Genetic polymorphism at the apolipoprotein E locus affects the outcome of chronic hepatitis B

Apolipoprotein E (ApoE) and H (ApoH) genotypes are known to affect plasma lipoprotein concentrations. By modulating transport and entry of the hepatitis B virus into hepatocytes, apolipoproteins may influence the course of infection. To verify this hypothesis, 105 patients with chronic HBV infection were examined. Sixty-two of the patients were followed-up for a median time of 21 years. One hundred two controls were included. ApoE and ApoH genotypes were determined by the restriction fragment length polymorphism method. A trend was found for progressive overrepresentation of ApoE3/E3 among patients with advanced liver disease: 13/27 (48%) of inactive HBV carriers, 36/61 (59%) of chronic hepatitis B patients and 16/17 (94%) of patients who received liver transplants (P < 0.005). Being an E3/* carrier was associated with a lower probability of loss of HBsAg: 9/56 (16%) versus 3/6 (50%) (P < 0.05); it was also associated with a longer time before HBsAg loss (P < 0.05). No influence of ApoH genotypes on clinical outcomes was found. The probability of disease progression was higher, and that of loss of HBsAg was lower, among patients with the ApoE3 allelic variant. Downregulation and/or reduced binding of the LDL receptor may explain the more benign course of hepatitis B among carriers of ApoE2-E4.