Editor’s Note: Complications related to portal hypertension are the main cause of death in patients with advanced chronic liver disease (ACLD). Even after the underlying cause is controlled, clinical events during the progression of portal hypertension, such as esophageal variceal bleeding, ascites, overt hepatic encephalopathy, and acute-on-chronic liver failure, are the most critical factors leading to high mortality in chronic liver disease. The hepatic venous pressure gradient is the “gold standard” for assessing portal hypertension, and upper gastrointestinal endoscopy is an essential tool for screening and evaluating esophagogastric varices and their severity. However, both are invasive procedures, making them unsuitable for screening and monitoring portal hypertension. Non-invasive diagnostic methods based on spleen stiffness measurement (SSM) using vibration-controlled transient elastography can be used for screening, stratifying diagnosis, and monitoring portal hypertension and esophageal varices. At the recent 2024 Jinling Liver Disease Conference, Professor Jinjun Chen from Nanfang Hospital, shared advances in the non-invasive diagnosis of portal hypertension and esophagogastric varices in ACLD patients using spleen stiffness. The content is summarized as follows for the readers.
Definition and Stratification of Progressive Chronic Liver Disease (cACLD)
Chronic liver disease patients can experience varying stages of fibrosis, ultimately progressing to cirrhosis. The prognosis of cirrhotic patients is divided into different stages, mainly including the compensated and decompensated stages. Once clinical manifestations such as esophagogastric variceal bleeding, ascites, and overt hepatic encephalopathy appear, it indicates progression from the compensated to the decompensated stage. Fibrosis-portal hypertension grading and clinical events.
The Baveno VI consensus introduced the concept of compensated advanced chronic liver disease (cACLD), referring to the continuum from severe liver fibrosis to compensated cirrhosis in patients with progressive chronic liver disease, which is more practical clinically than “compensated cirrhosis.” cACLD patients are at high risk of decompensation events; once decompensation occurs, the survival period is significantly shortened, necessitating early identification, referral, diagnosis, and monitoring. This condition can be diagnosed non-invasively and can predict the occurrence of cirrhosis complications. Compensated cirrhosis/cACLD patients can be divided into two stages, with or without clinically significant portal hypertension (CSPH). Portal hypertension is the main cause of decompensation events in cACLD patients, making the screening and management of portal hypertension crucial.
The Baveno VII consensus proposed a risk stratification standard for cACLD patients, known as the “five-step” method, based on liver stiffness measurement (LSM) data from FibroScan studies, with each 5 kPa increment representing a different risk level for cACLD and portal hypertension: below 5 kPa is normal, below 10 kPa excludes cACLD, below 15 kPa and platelet count (PLT) ≥150/μL excludes CSPH, above 15 kPa suggests cACLD, below 20 kPa and PLT >150/μL exempts upper gastrointestinal endoscopy, and above 25 kPa suggests CSPH (applicable to chronic liver diseases like HBV, HCV, alcoholic liver disease, and non-obese NASH).
Screening for High-Risk Varices
High-risk varices (HRV) refer to varices requiring treatment, with esophageal varices being particularly critical. In the evaluation of compensated cirrhotic patients, EV 2/3 and EV 1 with red signs are important indicators for high-risk varices. The first choice for treatment is non-selective β-blockers (NSBB), with carvedilol recommended first and propranolol as a secondary option.
To effectively screen for high-risk varices, LSM is a crucial tool. Moreover, when combined with other parameters related to portal hypertension (e.g., PLT, spleen size), its screening efficacy is further enhanced. According to the Baveno VI consensus, using LSM <20 kPa and PLT >150/μL measured by transient elastography can safely exclude HRV without the need for endoscopic screening. This conclusion has been validated in chronic liver diseases caused by various etiologies (e.g., HBV, HCV, NASH, alcoholic liver disease, and cholestatic liver diseases).
Given the simplicity and effectiveness of using LSM and PLT together, the Baveno VII consensus continues to recommend the Baveno VI criteria. For cACLD patients with LSM <20 kPa and PLT >150/μL, endoscopic screening for esophagogastric varices is unnecessary.
Advances in Spleen Stiffness Measurement (SSM) for Reducing Endoscopic Screening in HBV Cirrhosis
For cirrhotic patients not meeting the Baveno VI criteria (LSM <20 kPa and PLT >150/μL), the Baveno VII consensus suggests that SSM ≤40 kPa can also safely exclude HRV, exempting endoscopic screening.
A study by Professor Jinjun Chen’s team, published in the Journal of Hepatology, aimed to validate the Baveno VII algorithm (LSM ≤20 kPa and PLT ≥150/μL, otherwise SSM ≤40 kPa) for diagnosing HRV in HBV-related cirrhosis patients. They included 504 HBV cirrhosis patients in the statistical analysis. Among the 504 patients tested with a 50 Hz probe, the Baveno VII algorithm allowed more patients to safely avoid endoscopic screening (39.1% vs. 56.7%, P<0.001), with comparable HRV missed diagnosis rates (2.5% vs. 3.8%). Other non-invasive models had HRV missed diagnosis rates >5%: LSPS 11.3%, PSR 20.0%, and RESIST 8.8%. Among 232 patients assessed with the new 100 Hz spleen stiffness measurement, the Baveno VII algorithm using SSM 100 Hz exempted more patients from endoscopy than the 50 Hz algorithm (75.4% vs. 59.5%, P<0.001), with HRV missed diagnosis rates of 3.0% (1/33) for both. Additionally, the 50 Hz probe often overestimated spleen stiffness compared to the 100 Hz probe.
In 2021, another study by Professor Chen’s team, also published in the Journal of Hepatology, included 341 antiviral-treated HBV cirrhosis patients, undergoing LSM, SSM, and endoscopy, with antiviral regimen and virological response evaluated every 3-6 months. The study found that endoscopy exemption rates under the Baveno VI criteria were 37%, while the exemption rate under the combined Baveno VI and SSM (≤46 kPa) criteria was 61.6% (sensitivity 95.71%, specificity 76.38%, negative predictive value 98.57%), with an endoscopy positive rate of 51.5% and an HRV missed diagnosis rate of less than 5%. This study validated the diagnostic strategy of combining Baveno VI criteria with SSM, safely excluding HRV in HBV-related cirrhosis patients and exempting over 60% of endoscopic examinations.
Moreover, recent research by Professor Chen’s team shows that the success rate of stiffness measurements using the 100 Hz probe is extremely high for both healthy spleens and spleens with chronic liver disease. Specifically, the measurement failure rate was 0.00% in healthy livers and only 3.30% in chronic liver disease patients. The study also explored factors affecting SSM variability with the 100 Hz probe. It found that SSM variability is influenced by liver stiffness: higher liver stiffness results in lower SSM variability. Additionally, spleen size affects SSM variability: larger spleens exhibit lower SSM variability.
Exempting Compensated HBV-Related HCC Patients from Endoscopic Screening Using SSM 100 Hz
For hepatocellular carcinoma (HCC) patients, especially when systemic therapies significantly improve overall survival, endoscopic screening for HRV is needed. A recent study by Professor Chen’s team validated the use of SSM 100 Hz for risk stratification of esophageal varices in HBV-related HCC patients, effectively exempting more unnecessary endoscopic examinations compared to the Baveno VI criteria.
The study prospectively included HBV-related compensated cirrhosis patients recently diagnosed with HCC, who underwent liver stiffness measurement, SSM at 100 Hz frequency, and endoscopic examination. From September 2021 to August 2023, 219 HCC patients were enrolled, including 107 (48.9%) BCLC A patients, 28 (12.8%) BCLC B patients, and 84 (38.3%) BCLC C patients. The overall HRV prevalence was 28.8% (63/219). The Baveno VI criteria safely exempted 27.4% of unnecessary endoscopic examinations (HRV missed diagnosis rate 3.2%), while the Baveno VII algorithm exempted 49.3% (HRV missed diagnosis rate 7.9% [5/63]). Using SSM ≤40 kPa alone safely exempted 47.5% of endoscopic examinations (HRV missed diagnosis rate 4.8%), with a significantly better exemption ability than the Baveno VI criteria (P<0.001), and comparable to the Baveno VII algorithm (P=0.390). Using SSM ≤40 kPa alone safely exempted endoscopic examinations for Milan criteria-compliant patients, those with portal vein tumor thrombus, BCLC B/C stage patients, and those undergoing systemic therapy.
Furthermore, other studies by Professor Chen’s team have validated that Acoustic Radiation Force Impulse (ARFI) imaging can effectively reduce the need for endoscopic screening in HBV cirrhosis patients and found that when SSM >50 kPa (measured with a 100 Hz probe), CSPH can be reliably diagnosed.
Summary
The non-invasive diagnostic strategy for stratified management of portal hypertension in ACLD patients can be summarized as follows: When SSM <40 kPa, patients can be exempted from endoscopic screening or monitoring; when SSM >40 kPa, endoscopic screening and monitoring are recommended. For patients with SSM <21 kPa, portal hypertension screening or monitoring may be exempted; when SSM >50 kPa, CSPH can be diagnosed, and NSBB treatment may be recommended.