Coexisting Hepatitis B Surface Antigens, Antibodies Lead to More Severe Liver Disease

The coexistence of hepatitis B virus (HBV) surface antigens and antibodies against are an atypical serological profile for patients with chronic HBV infections.

Individuals infected with chronic hepatitis B virus (HBV) with hepatitis B surface antigens (HBsAg) and antibodies against HBsAg (anti-HBs) have worse outcomes, including more severe liver fibrosis and cirrhosis, according to a study published online in JAMA Network Open.

The study researchers, led by Jian Wang, MD, PhD, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, analyzed the link between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic HBV infection.

The coexistence of HBV surface antigens and antibodies against HBsAg are an atypical serological profile for patients with chronic HBV infections, according to the researchers. Further, the understanding of the link between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic HBV infection is limited.

The study authors examined 6534 treatment-naïve patients with chronic HBV from 2 medical institutions in China, with each patient enrolled between January 10, 2015, and March 31, 2021. Among those enrolled, 61.7% (n = 4033) were male and the median age of the patient population was 41 years (33.0-52.0), with 4.2% (n. = 277) of patients having coexistent HBsAg and anti-HBs.

The researchers observed severe liver fibrosis using the aspartate transaminase (AST) to platelet ratio index (APRI) based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography.

The researchers examined the rates of severe liver fibrosis and cirrhosis for patients with coexistent HBsAg and anti-HBs versus patients without, with severe liver fibrosis defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 of higher, or a liver stiffness measurement of 8kPa or higher.

Cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis.

The results showed that those with anti-HBs were older (median, 46.0 years versus 41.0 years) and had a higher proportion of HBV e antigen positivity (n = 123; 44.4%; vs. n = 2115; 33.8%; P <.001) versus patients without anti-HBs.

Those with anti-HBs also had greater ALT levels versus patients without (median, 45.1 vs. 36.7; P = .001) and higher AST levels (median, 35.0 U/L vs 28.3 U/L; P < .001). Further, the results showed that individuals with anti-HBs had lower median platelet counts, 173.0 × 103/μL vs 185.0 × 103/μL; P = .004), albumin levels (median, 4.37 g/dL vs 4.43 g/dL; P = .02), and HBsAg levels (median, 2.8 log10 IU/mL vs 3.3 log10 IU/mL; P < .001).

Those with anti-HBs also had higher APRI scores (median, 0.5 vs 0.4; P < .001), FIB-4 scores (median, 1.4 vs 1.1; P < .001), and liver stiffness values (median, 7.5 kPa vs 6.3 kPa; P = .003).

Similarly, patients with anti-HBs had higher proportions of severe liver fibrosis (n = 102; 36.8% vs n = 1397; 22.5%; P < .001) and cirrhosis (n = 87; 31.4% vs n = 1194; 19.2%; P < .001) versus patients without anti-HBs.

A multivariate analysis showed that the coexistence of HBsAg and anti-HBs were independently linked to severe liver fibrosis (OR, 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01); however, the association with cirrhosis was only found in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in those with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16).

“In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity,” the study authors wrote. “These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.”

Reference:

Wang J, Ding W, Liu J, et al. Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B. JAMA Netw Open. 2022;5(6):e2216485. doi:10.1001/jamanetworkopen.2022.16485. Accessed June 21, 2022.