Doctor Chao Wu’s team from the Department of Infectious Diseases, Nanjing Medical University Affiliated Drum Tower Hospital in China, has long been committed to clinical and basic research with a focus on immune regulation in viral hepatitis and liver fibrosis. At the 58th Annual Meeting of the European Association for the Study of the Liver (EASL 2023) and the EASL Congress 2023, the team had a total of 14 abstracts on clinical and basic research related to viral hepatitis and liver fibrosis selected for conference exchange, achieving significant success [1-14]. Hepatology Digest invited Doctor Rui Huang to introduce the team’s latest research progress at the conference. Follow along with the editor to get a glimpse of the team’s achievements!
According to Professor Rui Huang, the team, in collaboration with a multicenter research team in Jiangsu Province, has been engaged in clinical and basic research on chronic liver diseases, especially viral hepatitis. At this year’s EASL Congress, the team had a total of 14 research studies selected for poster presentation on liver disease’s clinical and basic aspects, with three studies receiving Young Researcher Awards.
01
Clinical Research Progress
First, in chronic hepatitis B (CHB) patients in the immune tolerance phase with different HBV DNA levels, the degree of liver tissue damage varies [1]. The study found that patients in the immune tolerance phase with HBV DNA levels in the range of 6-7 log10 IU/mL had a significantly higher proportion of liver fibrosis and cirrhosis compared to patients with HBV DNA levels >8 log10 IU/mL. Close monitoring of the progression of liver fibrosis is necessary, and liver biopsy or non-invasive methods may be needed to assess liver histological damage to determine the timing of antiviral treatment.
Second, regarding the threshold for alanine aminotransferase (ALT) in CHB patients receiving antiviral treatment. ALT is an important marker reflecting liver tissue damage, but its optimal threshold has been a topic of debate, with different guidelines offering varying recommendations for normal ALT values or thresholds for antiviral treatment. “We hope to find the optimal ALT threshold for diagnosing or excluding significant liver tissue damage.” The team analyzed data from a multicenter liver biopsy cohort in Jiangsu Province and found that ALT > 77 U/L had a positive predictive value and specificity of over 90% for diagnosing significant liver tissue damage, but it was difficult to find an accurate ALT threshold for excluding significant liver tissue damage. This study suggests that ALT is still not an ideal marker for excluding significant liver tissue damage, so there is a need to develop new non-invasive markers to assess the degree of liver tissue damage more effectively for guiding clinical diagnosis and treatment [2].
Third, regarding hypophosphatemia in CHB patients. The team found that the proportion of untreated CHB patients with hypophosphatemia was only 2.7%, but in the population with significant liver fibrosis and cirrhosis, the proportion of hypophosphatemia significantly increased. Therefore, monitoring blood phosphate levels should be given more attention in this population, and antiviral treatment should preferably involve drugs with minimal impact on phosphate levels [3].
Fourth, the team also established a machine learning prediction model for liver tissue inflammation and fibrosis in patients with hepatitis B and concomitant fatty liver, observed the effects of tenofovir alafenamide (TAF) antiviral treatment on blood lipids, and established a predictive model for HBeAg seroconversion in HBeAg-positive patients after antiviral treatment [4].
02
Advances in Basic Research
“Our related research provides some basis for guiding the treatment of CHB and revealing its chronicity.” The team observed that there were differences in the levels of peripheral blood HBsAg-specific B cells in CHB patients with different natural histories before and after pegylated interferon alpha (PEG-IFN-α) antiviral treatment. This suggests that the presence of HBsAg-specific B cells in peripheral blood before interferon treatment may be an important immunological indicator for predicting the effectiveness of interferon treatment [5].
In addition, the team found that upregulation of the immune inhibitory molecule CTLA-4 is an important mechanism for B cell secretion dysfunction in CHB patients against HBs [6]; serum CXCL16 and TSP-2 proteins may serve as potential markers for evaluating the degree of liver tissue inflammation and fibrosis in CHB patients [7,8].
References:
- Wang Jian, et al. Lower HBV DNA levels is associated more severe liver fibrosis in chronic hepatitis B with serological immune-tolerant phase. EASL 2023. Abstract WED-162.
- Zhang Zhiyi, et al. Identification and external validation of the optimal ALT thresholds for ruling in significant histologic disease in chronic hepatitis B. EASL 2023. Abstract WED-184.
- Jiang Suling, et al. Association of liver fibrosis and hypophosphatemia in treatmentnaïve patients with chronic hepatitis B. EASL 2023. Abstract WED-140.
[4] Gu Yan, et al. A novel nomogram for predicting HBeAg clearance in HBeAg positive chronic hepatitis B patients after nucleos (t)ide analogues treatment. EASL 2023. Abstract WED-212.
[5] Geng Yu, et al. Dynamic monitoring of HBsAg-specific B cells in CHB patients and its clinical significance in predicting interferon therapy efficacy. EASL 2023. Abstract WED-131.
[6] Mao Minxin, et al. CTLA4 inhibits anti-HBs secretion by blocking BCR signaling pathway in chronic hepatitis B infection. EASL 2023. Abstract FRI-225.
[7] Wan Yawen, et al. Serum CXCL16 serves as the predictor for liver inflammation functioning through a NKT cell-depend way in chronic hepatitis B patients. EASL 2023. Abstract WED-136.
[8] Chen Yun, et al. Serum thrombospondin-2 for predicting liver fibrosis in patients with chronic hepatitis B virus infection. EASL 2023. Abstract WED-164.
[9] Zhang Zhiyi, et al. Improved prediction for liver fibrosis of Fibrosis-4 using machine learning in patients with chronic hepatitis B. EASL 2023. Abstract WED-127.
[10] Liu Yilin, et al. Effects of tenofovir alafenamide fumarate on serum lipids in patients with chronic hepatitis B. EASL 2023. Abstract WED-142.
[11] Xue Ruifei, et al. Clinical characteristics and phase transition of chronic hepatitis B patients with HBeAg and anti-HBe coexistence. EASL 2023. Abstract WED-161.
[12] Li Jie, et al. Diabetes mellitus (DM) is the strongest risk factor of significant inflammation or fibrosis in chronic hepatitis B (CHB) combined with non-alcoholic fatty liver disease (NAFLD). EASL 2023. Abstract THU-471.
[13] Li Jie, et al. A diagnostic non-invasive model for liver advanced fibrosis and cirrhosis in chronic hepatitis B (CHB) concurrent with nonalcoholic fatty liver disease (NAFLD) based on machine learning (ML). EASL 2023. Abstract SAT-463.
[14] Li Jie, et al. Establishment and validation of a diagnostic model for liver inflammation in chronic hepatitis B (CHB) patients concurrent with non-alcoholic fatty liver disease (NAFLD) based on machine learning (ML). EASL 2023. Abstract SAT-510.
