Mannose-binding lectin (MBL) plays an important role in immune defense. We examined the MBL gene mutations and MBL levels in Chinese hepatitis B and hepatitis C patients with and without symptomatic cirrhosis. We recruited 190 hepatitis B and C patients, and 117 normal Chinese as controls. Serum MBL levels were measured by enzyme-linked immunosorbent assay. MBL gene mutation at codons 52, 54, and 57 was detected by polymerase chain reaction (PCR) assay. In asymptomatic hepatitis B and C patients, there was no increase in codons 52, 54, and 57 mutation, but the MBL levels were significantly lower than those in the controls. Codon 54 mutation rate was increased to 44.4% (P โซุโฌ .007) in symptomatic hepatitis B cirrhosis and 64.3% (P โซุโฌ .0026) in patients with spontaneous bacterial peritonitis (SBP). There was no increase in codon 54 mutation rate in hepatitis B-related hepatocellular carcinoma (HCC). In chronic hepatitis B infection, the odds ratio for an individual with codon 54 mutation to develop cirrhosis was 1.84 (95% CI: 1.21-2.81) and to develop SBP was 4.58 (95% CI: 1.73-12.16). Chronic hepatitis B and hepatitis C infection lowered the MBL levels, probably by suppressing MBL production. Codon 54 mutation of MBL was associated with progression of disease in chronic hepatitis B infection. (HEPATOLOGY 1999;29:1248-1251.)
Mannose-binding lectin (MBL) is a calcium-dependent C-type lectin with a structural analogy to complement component C1q, and plays an important role in host immune defense. It is important in the first line of defense because of its ability to activate the complement system and phagocytosis. [1][2][3][4] Through its collagen domain, it behaves as an opsonin by binding to collectin receptors. [5][6][7] Low serum MBL leads to an opsonic defect that impairs phagocytosis by polymorphonuclear leukocytes. 8 Previous studies have shown that MBL deficiency may confer a risk of infection in children and adults. 9,10 Point mutation at codons 52 (CGT=TGT), 54 (GGC=GAC), and 57 (GGA=GAA) of the MBL gene are associated with low serum level of MBL and thus immunode-ficiency caused by the opsonic defect. 11,12 MBL is synthesized by hepatocytes. 13 Recently, Thomas et al. showed that there was an association between MBL codon 52 mutation and persistent hepatitis B infection in whites. 14 The study did not find an association in the Asian hepatitis B carriers. It is known that the middle surface protein of the hepatitis B virus (HBV) envelope contains high mannose oligosaccharides for the binding of MBL. 15 Therefore, opsonization of the viral particles through MBL binding may be possible. However, whether this is associated with the clearance of serum HBV is not known.
Patients with cirrhosis have impaired serum opsonization. 16 Spontaneous bacterial peritonitis (SBP) is a frequent infection that occurs in cirrhotic patients with ascites. It is not known whether there is any relationship between cirrhosis, SBP, and MBL mutation.
We studied the serum MBL levels and MBL gene mutations in asymptomatic Chinese hepatitis B carriers, hepatitis C carriers, patients with hepatitis B-related hepatocellular carcinoma (HCC), and patients with hepatitis B-related cirrhosis with or without ascites and SBP. Our aim was to define the possible relationship between MBL levels and its mutations with these conditions.