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. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. 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 (R2). 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.

Portal Hypertension in Nonalcoholic Fatty Liver Disease: Challenges and Paradigms.

Portal hypertension in cirrhosis is defined as an increase in the portal pressure gradient (PPG) between the portal and hepatic veins and is traditionally estimated by the hepatic venous pressure gradient (HVPG), which is the difference in pressure between the free-floating and wedged positions of a balloon catheter in the hepatic vein. By convention, HVPG≥10 mmHg indicates clinically significant portal hypertension, which is associated with adverse clinical outcomes. Nonalcoholic fatty liver disease (NAFLD) is a common disorder with a heterogeneous clinical course, which includes the development of portal hypertension. There is increasing evidence that portal hypertension in NAFLD deserves special considerations. First, elevated PPG often precedes fibrosis in NAFLD, suggesting a bidirectional relationship between these pathological processes. Second, HVPG underestimates PPG in NAFLD, suggesting that portal hypertension is more prevalent in this condition than currently believed. Third, cellular mechanoresponses generated early in the pathogenesis of NAFLD provide a mechanistic explanation for the pressure-fibrosis paradigm. Finally, a better understanding of liver mechanobiology in NAFLD may aid in the development of novel pharmaceutical targets for prevention and management of this disease.

Correlation between hepatic venous pressure gradient and portal pressure gradient in patients with autoimmune cirrhotic portal hypertension and collateral branches of the hepatic vein.

AIM: To assess the correlation and agreement between hepatic venous pressure gradient (HVPG) and portal pressure gradient (PPG) in patients with autoimmune liver diseases (ALD) and portal hypertension, and to investigate the extent to which hepatic vein collateralization affects the accuracy of this assessment. METHODS: Ninety-eight patients with ALD between 2017 and 2021 who underwent transjugular intrahepatic portosystemic shunt with conventional and innovative 15 mL pressurized contrast were selected to measure wedged hepatic venous pressure (WHVP) and portal venous pressure and to calculate the HVPG and PPG. Pearson's correlation was used for correlation analysis between the two groups. Bland-Altman plots were plotted to estimate the agreement between paired pressures. RESULTS: The r values of PPG and HVPG in the early, middle, late, and portal venous visualization were 0.404, 0.789, 0.807, and 0.830, respectively, and the R2 values were 0.163, 0.622, 0.651, and 0.690, respectively. The p value for the r and R2 values in the early group was 0.015, and the p values in the remaining groups were less than 0.001. Bland-Altman plots showed that patients in the portal venous visualization group had the narrowest 95% limits of agreement. The mean value of the difference was close to the zero-scale line. CONCLUSIONS: In patients with ALD, the correlation between the HVPG and PPG was good, and the later the collateral development, the better the correlation. Hepatic vein collateral was an essential factor in underestimating WHVP and HVPG, and the earlier the collateral appeared, the more obvious the underestimation.

Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension.

BACKGROUND: The hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension. METHODS: A total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson's correlation coefficient were used for analysis. RESULTS: Conventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively. CONCLUSIONS: Innovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.

The evaluation of portal hypertension in cirrhotic patients with spectral computed tomography.

BACKGROUND: Iodine concentrations measured using dual-energy spectral CT (DESCT) have been recently proposed as providing good performance for examining tissues hemodynamics. PURPOSE: To evaluate the diagnostic efficacy of DESCT-derived parameters in evaluating portal venous pressure in patients with liver cirrhosis. MATERIAL AND METHODS: A total of 71 patients with liver cirrhosis who underwent percutaneous transhepatic portal vein puncture procedures were included in this study. All participants underwent DESCT and gastrointestinal endoscopy within one month before the operation. The direct portal venous pressure of each participant was measured preoperatively. RESULTS: Stepwise multivariate linear regression analysis showed that the iodine concentrations in the portal vein and hepatic parenchyma during the portal venous phase and the platelet count were independently correlated with the direct portal venous pressure (P < 0.001, P < 0.001, and P = 0.030, respectively). Receiver operating characteristic analysis revealed that the normalized iodine concentration of the hepatic parenchyma had the best performance for identifying clinically significant portal hypertension (≥10 mmHg), esophageal varices, and high-risk esophageal varices (the area under the curve values were 0.951, 0.932, and 0.960, respectively). CONCLUSION: The normalized iodine concentration of the hepatic parenchyma is a reliable parameter to non-invasively assess portal venous pressure in patients with liver cirrhosis.

Portal venous pressure in non-cirrhotic bilharzial patients undergoing elective splenectomy, can it affect mortality? A prospective study.

BACKGROUND AND STUDY AIMS: To evaluate the impact of intraoperatively measured portal vein pressure (PVP) on mortality in non-cirrhotic bilharzial patients undergoing splenectomy. METHODS: The present study is a prospective study that was conducted in Egypt from April 2014 to April 2018. Adult patients with non-cirrhotic bilharziasis who were scheduled to undergo splenectomy were included. Studied cases were divided into a survival cohort and a non-survival cohort. The main objective was the correlation between the incidence of mortality and intraoperative PVP. RESULTS: The present work comprised 130 cases with a mean age of 51.8 ± 6.4 years old. The in-hospital mortality rate was 22.3%, with sepsis as a major cause of death (37.9%). In term of the association between preoperative variables and mortality, survivors had statistically significant lower portal vein diameter (13.6 ± 1.8 versus 15.2 ± 1.8mm; p<0.001) and higher portal vein velocity (14.2 ± 1.8 versus 10.4 ± 2.3 cm/sec; p<0.001) than nonsurvivors. The survived patients had significantly lower PVP (13.9 ± 1.1 versus 17.7 ± 2.7; p<0.001). A cut-off value of ≥14.5 mmHg, the PVP yielded a sensitivity of 86.2% and a specificity of 69% for the prediction of mortality. The association analysis showed a statistically significant association between mortality and postoperative liver function parameters. CONCLUSIONS: High intraoperative PVP is linked to early postoperative death in non-cirrhotic cases undergoing splenectomy. Our study showed that PVP > 14.5mmHg was an independent predictor of death and showed good diagnostic performance for the detection of early postoperative mortality.

Effects of endoscopic gastric plication on portal pressure gradient in a patient with nonalcoholic steatohepatitis cirrhosis.

Video 1Endoscopic gastric plication (EGP) to treat obesity and nonalcoholic steatohepatitis (NASH) in a patient with compensated cirrhosis, as well as the application of EUS-guided portal pressure gradient (EUS-PPG) measurement to monitor changes in PPG after EGP.

Nonalcoholic fatty liver disease and portal hypertension.

Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent. Early increases in intrahepatic vascular resistance may contribute to the progression of liver disease. Specific pathophenotypes linked to the development of portal hypertension in NAFLD include hepatocellular lipid accumulation and ballooning injury, capillarization of liver sinusoidal endothelial cells, enhanced contractility of hepatic stellate cells, activation of Kupffer cells and pro-inflammatory pathways, adhesion and entrapment of recruited leukocytes, microthrombosis, angiogenesis and perisinusoidal fibrosis. These pathological events are amplified in NAFLD by concomitant visceral obesity, insulin resistance, type 2 diabetes and dysbiosis, promoting aberrant interactions with adipose tissue, skeletal muscle and gut microbiota. Measurement of the hepatic venous pressure gradient by retrograde insertion of a balloon-tipped central vein catheter is the current reference method for predicting outcomes of cirrhosis associated with clinically significant portal hypertension and guiding interventions. This invasive technique is rarely considered in the absence of cirrhosis where currently available clinical, imaging and laboratory correlates of portal hypertension may not reflect early changes in liver hemodynamics. Availability of less invasive but sufficiently sensitive methods for the assessment of portal venous pressure in NAFLD remains therefore an unmet need. Recent efforts to develop new biomarkers and endoscopy-based approaches such as endoscopic ultrasound-guided measurement of portal pressure gradient may help achieve this goal. In addition, cellular and molecular targets are being identified to guide emerging therapies in the prevention and management of portal hypertension.

Application of CT-based radiomics in predicting portal pressure and patient outcome in portal hypertension.

PURPOSE: Portal venous pressure (PVP) measurement is of clinical significance, especially in patients with portal hypertension. However, the invasive nature and associated complications limits its application. The aim of the study is to propose a noninvasive predictive model of PVP values based on CT-extracted radiomic features. METHODS: Radiomics PVP (rPVP) models based on liver, spleen and combined features were established on an experimental cohort of 169 subjects. Radiomics features were extracted from each ROI and reduced via the LASSO regression to achieve an optimal predictive formula. A validation cohort of 62 patients treated for gastroesophageal varices (GOV) was used to confirm the utility of rPVP in predicting variceal recurrence. The association between rPVP and response to treatment was observed. RESULTS: Three separate predictive formula for PVP were derived from radiomics features. rPVP was significantly correlated to patient response to endoscopic treatment for GOV. Among which, the model containing both liver and spleen features has the highest predictability of variceal recurrence, with an optimal cut-off value at 29.102 mmHg (AUC 0.866). A Kaplan Meier analysis further confirmed the difference between patients with varying rPVP values. CONCLUSION: PVP values can be accurately predicted by a non-invasive, CT derived radiomics model. rPVP serves as a non-invasive and precise reference for predicting treatment outcome for GOV secondary to portal hypertension.

Relationship between hemodynamic parameters and portal venous pressure in cirrhosis patients with portal hypertension.

Cirrhosis caused by viral and alcoholic hepatitis is an essential cause of portal hypertension (PHT). The incidence of PHT complication is directly proportional to portal venous pressure (PVP), and the clinical research of PVP and its hemodynamic indexes is of great significance for deciding the treatment strategy of PHT. Various techniques are currently being developed to decrease portal pressure but hemodynamic side effects may occur. In this article, the hemodynamic indexes of cirrhotic PHT patients were studied to explore the correlation between the index and PVP and to evaluate the clinical value of Doppler ultrasound in measuring PVP in patients with PHT. This was achieved by selecting 90 cirrhotic PHT patients who underwent transjugular intrahepatic portosystemic shunt in our hospital from June 2015 to September 2019. Fifty healthy people who had a physical examination in the hospital in the same period were selected as the control group. The liver hemodynamic parameters of two groups were measured by Doppler ultrasound, and the cirrhotic PHT patients were graded by the Child-Pugh grading method to evaluate the liver function and measure the PVP value. The results showed that both the central portal vein velocity (PVV) and splenic vein velocity (SVV) of the PHT group were lower than those of the control group. Also, the portal vein diameter (PVD), portal venous flow and splenic vein diameter (SVD) were higher than those of the control group (all Ps < 0.05). Among liver function graded PHT patients, the PVD, PVV, SVD and SVV were significantly different (all Ps < 0.05). Furthermore, the PVP of patients with liver function grades A, B and C was 38.9 ± 1.4, 40.6 ± 5.1 and 42.5 ± 4.8 cmH2O, respectively, with a significant difference. It can be concluded from this study that Doppler ultrasound can be used as a tool for clinical assessment of PHT in cirrhosis patients. Doppler ultrasound showed a good prospect in noninvasive detection of PHT in cirrhosis; however, this technique needs application on large sample population study to validate the results.

A Predictive Formula for Portal Venous Pressure Prior to Liver Resection Using Directly Measured Values.

Purpose: Despite refinements in surgical techniques for liver resection, evaluation of hepatic reserve disparity remains one of the most common problems in liver surgery, especially for hepatic malignancies such as hepatocellular carcinoma (HCC). Portal venous pressure (PVP) is regarded one of the important factors in selecting treatment strategy, although its measurement can be invasive and complex. Methods: To establish a formula for calculating PVP preoperatively, intraoperative directly measured PVP was used in 177 patients with preoperative factors and liver function tests such as age, sex, virus status, platelet count, prothrombin time, albumin, total bilirubin, alanine aminotransferase (ALT), Child-Pugh grade, liver damage defined by the Liver Cancer Study Group of Japan, indocyanine green retention rate at 15 min (ICG-R15), and the aspartate transaminase (AST)-platelet ratio index (APRI). Results: Although 90% of the patients were classified as Child-Pugh A, median direct PVP was 16.5 cm H2O (5.5-37.0) and the percentage of PVP greater than 20 cm H2O was 27.1%, reflecting portal hypertension due to liver damage. After multiple regression analysis, the formula PVP (cmH2O) = EXP[2.606 + 0.01 × (ICG-R15) + 0.015 × APRI] was established from the measured data. Conclusion: Considering its simplicity of use, we have adopted this formula for predicting PVP in determining treatment strategy for HCC and other hepatic malignancies.

A novel fiber-optic pressure sensor device for measuring variceal pressure.

It has been reported that variceal pressure can predict the occurrence of variceal bleeding. However, the majority of methods presently used to measure variceal pressure are either invasive or inconvenient. In the present study, a fiber-optic pressure sensor was constructed to detect variceal pressure. The prospective study focused on the in vitro accuracy of a fiber-optic pressure sensor and investigated the clinical reliability and feasibility of this method. The fiber-optic pressure sensor covered a pressure-sensitive probe containing a fiber-optic pressure sensor and a workstation to record the pressure tracing. It was hypothesized that the endoscopic fiber-optic pressure sensor can effectively predict the risk of variceal bleeding. To test this hypothesis, 80 patients who suffered from cirrhosis and who had a history of variceal bleeding were included in the present study. The fiber-optic pressure sensor was guided through the biopsy channel using an endoscope in the patient cohort. Transjugular intrahepatic stent-shunt (TIPS) was subsequently performed within 24 h after measuring variceal pressure. A comparison of the results of the 80 patients was made between variceal pressure measured by the endoscopic fiber-optic pressure sensor and the portal pressure gradient (PPG) measured by a TIPS. The variceal pressure measurements with the fiber-optic pressure sensor were technically satisfactory in 78 patients. The results indicated that there was a linear correlation between the variceal pressure measured by the endoscopic fiber-optic pressure sensor and the PPG (r=0.940, P<0.001). These observations suggest that the fiber-optic pressure sensor is an accurate and feasible measurement technique. Therefore, the results of the present study indicate that the endoscopic fiber-optic pressure sensor is effective in predicting the risk of variceal bleeding.

Splenectomy in living donor liver transplantation and risk factors of portal vein thrombosis.

BACKGROUND: Graft inflow modulation (GIM) during adult-to-adult living donor liver transplantation (LDLT) is a common strategy to avoid small-for-size syndrome, and some transplant surgeons attempt small size graft strategy with frequent GIM procedures, which are mostly performed by splenectomy, in LDLT. However, splenectomy can cause serious complications such as portal vein thrombosis and overwhelming postsplenectomy infection. METHODS: Forty-eight adult-to-adult LDLT recipients were enrolled in this study and retrospectively reviewed. We applied the graft selection criteria, which routinely fulfill graft-to-recipient weight ratio ≥ 0.8%, and consider GIM as a backup strategy for high portal venous pressure (PVP). RESULTS: In our current strategy of LDLT, splenectomy was performed mostly due to hepatitis C and splenic arterial aneurysms, but splenectomy for GIM was intended to only one patient (2.1%). The final PVP values ≤ 20 mmHg were achieved in all recipients, and no significant difference was observed in patient survival or postoperative clinical course based on whether splenectomy was performed or not. However, 6 of 18 patients with splenectomy (33.3%) developed postsplenectomy portal vein thrombosis (PVT), while none of the 30 patients without splenectomy developed PVT after LDLT. Splenectomy was identified as a risk factor of PVT in this study (P < 0.001). Our study revealed that a lower final PVP could be risk factor of postsplenectomy PVT. CONCLUSIONS: Using sufficient size grafts was one of the direct solutions to control PVP, and allowed GIM to be reserved as a backup procedure. Splenectomy should be avoided as much as possible during LDLT because splenectomy was found to be a definite risk factor of PVT. In splenectomy cases with a lower final PVP, a close follow-up is required for early detection and treatment of PVT.

Transjugular Intrahepatic Portosystemic Shunt:The Impact of Portal Venous Pressure Declines on Shunt Patency and Clinical Efficacy.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) placement using the same-diameter covered stents can lead to differed declines of portal venous pressure declines (PVDs). This study aimed to compare the long-term shunt patency and clinical efficacy of TIPS placement that caused low PVDs (≤9 mmHg) and high PVDs (>9 mmHg). MATERIALS AND METHODS: A total of 129 patients treated by TIPS placement with 8 mm-diameter polytetrafluoroethylene covered stents were included and analyzed retrospectively. They were stratified into group A with low PVDs (n = 69) and group B with high PVDs (n = 60). RESULTS: The 6-year actuarial probabilities of remaining free of shunt dysfunction (47.2% vs 64.6%; p = 0.007) and variceal rebleeding (48.3% vs 63.9%; p = 0.038) were significantly lower in group A than in group B. The 6-year actuarial probability of remaining free of hepatic encephalopathy was significantly higher in group A than in group B (44.5% vs 32.5%; p = 0.010), though the 6-year cumulative survival rate was similar in both groups (A vs B: 65.5% vs 56.0%; p = 0.240). The baseline portal vein thrombosis (hazard ratio [HR]: 6.045, 95% confidence interval [CI]: 2.762-13.233; p = 0.000) and stent type (HR: 4.447, 95%CI: 1.711-11.559, p = 0.002) were associated with shunt dysfunction, whereas only ascites was associated with mortality (HR: 1.373, 95%CI: 1.114-3.215; p = 0.024). CONCLUSION: High PVDs (>9 mmHg) were associated with higher shunt patency, lower incidence of variceal rebleeding, but higher frequency of hepatic encephalopathy and similar survival rate than low PVDs (≤9 mmHg) after TIPS placement.

EUS-guided portal pressure measurement (with videos).

A growing number of studies have explored EUS-guided vascular catheterization due to the relative proximity of the gastrointestinal tract to the major blood vessels of the mediastinum and abdomen. In particular, EUS-guided access of the portal vein (PV) may be favorable given the relative difficulty of PV access through standard percutaneous routes. Two major diagnostic applications of EUS-guided vascular access include angiography and assessment of intravascular pressure. This review will outline the different devices and techniques employed to obtain angiographic visualization and/or direct pressure measurements of the portal circulation. Ease of access, safety, and important lessons learned from each approach will be highlighted.

Is Portal Venous Pressure or Porto-systemic Gradient Really A Harbinger of Poor Outcomes After Living Donor Liver Transplantation?

BACKGROUND: Portal hyperperfusion as a cause of small for size syndrome (SFSS) after living donor liver transplantation (LDLT) remains controversial. Portal venous pressure (PVP) is often measured indirectly and may be confounded by central venous pressure (CVP). METHODS: In 42 adult cirrhotics undergoing elective LDLT, PVP was measured by direct canulation of portal vein and porto systemic gradient (PSG) was obtained after subtracting CVP from PVP. None underwent portal inflow modulation. SFSS was looked in 27 patients after excluding 15 with technical complications. RESULTS: Clinical features of SFSS found in 6 patients, 5 with graft recipient weight ratio (GRWR) > 0.8% and PVP < 20 mm of Hg. One with GRWR < 0.8% could truly be labeled as SFSS. Incidence of SFSS was not higher in patients with elevated PVP > 20 mm of Hg (14.3% vs 0%, P = 0.259) or PSG > 13 mm of Hg (33.3% vs 0%, P = 0.111). Intensive care unit (ICU) stay was longer in patients with elevated PVP (14.55 vs 9.13 days, P = 0.007) and PSG (16.8 vs 9.72 days, P = 0.009). There was no difference in graft functions, post-operative complications and mortality in first month post-LDLT. CONCLUSION: Elevated PVP or PSG increased morbidity but neither predicted SFSS nor affected survival.

Comparison of physical parameter measurements between peripheral and portal blood samples in patients with portal hypertension.

BACKGROUND: Measuring portal venous pressure is necessary to examine, diagnose, and treat portal hypertension, but current methods are invasive. OBJECTIVE: This study aimed to determine whether a noninvasive peripheral blood measurement could be used to estimate portal venous pressure by investigating correlations between certain physical parameter measurements in the peripheral blood with those obtained in portal blood samples. METHODS: A total of 128 peripheral and portal blood samples from patients (n= 128) were analyzed for blood rheology and routine blood parameters. RESULTS: The mean peripheral and portal whole blood viscosities under the shear rates of 200 s-1 (BV 200 s-1) were 2.97 ± 0.50 mPa.s and 3.06 ± 0.39 mPa.s. The mean peripheral and portal BV 30 s-1 values were 3.96 ± 0.79 mPa.s and 4.16 ± 0.64 mPa.s. We observed strong correlations between peripheral and portal blood measurements of BV 200 s-1 (r2= 0.9649), BV 30 s-1 (r2= 0.9622), BV 5 s-1 (r2= 0.9610), and BV 1 s-1 (r2= 0.9623). CONCLUSIONS: Our results indicate that peripheral blood can be used to evaluate certain parameters in portal blood for use in biofluid mechanics studies, and to provide noninvasive measurement of portal venous pressure.

Umbilical Venous Catheter Malposition Is Associated with Necrotizing Enterocolitis in Premature Infants.

OBJECTIVE: The etiology of necrotizing enterocolitis (NEC) remains elusive despite known associations with several factors, including intestinal ischemia related to the effects of umbilical arterial catheterization on the mesenteric circulation. However, the role of the mesenteric venous circulation has yet to be studied as a potential cause of NEC. We examined the association between umbilical venous catheter (UVC) position and the development of NEC in premature infants. DESIGN: A prospective cohort study was performed to examine the effect of UVC on portosystemic shunting via the ductus venosus (DV) and its potential role in NEC. RESULTS: We recruited 132 premature infants, 62 of which had a birth weight ≤1,500 g. NEC was noted in 12 (19%) patients. All infants weighing ≤1,500 g underwent an attempt at UVC insertion. The UVC status was classified as appropriate (n = 39), unsuccessful (n = 9), or malpositioned (n = 14). Among the NEC patients, 7 (58%) had a UVC malposition and 3 (25%) had an unsuccessful attempt. These rates were significantly higher than in patients without NEC (14 and 12%, respectively). Multivariable logistic regression analysis confirmed birth weight (OR 2.2, 95% CI 1.2-4.7, p = 0.001) and UVC malpositioning (OR 6.9, 95% CI 1.6-35.4, p = 0.007) as independent risk factors associated with NEC. CONCLUSIONS: Unrecognized withdrawal of a UVC into the portal vein or DV is associated with an increased incidence of NEC in infants weighing ≤1,500 g. The data support the need for additional studies to examine this effect. Confirmation of a causal relationship will raise the need to reassess UVC insertion criteria and strategies for more closely monitoring the catheter tip position.

Role of portal venous pressure changes in the liver dysfunction caused by hepatic congestion after extended liver resection / 中华消化外科杂志

Objective To explore the role of portal venous pressure changes in the liver dysfunction caused by hepatic congestion after extended liver resection.Methods The experimental study was adopted.According to the random number table,90 Sprague-Dawley rats were divided into 3 groups,30 in each group:30 rats in the non-congestion group received 70％ of liver resection (median lobe + left lobe),30 rats in the congestion group received 70％ of liver resection (median lobe + left lobe) with whole caudal lobe congestion by ligation of veins and 30 rats in the congestion + splenectomy group received 70％ of liver resection (median lobe + left lobe) with whole caudal lobe congestion by ligation of veins and splenectomy.(1) Twenty rats in each group were used to make postoperative survival analysis.Ten rats in each group were used for related experiments.The portal venous pressures (PVPs) of 5 rats in each group were detected at postoperative 12 hours and 24 hours,and then blood and liver specimens were collected.(2) PVP changes were detected at postoperative 12 hours and 24 hours.(3) Clinical and biochemical test:level of total bilirubin (TBil) was tested at postoperative 12 hours and 24 hours.(4) Pathological examination:liver pathological damage was detected by HE staining.(5) The expression of CD68 macrophagocyte was detected by immunohistochemical staining.(6) The relative expressions of Cleaved Casepase-3 and hypoxia inducible factor-1α (HIF-1α) proteins at postoperative 24 hours were detected by Westein blot.(7) The relative expressions of mRNA of vascular regulation related genes (ET-1/eNOS) and inflammatory factors (TNF-α and IL-6) were detected by real-time polymerase chain reaction (RT-PCR).(8)The hyaluronic acid (HA) was measured by enzyme-linked immuno-sorbent assay (ELISA).Measurement data with normal distribution were represented as （x） ± s.Comparison among 3 groups was done using the ANOVA,and pairwise comparison was done by the LSD test.The postoperative 5-day survival curve was drawn by the KaplanMeier method,and the survival was compared using the Log-rank test.Results (1) Survival analysis:5-day survival rate in the non-congestion group,congestion group and congestion + splenectomy group were respectively 75％,10％ and 55％,with a statistically significant difference among the 3 groups (x2=18.21,P ＜0.05).(2)Changes of PVPs and TBil:levels of PVP and TBil in the non-congestion group,congestion group and congestion + splenectomy group were respectively (15.77 ±0.67)cmH2O,(18.33 ±0.28) cmH2O,(14.87 ± 0.58) cmH2O,(1.48 ±0.10)μmol/L,(1.76±0.15) μ mol/L,(1.62 ±0.11) μmol/L at postoperative 12 hours and (13.49 ± 0.45) cmH2 O,(16.96 ± 0.82) cmH2 O,(15.69 ± 0.85) cmH2 O,(1.47 ± 0.11) μmol/L,(1.94 ± 0.07) μmol/L,(1.67 ± 0.11) μmol/L at postoperative 24 hours,showing statistically significant differences among 3 groups (F =56.53,29.01,6.81,27.85,P ＜ 0.05).(3) Results of pathological examination:compared with noncongestion group,there were a lot of vacuolar cells with degeneration appearing in non-congestion liver tissues,severe liver cell swelling and hepatic sinus congestion in the congestion group at postoperative 24 hours.Compared with congestion group,vacuolar degeneration appearing in non-congestion liver tissues have some improvement in the congestion + splenectomy group.(4) Immunohistochemical staining:compared with non-congestion group and congestion + splenectomy group,the positive CD68 marked macrophages in the congestion group were increased at postoperative 24 hours.(5) Western blot assay:the relative expressions of Cleaved Casepase-3 and HIF-1α proteins in the non-congestion group,congestion group and congestion + splenectomy group were 0.63 ± 0.05,1.17 ± O.18,0.95 ± 0.17 and 0.63 ± 0.14,1.48 ± 0.08,1.13 ± 0.17,respectively,showing statistically significant differences among 3 groups (F =17.42,50.58,P ＜ 0.05).(6) Results of RT-PCR:the relative expression of mRNA of ET-1/eNOS in the non-congestion group,congestion group and congestion + splenectomy group was respectively 1.01 ± 0.63,2.09 ± 0.27,0.82 ± 0.12 at postoperative 12 hours and 0.73 ± 0.17,2.16 ± 0.94,0.80 ± 0.24 at postoperative 24 hours,showing statistically significant differences among 3 groups (F =62.91,10.65,P ＜0.05).The relative expression of mRNA of TNF-α in the non-congestion group,congestion group and congestion + splenectomy group was respectively 0.99 ± 0.08,127.80 ± 13.15,7.34 ± 1.56 at postoperative 12 hours and 0.99 ± 0.06,116.62 ± 13.32,58.62 ± 12.12 at postoperative 24 hours,showing statistically significant differences among 3 groups (F =436.77,154.54,P ＜ 0.05).The relative expression of mRNA of IL-6 in the non-congestion group,congestion group and congestion + splenectomy group was respectively 0.98 ±0.06,1.87 ±0.34,1.54 ±0.15 at postoperative 12 hours and 0.99 ±0.05,2.02 ±0.27,1.51 ±0.11at postoperative 24 hours,with statistically significant differences among 3 groups (F =22.08,46.71,P ＜ 0.05).(7) Results of ELISA:the level of HA in the non-congestion group,congestion group and congestion + splenectomy group was respectively (149 ± 9) ng/L,(200 ± 19) ng/L,(174 ± 9) ng/L at postoperative 12 hours and (136 ± 16) ng/L,(202 ± 13) ng/L,(91 ± 11) ng/L at postoperative 24 hours,with statistically significant differences among 3 groups (F =19.23,34.68,P＜0.05).Conclusions On the basis of extended liver resection,a wide range of liver congestion through increasing PVP causes hepatic microcirculation disorders,hypoxia,inflammation,vacuoles degeneration cells,increased cells apoptosis,aggravated damage of liver function and increased mortality of rats.Splenectomy could reduce PVP and then improve the liver tissues damage caused by liver congestion,meanwhile,increase the survival rate of rats.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

AIM: To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. METHODS: Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. RESULTS: Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CONCLUSION: CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.