Coexistence of HBsAg and anti-HBs Results in More Severe Liver Disease in HBV Patients

Patients with chronic hepatitis B virus (HBV) who have both hepatitis B surface antigen (HBsAg) and antibodies against HBsAg (anti-HBs) face more severe outcomes, including more severe liver fibrosis and cirrhosis.

A team, led by Jian Wang, MD, PhD, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, identified the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B virus infections.

The Need of More Research

The coexistence of hepatitis B surface antigen and antibody against HBsAg are an atypical serological profile for patients with chronic HBV infections. In addition, the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic HBV infections are not well understood.

In the study, the investigators examined 6534 consecutive treatment-naïve patients with chronic hepatitis B infections from 2 medical institutions in China. Each participant was enrolled between January 10, 2015 and March 31, 2021.

Of the patient population, 61.7% (n = 4033) and the median age was 41 years (33.0-52.0). In addition, 4.2% (n. = 277) of patients had coexistent HBsAg and anti-HBs.

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

The investigators sought primary outcomes of the rates of severe liver fibrosis and cirrhosis for patients with coexistent HBsAg and anti-HBs compared to patients without and defined severe liver fibrosis 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.

In addition, they defined cirrhosis 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.

Data Points

Overall, patients with anti-HBs were an older population (median, 46.0 years vs. 41.0 years) and had a higher proportion of hepatitis B e antigen positivity (n = 123; 44.4%; vs. n = 2115; 33.8%; P <.001) compared to patients without anti-HBs.

Patients with anti-HBs also had higher ALT levels compared to 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).

In addition, the investigators found patients with anti-HBs had lower platelet counts median, 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).

Patients 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).

Keeping the same trends, 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) compared to patients without anti-HBs.

After conducting a multivariate analysis, the investigators found the coexistence of HBsAg and anti-HBs were independently associated with both 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, this association with cirrhosis was only identified in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients 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 authors wrote. “These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.”

The study, “Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B,” was published online in JAMA Network Open.