Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension

BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to measure,has replaced the portal venous pressure gradient(PPG)as the gold standard for diagnosing PHT in clinical practice.Therefore,attention should be paid to the correlation between HVPG and PPG.METHODS Between January 2017 and June 2020,134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures.Correlations were assessed using Pearson’s correlation coefficient to estimate the correlation coefficient(r)and determination coefficient(R^(2)).Bland-Altman plots were constructed to further analyze the agreement between the measurements.Disagreements were analyzed using paired t tests,and P values<0.05 were considered statistically significant.RESULTS In this study,the correlation coefficient(r)and determination coefficient(R2)between HVPG and PPG were 0.201 and 0.040,respectively(P=0.020).In the 108 patients with no collateral branch,the average wedged hepatic venous pressure was lower than the average portal venous pressure(30.65±8.17 vs.33.25±6.60 mmHg,P=0.002).Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography(19.4%),while the average PPG was significantly higher than the average HVPG(25.94±7.42 mmHg vs 9.86±7.44 mmHg;P<0.001).The differences between HVPG and PPG<5 mmHg in the collateral vs no collateral branch groups were three cases(11.54%)and 44 cases(40.74%),respectively.CONCLUSION In most patients,HVPG cannot accurately represent PPG.The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.

Computed tomography perfusion in liver and spleen for hepatitis B virus-related portal hypertension:A correlation study with hepatic venous pressure gradient

BACKGROUND Hepatic venous pressure gradient(HVPG)is the gold standard for diagnosis of portal hypertension(PH).However,its use can be limited because it is an invasive procedure.Therefore,it is necessary to explore a non-invasive method to assess PH.AIM To investigate the correlation of computed tomography(CT)perfusion of the liver with HVPG and Child-Pugh score in hepatitis B virus(HBV)-related PH.METHODS Twenty-eight patients(4 female,24 male)with gastroesophageal variceal bleeding induced by HBV-related PH were recruited in our study.All patients received CT perfusion of the liver before transjugular intrahepatic portosystemic stent-shunt(TIPS)therapy.Quantitative parameters of CT perfusion of the liver,including liver blood flow(LBF),liver blood volume(LBV),hepatic artery fraction,splenic blood flow and splenic blood volume were measured.HVPG was recorded during TIPS therapy.Correlation of liver perfusion with Child-Pugh score and HVPG were analyzed,and the receiver operating characteristic curve was analyzed.Based on HVPG(>12 mmHg vs≤12 mmHg),patients were divided into moderate and severe groups,and all parameters were compared.RESULTS Based on HVPG,18 patients were classified into the moderate group and 10 patients were classified into the severe group.The Child-Pugh score,HVPG,LBF and LBV were significantly higher in the moderate group compared to the severe group(all P<0.05).LBF and LBV were negatively associated with HVPG(r=-0.473,P<0.05 and r=-0.503,P<0.01,respectively),whereas splenic blood flow was positively associated with hepatic artery fraction(r=0.434,P<0.05).LBV was negatively correlated with Child-Pugh score.Child-Pugh score was not related to HVPG.Using a cutoff value of 17.85 mL/min/100 g for LBV,the sensitivity and specificity of HVPG≥12 mmHg for diagnosis were 80%and 89%,respectively.CONCLUSION LBV and LBF were negatively correlated with HVPG and Child-Pugh scores.CT perfusion imaging is a potential non-invasive quantitative predictor for PH in HBV-related liver cirrhosis.

Cirrhosis and portal hypertension: The importance of risk stratification, the role of hepatic venous pressure gradient measurement

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 approachfor 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.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient

BACKGROUND The liver is one of the most important organs in the human body,with functions such as detoxification,digestion,and blood coagulation.In terms of vascular anatomy,the liver is divided into the left and the right liver by the main portal vein,and there are three hepatic efferent veins(right,middle,and left)and two portal branches.Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation,which may lead to an increase in the portal pressure gradient(PPG)and cause portal hypertension(PHT).In order to measure the increased pressure gradient of portal vein,the hepatic venous pressure gradient(HVPG)can be measured to reflect it in clinical practice.The accuracy of PPG measurements is directly related to patient prognosis.AIM To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT.METHODS From January 2017 to December 2019,102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed.RESULTS The mean HVPG of the middle hepatic vein was 17.47±10.25 mmHg,and the mean HVPG of the right and left hepatic veins was 16.34±7.60 and 16.52±8.15 mmHg,respectively.The average PPG was 26.03±9.24 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.15 and 0.02(P=0.164);0.25 and 0.05(P=0.013);and 0.14 and 0.02(P=0.013),respectively.The mean wedged hepatic vein/venous pressure(WHVP)of the middle and left hepatic veins was similar at 29.71±12.48 and 29.1±10.91 mmHg,respectively,and the mean WHVP of the right hepatic vein was slightly lower at 28.01±8.95 mmHg.The mean portal vein pressure was 34.11±8.56 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.26 and 0.07(P=0.009);0.38 and 0.15(P<0.001);and 0.26 and 0.07(P=0.008),respectively.The average free hepatic venous pressure(FHVP)of the right hepatic vein was lowest at 11.67±5.34 mmHg,and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19±4.88 and 11.67±5.34 mmHg,respectively.The average inferior vena cava pressure was 8.27±4.04 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.30 and 0.09(P=0.002);0.18 and 0.03(P=0.078);and 0.16 and 0.03(P=0.111),respectively.CONCLUSION Measurement of the middle hepatic vein HVPG could better represent PPG.Considering the high success rate of clinical measurement of the right hepatic vein,it can be the second choice.

Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

AIM： To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient （HVPG） in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown. METHODS： Ten patients with biopsy proven cirrhosis （five females/five males, mean age 54：1：8 years） and an HVPG above 12 mmHg were studied after informed consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick＇s principle, with correction for non-steady state. RESULTS： The plasma concentration of sildenafil was 222 ± 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 ±7 mmHg to 66 ± 12 mmHg, P = 0.003, while the splanchnicblood flow and oxygen consumption remained unchanged at 1.14 ± 0.71 L/min and 2.3 ± 0.6 mmol/ min, respectively. Also the HVPG remained unchanged （18 ± 2 mmHg vs 16 ± 2 mmHg） with individual changes ranging from -8 mmHg to ±2 mmHg. In seven patients, HVPG decreased and in three it increased. CONCLUSION： In spite of arterial blood pressure decreases 80 min after administration of the phosphodiesterase type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG.

Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.

Use of portal pressure studies in the management of variceal haemorrhage

Portal hypertension occurs as a complication of liver cirrhosis and complications such as variceal bleeding lead to significant demands on resources. Endoscopy is the gold standard method for screening cirrhotic patients however universal endoscopic screening may mean a lot of unnecessary procedures as the presence of oesophageal varices is variable hence a large time and cost burden on endoscopy units to carry out both screening and subsequent follow up of variceal bleeds. A less invasive method to identify those at high risk of bleeding would allow earlier prophylactic measures to be applied. Hepatic venous pressure gradient (HVPG) is an acceptable indirect measurement of portal hypertension and predictor of the complications of portal hypertension in adult cirrhotics. Varices develop at a HVPG of 10-12 mmHg with the appearance of other complications with HPVG > 12 mmHg. Variceal bleeding does not occur in pressures under 12 mmHg. HPVG > 20 mmHg measured early after admission is a significant prognostic indicator of failure to control bleeding varices, indeed early transjugular intrahepatic portosystemic shunt (TIPS) in such circumstances reduces mortality significantly. HVPG can be used to identify responders to medical therapy. Patients who do not achieve the suggested reduction targets in HVPG have a high risk of rebleeding despite endoscopic ligation and may not derive significant overall mortality benefit from endoscopic intervention alone, ultimately requiring TIPS or liver transplantation. Early HVPG measurements following a variceal bleed can help to identify those at risk of treatment failure who may benefit from early intervention with TIPS. Therefore, we suggest using HVPG measurement as the investigation of choice in those with confirmed cirrhosis in place of endoscopy for intitial variceal screening and, where indicated, a trial of B-blockade, either intravenously during the initial pressure study with assessment of response or oral therapy with repeat HVPG six weeks later. In those with elevated pressures, primary medical prophylaxis could be commenced with subsequent close monitoring of HVPG thus negating the need for endoscopy at this point. All patients presenting with variceal haemorrhage should undergo HVPG measurement and those with a gradient greater than 20 mmHg should be considered for early TIPS. By introducing portal pressure studies into a management algorithm for variceal bleeding, the number of endoscopies required for further intervention and follow up can be reduced leading to significant savings in terms of cost and demand on resources.

Extrahepatic aneurysm of the portal venous system and portal hypertension

Portal venous aneurysm (PVA) is a rare condition characterized by dilatation of the portal venous system. PVA manifestation of symptoms is varied and depends on the aneurysm size, location and related-complications, such as thrombosis. While the majority of reported cases of PVA are attributed to portal hypertension, very little is known about the condition's pathophysiology and clinical management remains a challenge. Here, we describe a 67-year-old woman who presented with complaint of dyspepsia and without a significant medical history, for whom PVA was incidentally diagnosed. The initial upper abdominal ultrasound revealed marked dilatation of the main portal vein, and subsequent contrast-enhanced computed tomography with angiography revealed a large aneurysm arising from the extrahepatic troncus portion of the portal vein, as well as gastroesophageal varices. A conservative approach using beta-blocker therapy was chosen. The patient was followed-up for 60 mo, during which time the asymptomatic status was unaltered and the PVA remained stable.

Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10-6) and -1.3 kg (P = 1.83 × 10-5), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10-4). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Hepatic venous pressure gradient measurement guiding nonselective beta-blocker therapy in a patient with clinically significant portal hypertension

Clinically significant portal hypertension(CSPH),defined as a hepatic venous pressure gradient(HVPG)≥10 mmHg,is an independent risk factor for decompensated events in patients with compensated cirrhosis.Currently,the Baveno VII consensus recommends using nonselective beta-blockers to treat compensated cirrhosis in patients with CSPH.Here,we report a unusual case of compensated cirrhosis with CSPH caused by hepatitis B,and we successfully adjust NSBBs drug treatment strategies monitoring by HVPG results and achieve response standards.Timely adjustment of NSBBs drug treatment strategies based on HVPG test results for patients with CSPH can improve the final response rate.

内镜超声在肝硬化门脉高压症诊治中的研究进展

内镜超声(endoscopic ultrasound,EUS)的发展及创新扩大了其在肝脏疾病诊治中的作用,EUS不仅被广泛应用于胆胰疾病的诊治,其在肝实质和门脉系统疾病中的应用也在迅速发展。本文回顾相关文献,概述了EUS在肝硬化门脉高压症的诊断及其并发症治疗中的研究现状及前景,重点介绍EUS引导下肝活检、EUS引导下门静脉压力梯度测量及EUS引导下胃静脉曲张治疗的研究进展。目前的数据表明:EUS引导下肝活检安全有效,在取样充分性上可与传统活检方式相媲美,而且术后恢复更快、疼痛程度更低。EUS引导下门静脉压力梯度测量较肝静脉压力梯度更准确地反映以窦前性门脉高压为主疾病的门静脉压力的程度,适用疾病更广。与常规内镜相比,EUS引导下血管介入术治疗胃静脉曲张优势众多,其中EUS引导弹簧圈联合组织胶治疗比单独使用弹簧圈或组织胶治疗更有效、并发症更少。

Subharmonic aided pressure estimation in portal hypertension:A noninvasive ultrasound-based technique to assess portal pressure gradient

Portal hypertension(PH)is a clinical syndrome,characterized by elevated pressure gradient between portal vein and inferior vena cava.These elevated pressures gradient due to increased vascular resistance and/or increased volume of blood flowing through the portal vein circulation,results in blood outflow difficulty from portal vein to hepatic veins and inferior vena cava.

Management of small hepatocellular carcinoma in cirrhosis:Focus on portal hypertension

The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.RESULTS: The mean value of HVPG was 16.18 &#x000b1; 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P &#x0003c; 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 &#x000b1; 2.6 years. The probability of cumulative survival was 39% for patients with HVPG &#x0003e; 10 mmHg and 65% for those with HVPG &#x02264; 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin &#x02264; 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

With advances in the management and treatment of advanced liver disease,including the use of antiviral therapy,a simple,one stage description for advanced fibrotic liver disease has become inadequate.Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential,current diagnostic tests have not kept pace with the progression of this new paradigm.Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension(PHT),respectively,and they have diagnostic and prognostic value.However,they are invasive and,as such,cannot be used repeatedly in clinical practice.The ideal noninvasive test should be safe,easy to perform,inexpensive,reproducible as well as to give numerical and accurate results in real time.It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification.Recently,many types of noninvasive alternative tests have been developed and are under investigation.In particular,imaging and ultrasound based tests,such as transient elastography,have shown promising results.Although most of these noninvasive tests effectively identify severe fibrosis and PHT,the methods available for diagnosing moderate disease status are still insufficient,and further investigation is essential to predict outcomes and individualize therapy in this field.

Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH)is the most important prognostic factor for the decompensation of liver cirrhosis and death,therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH)and severe PH(SPH).As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG),the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study.Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero,dretro,dRMS)and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm.Average endogenous strainμand standard deviationσof strain were assessed in the regions of interest(ROI)(1 cm×1 cm and 2 cm×2 cm in size)and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P<0.05)correlation with HVPG measurement.The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm×2 cm ROI size).Three parameters showed statistically significant differences between patient groups with CSPH,but only dretro showed significant results in SPH analysis.According to ROC analysis area under the curve(AUC)of theσROI[0…10Hz,2 cm×2 cm]parameter reached 0.71(P=0.036)for the diagnosis of CSPH;with a cut-off value of 1.28μm/cm providing 73%sensitivity and 70%specificity.AUC for the diagnosis of CSPH forμROI[0…10Hz,1 cm×1 cm]was 0.78(P=0.0024);with a cut-off value of 3.92μm/cm providing 73%sensitivity and 80%specificity.Dretro parameter had an AUC of 0.86(P=0.0001)for the diagnosis of CSPH and 0.84(P=0.0001)for the diagnosis of SPH.A cut-off value of-132.34μm yielded 100%sensitivity for both conditions,whereas specificity was 80%and 72%for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.

Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis

BACKGROUND Clinically significant portal hypertension(CSPH) and severe portal hypertension(SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor(PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is scarce.AIM To determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis,CSPH, SPH and potential to predict portal hypertension.METHODS A cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient(HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffnessvalues were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age-and sex-matched individuals.RESULTS Peripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis(23.20 vs 9.85;P < 0.0001 and 2.19 vs 3.12;P = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG(r = 0.338, P = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG(r =-0.267, P = 0.007). PlGF levels were higher in CSPH and SPH(P = 0.006;P < 0.0001) whereas Nogo-A levels were lower(P = 0.01;P < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68(P = 0.003) and for Nogo-A-0.67(P = 0.01);for SPH 0.714(P <0.0001) and 0.65(P = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices(P < 0.05). PlGF cut-off value of 25 pg/mL distinguished patients with CSPH at 55.7% sensitivity and76.7% specificity;whereas Nogo-A cut-off value of 1.12 ng/mL was highly specific(93.1%) for the diagnosis of CSPH.CONCLUSION Plasma PlGF levels were higher while Nogo-A levels were lower in patients with liver cirrhosis and portal hypertension. Biomarkers showed moderate predictive value in determining CSPH and SPH.

门静脉高压症:经颈静脉肝内门体分流术的合理应用及其相关并发症的预防和处理

肝硬化是引起门静脉高压最主要的原因,而门静脉高压可引起一系列严重的临床表现[1].肝静脉压力梯度(hepatic venous pressure gradient;HVPG)是诊断门静脉高压的金标准;HVPG≥10 mmHg提示临床显著门静脉高压[2].经颈静脉肝内门体静脉分流术(transjugular intrahepatic portosystemic shunt,TIPS)通过在肝静脉与门静脉之间的肝实质内建立分流道,以微创的方法,从结构上显著降低门静脉阻力,是介入治疗门静脉高压有效的措施之一.Richter于1989年首次将TIPS成功应用于临床[3].目前,TIPS已广泛地用于治疗肝硬化门静脉高压所致的食管胃静脉曲张破裂出血、顽固性胸腹水和肝肾综合征等.TIP S术的并发症发生率高,在操作过程中并发症主要是胆道出血和腹腔出血,而术后常见的并发症为肝性脑病、肝功能损伤、支架阻塞等[4].因此,临床医师需要对TIPS术有一个全面的了解,严格掌握适应证,预防和减少常见并发症的发生.

肝静脉压力梯度对肝移植受者术前评估及预后预测的价值

肝静脉压力梯度(HVPG)是诊断门静脉高压的“金标准”,可用于肝硬化的评估,与终末期肝病模型(MELD)评分系统联合应用能更精准地匹配肝硬化肝移植供受者,选择合适的手术时机,并为患者在等待肝移植期间的桥接治疗提供指导。除此之外,HVPG也能预测肝移植受者的预后,并为可能出现的并发症提供早发现、早干预的依据。因此,本文通过对HVPG在肝移植受者术前评估及预后预测的价值进行综述,以期为临床肝移植受者术前和术后的诊疗提供指导。

Gd-EOB-DTPA增强MRI联合剪切波弹性成像对肝硬化并发食管胃静脉曲张破裂出血风险的预测价值

目的探讨肝脏Gd-EOB-DTPA增强MRI联合剪切波弹性成像对临床显著门静脉高压(clinically significant portal hypertension,CSPH)及食管胃静脉曲张出血(esophagogastric variceal bleeding,EVB)风险的预测价值。方法选取我院行肝脏Gd-EOB-DTPA增强MRI检查、剪切波弹性成像并行HVPG测定的32例患者的资料。Pearson相关分析门静脉、脾静脉管径、肝脾体积、肝胆期相对强化程度(relative enhancement,RE)值、肝硬度值(liver stiffness,LS)等参数与HVPG的相关性。对易出血组(HVPG>12 mmHg)进行二元logistic回归建立联合诊断模型(RE_(20min)与肝硬度值)并检验拟合度,绘制单一诊断指标及联合诊断指标的受试者工作特征曲线(ROC),计算曲线下面积(AUC)。结果患者存在CSPH,相关性分析结果显示门静脉管径、脾脏体积、LS均呈正相关(r=0.375、0.591、0.749,P<0.05),与RE_(10min)、RE_(20min)呈负相关性(r=-0.453、-0.548,P<0.01),与肝脏体积、脾静脉无相关性(r=0.032、0.287,P>0.05)。门静脉管径、脾体积、RE_(10min)、RE_(20min)、LS、联合诊断模型(RE_(20min)与肝脏硬度)的AUC值分别为0.806,0.813,0.759,0.721,0.881,0.883。结论肝脏Gd-EOB-DTPA增强MRI相关参数与HVPG密切相关,有助于CSPH的诊断。在CSPH患者中,对肝脏硬度明显增高、肝胆期相对强化程度明显降低的患者应进行早期干预,以降低食管胃静脉曲张破裂出血风险。RE_(20min)联合肝硬度值较单一因素有更好的敏感性和特异性,但有待进一步模型优化。