Portal Hypertension In Liver Cirrhosis Research Articles

Transjugular intrahepatic portosystemic shunting in patients over 60 years with cirrhosis and comorbidities when liver transplantation is reasonably denied

Aim. To determine the potential of TIPS that provides effective portal decompression for longevity and quality of life of patients over 60 years with cirrhosis and concomitant pathology when liver transplantation is reasonably denied.Materials and methods. The study included 27 patients aged over 60 with comorbidities, who underwent TIPS in 2016–2023 due to life-threatening manifestations of complicated portal hypertension of cirrhotic origin.Results. TIPS provided effective portal decompression in all 27 patients, confirmed by a 55.4 ± 5.2% reduction in portal pressure gradient. No hospital and 6-week mortality was recorded. 2 deaths (7.4%) were registered within one year after shunt surgery.Conclusion. In addition to lessening the risk of life-threatening complications, reduction of portal hypertension in liver cirrhosis provides favorable conditions for therapy of concomitant diseases, limited by concerns regarding hepatic decompensation. Due to the achieved stabilization of comorbidities, the denial to include the patient in the waiting list for liver transplantation can be reconsidered.

Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.

Performance of Spleen Stiffness, Liver Stifness, and their Combination for Predicting Esophageal among Patient with HBV-Related Cirrhosis

Background: Liver cirrhosis in Indonesia still become a burden disease, and the etiology is mostly from the hepatitis B virus. Esophageal varices (EV) is the most common complication of portal hypertension in liver cirrhosis. Due to many reasons, esophagogastroduodenoscopy is still not fully suitable for routine surveillance in daily practice. Hence, studies that work in the search for the best non-invasive test are still important for predicting EV.Method: A total of 71 patients with liver cirrhosis due to hepatitis B who had undergone endoscopy, spleen stiffness measurement (SSM), and liver stiffness measurement (LSM), between January–April 2023 were enrolled. Diagnostic applicability was assessed by the area under the receiver-operator curve (AUC) to measure and compare the performance of each measurement and combination for predicting EV and to obtain the corresponding optimal prediction value.Results: This study was participated by 71 subjects with liver cirrhosis. The prevalence of Child-Pugh A was 74.6% (53 patients), Child-Pugh B 22.5% (16 patients), and 2.8% (2 patients) with Child-Pugh C. Among these patients, the proportion of EV was 71.8%. This study showed that SSM with a cut-off of 38.8 kPa had AUC 0.867 (95% CI: 0.774–0.960) (sensitivity 78.4%, specificity 80%) and LSM with a cut-off of 10.55 kPa had AUC 0.822 (95% CI: 0.701–0.943) (sensitivity 88.2%, specificity 65%).Conclusion: Spleen stiffness and liver stiffness measurements have a good performance for predicting EV in patients with liver cirrhosis caused by hepatitis B.

The Role of Non-Selective Beta-Blockers (NSBBs) in Liver Cirrhosis

Non-selective beta-blockers (NSBBs) are one of the recommended treatments for portal hypertension in liver cirrhosis (LC). NSBB plays the role of primary as well as secondary prophylactic upper gastrointestinal bleeding in LC. NSBB therapy has been shown to effectively reduce the risk of variceal bleeding, reduction of portal pressure, and treat other complications of portal hypertension. The safety of NSBB therapy in cirrhosis requires a good therapeutic guide and considers the side effects. The indication of NSBB administration is adjusted according to the cirrhosis stage and the specific pathophysiology that occurs in cirrhosis. Conventional NSBBs such as propranolol and nadolol which are antagonists of β1 and β2 adrenergic receptors would induce decreased cardiac output and splanchnic vasoconstriction. Carvedilol is an NSBB with the addition of α1-adrenergic activity in reducing portal pressure stronger than conventional NSBB, so carvedilol can cause greater systemic arterial pressure reduction when compared to conventional NSBB. The appropriate treatment strategies can be applied in the use of NSBB to prevent more severe complications and reduce morbidity and mortality.

ОЦЕНКА ТЯЖЕСТИ ПОРТАЛЬНОЙ ГИПЕРТЕНЗИИ ПРИ ЦИРРОЗЕ ПЕЧЕНИ

Objective. Development of a non-invasive assessing diagnostic and severity grading accuracy of portal hypertension in cirrhosis of the liver. Methods. To identify diagnostically significant indicators, a statistical analysis of the data of laboratory and instrumental diagnostics was carried out in 60 patients with liver cirrhosis. The followingbiochemical indicators weredetermined: general and biochemical blood tests, coagulogram, general urine analysis; the level of interleukin-6 (IL-6), matrix metalloproteinases 1 and 9 (MMP-1, MMP-9), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), hepatocyte growth factor (HGF); abdominal ultrasound examination, esophagogastroscopy. The index of the ratio of the number of blood platelets (N×10<sup>9</sup> / L) to the transverse size (D) of the spleen in millimeters (PSR - Platelet count to Spleen diameter Ratio) was calculated: PSR = NTr / D spleen. Results. The following indicators turned out to be diagnostically significant (predictive values based on ROC analysis are presented): blood levels of IL-6 (>19.9 pg/ml), MMP-1 (>8.06 ng/ml), cholesterol (≤4,5mmol/L), portal vein diameter (>13 mm), PSR (≤1.89). Diagnosticmethods for cirrhosis and portal hypertension was developed, based on a point assessment of a set of laboratory and instrumental criteria (AUC = 0.931; p <0.001). The method can be used in a complex of medical services aimed at diagnosis of portal hypertension severity in patients with cirrhosis of the liver, as well as medical prevention of life-threatening complications of the disease. Conclusion. The developed method makes it possible to identify patients with a «severe» form of portal hypertension, to recommend an unscheduled FEGDS with an endoscopic assessment of the risk of bleeding, and to carry out preventive and therapeutic procedures. If a low probability of a “severe” form of PH is identified, FEGDS should be refrained from if the patient has absolute or relative contraindications to the use of this diagnostic method. The method can be used in a complex of medical services aimed at diagnosing the severity of portal hypertension against the background of liver cirrhosis. What this paper adds For the first time, a method for diagnosis of portal hypertension in liver cirrhosis has been developed. It is based on a score assessment of a set of laboratory and instrumental criteria, including blood levels of interleukin-6, matrix metalloproteinase-1, cholesterol, platelet count, portal vein diameter and transverse size of the spleen. The method can be used in a complex of medical services aimed to estimate the severity of portal hypertension in cirrhosis of the liver, as well as medical prevention of life-threatening complications of the disease.

Risk Factors for Esophageal Collateral Veins in Cirrhosis with and without Previous Endoscopic Esophageal Variceal Therapy.

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.

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis.

Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced liver disease management. By establishing portal vein access, endoscopic ultrasound (EUS) has been utilized in various clinical applications. In comparison to standard upper gastrointestinal endoscopy, EUS-Doppler has been shown to be a better modality for detecting esophageal and gastric varices along with peri-esophageal collateral veins, para-esophageal collateral veins, and perforating veins, and may be used to objectively predict the recurrence of bleeding. EUS-guided portal vein catheterization has also been proposed to overcome the limitations of trans-jugular approaches. The combination of EUS-elastography and azygos vein evaluation can also enhance the diagnostic accuracy of each modality. Another well-known implementation of EUS-guided procedures is in the management of ascites; particularly in paracentesis and ascitic fluid analysis. In addition, the most common clinical application of EUS in the treatment of portal hypertension is through vascular therapy or creation of intrahepatic portosystemic shunts. Major drawbacks of EUS mainly revolve around technical difficulties, the high cost of the procedure, as well as the requirement of more studies in humans to evaluate EUS-guided advanced therapeutic modalities in portal hypertension.

Correlation between Ascites and Total Lymphocyte Count with Occurrence of Hepatic Encephalopathy in Liver Cirrhosis Patients

Hepatic encephalopathy (HE) is brain dysfunction manifested as a broad spectrum of neuropsychiatric abnormalities caused by hepatic insufficiency or portosystemic shunting due to portal hypertension. Portal hypertension in liver cirrhosis also causes ascites, as the most common clinical manifestation. Further, immune dysfunction, one of which is decreased total lymphocyte count (TLC), happens at liver cirrhosis, which triggers the systemic inflammatory response. This systemic inflammatory response plays a role in HE. Objective of this study is to know the correlation between ascites and TLC with occurence of HE in liver cirrhosis patient. This study was conducted by retrospective cohort design in Saiful Anwar Hospital. Determination of sample amount at this study used total sampling method. Hepatic encephalopathy diagnosis was based on West Haven Criteria. Ascites was determined by physical examination and/or abdominal ultasonography. Total lymphocyte count data was taken from medical record, with complete blood count examination used XS-800i hematology analyzer machine. Data were analyzed using a logistic regression test, with p<0.05 was considered significant and Confidence Interval (CI) 95%. Seventy-eight liver cirrhosis patients were observed using a retrospective cohort method regarding the HE occurrence, and physical examination for ascites and laboratory examination were performed. The statistical analysis result of the correlation between ascites and HE is significant with an odds ratio of 5.108 and CI of 1.36-19.25. On the other hand, TLC has no significant correlation with the occurrence of HE. Based on this analysis result, it is concluded that ascites has a correlation with HE, but TLC does not.Â

Expression of miR-9a-5p in cirrhosis patients with recurrent portal hypertension after treatment.

MicroRNA (miR) influences the biological activities of cirrhotic patients with recurrent portal hypertension. The current study was designed to investigate risk factors related to the survival of cirrhosis patients and assessed the possibility of using miR-9a-5p predictability to prevent post-treatment portal hypertension. Patients with portal hypertension due to liver cirrhosis treated from January 2015 to September 2016 were included in this study. Patients without relapse after treatment were selected as the success group while patients with relapse after treatment were selected as the recurrence group. Serum samples from healthy people were also collected. The blood indexes of the 2 groups of patients before and after treatment were compared and the miR-9a-5p serum level in each group was determined. The Kaplan-Meier method was applied to analyze three-year survival, Cox univariate regression was used to analyze the risk factors for recurrence of cirrhotic portal hypertension, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of serum miR-9a-5p, total bilirubin (TBIL) and platelet (PLT) levels in patients with recurrence. The miR-9a-5p level in the recurrence group was higher than that in the success group after treatment. In patients with recurrence, the miR-9a-5p level was negatively correlated with red blood cell count, TBIL, white blood cell count, and PLT count, and positively correlated with albumin. The miR-9a-5p, TBIL and PLT are potential markers of recurrent portal hypertension in liver cirrhosis. The miR-9a-5p had the highest area under the curve (AUC) value in patients with relapse. The miR-9a-5p is a risk factor for the recurrence of cirrhotic portal hypertension after treatment. It may be used as a marker of recurrence, and so has potential clinical value for the diagnosis and treatment of recurrent portal hypertension.

Assessment of hemodynamic parameters of hepatic and visceral blood flow in decompensated liver cirrhosis

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.

Splanchnic Vein Thrombosis in Liver Cirrhosis After Splenectomy or Splenic Artery Embolization: A Systematic Review and Meta-Analysis.

Splenectomy and splenic artery embolization are major treatment options for hypersplenism and portal hypertension in liver cirrhosis, but may lead to splanchnic vein thrombosis (SVT), which is potentially lethal. We conducted a systematic review and meta-analysis to explore the incidence of SVT in liver cirrhosis after splenectomy or splenic artery embolization and the risk factors for SVT. All relevant studies were searched through the PubMed, EMBASE, and Cochrane Library databases. The incidence of SVT in liver cirrhosis after splenectomy or splenic artery embolization was pooled. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sixty-six studies with 5632 patients with cirrhosis were included. The pooled incidence of SVT after splenectomy and splenic artery embolization was 24.6% (95% CI 20.2-29.3%) and 11.7% (95% CI 7.1-17.3%), respectively. A meta-analysis of three comparative studies demonstrated that the incidence of SVT after splenectomy was statistically similar to that after splenic artery embolization (OR 3.15, P = 0.290). Platelet count, mean platelet volume, preoperative splenic or portal vein diameter, preoperative or postoperative portal blood velocity, splenic volume and weight, and periesophagogastric devascularization were significant risk factors for SVT after splenectomy. Postoperative use of preventive antithrombotic therapy was a significant protective factor against SVT after splenectomy. SVT is common in liver cirrhosis after splenectomy and splenic artery embolization. Coagulation and hemostasis factors, anatomical factors, and surgery-related factors have been widely identified for the assessment of high risk of SVT after splenectomy. Prophylactic strategy after splenectomy, such as antithrombotic therapy, might be considered in such high-risk patients. This study was registered in PROSPERO with a registration number of CRD42019129673.

Impact of spontaneous splenorenal shunt on liver volume and long-term survival of liver cirrhosis.

Spontaneous splenorenal shunt (SSRS) is one of the manifestations of portal hypertension in liver cirrhosis. However, the impact of SSRS on long-term survival of cirrhotic patients remains unclear. We hypothesize that SSRS may worsen liver dysfunction and deteriorate prognosis in liver cirrhosis by decreasing hepatic perfusion. Patients with liver cirrhosis who were admitted to our department between December 2014 and August 2019 and underwent contrast-enhanced computed tomography or magnetic resonance imaging scans were prospectively collected. The maximum diameters of SSRS and portal vein system vessels were retrospectively measured. Liver-to-abdominal area ratio, Child-Pugh, and model for end-stage liver disease scores were calculated. Overall, 122 cirrhotic patients were included. The prevalence of SSRS was 30.3% (37/122). Median diameter of SSRS was 13.5mm. Patients with SSRS had significantly thinner diameters of right portal vein (9mm vs 11.2mm, P=0.001) and main portal vein (15.3mm vs 16.8mm, P=0.017) than those without SSRS. Patients with SSRS had significantly lower liver-to-abdominal area ratio score (25.39 vs 31.58, P<0.001) and higher Child-Pugh (7 vs 6, P=0.046) and model for end-stage liver disease (12.17 vs 9.79, P<0.006) scores than those without SSRS. Patients with SSRS had a significantly lower cumulative survival rate than those without SSRS (P=0.014). Cox regression analysis also showed that SSRS was a risk factor of death of cirrhotic patients (hazard ratio=4.161, 95% confidence interval=1.215-14.255, P=0.023). Spontaneous splenorenal shunt may narrow portal vein diameter and shrink liver volume, thereby worsening liver function and increasing mortality in liver cirrhosis.

Лечение и профилактика кровотечений из варикозно расширенных вен пищевода

Liver cirrhosis is the result of various chronic liver diseases. Portal hypertension is a serious complication of cirrhosis. Its consequences, in turn, along with other complications are gastroesophageal varicose bleeding, which cause high mortality rates. The article contains analysis of the results of laparoscopic esophagogastric devascularization without esophageal transsection and splenectomy in a patient with liver cirrhosis portal hypertension and recurrent bleeding from varicose veins of the esophagus. First successful surgery according to this method was introduced in the Grodno Municipal Clinical Hospital No. 4 in November 2011. Immediate and long-term results show a rather high efficiency of using this operation in the treatment and prevention of bleeding from varicose veins of the esophagus with cirrhosis. It is advisable to conduct further studies of the effectiveness of using this operation, despite the encouraging results of the use of this modification of laparoscopic esophagogastric devascularization.

The Clinical Efficacy and Safety of Simvastatin in the Management of Portal Hypertension in Cirrhotic Patients: A Systematic Review

Background: Variceal bleeding is a serious complication of portal hypertension in liver cirrhosis. Current guidelines recommend non-selective beta blockers (NSBBs) and endoscopic variceal ligation for primary prophylaxis of variceal bleeding. However, NSBBs are associated with low response rates and systemic adverse effects. Simvastatin has been shown to reduce portal hypertension in previous studies. Our aim was to assess its clinical efficacy and safety in reducing portal hypertension in cirrhotic patients. Method: We searched PubMed, The Cochrane Library, ScienceDirect, ProQuest, CINAHL, Scopus, and Clinicaltrials.gov, and manually browsed abstracts of major hepatology conferences for selection of studies. We selected randomized controlled trials with a population of cirrhotic patients, simvastatin as an intervention, HVPG change as an outcome, and English as the primary language. The quality of selected studies was assessed using the Cochrane Risk of Bias tool. We extracted change in HVPG from baseline to post-treatment as the principal summary measure, with safety as the secondary outcome.Results: Two full articles were included for qualitative analysis. Both studies reported reductions in HVPG from baseline to post-treatment in the simvastatin group, with this reduction being significantly higher as compared to the control group. Adverse effects were homogenously distributed in both groups, and good safety was reported by both studies. Simvastatin’s HVPG lowering effects are possibly additive to those of NSBBs. Conclusion: Simvastatin effectively reduces HVPG in cirrhotic patients with portal hypertension, although more clinical trials are needed to validate these results. Simvastatin could potentially be combined with NSBBs to achieve greater results.

Hipertensión portal

The development of portal hypertension (PHT) is unequivocally coupled with progressed liver cirrhosis and is the direct cause of the typical complications of cirrhosis, such as the development of oesophageal and gastric varices, PHT gastropathy, hepatorenal syndrome, spontaneous bacterial peritonitis, ascites, pancytopaenia by hypersplenism and portosystemic encephalopathy. The presence of any of these complications marks the transition from the compensated phase to the decompensated phase of the disease, which entails a drastic change in the prognosis and a significant worsening of survival. In the genesis and maintenance of PHT associated with hepatic cirrhosis, there are 2 mechanisms that act synergistically: first, there is an increase in intrahepatic vascular resistance, which results in the formation of collateral vessels and the onset of the second mechanism: splanchnic hyperflow. A better understanding of the pathophysiology of portal hypertension in liver cirrhosis has enabled the development of drugs aimed at blocking these mechanisms, which has resulted in reduced morbidity and mortality for these patients.

Activation of BK Channels Prevents Hepatic Stellate Cell Activation and Liver Fibrosis Through the Suppression of TGFβ1/SMAD3 and JAK/STAT3 Profibrotic Signaling Pathways.

Large-conductance and Ca2+-activated K+ (BK) channels are expressed in human hepatic stellate cells (HSCs), where they have roles in normal hepatic microcirculation, as well as in portal hypertension in liver cirrhosis through the regulation of contractility in activated HSCs. Nevertheless, whether BK channel activity exerts protective effects against aberrant HSC activation and hepatic fibrosis is unknown. Here, we report that BK channels are expressed in activated primary rat HSCs as well as in a human HSC line. Moreover, whole-cell K+ currents recorded from activated HSCs were markedly increased by exposure to rottlerin, a BK channel-specific activator, but were inhibited by treatment with the BK channel-specific inhibitor, paxilline, suggesting that BK channels are functional in activated HSCs. Overexpression but not downregulation of the BK channel pore-forming alpha subunit, KCNMA1, led to reduced migration and collagen expression in activated HSCs. Consistently, rottlerin treatment suppressed the fibrogenic cell function both in vitro and in CCl4-induced liver fibrosis in vivo. Microarray and pathway analysis, combined with a luciferase reporter assay and western blotting, further showed that rottlerin treatment led to a significant downregulation of the profibrotic TGFβ1/SMAD3 and JAK/STAT3 signaling pathways, both in vitro and in vivo. Our findings not only link BK channel function to profibrotic signaling pathways, but also provide evidence that BK channel activation represents a promising therapeutic strategy for the treatment of liver fibrosis.

КЛИНИЧЕСКИЙ СЛУЧАЙ ЛЕЧЕНИЯ ПАЦИЕНТА С ПОРТАЛЬНОЙ ГИПЕРТЕНЗИЕЙ, РАЗВИВШЕЙСЯ НА ФОНЕ ТРОМБОЗА ВОРОТНОЙ ВЕНЫ

Non-cirrhotic causes of the development of portal hypertension make up about 10%. The factors leading to its development are the development of thrombosis in the portal vein system, occlusion due to pancreatitis, pancreatic tumors, and other causes. Acute bleeding from esophageal varices is a formidable complication of portal hypertension, regardless of its etiology. The tactics of treatment and prevention of bleeding from esophageal varices in patients with portal vein thrombosis generally corresponds to that for intrahepatic portal hypertension in liver cirrhosis with some additions. Aim. Presentation of the results of clinical observation of an open Hassab operation (esophagogastric devascularization without esophageal transection + splenectomy) in a patient with portal vein thrombosis complicated by portal hypertension and esophageal varices, as well as a short literary excursion on this issue. Materials and methods. The patient was admitted to the surgical department with thrombosis of the portal, splenic and superior mesenteric veins complicated by subhepatic portal hypertension with splenomegaly, varicose veins of the esophagus and stomach of the 2nd-3rd degrees, left-sided hydrothorax, moderate anemia. Direct anticoagulants, antibiotics, non-steroidal anti-inflammatory drugs, proton pump inhibitors were used. Given the risk of bleeding from varicose veins of the esophagus and stomach, as well as existing necrosis in the spleen, Hassab operation (esophagogastric devascularization in combination with splenectomy) was performed at the fourth level of surgical management. Results. Despite ongoing therapy with antiplatelet agents, in 2 months after the operation the patient developed thrombosis of the left subclavian and internal jugular veins as well as recurrent left-sided hydrothorax. Conservative therapy has been successful. Relapse of esophageal varices bleeding was diagnosed in a patient 4 years after surgery, conservative and endoscopic hemostasis being successful. Acute thrombophlebitis of the saphenous veins of the right lower leg was diagnosed in the patient 9 years after surgery, it having been treated conservatively. Acute adhesive intestinal obstruction developed 11 years after surgery, conservative therapy was successful. Currently, the patient is being followed at the outpatient department, his condition being satisfactory and hydroxycarbamide, antiplatelet agents and non-selective betablockers being taken by him on a regular basis takes. Based on this clinical observation, it seems difficult to judge the effect of Hassab operation on the course of the disease in the described patient. However, it is worth noting a persistent increase in the level of platelets in the general blood test in the postoperative period, which could contribute to the recurrence of venous thrombosis in the patient. Conclusions. According to the current scientifically based recommendations in the treatment of these patients priority should be given to conservative and minimally invasive endoscopic and interventional X-ray endovascular techniques.

Vascular branching geometry relating to portal hypertension: a study of liver microvasculature in cirrhotic rats by X-ray phase-contrast computed tomography.

Portal hypertension is one of the major complications of cirrhosis. The changes in hepatic microvasculature are considered as critical pathophysiological characteristics of portal hypertension. X-ray phase-contrast computed tomography (PCCT) is a new imaging technique that can detect liver vessels at a micrometric level without contrast agents. In this study, male Sprague-Dawley rats with liver cirrhosis induced by carbon tetrachloride (CCl4) or bile duct ligation (BDL) were investigated with PCCT. The portal pressures of rats were recorded before euthanasia. The branch angle and Murray's deviation (MD) were measured based on the branching geometry of the three-dimensional (3D) microvasculature of liver cirrhosis in rats. Statistical analyses were performed to determine the correlation between branching geometry and portal pressure in liver fibrosis. The results demonstrated that the branch angle and MD significantly increased in the CCl4 model and BDL model compared with their corresponding normal group or sham group. The portal pressure was significantly correlated with the branching morphologic features (all R≥0.761 and P<0.01). The branch angle and MD could accurately distinguish portal pressure in cirrhotic rats, suggesting that branching geometric characteristics of the microvasculature may be a promising marker in the prognosis of portal hypertension in liver cirrhosis.

Diagnostic accuracy of non-invasive methods detecting clinically significant portal hypertension in liver cirrhosis: a systematic review and meta-analysis.

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.

Noninvasive Assessment of Portal Hypertension Using Spectral Computed Tomography.

Early diagnosis of portal hypertension is imperative for timely treatment to reduce the mortality rate. However, there is still no adequate method to noninvasively and accurately assess the portal hypertension in routine clinical practice. We aimed to evaluate the accuracy of parameters measured using dual energy spectral computed tomography (LightSpeed CT750 HD) in assessing portal venous pressure in patients with liver cirrhosis. Forty-five patients with liver cirrhosis who underwent percutaneous transhepatic portal vein puncture as part of their treatment for liver disease were enrolled in this study. Measurement of direct portal venous pressure was performed preoperatively. All patients underwent dual energy spectral computed tomography within 3 days before their operations. The iodine concentrations of portal vein and hepatic parenchyma during the portal venous phase and the alanine aminotransferase level were found to be independently correlated with the direct portal venous pressure according to stepwise multivariate linear regression analysis (P<0.001, 0.004, and 0.024, respectively). In a receiver operating characteristic analysis, the area under the receiver operating characteristic of iodine concentrations of the portal vein (ICPV) for identifying clinically significant portal hypertension (≥10 mm Hg) was significantly higher than that of iodine concentrations of hepatic parenchyma (ICliver) and the alanine aminotransferase level (0.944, 0.825, and 0.301, respectively). The threshold ICPV of 58.27 yielded a sensitivity of 93.8%, specificity of 69.2%, positive predictive value of 88.2%, and negative predictive value of 81.8%, respectively. ICPV values may be a useful tool in noninvasively assessing the portal venous pressure and identifying clinically significant portal hypertension in liver cirrhosis.