Longitudinal Analysis of the Effect of Repeated Transarterial Chemoembolization for Liver Cancer on Portal Venous Pressure

ObjectivesInvestigate long-term effects of repeated transarterial chemoembolization (TACE) on portal venous pressure (PVP) using non-invasive surrogate markers of portal hypertension.MethodsRetrospective, Institutional Review Board-approved study. 99 patients [hepatocellular carcinoma (HCC) group (n=57); liver metastasis group (n=42)] who underwent 279TACEs and had longitudinal pre-/post-therapy contrast-enhanced-MRI (n=388) and complete blood work were included. Outcomes of interest were platelet count (PC), spleen volume, ascites and portosystemic collaterals. Variables included TACE type/number, tumor type, microcatheter location, Child-Pugh, baseline tumor burden (tumor number/total/largest size), vessel invasion, alpha-fetoprotein, Eastern Cooperative Oncology Group (ECOG) performance status, and Model for End-Stage Liver Disease (MELD) score. Generalized Estimating Equations assessed the associations between TACE and outcomes. Power analysis determined the sample size was sufficient.ResultsNo significant change in PC over time was observed in either groups, regardless of liver function (P>0.05). Baseline spleen volume was 226 cm3 for metastatic group, and was larger by 204 cm3 for HCC group (P<0.001). Spleen volume increased by 20 cm3 (95%CI: 8-32; P=0.001) for both groups after 1stTACE and by 16cm3/TACE (P=0.099) over the full follow-up (up to 9TACEs). Spleen volume also tended to increase by 23cm3 (95%CI: -1–48; P=0.064) with higher tumor burden. Odds of developing moderate/severe ascites for metastatic patients was decreased by 0.5 (95%CI: 0.3–0.9; P=0.014), regardless of the Child-Pugh, and increased by 1.5 (95%CI: 1.2–1.9; P<0.001) among HCC patients with unstable Child-Pugh, whereas no change was noted with stable Child-Pugh. HCC patients with unstable Child-Pugh demonstrated a significant increase in portosystemic collaterals number over time (P=0.008). PVP-related complications such as variceal bleeding post-TACE were low (0.4%).ConclusionRepeated TACEs did seem to have an impact on PVP. However, the increase in PVP had marginal effects with low portal hypertension-related complications.

Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model

Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.

Portal Vein Aneurysm Treated With Trans-Jugular Intrahepatic Porto-Systemic Shunt

Portal vein aneurysm (PVA) is a rare entity that can lead to hemorrhage or thrombosis. Although there is no standard treatment, most cases can be managed conservatively; intervention is reserved for symptomatic or enlarging aneurysms. For patients who are not surgical candidates due to cirrhosis and portal hypertension, endovascular creation of a trans-jugular intrahepatic porto-systemic shunt (TIPS) is an option to reduce portal venous pressure. This report describes a case of an enlarging PVA successfully treated with TIPS in a patient with cryptogenic cirrhosis.

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.

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.

Portal Venous Pressure as a Predictor of Mortality in Child’s A Cirrhotic Patients Undergoing Elective Surgery: A Prospective Study

BACKGROUND: Recently, portal venous pressure (PVP) exhibited high sensitivity and specificity in anticipating death in cirrhotic cases submitted to emergency operations. AIM: The current prospective work aimed to evaluate the utility of PVP in predicting 1st month post-operative death in Child’s A cirrhotic cases who underwent elective operations. METHODS: One-hundred and twenty cirrhotic cases that were planned to undergo elective surgery were enrolled in the current prospective work. The intraoperative (I.O) PVP and central venous pressure (CVP) were measured. The statistical analysis was performed using the SPSS version 22.0. The receiver operative curve was plotted to measure the predictive value of PVP. Multivariate analysis was done using logistic regression method for the significant variables impacting mortality on univariate analysis. RESULTS: Twenty-nine patients died in the current work. Patients who survived had statistically considerably lower PVP than patients who died (8.2 ± 1.5 vs. 12.5 ± 1.6 mmHg, respectively, p < 0.001). Similarly, patients who died had significantly higher I.O CVP (p < 0.001), body mass index (p < 0.001), and were more likely to have model for end-stage liver disease score between 9 and 16 (p = 0.003). At a cutoff value ≥10.5 mmHg, the PVP had a sensitivity of 82.8% and specificity of 93.4% for the prediction of mortality. The logistic regression analysis showed that only PVP (odds ratio [OR] =3.1, 95% confidence interval [CI] 1.25–7.5) and CVP (OR = 2.8, 95% CI 1.2–6.5) were the only independent predictors of mortality. CONCLUSION: PVP is a significant predictor of death in Child’s A cirrhotic cases submitted to elective operations.