The assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is of significant importance for initiating antiviral treatment and evaluating treatment efficacy. Serum models represented by Fibrosis-4 index (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) exhibit inconsistent diagnostic performance for liver fibrosis in different study populations. Moreover, there is controversy regarding whether the dynamic changes in liver stiffness measurement (LSM) during antiviral treatment can predict fibrosis reversal. Therefore, new models or indicators are still needed for fibrosis assessment in CHB patients before and after antiviral treatment.
On June 21st, at the 58th Annual Meeting of the European Association for the Study of the Liver (EASL 2023) and the EASL Congress 2023, Dr. Jinlin Hou and Dr. Rong Fan’s team from Southern Medical University Affiliated Nanfang Hospital in China presented the aMAP score as an accurate liver cancer risk prediction model. It can also diagnose HBV-related cirrhosis and advanced fibrosis. In addition, a sequential application method (aMAP score → LSM) proposed for untreated CHB patients can spare more patients from liver biopsy. For treated CHB patients, a new logistic regression model (aMAP-LSM model) accurately assesses cirrhosis and advanced fibrosis after antiviral treatment. This report is published in Hepatology Digest.
Dr. Yu Zhu presented the poster on behalf of the team.
Early identification of cirrhosis and intervention is a key strategy for preventing the development of hepatocellular carcinoma and is an important aspect of chronic liver disease management. Non-invasive diagnosis of liver fibrosis, due to its advantages such as non-invasiveness, repeatability, affordability, and patient tolerance, has become an alternative to liver biopsy. However, serum models represented by FIB-4 and APRI exhibit only moderate diagnostic efficiency in diagnosing CHB-related cirrhosis and advanced fibrosis. LSM is currently the most accurate method in non-invasive fibrosis diagnosis, but it can be affected by factors like liver inflammation and bile stasis, leading to abnormally high LSM values. Furthermore, several studies have observed reduced efficiency in diagnosing liver fibrosis using LSM in treated hepatitis B patients, and some scholars have pointed out that the decrease in LSM values after antiviral treatment does not necessarily reflect fibrosis regression.
The aMAP score (age-male-albumin-bilirubin-platelet) is a predictive model developed by our team in 2020 based on the International Hepatitis Collaboration Network. It accurately predicts the risk of liver cancer development in various liver disease patients. Considering that most liver cancers progress on the basis of cirrhosis or liver fibrosis, and the parameters involved in the aMAP score are closely related to the degree of liver fibrosis, we believe that the aMAP score can also serve as a non-invasive diagnostic model for liver fibrosis.
To validate this hypothesis, we conducted a multicenter study aimed at evaluating whether the aMAP score can be used for diagnosing CHB-related cirrhosis and advanced fibrosis. We also attempted to improve the diagnostic efficiency of liver fibrosis in untreated and treated CHB patients by combining non-invasive diagnostic models.
Research Method:
This study included 2 real-world cohorts from China and 2 multicenter randomized controlled trials, totaling 2053 CHB patients who underwent liver biopsy. Among them, 2053 patients were included in the cross-sectional analysis to assess and compare the diagnostic performance of the aMAP score, FIB-4, and APRI for cirrhosis and advanced fibrosis. A total of 889 patients from the multicenter randomized controlled trials, who underwent liver biopsy at baseline and at 72 weeks (or 104 weeks) of antiviral treatment, were included in the longitudinal analysis to construct a new model for diagnosing cirrhosis and advanced fibrosis in CHB patients after antiviral treatment.
Research Findings:
Cross-Sectional Study:
In the cross-sectional analysis, we found that the area under the receiver operating characteristic curve (AUROC) of the aMAP score for diagnosing cirrhosis and advanced fibrosis was 0.788 (0.770, 0.805) and 0.757 (0.738, 0.775), respectively. These values were significantly higher than FIB-4 [0.763 (0.744, 0.781), P=0.010; 0.753 (0.734, 0.772), P=0.094] and APRI [0.607 (0.586, 0.629), P<0.001; 0.613 (0.591, 0.634), P<0.001], or comparable to them.
However, when using dual cutoff values for liver fibrosis diagnosis (dual diagnostic cutoff values defined as achieving 90% or 95% sensitivity and specificity), the performance of the aMAP score in diagnosing cirrhosis was superior to FIB-4 and APRI, with a smaller uncertain area (UA: 68.3%) and higher diagnostic accuracy (DA: 85.2%) (FIB-4: 74.2%, 84.5%; APRI: 79.0%, 78.0%). Furthermore, compared to the sequential approach using FIB-4 (or APRI) and LSM, the sequential approach using the aMAP score and LSM also had a smaller UA and good DA in diagnosing cirrhosis (UA: 29.7%, DA: 82.3%) and advanced fibrosis (UA: 46.2%, DA: 79.8%).
Longitudinal Study:
In the longitudinal analysis, we constructed a new model (aMAP-LSM model) using baseline and week 72 (or 104) aMAP scores and week 72 (or 104) LSM values. The aMAP-LSM model demonstrated good performance in identifying cirrhosis and advanced fibrosis in CHB patients after antiviral treatment and significantly outperformed LSM [AUROC (95% CI) of 0.839 (0.813, 0.865) vs. 0.799 (0.746, 0.812), P<0.001, and 0.840 (0.815, 0.866) vs. 0.776 (0.745, 0.808), P<0.001]. In the subgroup of patients with significant LSM reduction after treatment (significant LSM reduction defined as a decrease in LSM of more than 30% compared to baseline after 72 or 104 weeks of treatment), the aMAP-LSM model’s AUROC (95% CI) remained significantly higher than LSM [cirrhosis: 0.828 (0.792, 0.864) vs. 0.748 (0.700, 0.796), P<0.001; advanced fibrosis: 0.825 (0.789, 0.862) vs. 0.750 (0.705, 0.794), P<0.001].
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Research Conclusion:
The aMAP score can be used as a new, accurate, and promising non-invasive diagnostic method for assessing CHB-related cirrhosis and advanced fibrosis. The combined use of the aMAP score and LSM can further improve the diagnostic efficiency of cirrhosis and advanced fibrosis, sparing more patients with chronic hepatitis B from liver biopsy.
☝ The results of this study presented at the EASL Congress are published in Clinical Gastroenterology and Hepatology.
References:
1. Ji D, Chen Y, Shang Q, et al. Unreliable Estimation of Fibrosis Regression During Treatment by Liver Stiffness Measurement in Patients With Chronic Hepatitis B. Am J Gastroenterol, 2021,116(8):1676-1685.
2. Fan R, Papatheodoridis G, Sun J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol 2020; 73(6): 1368-78.
