Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily-available data in predicting the presence of significant portal hypertension and esophageal varices.
Methods:  This study included a total of 61 consecutive treatment-naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.
Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically-significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log₁₀ (platelet [10⁹/L]) + 4.2 × log₁₀ (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut-off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut-off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).
Conclusion:  A predictive model that uses readily-available laboratory results may reliably identify advanced fibrosis patients with clinically-significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.     

Wedged hepatic venous pressure reflects portal venous pressure during vasoactive drug administration in nonalcoholic cirrhosis

Hepatic venous catheterization is widely used to assess portal pressure. However, it remains unclear whether wedged hepatic venous pressure is a close indicator of portal venous pressure during vasoactive drug administration in nonalcoholic cirrhosis. To address this issue, we analyzed the data from our previous published studies. Forty patients with nonalcoholic cirrhosis (HBV infection in five, HCV infection in 28, and cryptogenic in seven) were available in this analysis. A vasoconstrictor (N=14), vasodilator (N=10), or combination (N=16) was administered. The agreement of the changes between portal and wedged hepatic venous pressures during pharmacological manipulation was assessed by an intraclass correlation coefficient. The intraclass correlation coefficient in each subgroup was more than 0.60 (0.62 in vasoconstrictor group, 0.87 in vasodilator group, and 0.73 in combination group). When the analysis was performed according to the cause of liver disease, the values were 0.67 in HBV infection, 0.73 in HCV infection, and 0.74 in cryptogenic cirrhosis. These results suggest that wedged hepatic venous pressure reflects portal venous pressure during vasoactive drug administration in patients with nonalcoholic cirrhosis.     

Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis

BACKGROUND AND AIM: This prospective study aimed to determine whether Doppler ultrasonography can represent the hepatic venous pressure gradient (HVPG) as an assessment of the severity of portal hypertension and the response to terlipressin, which reduces the portal pressure in liver cirrhosis. METHODS: The HVPG and the Doppler ultrasonographic parameters, such as the portal venous velocity and the splenic venous velocity, the pulsatility and the resistive index of the hepatic, splenic and renal arteries were measured in 138 patients with liver cirrhosis. The changes in the HVPG and the portal venous velocity after administering terlipressin were evaluated in 43 of the 138 patients. The patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: None of the Doppler ultrasonographic parameters correlated with the HVPG. Both the HVPG (28.0 +/- 19.8%) and the portal venous velocity (29.7 +/- 13.2%) showed a significant reduction after terlipressin administration. However, the portal venous velocity decreased significantly, not only in the responders (31.0 +/- 12.0%) but also in the non-responders (25.2 +/- 16.4%). CONCLUSIONS: Doppler ultrasonography does not represent the HVPG, and is therefore not suitable for replacing HVPG as a means of assessing the severity of portal hypertension and the response to drugs which reduce the portal pressure in liver cirrhosis.     

Modern management of portal hypertension

The development of portal hypertension plays a major role in the pathogenesis of many of the complications of chronic liver disease. In developed countries, most patients with portal hypertension have cirrhosis, and, in this condition, portal pressure is elevated as a result of both an increase in hepatic resistance to portal perfusion and increased mesenteric blood flow. Bleeding from oesophageal varices is a major cause of mortality in patients with significant portal hypertension. This review concentrates on the recognition, prevention and acute management of this life threatening complication of cirrhosis.     

肝静脉压力梯度在肝硬化门静脉高压症患者中的临床应用

测量肝静脉压力梯度（HVPG）是评估门静脉高压症最常用的方法。大量研究表明,HVPG可作为食管静脉曲张出血的预测因子,此外,HVPG还可作为一个预后指标,可方便临床医生以其做参考为静脉曲张出血的一级预防和二级预防来制定合适的治疗策略。现阶段的治疗目标是使HVPG下降到12 mm Hg以下或比基线值下降20%,达到此目标的患者其食管静脉曲张的首次出血和再出血的风险均大大降低。对于一级预防,非选择性的β受体阻滞剂,如心得安,临床已广泛应用;然而,再出血的发生率仍然很高,临床上常用包括非选择性β受体阻滞剂在内的药物联合治疗和内镜干预,如经颈静脉肝内门体静脉分流术（TIPS）、内镜下硬化剂注射和内镜下套扎。主要探讨目前HVPG的测量方法及其临床应用,并重点对在肝硬化中HVPG对食管静脉曲张出血和再出血及治疗反应的预测作用做详细阐述。     

HVPG measurement: is it mandatory for the management of portal hypertension?—Con

Abstract   Complications of portal hypertension are common in the cirrhotic, and bleeding varices are a significant cause of morbidity and mortality in this population. We currently can identify the patients at greatest risk for bleeding by the endoscopic appearance of the varices and we know that once a patient bleeds, rebleeding is almost inevitable. Thus, both groups of patients are targets for preventative therapy. Currently, non-selective beta-blockers are used to reduce the risk of bleeding in both types of patients but many patients fail this form of therapy and bleed or rebleed. Recent studies have shown that patients who fail to have a hemodynamic response to beta blocker therapy are most likely to fail therapy and it has been suggested that measurement of the hepatic vein pressure gradient (HVPG) be used in the routine management of this group of patients. Unfortunately, there are many unresolved issues as to the utility of the hemodynamic response in the management of cirrhotics. Outside of academic medical centers, the ability to measure pressures accurately is limited and thus significant training would be required before the test can have widespread acceptance. More importantly, it has not been shown in prospective randomized trials that using the hemodynamic response to define the therapeutic approach is any better than the current approach of giving everyone beta-blockers and using variceal band ligation in those who bleed or rebleed. Pending the completion and publishing of these types of controlled trials, measurement of the HVPG will remain of academic interest only.     

非肝硬化门脉高压患者临床特点分析

目的 总结非肝硬化门脉高压症(NCPH)患者的临床特点和肝静脉压力梯度(HVPG)的变化.方法 2017年1月～2019年12月南京市第二医院住院的28例NCPH患者,采用Seldinger法穿刺右侧颈内静脉,使用一次性球囊导管测定肝静脉压力,计算HVPG,接受肝活检检查.结果 在本组28例NCPH患者中,诊断特发性门...     

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis

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Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension

Portal hypertension is a predictor of liver‐related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon‐free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child‐Pugh‐Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open‐label sofosbuvir plus ribavirin at Day 1 or after a 24‐week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by ‐1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow‐up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long‐term follow‐up. (EudraCT 2012‐002457‐29).     

New angiotensin II type 1 receptor blocker olmesartan improves portal hypertension in patients with cirrhosis

Aim: To evaluate the effect of the new oral angiotensin II type 1 receptor blocker olmesartan on portal hemodynamics in patients with cirrhosis. Methods: From January 2005 to March 2006, 18 cirrhosis patients treated with endoscopic band ligation for primary esophageal variceal bleeding were included in the present study. Hepatic venous pressure gradient (HVPG) of the patients was >/=12 mmHg at baseline measurement. The patients were given 10 mg olmesartan orally once daily for 2 weeks. Eighteen cirrhosis patients with esophageal variceal bleeding who did not receive any antihypertensive agents were included in the study as control. On day 14, HVPG, blood pressure, heart rate, and parameters of hepatic and renal function were examined after the treatment. Responders were defined as those with HVPG reduction of >20% versus baseline. Results: Olmesartan significantly reduced HVPG by -16.8 +/- 22.0% (P = 0.031) and mean arterial pressure by -13.1 +/- 10.8% (P = 0.0041). Six of 18 (33.3%) patients in the olmesartan group showed >20% reduction of HVPG from baseline values. None of the patients treated with olmesartan had any complications. Conclusion: Olmesartan reduces portal pressure and may be safe and highly effective in the treatment of portal hypertension.     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

Haemodynamic effects of a combination of propranolol and clonidine in patients with post-hepatitic cirrhosis

Abstract The haemodynamic effects of a combination of propranolol and clonidine were evaluated in 20 patients with post-hepatitic cirrhosis. Haemodynamic measurements were taken before and 30 min after an intravenous injection of 0.1 mg/kg of propranolol. Thereafter, each patient was given an oral dose of 150 μ g of clonidine and re-measured 60 min later. In this series, eight patients were defined as 'non-responders' (a decrease in hepatic venous pressure gradient of < 10%) after propranolol treatment. Of both the responders and non-responders, propranolol caused expected decreases in the cardiac index and heart rate while mean arterial pressure remained unchanged. Of the propranolol responders, a significant decrease in hepatic venous pressure gradient was observed. After the addition of clonidine, in both the responders and non-responders there was a further decrease in hepatic venous pressure gradient with a concurrent drop in mean arterial pressure, but cardiac index and heart rate remained unaltered. In conclusion, the combination of propranolol and clonidine in post-hepatitic cirrhotic patients enhanced the reduction of portal pressure achieved by propranolol alone. The beneficial effects of the combination of the two in the reduction of portal pressure appeared to be similar in both the propranolol responders and non-responders. However, the drop in mean arterial pressure following the addition of clonidine may be hazardous to cirrhotic patients.     

肝硬化后门静脉血栓形成的临床特点研究

目的研究肝硬化(liver cirrhosis,LC)后门静脉血栓(portal vein thrombosis,PVT)形成的临床特点。方法对9678例LC患者进行回顾性分析,采用腹部B超/腹部增强CT及腹部增强MRI检查门脉主干或左右分支,筛选出LC伴PVT形成者(PVT组),同时将LC后无PVT患者纳为对照组,比较2组的Child-Pugh分级、门静脉及脾静脉宽度、脾脏面积及厚度、腹水、上消化道出血、肝性脑病和肝肾综合征等并发症。结果 LC患者中有396例(4.09%)PVT形成。PVT组中LC的病因主要有乙型肝炎、酒精性及丙型肝炎LC,PVT主要分布在门静脉主干、门静脉右支、肠系膜上静脉、门静脉左支和脾静脉。按Child-Pugh进行分级,PVT组与对照组比较,肝损伤较重(P<0.01)。PVT组合并腹水、上消化道出血、肝性脑病及肝肾综合征等并发症的发病率均较对照组高(P<0.01)。PVT组门静脉和脾静脉宽度分别为(1.50±0.23)cm和(1.25±0.34)cm,对照组为(1.38±0.23)cm和(1.06±0.29)cm。PVT组脾脏面积为(97.48±32.90)cm2,脾脏厚度为(6.09±1.21)cm;对照组分别为(81.19±29.10)cm2和(5.26±0.99)cm。PVT组门静脉及脾静脉宽度和脾脏厚度均大于对照组,差异有统计学意义(P<0.05)。PVT组有侧支循环开放的患者占96.21%,对照组为78.25%,2组比较差异有统计学意义(P<0.05)。结论 LC后PVT形成对LC患者的临床转归有重要影响。     

Hepatic venous pressure gradient measurement: is it mandatory in the management of portal hypertension?

Abstract   Portal hypertension can be evaluated by hepatic vein catheterization and measurement of wedged and free hepatic vein pressures. The hepatic venous pressure gradient (HVPG) is the difference between both pressures and its normal value is lower than 5 mmHg. The technique is safe and reliable provided several requirements are fulfilled to get accurate results. HVPG measurement is useful to determine the site of increased resistance either presinusoidal, sinusoidal or postsinusoidal. If HVPG is normal in the presence of clinical signs of portal hypertension, evaluation of the portal venous system and direct measurement of portal vein pressure is required. HVPG measurement may also be used as a prognostic marker to evaluate the risks of developing complications such as ascites or variceal bleeding; in addition, it has been suggested that it could provide prognostic information for variceal rebleeding or survival. Primary and secondary prophylaxis of variceal bleeding can be achieved with a pharmacological treatment using beta blockers and/or nitrates. Repeated HVPG measurements are probably useful to monitor the treatment; it has been suggested that decreasing HVPG by 20% or below 12 mmHg is a reasonable target to define a good hemodynamic response and hopefully a low risk of bleeding; endoscopic therapy can be used in non-responders. Repeated hemodynamic evaluation, however, is invasive and must be performed in specialized liver units; therefore, future clinical trials must demonstrate unequivocally the clinical usefulness of this approach prior to recommending repeated HVPG measurement on a routine basis.