Technique innovation of endoscopic ultrasound portal pressure gradient measurement using standard manometer set for portal hypertension assessment

Abstract

Portal hypertension (PH) is still a major challenge to be managed in clinical practice. However, hepatic vein pressure gradient (HVPG) measurement is not always reliable for portal hypertension (PH) diagnosis. This study showed the impact of endoscopic ultrasound (EUS) as a promising tool for diagnosis and management PH condition.

INTRODUCTION

Portal hypertension (PH) is still a major challenge to be managed in clinical practice. Liver cirrhosis (LC) is still one of the main players for all PH complications' development.¹ The gold standard for portal pressure evaluation is hepatic vein pressure gradient (HVPG) measurement. However, it is still not recommended as a routine assessment in clinical practice due to its invasiveness, the need of specific training and good expertise.² On the contrary, HVPG measurement is not a reliable measurement in non-cirrhotic portal hypertension (NCPH) patients.³ Recently, endoscopic ultrasound (EUS) has been studied for PH complication diagnosis and management, such as the presence of deep esophageal varices as well as bleeding esophageal or gastric varices management.^4–6 There has been an innovation for portal pressure measurement using an innovative compact manometer.⁷ However, this innovation device has not been commercially available and not fully distributed in most Asian countries. Therefore, in this preliminary innovation study, the use of innovation standard manometer for EUS portal pressure gradient (PPG) measurement is reported.

CASE HISTORY/EXAMINATION

Thirteen consecutive patients (12 liver cirrhosis patients and 1 non-cirrhotic portal hypertension) were included in this preliminary study after written informed consent where previously they have been diagnosed with PH condition based on imaging evaluation, esophagogastroduodenoscopy (OGD) procedure, or history of variceal bleeding. The EUS-PPG measurement was performed at Integrated Non-Surgical Procedural Unit, Dr. Cipto Mangunkusumo National General Hospital, Jakarta. This study has been approved by Health Research Ethics Committee Medical Faculty Universitas Indonesia (KET-980/UN2F1/ETIK/PPM.00.02/2021). The exclusion criteria were, history of any blood thinner consumption within the last 5 days, hepatocellular carcinoma (HCC), massive ascites, or prolonged INR (>1.4) based on our hematology division criteria for invasive procedure. EUS equipment used was EG-580UT Fujinon (Fujifilm, Japan). The needle used for hepatic vein pressure (PVP) as well as portal vein pressure (PVP) measurement was 22-ga FNA needle (Expert Slimline Boston Scientific). The standard manometer set used was GE B 20i pressure monitor, pressure sensor (Biotrans), and pressure infusor (iPeX, New Delhi, India) as showed at Figure 1. Patient preparations, including 8 h fasting, and blood test. Patients were under sedation during endoscopic (EUS) procedure. The 500 ml saline infusion was mixed with heparin (3000 IU) for needle flushing. After identification of the hepatic vein (HV) and portal vein (PV), the FNA needle was inserted with the ultrasound image guided into the HV, then the needle was flushed. Then, the catheter was connected to the needle where it was also connected to the pressure sensor. The CVP mode and zero level were set before the pressure measured. After 30–60 seconds, the pressure was stable, then the pressure was recorded. Similar step by step procedure was also then performed for the PV (Figure 2). The result of PPG is PVP minus HVP. This procedure was repeated until three times to assure the correct result.

FIGURE 1. EUS-PPG measurement procedure using standard manometer set

FIGURE 2. Hepatic vein and portal vein puncturing using 22-G FNA needle and heparinized saline flushing before pressure measurement

OUTCOME AND FOLLOW-UP

All study subjects were successfully undergoing EUS-PPG procedure. The patients' EUS-PPG database is shown in Table 1. The lowest platelet count in this case series study was 42,000/μl. Four patients underwent only EUS-PPG measurement, five patients underwent EUS-PPG measurement followed by endoscopic band ligation (EBL), three patients underwent EUS-PPG measurement followed by EUS guided cyanoacrylate injection, and one patient underwent EUS-PPG measurement followed by EUS-guided cyanoacrylate injection and EBL in one session. Twelve patients were confirmed to have clinically significant portal hypertension (CSPH) based on EUS-PPG measurement. No adverse events, such as pain, bleeding, or perforation were recorded during and after the procedure.

TABLE 1 Patients underwent EUS-PPG

Patient	Liver Cirrhosis	CP Score	PVP (mmHg)	HVP (mmHg)	PPG (mmHg)
1	Y	B	32	15	17
2	Y	A	28	15	13
3	Y	B	35	16	19
4	Y	C	42	21	21
5	Y	A	23	9	14
6	Y	B	39	21	18
7	Y	A	23	16	7
8	Y	A	39	16	23
9	Y	C	26	11	15
10	Y	A	37	19	18
11	Y	B	35	16	19
12	Y	B	31	14	17
13	N	N/A	45	30	15

DISCUSSION

This is the first study in Southeast Asia, reported the clinical impact of EUS-PPG measurement using standard manometer set for pre-assessment before managing patients with PH condition and its complications. In 1977, Boyer et al. introduced the first time a direct technique of portal vein pressure measurement using percutaneous transhepatic approach. It showed a good correlation between wedge hepatic vein pressure (WHVP) and PVP in patients with alcoholic liver disease, but not in chronic active hepatitis or acute hepatitis. However, this pioneered study has given an important message that direct portal pressure measurement is more meaningful in the clinical setting.⁸ In 1979, Groszmann et al. did a pioneered animal study for HVPG measurement, where he showed the free hepatic vein pressure (FHVP) measurement can be used for reference in PH condition.⁹ But in 1987, Sarin et al. performed a hemodynamic study in patients with liver cirrhosis as well as in non-cirrhotic patients with PH, where in this study, lower WHVP were seen among non-cirrhotic patients.¹⁰ This concluded that HVPG as a gold standard of portal pressure measurement is not always reliable in early stage of liver fibrosis and in non-liver cirrhotic condition. Another technique innovation has been studied and published by Brensing et al. in 1998 using endoscopic manometry of esophageal varices; however, it is concluded that this technique could not predict accurately the portal pressure due to variance of collateral vessels, and acute pressure changes individually.¹¹ In this innovation study, it has been shown the clinical benefit of EUS approach in patients with PH condition. Several pioneered studies have shown a good correlation between EUS-PPG measurement and the presence of PH condition and complications. A case series study published by Zhang et al. in 2021 showing successful EUS-PPG measurement using electrocardiograph monitor with a central venous pressure (CVP) module from Philips, Netherlands, via a pressure transducer. This study also showed a consistency result between EUS-PPG and HVPG measurement.^7,12,13

CONCLUSIONS

The development of EUS-PPG measurement has become a promising tool in diagnosis and management of patients with advance liver disease or non-cirrhotic portal hypertension. The standard manometer set is seemed to be practical to be used together for other patients' parameters monitoring, and it might be considered as a cost-friendly and one stop shopping procedure. However, it would need larger studies before it can be recommended as a routine practice.

AUTHOR CONTRIBUTIONS

Dr. Cosmas Rinaldi Lesmana involved in concept the idea of the study, the innovation technique, conducting the procedure, and writing the manuscript.

ACKNOWLEDGMENTS

I would like to thank Dr. Saut Horas Nababan and Dr. Kemal Fariz Kalista for their support in patients' data collection.

CONFLICT OF INTEREST

Cosmas Rinaldi A. Lesmana has no conflict of interest.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

ETHICAL APPROVAL

This case series study has been approved by the Ethics Committee Medical Faculty Universitas Indonesia, Jakarta.

CONSENT

Written informed consent were obtained from the patients for the study and publication.