertension. In primary prophylaxis of variceal bleeding, carvedilol has been demonstrated to be more effective than endoscopic variceal ligation (EVL). In patients with compensated cirrhosis carvedilol achieves higher rate of hemodynamic response than propranolol, resulting in a decreased risk of hepatic decompensation. In secondary prophylaxis, the combination of EVL with carvedilol may prevent rebleeding and non‐bleeding further decompensation better than that with propranolol. In patients with ascites and gastroesophageal varices, carvedilol is safe and may improve survival, as long as no impairment of the systemic hemodynamic or renal dysfunction occurs, with maintained arterial blood pressure as suitable safety surrogate. The target dose of carvedilol to treat PH should be 12.5 mg/day. This review summarizes the evidence behind Baveno‐VII recommendations on the use of carvedilol in patients with cirrhosis.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Fibrosis is the main consequence of any kind of chronic liver damage. Coagulation and thrombin generation are crucial in the physiological response to tissue injury; however, the inappropriate and ...uncontrolled activation of coagulation cascade may lead to fibrosis development due to the involvement of several cellular types and biochemical pathways in response to thrombin generation. In the liver, hepatic stellate cells and sinusoidal endothelial cells orchestrate fibrogenic response to chronic damage. Thrombin interacts with these cytotypes mainly through protease-activated receptors (PARs), which are expressed by endothelium, platelets and hepatic stellate cells. This review focuses on the impact of coagulation in liver fibrogenesis, describes receptors and pathways involved and explores the potential antifibrotic properties of drugs active in hemostasis in studies with cells, animal models of liver damage and humans.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the ...metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
Portal hypertension is the main prognostic factor in cirrhosis. The recent emergence of potent antiviral drugs and new algorithm of treatment for the management of complications due to portal ...hypertension have sensibly changed our perception of cirrhosis that can be now considered as a multistage liver disease whose mortality risk can be reduced by a tailored approach for any stage of risk. Experts recommend to move toward a pathophysiological classification of cirrhosis that considers both structural and functional changes. The hepatic venous pressure gradient HVPG, is the reference gold standard to estimate the severity of portal hypertension in cirrhosis. It correlates with both structural and functional changes that occur in cirrhosis and carries valuable prognostic information to stratify the mortality risk. This article provides a general overview of the pathophysiology and natural course of cirrhosis and portal hypertension. We propose a simplified classification of cirrhosis based on low, intermediate and high mortality stage. The prognostic information provided by HVPG is presented according to each stage. A comparison with prognostic models based on clinical and endoscopic variables is discussed in order to evidence the additional contribute given by HVPG on top of other clinical and instrumental variables widely used in clinical practice.
...he was admitted to our COVID-19 unit and enoxaparin at 4000 IU o.d. was added to the therapy.Table 1. See PDF For the acute presentation of thrombosis, the dose of enoxaparin was increased to 100 ...IU/Kg b.i.d. Active causes of chronic liver disease were excluded (e.g., alcohol, hepatitis C virus, and hepatitis B virus infection). The temporary hypertransaminasemia and hyperbilirubinemia detected at presentation were likely a manifestation of an acute ischemic hepatitis because both arterial and venous hepatic blood flow were impaired due to sepsis-related hypotension and PVT. Inherited and acquired thrombophilia was also excluded, considering the systemic inflammation as the main risk factor for thrombosis.
Nonselective β-blockers improve decompensation-free survival in viremic hepatitis C virus compensated cirrhotic patients with clinically significant portal hypertension, but their protective role ...after sustained virological response by direct-acting antiviral (DAA) is undefined. We evaluated the incidence of decompensation in DAA-cured Child-A patients without high-risk varices. During the 49-month (12-60) follow-up, only one of 148 patients decompensated (ascites), with a 4-year cumulative risk of 1%, but decompensation was associated with hepatocellular carcinoma. The risk of decompensation in DAA cured hepatitis C virus compensated Child-A cirrhotic patients with clinically significant portal hypertension but without high-risk varices is negligible; thus, questioning the need for nonselective β-blocker treatment in this setting (see Visual abstract, Supplemental Digital Content, 1, http://links.lww.com/AJG/B861).
Background
Preliminary reports suggest a hypercoagulable state in COVID-19. Deep vein thrombosis (DVT) is perceived as a frequent finding in hospitalized COVID-19 patients, but data describing the ...prevalence of DVT are lacking.
Objectives
We aimed to report the prevalence of DVT in COVID-19 patients in general wards, blinded to symptoms/signs of disease, using lower extremities duplex ultrasound (LEDUS) in random patients. We tested the association of DVT with clinical, laboratory and inflammatory markers and also reported on the secondary endpoint of in-hospital mortality.
Patients/Methods
n
= 263 COVID-19 patients were screened with LEDUS between March 01, 2020 and April 05, 2020 out of the overall
n
= 1012 admitted with COVID-19.
Results
DVT was detected in
n
= 67 screened patients (25.5%),
n
= 41 patients (15.6%) died during the index hospitalization. Multiple logistic regression demonstrated that only C-reactive protein (odds ratio 1.009, 95% CI 1.004–1.013,
p
< 0.001) was independently associated with the presence of DVT at LEDUS. Both age (odds ratio 1.101, 95% CI 1.054–1.150,
p
< 0.001) and C-reactive protein (odds ratio 1.012, 95% CI 1.006–1.018,
p
< 0.001) were instead significantly independently associated with in-hospital mortality.
Conclusions
The main study finding is that DVT prevalence in COVID-19 patients admitted to general wards is 25.5%, suggesting it may be reasonable to screen COVID-19 patients for this potentially severe but treatable complication, and that inflammation, measured with serum C-reactive protein, is the main variable associated with the presence of DVT, where all other clinical or laboratory variables, age or D-dimer included, are instead not independently associated with DVT.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt ...hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
Display omitted
•Total cross-sectional SPSS area (TSA) predicts survival in patients with advanced chronic liver disease.•The cut-off for TSA that is associated with worse survival corresponds to a single shunt of >10 mm diameter.•This study may impact on the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
