Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients

Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged ≥ 35 years, HBV DNA ≥ 4 log copies/mL and positive HBeAg at diagnosis (n=184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p=0.013). Among the patients aged ≥ 35 years with HBV DNA ≥ 4 log copies/mL and negative HBeAg (n=237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p>0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged≥35 years with HBV DNA ≥4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development

Gross pathology, histopathology and immunohistochemistry of chickens experimentally inoculated with Km_5666.

<p>(A) Grayish-white ill-defined tissue was located in the septum at 35 days old. (B) Locally extensive growth of hypertrophied cardiomyocytes. Bar  = 75 µm. (C) Mitosis (arrowhead) observed in hypertrophied cardiomyocytes. Bar  = 30 µm. (D) Numerous nuclei in atypical myocardium were positive for PCNA. Bar  = 20 µm. (E–F) Hypertrophied cardiomyocytes positive for p-Akt (E) and p-tuberin (F). Bars  = 20 µm.</p

Phylogenic tree based on <i>pol</i> gene of the isolates.

<p>Phylogenic tree constructed by the neighbor-joining method showing the relationships among Km_5892, FGV prototype and standard ALSVs based on the <i>pol</i> gene. The nucleotide sequences were aligned with the Clustal W 1.8.3 program. Bootstrap values of 1000 trials using the neighbor-joining method. Scale bar corresponds to a distance of 0.03 as the frequency of amino acid substitutions in the pairwise comparison of two sequences according to the Kimura two-parameter method.</p

The degree of cardiac lesions in chickens experimentally infected with Km_5666 and Km_5892.

a<p>The degree of hypertrophied cardiomyocytes with atypical nuclei was defined as follows: +, individual cells; ++, multiple and/or small clusters; +++, multiple and extensive growth.</p>b<p>The degree of non-suppurative myocarditis was defined as follows: +, focal or multifocal (under 25 µm in diameter); ++, multifocal (from 25 µm to 200 µm); +++, multifocal (over 200 µm).</p>c<p>The degree of fibrosis was defined as follows: +, interstitial; ++, multifocal interstitial (under 400 µm in diameter); +++, multifocal interstitial (over 400 µm in diameter).</p>d<p>Total number in 10 high-power field.</p

Histopathology and immunohistochemistry of hearts in Japanese native fowls.

<p>(A) Mononuclear cells infiltrate into myocardial fibers. Chicken No. 5. Bar  = 40 µm. (B) Disarrangement of myocardial fibers with interstitial fibrosis. Chicken No. 9. Bar  = 90 µm. (C) Interstitial myocardial fibrosis confirmed by Masson's trichrome stain. Chicken No. 14. Bar  = 25 µm. (D) Hypertrophied cardiomyocytes with multiple atypical nuclei. Mitosis (arrowhead) is occasionally noted in these cardiomyocytes. Chicken No. 14. Bar  = 20 µm. (E) Matrix inclusion bodies (arrowhead) in the cytoplasm of Purkinje fibers. Chicken No. 14. Bar  = 20 µm. (F) Purkinje fibers and matrix inclusion bodies positive for ALV common antigen. Chicken No. 14. Bar  = 20 µm. (G) A large atypical nucleus in a hypertrophied cardiomyocyte is positive for PCNA. Chicken No. 14. Bar  = 20 µm.</p

Clinical signs, gross findings, cardiac histopathology and results of ALV isolation in chickens.

a<p>M: male, F: female</p>b<p>The degree of hypertrophied cardiomyocytes with atypical nuclei was defined as follows: +, individual cells; ++, multiple and/or small clusters; +++, multiple and extensive growth.</p>c<p>The degree of non-suppurative myocarditis was defined as follows: +, focal or multifocal (under 25 µm in diameter); ++, multifocal (from 25 µm to 200 µm); +++, multifocal (over 200 µm).</p>d<p>The degree of fibrosis was defined as follows: +, interstitial; ++, multifocal interstitial (under 400 µm in diameter); +++, multifocal interstitial (over 400 µm in diameter).</p>e<p>Total number in 10 high-power fields.</p>f<p>+: positive,−: negative,ND: no data.</p

Sequence of the oligonucleotide primers and targets.

<p>Sequence of the oligonucleotide primers and targets.</p