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Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis in relation to the basic core promoter and precore mutations


Toru Takahashi, Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, 297-1 Terashimacho, Nagaoka, Niigata 940-2085, Japan. Email:


Background: The clinicopathological profiles and outcome of chronic hepatitis B can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are two major HBV genotypes. The basic core promoter and precore mutations are other known viral factors for disease activity, although the relationship between HBV genotypes and these mutations is not fully understood.

Methods: The HBV genotypes in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained data were correlated with clinicopathological parameters, basic core promoter, precore and the nucleotide 1858 mutations of the HBV genome.

Results: Among 90 cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B patients were older than genotype C patients (44.0 ± 13.9 vs 34.7 ± 11.0 P = 0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008) while anti-HBe was more common in genotype B than C patients (P = 0.0002). Serum aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 ± 612.8/257.0 ± 498.0 IU/L vs C: 111.3 ± 122.8/201.6 ± 229.4 IU/L, P = 0.16/0.48) and HBV viral loads in blood (B: 6.1 ± 3.1 log genome equivalent [LGE]/mL vs C: 6.7 ± 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion from HBeAg to anti-HBe occurred significantly earlier in genotype B than C patients (62 ± 53 months vs 136 ± 54 months, P = 0.0028) during the mean observation period of 149 ± 82 months even under various therapeutic modalities. The categories III and IV of the histological activity index in genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B patients whereas category II was higher in genotype B than C patients (P < 0.05). The double mutation (1762T/1764A) in the basic core promoter was more frequently found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of 1858C that was complementary to the precore mutation site in the stem-loop structure ∈, was equally rare in both genotype B and C HBV.

Conclusions: Genotype B patients were older, had earlier HBeAg seroconversion and exhibited more severe lobular necroinflammation, less portal inflammation and fibrosis than genotype C patients. This genotypic difference is related to the basic core promoter and precore mutations irrespective of 1858C.

© 2004 Blackwell Publishing Asia Pty Ltd