MicroRNAs (miRNAs) are a non-coding family of genes involved in post-transcriptional gene regulation. These transcripts are associated with cell proliferation, cell differentiation, cell death and carcinogenesis. We analysed the miRNA expression profiles in 25 pairs of hepatocellular carcinoma (HCC) and adjacent nontumorous tissue (NT) and nine additional chronic hepatitis (CH) specimens using a human miRNA microarray. Targets and references samples were co-hybridized to a microarray containing whole human mature and precursor miRNA sequences. Whereas three miRNAs exhibited higher expression in the HCC samples than that in the NT samples, five miRNAs demonstrated lower expression in the HCC samples than in the NT samples (Po0.0001). Classification of samples as HCC or NT by using support vector machine algorithms based on these data provided an overall prediction accuracy of 97.8% (45/46). In addition, the expression levels of four miRNAs were inversely correlated with the degree of HCC differentiation (Po0.01). A comparison of CH and liver cirrhosis samples revealed significantly different pattern of miRNA expression (Po0.01). There were no differences, however, between hepatitis B-positive and hepatitis C-positive samples. This information may help clarify the molecular mechanisms involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

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The scoring system with abdominal ultrasonography could provide accurate information about hepatic steatosis, visceral obesity, and the metabolic syndrome in apparently healthy people who do not consume alcohol.

The geographic distribution of hepatitis B virus (HBV) genotypes in Japan and its clinical relevance are poorly understood. We studied 731 Japanese patients with chronic HBV infection. HBV genotype was determined by the restriction fragment length polymorphism (RFLP) method after polymerase chain reaction (PCR). Of the 720 patients with positive PCR, 12 (1.7%) were HBV genotype A, 88 (12.2%) were genotype B, 610 (84.7%) were genotype C, 3 (0.4%) were genotype D, and 7 (1.0%) were of mixed genotype. Over 94% of patients on the Japanese mainland had genotype C, while 60% of the patients on Okinawa, the most southern islands, and 22.9% in the Tohoku area, the northern part of the mainland, harbored genotype B. Compared with genotype C patients, genotype B patients were older (53.6 to 42.2 years; P < .01), had a lower rate of positive hepatitis B e antigen (HBeAg) (18.4% to 50.6%; P < .01), and a lower level of serum HBV DNA (5.02 to 5.87 log genome equivalents (LGE)/mL; P < .01). The mean age of the genotype B patients with hepatocellular carcinoma was 70.1 ؎ 9.2 years, compared with 55.2 ؎ 9.7 of genotype C patients (P < .01). These results indicate that genotypes C and B are predominant in Japan, and there are significant differences in geographic distribution and clinical characteristics among the patients with the different genotypes. (HEPATOLOGY 2001;34:590-594.)Hepatitis B virus (HBV), a member of hepadnaviridae, is a circular double-stranded DNA virus, and is one of the major causative agents of chronic liver diseases, especially in Asian and African countries. HBV had formerly been classified into 4 major subtypes, which were defined serologically. 1 However, the classification of HBV by serologic subtype is not rational because of a change of subtype resulting from one point mutation at the S gene. 2 Thus, according to the molecular evolutionary analysis of the genomic DNA sequence, HBV strains isolated in various countries are classified into 7 genotypes: genotypes A to G. 3

Clinical and molecular virological differences were evaluated in 50 Japanese patients chronically infected with HBV of genotype B and C who were matched for age and sex as well as the severity of liver disease in a case-control study. Hepatitis B e antigen (HBeAg) was significantly less frequent (16% vs. 42%, P < .01), whereas antibody to HBeAg (anti-HBe) was significantly more common (84% vs. 56%, P < .01) in genotype B than C patients. The predominance of mutants with G-to-A mutation at nucleotide (nt) 1896 in the precore region (A1896) over the wild-type was comparable between genotype B and C patients (60% and 62%, respectively), and it correlated with anti-HBe. The double mutation in the basic core promoter (A-to-T at nt 1762 and G-to-A at nt 1764), however, was significantly more frequent in genotype C than B patients (58% vs. 16%, P < .01), and it did not correlate with anti-HBe or HBeAg. By the multiple logistic regression analysis, the double mutation in the basic core promoter (T1762/A1764) was significantly associated with genotype C [odds ratio (OR), 9.3; 95% confidence interval (