ОЦЕНКА ТЯЖЕСТИ ПОРТАЛЬНОЙ ГИПЕРТЕНЗИИ ПРИ ЦИРРОЗЕ ПЕЧЕНИ

We attempted to investigate non-invasive techniques and their diagnostic performances for evaluating clinically significant portal hypertension. The systematic search was performed on PubMed, Embase, Scopus, and Web of Science TM core index databases before 13 December 2018 restricted to English language and human studies. Thirty-two studies were included, with total populations of 3,987. The overall pooled analysis was performed by bivariate random effect model, which revealed significantly higher sensitivity and specificity of 77.1% (95% confidence interval, 76.8-78.5%) and 80.1% (95% confidence interval, 78.2-81.9%), respectively; positive likelihood ratio (3.67), negative likelihood ratio (0.26); and diagnostic odd ratio (16.24). Additionally, the area under curve exhibited significant diagnostic accuracy of 0.871. However, notable heterogeneity existed in between studies (I2=87.1%), therefore, further subgroup analysis was performed. It demonstrated ultrasonography, elastography, biomarker, and computed tomography scan had a significant overall summary sensitivity (specificity) of 89.6% (78.9%), 81.7% (83.2%), 72.2% (76.8%), and 77.2% (81.2%), respectively. Moreover, the areas under curve values were significantly higher in elastography (0.906), followed by computed tomography scan (0.847), biomarker (0.825), and ultrasonography (0.803). In future, non-invasive techniques could be the future choice of investigations for screening and diagnosis of clinically significant portal hypertension in cirrhosis. However, standardization of diagnostic indices and their cut-off values in each non-invasive method needs to be addressed.

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension (PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: “liver cirrhosis”, “portal hypertension”, “pathogenesis”, “angiogenesis”, and “antiangiogenic therapy”. Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.

This study aimed to develop and validate a noninvasive automated computer-aided diagnosis framework for clinically significant portal hypertension (CSPH) in cirrhosis based on contrast-enhanced computed tomography (CE-CT) images. The framework was developed using segmentation convolutional neural networks (CNNs) and radiomics-based classification. Patients who had both HVPG measurement and contrast-enhanced -CT were obtained within 14 days prior to the catheterization were collected. The contrast-enhanced -CT training cohort consisted of 275 patients and was validated in internal and external validation cohorts. Our CSPH computer-aided diagnosis framework performed well in detecting CSPH in training cohort with the area under receiver operating characteristic curves (AUC) of 0.9203(95%CI: 0.8751-0.9865). The application of CSPH computer-aided diagnosis framework in the external validation performed excellently with an AUC of 0.8135(95%CI: 0.7711-0.951). Results also showed outstanding performance in the segmentation of liver and spleen with Dice coefficients of 0.893± 0.0549 and 0.931± 0.0629, respectively. In conclusion, this study demonstrated the feasibility of using a fully automated computer-aided diagnosis framework for the noninvasive detection of CSPH in cirrhosis with high diagnostic performance. Funding Statement: This work was supported by the National Natural Science Foundation of China under Grant No. 61671230 and No.61971213, the Science and Technology Program of Guangdong Province under Grant No.2017A020211012, the National Natural Science Foundation of Guangdong Province under Grant No.2019A1515010417. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The study was performed in accordance with the Helsinki declaration and approved by all institutional review board. Written informed consent was obtained from participants.

Background: Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and...

Evaluation and follow-up of patients with cirrhosis and oesophageal varices

Objective Gastroesophageal varices are a direct consequence of portal hypertension in cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in reduced mortality and morbidity rates. The study was aimed to analyze the short-term and long-term efficacy of different endoscopic methods in the treatment of gastric varices in cirrhotic patients. Methods From January 2016 to December 2019, 135 patients with liver cirrhosis and gastric varices undergoing different endoscopic treatment protocols were retrospectively analyzed. The patients were divided into three groups according to endoscopic variceal ligation, endoscopic sclerotherapy, and a combination of both, respectively. Main outcomes including the overall response rate, hemostasis, short- and long-term rebleeding (3 months before and after treatment), complication, blood pressure, heart rate, portal venous pressure (PVP), portal vein diameter (PVD), portal vein velocity (PVV), portal vein blood flow (PVF) detected by ultrasound, recurrence rate, and mortality were analyzed after treatments. Results The overall response rate in the combined group was higher than that in the ligation group and the sclerotherapy group (P < 0.05). The incidence rate of complications in the combined group and the ligation group was lower than that in the sclerotherapy group (P < 0.05). After treatment, the PVP, PVD, and PVF were reduced in the combined group compared with the ligation group and the sclerotherapy group, while the PVV was not (P < 0.05). Lower rates of long-term rebleeding, recurrence, and mortality were noted in the combined group compared to the ligation group and the sclerotherapy group (P < 0.05). Conclusion Endoscopic variceal ligation combined with endoscopic sclerotherapy is more effective than both alone in treating liver cirrhosis and gastric varices. The combined therapy contributed to reduced short-term and long-term rebleeding rate, decreased long-term recurrence rate, and mortality.

The aim. To assess the hemodynamic parameters of the hepatic and visceral blood flow in patients with compensated and decompensated liver cirrhosis. Materials and methods. 290 patients with liver cirrhosis were examined: 206 had gastrointestinal bleeding, 84 had diuretic-resistant ascites. Ultrasonic scanning, Doppler sonography, esophagogastroduodenoscopy, angiography, radioisotope scintigraphy were performed to assess blood flow in the portal, splenic and superior mesenteric veins and in the hepatic, splenic and superior mesenteric arteries. Results. Change in the hepatic microcirculatory blood flow in the natural course of liver cirrhosis was characterized by decreased portal and increased arterial blood flow, “arterialization” of hepatic blood flow based on scintigraphy. Decompensation of the disease was associated with progressive reduction in both portal and arterial hepatic blood flow, which were correlated with the severity of functional liver disorders regardless of the complication nature. The portal blood flow in the natural course of liver cirrhosis was characterized by 3.5–4.5 times increased volume of visceral blood. Decompensation of the disease was accompanied by a decrease in blood flow in the portal vein as compared to the splenic and superior mesenteric veins by 1.8–2.2 and 1.5–2.7 times, respectively. Arterial blood flow in the natural course of liver cirrhosis was characterized by a relatively increased hepatic arterial flow. The ultrasound criterion of hepatic blood flow “arterialization” was an increase in hepatic-splenic arterial index, which can be used as a sign to differentiate between different forms of portal hypertension. Decompensation of the disease was characterized by an average of 8.2 % decreased arterial blood flow in the hepatic artery compared to the splenic artery in dynamics. Prognostically unfavorable signs were the progression of splenomegaly degree, the increase in the portal vein diameter with the decreased velocity characterizing the increase in congestive index by 2.4–2.6 times, the decrease in the hepatic artery diameter and velocity in it over time.Conclusions. The hepatic and visceral blood flow characteristics should be considered when choosing method of conservative, surgical or minimally invasive treatment of liver cirrhosis complications. Based on the hepatic hemodynamic characteristics, the mismatch between portal perfusion (reduced) and visceral blood flow (increased) is the essence of portal hypertension in liver cirrhosis. Accordingly, the criterion of treatment effectiveness in decompensated liver cirrhosis should be improved portal liver perfusion and (or) reduced volume of visceral blood flow.

To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis.

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

Decreasing hepatic vascular tone by liver-specific NO donors: wishful thinking or a promising reality?

Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assessed. The aim was to measure the processing of activated VWF (VWF-A) in addition to VWF release (VWF-N) to investigate the association of primary hemostasis with disease activity and portal hypertension in liver cirrhosis. Plasma samples from 105 participants undergoing liver vein catheterization and with liver cirrhosis of varying severity were included in the study together with 20 controls without liver disease. Competitive enzyme-linked immunosorbent assay format was used to estimate biomarkers of VWF turnover using neo-epitope-specific monoclonal antibodies. VWF-N levels and VWF-A levels were significantly elevated in cirrhotic patients compared with controls (P<0.0001), and both markers could discriminate mild from severe cirrhosis (VWF-N, P<0.0001; VWF-A, P<0.05). Both markers correlated well with increasing portal hypertension and could identify patients with clinically significant portal hypertension (VWF-N, area under the curve: 0.78; VWF-A, area under the curve: 0.67). Only VWF-A significantly separated compensated from decompensated patients (P<0.05). The data indicate that both VWF release and processing of active VWF are increased in cirrhosis, reflecting ongoing wound healing initiation. VWF-N and VWF-A may specifically contain information to assess the presence and severity of PHT as an early indicator of cirrhosis, and for acute damage in decompensated cirrhosis. Whether the increased wound healing affects long-term outcome needs to be addressed in future studies.

Objective: Cirrhosis is a final stage of chronic liver disease. High morbidity and mortality are mostly related to complications of portal hypertension. Remodelling of liver fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process leading to cirrhotic scar formation. The aim was to study the significance of functional metalloproteinase MMP-1 and MMP-7 gene variants in cirrhotic patients and their relationship to portal hypertension. Patients and Methods: 179 patients with liver cirrhosis (mean age 55.2±11.6 years) were examined for functional variants of MMP-1 (-A; rs1799750 ) and MMP-7 (G/A; rs17884789 ) genes. Measurement of hepatic venous pressure gradient, laboratory and ultrasound examination were performed in all patients. Literary data from healthy population were used for comparison of allele frequencies with our cirrhotic patients. Results: The frequency of rs1799750 (1G-1G 25%, 1G-2G 56%, 2G-2G 22%) genotypes in cirrhotic patients does not differ from the healthy population (p>0.05). In MMP-7 gene, one genotype (wild type GG) was found in our patients uniformly for rs17884789 variant. No relationship was found between the frequency of examined genotypes and either the severity of portal hypertension or Child-Pugh or MELD score. Conclusions: Functional variants of MMP-1 and MMP-7 have no relationship to portal hypertension in liver cirrhosis.

Update on ultrasound imaging of liver fibrosis

Carvedilol, probably the β-blocker of choice for everyone with cirrhosis and portal hypertension: But not so fast!

Background Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear. Methods We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). Results Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250, p = 0.026), previous EVL (OR = 1.929, p = 0.044), platelet (OR = 0.993, p = 0.008), and esophageal varices needing treatment (EVNTs) (OR = 2.422, p = 0.006). The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers (OR = 0.294, p = 0.042) and EVNTs (OR = 3.714, p = 0.006) in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively. Conclusions The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL.