Endoscopic ultrasound-guided portal pressure gradient measurement in managing portal hypertension

Portal hypertension(PH)is still a challenging clinical condition due to its silent manifestations in the early stage and needs to be measured accurately for early detection.Hepatic vein pressure gradient measurement has been considered as the gold standard measurement for PH;however,it needs special skill,experience,and high expertise.Recently,there has been an innovative development in using endoscopic ultrasound(EUS)for the diagnosis and management of liver diseases,including portal pressure measurement,which is commonly known as EUS-guided portal pressure gradient(EUS-PPG)mea-surement.EUS-PPG measurement can be performed concomitantly with EUS evaluation for deep esophageal varices,EUS-guided liver biopsy,and EUS-guided cyanoacrylate injection.However,there are still major issues,such as different etiologies of liver disease,procedural training,expertise,availability,and cost-effectiveness in several situations with regard to the standard management.

Accurate ultrasonography-based portal pressure assessment in patients with hepatocellular carcinoma

BACKGROUND Portal pressure is of great significance in the treatment of hepatocellular carcinoma(HCC),but direct measurement is complicated and costly;thus,noninvasive measurement methods are urgently needed.AIM To investigate whether ultrasonography(US)-based portal pressure assessment could replace invasive transjugular measurement.METHODS A cohort of 102 patients with HCC was selected(mean age:54±13 years,male/female:65/37).Pre-operative US parameters were assessed by two independent investigators,and multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for the portal pressure gradient(PPG).The estimated PPG predictors were compared with the transjugular PPG measurements.Validation was conducted on another cohort of 20 non-surgical patients.RESULTS The mean PPG was 17.32±1.97 mmHg.Univariate analysis identified the association of the following four parameters with PPG:Spleen volume,portal vein diameter,portal vein velocity(PVV),and portal blood flow(PBF).Multiple linear regression analysis was performed,and the predictive formula using the PVV and PBF was as follows:PPG score=19.336-0.312×PVV(cm/s)+0.001×PBF(mL/min).The PPG score was confirmed to have good accuracy with an area under the curve(AUC)of 0.75(0.68-0.81)in training patients.The formula was also accurate in the validation patients with an AUC of 0.820(0.53-0.83).CONCLUSION The formula based on ultrasonographic Doppler flow parameters shows a significant correlation with invasive PPG and,if further confirmed by prospective validation,may replace the invasive transjugular assessment.

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.

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.

Transjugular intrahepatic portosystemic shunt:A promising therapy for recompensation in cirrhotic patients

This is a retrospective study focused on recompensation after transjugular intrahepatic portosystemic shunt(TIPS)procedure.The authors confirmed TIPS could be a treatment for recompensation of patients with cirrhosis according to Baveno VII.The paper identified age and post-TIPS portal pressure gradient as independent predictors of recompensation in patients with decompensated cirrhosis after TIPS.These results need to be validated in a larger prospective cohort.

A rabbit model of non- cirrhotic portal hypertension by repeated injections of E. coli through indwelling cannulation of the gastrosplenic vein

BACKGROUND: Non-cirrhotic portal hypertension is acommon cause of portal hypertension in developing coun-tries. To understand its etiopathogenesis we developed ananimal model by repeated portal endotoxemia inducedthrough the gastrosplenic vein.METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divid-ed into control (group n = 13) and experimental ( groupn = 16) groups. Heat killed E. coli were injected throughan indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacriflced at 1, 3 and6 months.RESULTS: The mean portal pressure in group animalswas significantly (P < 0. 05) higher than in group at 1(17.5 ±3.4 vs 10.4±2.2 mmHg), 3 (17.8±1.3 vs7.2 +3.6mmHg), and 6 (19.8±3.1 vs 10.3±4.8 mmHg) months.Similarly, the mean splenic weight in group was signifi-cantly greater than in group (P <0.05). Histopathologi-cally, the spleen showed medullary congestion, hemosid-rin-laden macrophages and mild fibrosis. Histologically,the liver had normal parenchyma with mild portal lympho-cytic infiltrates and kupffer cell hyperplasia. No significantanomalies were detected by liver function tests.CONCLUSIONS: The rabbit model showed significantsplenomegaly with a persistent increase in portal pressureand mild fibrosis without hepatic parenchymal injury, quiteakin to non-cirrhotic portal fibrosis as seen in humans. Re-current intra-abdominal infection may play an importantrole in the pathogenesis of non-cirrhotic portal fibrosis.

Endoscopic ultrasound-guided vascular interventions: An expanding paradigm

Endoscopic ultrasound(EUS)has expanded its arena from a mere diagnostic modality to an essential therapeutic tool in managing gastrointestinal(GI)diseases.The proximity of the GI tract to the vascular structures in the mediastinum and the abdomen has facilitated the growth of EUS in the field of vascular interventions.EUS provides important clinical and anatomical information related to the vessels'size,appearance and location.Its excellent spatial resolution,use of colour doppler with or without contrast enhancement and ability to provide images“real-time”helps in precision while intervening vascular structures.Additionally,structures such as venous collaterals or varices can be dealt with optimally using EUS.EUS-guided vascular therapy with coil and glue combination has revolutionized the management of portal hypertension.It also helps to avoid radiation exposure in addition to being minimally invasive.These advantages have led EUS to become an upcoming modality to complement traditional interventional radiology in the field of vascular interventions.EUS-guided portal vein(PV)access and therapy is a new kid on the block.EUS-guided portal pressure gradient measurement,injecting chemotherapy in PV and intrahepatic portosystemic shunt has expanded the horizons of endo-hepatology.Lastly,EUS has also forayed into cardiac interventions allowing pericardial fluid aspiration and tumour biopsy with experimental data on access to valvular apparatus.Herein,we provide a comprehensive review of the expanding paradigm of EUS-guided vascular interventions in GI bleeding,portal vein access and its related therapeutic interventions,cardiac access,and therapy.A synopsis of all the technical details involving each procedure and the available data has been tabulated,and the future trends in this area have been highlighted.

Subharmonic scattering of ultrasound contrast agent microbubbles may be an effective and promising tool for portal vein pressure estimation

Portal hypertension(PH)is a commonly observed syndrome in patients with cirrhosis and other chronic liver diseases(1).It is closely associated with severe clinical complications,including upper gastrointestinal hemorrhage,ascites,hepatic encephalopathy,and liver failure(2-6).Portal vein pressure(PVP)is a prognostic indicator for patients with cirrhosis,and PH is a contraindication for hepatectomy(7,8).Currently,the gold standard for assessing PVP is the measurement of PVP gradient[hepatic venous pressure gradient(HVPG)],which is indirectly determined by placing a catheter in the hepatic vein(3).

Update on endoscopic ultrasound-guided liver biopsy

Endoscopic ultrasound guided liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)liver biopsy techniques for the diagnosis of liver parenchymal diseases.Potentially,EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure.Additionally,EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy.Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield,increased acquisition of complete portal tracts,and longer specimen length as compared to the traditional approaches.EUS-LB is associated with lesser post-procedural pain and shorter recovery time,while providing lower risk of complications when compared to traditional liver biopsy.Innovations in needle types,needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique.This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB,and compares EUS-LB with traditional methods of liver biopsy.

Hemoperitoneum in cirrhotic patients without abdominal trauma or tumor

BACKGROUND:Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis.This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum.METHODS:We reviewed the clinical records of 1276 consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009.Hemoperitoneum was confirmed by abdominal paracentesis.RESULTS:Of the 1276 cirrhotic patients,19 were found to have hemoperitoneum,but only 6 did not have abdominal trauma or tumor.The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%.Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test.Most patients presented with abdominal distension,abdominal pain,increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level.Three patients died of hemorrhagic shock within 24 hours,and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver.CONCLUSIONS:Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor.It mainly occurs in severely decompensated end-stage cirrhotic patients.Cirrhotic patients with hemoperitoneum have a poor prognosis.

Recent evolution of living donor liver transplantation at Kyoto University:How to achieve a one-year overall survival rate of 99%?

Previously,living donor liver transplantation was considered as a“high-risk,high-return”medical treatment due to the relatively high short-term mortality.It is our task to change“high-risk,high-return”into a“low-risk,high-return”situation.In this review article,the recent evolutions in living donor liver transplantation for both donors and recipients at Kyoto University such as portal vein pressure modulation,hybrid donor operation,and perioperative management considering sarcopenia,focusing on improvement of short-term outcomes are described.Under a paradigm of“marketing and innovation”,various innovations and efforts have been made over the last decade aiming at improving the short-term outcomes of both donors and recipients.By doing so,excellent short-term results after living donor liver transplantation have been achieved,along with a potentially epoch-making discoveries.

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≥10mmHg 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 pressurefibrosis 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.

Correction to“Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation”

We found a mistake in Figure 6. Panels A (Sham group) and F (DFX group) (180degrees rotated) is same images. We have replaced the incorrect images (Panels F)with the correct Figure. This error does not change the meaning of the picture orthe conclusion of the manuscript. We apologize for our unintentional mistakes,which caused great inconvenience.

Effects of portal venous arterialization on acute occlusion of hepatic artery in rats

Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. Methods Rat PVA models were established and then randomly divided into Group 1 （control group）, Group 2 （jaundice group）, Group 3 （bile duct recanalization group）, and Group 4 （portal vein arterilization group）. Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. Results Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference （P 〈0.01）. These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure （P 〉0.05）. Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. Conclusion Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

Background:Excessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery,contributing to developing post-hepatectomy liver failure.This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism,using a 70%hepatectomy porcine model.Methods:Eighteen pigs undergoing 70%hepatectomy were involved in this study and divided into three groups:control(n=6),terlipressin(n=6),and octreotide(n=6).Terlipressin(0.5 mg)and octreotide(0.2 mg)were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day,at which time the surviving pigs were sacrificed.During the period,portal pressure,liver weight,biochemical analysis,histological injury score,and molecular markers were evaluated and compared between groups.Results:The 7-day survival rates in the octreotide,terlipressin,and control groups were 100%,83.3%,and 66.7%,respectively.The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes,1 hour and 6 hours after hepatectomy.The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group(117%vs.129%,P=0.03).Serum aspartate aminotransferase(AST)and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio(PT/INR)at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group.Serum endothelin-1(ET-1)was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy(P<0.01).The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day(P<0.01).Conclusions:Splanchnic vasoactive agents,such as terlipressin and octreotide,could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.