NEW YORK (Reuters Health) – Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) in patients with chronic hepatitis B, while unusual, is associated with more advanced liver disease, such as severe fibrosis and cirrhosis, new research from China shows.
In a cross sectional study of 6,534 treatment-naive patients with chronic hepatitis B, Jian Wong MD and colleagues from Nanjing Drum Tower Hospital and Huai’an No. 4 People’s Hospital found the combination of HBsAg and anti HBs in 277 patients (4.2%).
Compared to patients without anti-HBs, patients with anti-HBs were older (median age, 46.0 vs 41; P=0.005), with higher levels of alanine aminotransferase (ALT; 45.1 vs 36.7 U/L; P=0.001) and aspartate aminotransferase (AST; 35.0 vs 28.3 U/L; P <0.001) and lower platelet counts (173.0 vs 185.0 × 103/uL; P=0.004) and albumin levels (4.37 vs 4.43 g/dL; P=0.02 ). Patients with anti-HBs also had a higher rate of HBeAg positivity (44.4% vs 33.8%; P <0.001). And while they had lower serum HBsAg levels, they had higher median serum HBV DNA levels (4.2 vs 3.4 log10 IU/mL; P=0.045).
Markers of fibrosis were higher in patients with vs without anti-HBs, including median AST to platelet ratio index (APRI; 0.5 vs 0.4; P <0.001) and fibrosis index based on age, AST level, ALT level, and platelet count (FIB-4; 1.4 vs 1.1; P < .001).
On the basis of APRI cutoff scores, more patients with anti-HBs had severe liver fibrosis (cutoff score of 1.5, 23.5% vs 16.8%; P=0.004) and cirrhosis (score 2.0, 18.1% vs 13.0%; P=0.02).
According to FIB-4 cutoff values, a greater proportion of patients with anti-HBs had severe liver fibrosis (score 3.25, 19.1% vs 14.7%; P=0.04), but there was no difference in rate of cirrhosis (7.2% vs 6.3%; P=0.55).
Among patients with abdominal ultrasonographic data, 24.8% of patients with anti-HBs had cirrhosis compared to 12.9% of patients without anti-HBs (P<0.001). Of the 716 patients with liver stiffness measurement (LSM), patients with anti-HBs had higher values (7.5 vs 6.3 kPa; P=0.003) .
Using any definition of severe fibrosis (APRI score of 1.5 or higher, or FIB-4 score of 3.25 or higher, or LSM of 8 kPa or higher), more patients with anti-HBs had severe liver fibrosis (36.8% vs 22.5%; P<0.001). Using any definition of cirrhosis (APRI score of 2.0 or higher, or FIB-4 score of 6.5 or higher, or LSM of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis), cirrhosis was more common in patients with vs without anti-HBs (31.4% vs 19.2%; P<0.001).
Among 277 patients with anti-HBs, 123 (44.4%) were HBeAg positive; that proportion was 2,115 of 6,257 (33.8%) among those without anti-HBs. Overall, among all HBeAg-positive patients, those with anti-HBs had lower serum HBV DNA levels than patients without anti-HBs (6.1 vs 7.1 log10 IU/mL; P<0.001). However, serum HBsAg levels remained lower in patients with vs without anti-HBs regardless of HBeAg status.
In the HBeAg-positive group, anti-HBs status was not linked with APRI and LSM scores or with likelihood of severe fibrosis or cirrhosis. In the HBeAg-negative group, however, patients with anti-HBs had higher APRI scores (0.4 vs 0.3; P=0.008) and a higher rate of severe liver fibrosis based on APRI (score 1.5; 17.5% vs 11.0%; P=0.01).
Using LSM values, in the HBeAg-negative group, patients with anti-HBs had higher LSM values (7.7 kPa vs 6.3 kPa; P0=0.003 and higher rates of severe liver fibrosis (45.8% vs 25.7%; P=0.03) and cirrhosis (20.8% vs 7.3%; P=0.02).
On univariate analysis, male sex , higher ALT levels, higher serum HBV DNA levels , coexistence of HBsAg and anti-HBs positivity and the interaction between HBeAg and anti-HBs were associated with severe liver fibrosis. On multivariate analysis, coexistence of HBeAg and anti-HBs remained the primary risk factor for severe liver fibrosis (odds ratio 2.29; P<0.001) and cirrhosis (OR, 1.73; P=0.01).
Of the 303 patients with liver biopsy data, 13 had anti-HBs. Patients with anti-HBs had higher rates of severe liver fibrosis (61.5% vs 32.1%; p=0.03) and cirrhosis (15.4% vs 3.1%; p=0.02).
The authors note that HBeAg patients with anti HBs have higher transaminase levels, which suggests that this serological pattern may be associated with active chronic hepatitis, despite the potential protective effect of anti-HBs as noted by lower serum Ag levels.
They further state that “coexistent HBsAg and anti-HBs was associated with a higher proportion of liver cirrhosis, which may partially explain why the risk of HCC is higher in patients with anti-HBs, considering that the presence of liver cirrhosis is the single most important risk factor for HCC in patients with chronic hepatitis B.”
“There may be several possible reasons for this result,” they continue. “First, patients with anti-HBs had high levels of HBV DNA and HBeAg positivity, which have always been regarded as risk factors for advanced disease among patients with chronic hepatitis B. Second, patients with anti-HBs had a longer duration of chronic HBV infection, as reflected in the median age of these patients, which was higher than that of patients without anti-HBs.”
Finally, they conclude, “Close monitoring and attention to the potential development of liver fibrosis and cirrhosis during follow-up are warranted for patients with anti-HBs.”
SOURCE: https://bit.ly/3OJDkko JAMA Network Open, online June 13, 2022.
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