Fumihiko Komine

Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection

To confirm the possibility that some hepatitis B virus (HBV) variants do not induce HB s antigen (HBsAg), anti-HB core antibody (anti-HBc) and anti-HBc IgM in a transient infection, polymerase chain reaction (PCR) was performed in 20 patients with acute hepatitis and 7 patients with fulminant hepatitis. Patients were diagnosed with non-A, non-B hepatitis by serological markers at admission. PCR successfully amplified the precore/core gene in 5 (25%) of the patients with acute hepatitis and 2 (29%) of the patients with fulminant hepatitis. Subsequent sequencing revealed frequent mutations including precore-defects in the precore/core gene.

Telomerase activity of needle-biopsied liver samples : its usefulness for diagnosis and judgment of efficacy of treatment of small hepatocellular carcinoma

BACKGROUND/AIMS High values for telomerase activity in malignant tumors have been reported. The clinical usefulness of measurements of telomerase activity as a diagnostic tool and to evaluate treatment efficacy in small hepatocellular carcinoma was investigated. METHODS We investigated 22 patients (26 nodules) with intrahepatic abnormal nodules < or =20 mm in size determined by abdominal ultrasound. All underwent needle biopsies of tumorous nodules and extranodular regions of the liver by ultrasound guidance for histopathological diagnosis and measurement of telomerase activity by the fluorescence-based telomeric repeat amplification protocol. Re-biopsy of the same nodule was performed 1 week after percutaneous ethanol injection therapy to measure telomerase activity in 10 patients (10 nodules) found to have hepatocellular carcinoma. Liver-biopsied samples from 30 patients with chronic hepatitis C were used as a control. RESULTS Telomerase activity increased with statistical significance stepwise: chronic hepatitis (n=30, mean: 0.00 U) extranodular regions (pre-cirrhosis or cirrhosis, n=22, mean: 1.80 U), atypical hyperplasia (borderline or premalignant lesions, n= 15, mean: 7.02 U) and low-grade malignant hepatocellular carcinoma (n=11, mean: 31.96 U) (p<0.0001 by the Kruskal-Wallis test). Percutaneous ethanol injection therapy resulted in loss (0.00 U) of telomerase activity in 9 nodules and persistence in 1 nodule. CONCLUSIONS Measurement of telomerase activity appeared useful for diagnosis of intrahepatic abnormal nodules and assessment of the efficacy of percutaneous ethanol injection therapy and may be used as an alternative diagnostic method, especially when pathohistological discrimination between atypical hyperplasia and well-differentiated hepatocellular carcinoma is difficult.

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

Abstract: Background: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters.

A case of sexually transmitted acute hepatitis C: confirmation by analysis of viral genome

Abstract We report a case of acute hepatitis C that appears to have been sexually transmitted. The patient was a 21-year-old female with no history of blood transfusion and no personal or family history related to hepatic decease. The patient first had sexual intercourse with her male partner in November 1994 and she visited our hospital with a chief complaint of general weakness in March 1995. She was admitted because of abnormal liver function test results (ALT 329; AST 152 IU l −1 ). She was negative for serum second-generation anti-hepatitis C virus (HCV) antibody, anti-hepatitis A IgM antibody, anti-hepatitis B core IgM antibody, anti-Epstein–Barr virus IgM antibody, anti-nuclear antibody, anti-DNA antibody and anti-mitochondrial antibody at admission. A serum HCV RNA test gave a positive result on the 7th day after admission; her HCV RNA level was 10 3.5 copies 50 μl −1 serum on the 21st day. Her anti-HCV antibody status became positive on the 30th day after admission. A liver needle biopsy specimen taken on the 35th day showed well-preserved lobular architecture and mild necroinflammation within the parenchyma without accompanying fibrosis. Abdominal ultrasound and computed tomography did not show significant change in the liver or spleen. Taking the above findings together a diagnosis of acute hepatitis C was maden. Treatment by interferon-β succeeded in eradicating the HCV and the patient was free of HCV RNA 1 year later. The patients partner had untreated chronic hepatitis C. The HCVs isolated from the patient and her partner both had the 2b genotype and single-strand conformation polymorphism analysis revealed three virtually identical bands. The nucleotide sequences (E1-E2/NS1 region) of the two HCVs showed 98% homology. These genetic findings suggest that the sexual transmission of HCV occurred in this case.

Genetic variants of the IgA Fc receptor (FcαR, CD89) promoter in chronic hepatitis C patients

Fc receptor for IgA (FcαR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcαR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two −311T/C and −142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both −311CC and −142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53–6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14–3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, −311CC and −142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) ( < 150,000/μl) (5.1 and 8.5%) compared with 91 patients with normal PLT ( ≥ 150,000/μl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), −311CC or −142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcαR expression affecting IgA-mediated immune responses and/or IgA catabolism.

Changes of chronic hepatitis C virus anti-core and envelope antibodies by interferon therapy

Abstract We measured the levels of three antibodies against core (JCC-2), E1 (E1–5), and E2 NS1 (E2-1) hepatitis C virus (HCV) before and after interferon (IFN) therapy in 22 patients with chronic hepatitis C and assessed the relationship between the changes in these antibody titers and the response to IFN. The titers of serum JCC-2 and E2-1 antibodies before the IFN therapy did not show any significant relationship with IFN efficacy. In contrast, the titer of E1–5 antibody was significantly lower in the complete responder (CR) group than in the non-responder (NR) group. The JCC-2 antibody titer of the CR group to IFN therapy showed a significant decrease immediately, at 6 months and 1 year after the completion of IFN administration. However, that of the NR group either did not change or rose again 6 months or 1 year after therapy following an immediate short-term decrease. Thus the E1–5 antibody titer before IFN therapy and the JCC-2 antibody titer during IFN therapy seems to be a good indicator of IFN efficacy. In contrast, the E2-1 antibody did not correlate with IFN efficacy.