Could complement C4 be an alternative to biopsy for chronic hepatitis B histopathologic findings?
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Updated: Jun 3, 2026
Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
Mehmet Sait Bugdaci1, Canan Alkim, Cetin Karaca
1Gastroenterohepatology Clinic, Sisli Etfal Training and Research Hospital, Department of Gastroenterohepatology, Istanbul Medical Faculty of Istanbul University, İstanbul. msbugdaci@gmail.com
Insights
Serum complement C4 levels correlate with liver biopsy findings in chronic hepatitis B (CHB) patients, offering a potential indicator of disease activity. This study highlights C4 as a useful marker for monitoring CHB, especially in those with elevated transaminases.
Area of Science:
- Hepatology
- Immunology
Background:
- Chronic hepatitis B (CHB) poses risks including liver disease, cirrhosis, and cancer.
- Current diagnostic markers for CHB often lack correlation with disease activity and histopathology.
- Novel indicators are needed for effective CHB management.
Purpose of the Study:
- To evaluate the utility of serum complement levels (C3 and C4) for monitoring CHB patients.
- To assess complement levels in CHB patients with both normal and high transaminase levels.
- To correlate complement levels with liver histopathology (Knodell HAI) and clinical scores (Child score).
Main Methods:
- Study included 143 patients evaluated between 2009-2010, categorized into CHB with high transaminases, inactive CHB carriers, and cirrhosis.
- Compared demographic, viral, liver function tests, and complement C3/C4 levels across groups.
- Investigated correlations between serum complement levels, Knodell HAI, fibrosis, and Child score.
Main Results:
- Serum C3 and C4 levels were significantly lower in CHB patients with high transaminases compared to those with normal levels.
- Low serum complement levels negatively correlated with Knodell HAI scores in CHB patients with high transaminases.
- Complement levels correlated negatively with Child scores in cirrhotic patients, but not with HBV DNA, ALT, AST, or GGT.
Conclusions:
- Serum complement C4 levels correlate significantly with liver biopsy findings in CHB patients with high transaminases.
- Complement C4 may serve as a valuable indicator of disease activity and/or damage in CHB.
- Complement levels show potential as a non-invasive marker for CHB monitoring.
Background:
Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We aimed to investigate the utility of serum complement levels for follow-up in patients with CHB with normal and high transaminase levels.
Methods:
One hundred forty-three patients that were evaluated between 2009 and 2010 were included in the study. Hepatitis B early antigen negative CHB cases with high transaminase levels were evaluated as the first group, and cases with normal transaminase level (inactive hepatitis B surface antigen carrier) as the second group, patients with cirrhosis were included as a third group. Age, sex, hepatitis B surface antigen, anti-HBcAg IgM, hepatitis B early antigen, anti-δ, anti-HCV, anti-HIV, serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), complement C3, and C4 levels of both groups were compared. The relationship between Knodell histologic activity index (HAI) score and fibrosis in liver biopsy specimens and serum complement levels of cases with high transaminase levels were investigated.
Findings:
There were 49 patients with CHB with high transaminase levels; (Female/Male: 22/27). Mean age was 42.3±15.7 y, ALT=104.41±101.74, AST=69.7±65.2, GGT=35.37±20.4, C3 level=104.2±28.8, C4=16.11±4.17, and HBV DNA >2000 IU/mL (>105 copies/mL) in all cases. Remaining 27 patients had cirrhosis. There were 67 patients with CHB with normal transaminase levels (Female/Male: 32/35). Mean age was 39.56±12.9 y, ALT=22.7±5.5, AST=22±5.18, GGT=48.8±60.4, C3=117.85±22.15, and C4=21.44±5.46. Serum complement C4 level in 4 of the CHB cases with normal transaminase levels was low. Serum C3 (P=0.024) and C4 (P=0.001) levels in patients with CHB with high transaminase level were significantly lower. Low serum complement levels were negatively correlated with Knodell-HAI scores in patients with high transaminase levels (r=-0.84; P<0.001). There was no correlation between HAI and HBV DNA, AST, ALT, and GGT. There was no significant correlation between complement C3 and C4 levels and ALT, AST, HBV DNA, and GGT in any of the groups. Child score in patients with cirrhosis negatively correlated with both C3 (P=0.001) and C4 levels (P=0.001). Complement levels in patients with cirrhosis and CHB with high transaminase levels did not significantly differ.
Results:
Serum complement C4 levels (in contrast to virologic markers and transaminases) significantly correlate with liver biopsy findings and may be a useful indicator of disease activity and/or damage in patients with CHB with high transaminase levels.
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