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  • 1
    Electronic Resource
    Electronic Resource
    Progressive and sufficient decrease of hepatitis B core antibody can predict the disappearance of hepatitis B virus DNA in Japanese patients with hepatitis B surface antigen clearance (2000)
    Springer
    Journal of gastroenterology 35 (2000), S. 753-757 
    Details
    ISSN: 1435-5922
    Keywords: Key words: hepatitis B virus ; hepatitis B surface antigen ; prednisolone withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The aim of this study was to elucidate the relationships among serum levels of hepatitis B virus (HBV) DNA, periods after hepatitis B surface (HBs) antigen clearance, and the titer of hepatitis B core (HBc) antibody in 200-fold diluted serum. Twelve patients who had clearance of HBs antigen from serum were studied. Five patients had not received any treatment (group A), and seven had received prednisolone withdrawal therapy. The patients in groups A and B were followed up for 86 months and 108 months (median), respectively. Serum HBV was measured by the nested polymerase chain reaction method. In both groups, serum HBV tended to become gradually undetectable after HBs antigen clearance. The positive rate of HBV in the sera 5 years or more after HBs antigen clearance was significantly lower than that in the sera at less than 5 years, both in group A (P = 0.004) and group B (P = 0.010). In both groups, the titer of HBs tended to decline every year after HBs antigen clearance. HBV was still detectable in the sera of some patients for a long period of time after they showed seroconversion to HBs antibody. The results suggest that detection of HBV was difficult in sera with an HBc titer of 30% or lower and at more than 5 years after HBs antigen clearance in both groups. It is important to note that HBV DNA rarely exists in the serum, even when HBs antigen and HBc are both negative.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350070034
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  • 2
    Electronic Resource
    Electronic Resource
    Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C (2000)
    Springer
    Journal of gastroenterology 35 (2000), S. 221-225 
    Details
    ISSN: 1435-5922
    Keywords: Key words: hepatitis C virus, serum HCV-RNA level, HCV genotype, branched DNA probe assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/b ratio was 1–5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5–10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350050334
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  • 3
    Electronic Resource
    Electronic Resource
    Hepatitis C virus subtype 3b infection in a hospital in Japan: Epidemiological study (1996)
    Springer
    Journal of gastroenterology 31 (1996), S. 801-805 
    Details
    ISSN: 1435-5922
    Keywords: hepatitis C virus subtype 3b ; epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the epidemiology of infection with hepatitis C virus (HCV) subtype 3b (a rare subtype thought to have originated in Southeast Asia) in Japan, we examined the genotypic subtype in 1397 patients with HCV-related chronic liver diseases. Of 1330 patients with identified HCV RNA genotypes, 960 had subtype 1b, 243 had subtype 2a, 97 had subtype 2b, 14 (1.1%) had subtype 3b, and 16 had other types of HCV or mixed subtypes. The age, gender, and severity of liver disease in patients with HCV subtype 3b did not differ from these features in patients with other subtypes. Eleven of the 14 patients with the 3b subtype had once worked at Company A in Tokyo, Japan. Multivariate logistic analysis showed that working history at that company was independently associated with the incidence of the subtype; the risk ratio was 207.2 (P〈0.0001). All 11 patients from Company A had received medical services, between 1953 and 1981, at Clinic C, which undertook medical care of the company staff. All 11 patients had received repeated intramuscular or intravenous injections for treatment of various diseases or for preventive vaccination for contagious diseases. The rare HCV subtype 3b, appeared to have been transmitted among the employees of a company through the performance of certain medical practices.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02358605
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  • 4
    Electronic Resource
    Electronic Resource
    Relationship between pretreatment viremia level and response to interferon-α therapy in chronic hepatitis c differs in viral type 1 and 2 infections (1996)
    Springer
    Digestive diseases and sciences 41 (1996), S. 1925-1932 
    Details
    ISSN: 1573-2568
    Keywords: chronic hepatitis C virus infection ; interferon-α ; hepatitis C viremia level ; hepatitis C virus type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the contribution of virus-related factors to long-term remission of chronic hepatitis C infection, we analyzed viral type and viremia level in 185 patients who had undergone a six-month course of interferon-α therapy. These virus-related factors were measured by an enzyme-linked immunosorbent assay with use of viral type-specific antigens and the branched DNA (bDNA) signal amplification assay, respectively. Sustained and long-term sustained responses were achieved in 55% and 50% of the patients, respectively. Transient or no responses were observed in 30% and 15% of the patients, respectively. Thirty-five percent of viral type 1 patients and 82% of viral type 2 patients had long-term sustained responses. Forty-two percent of bDNA-positive and 71% of bDNA-negative patients experienced long-term sustained responses. On multivariate analysis, viral type, Knodell's intralobular score, and viremia level were strong independent predictors of long-term sustained response (P〈0.0001, =0.0060, and 0.037, respectively). Viremia level, however, was a significant predictor only in viral type 1, not type 2, patients. The relation between pretreatment viremia level and response to interferon-α therapy in chronic hepatitis C differs in viral type 1 and 2 infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02093591
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of arterial administration of a high-molecular weight antitumor agent, styrene maleic acid neocarzinostatin, in embolization-resistant liver cancer (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 148-155 
    Details
    ISSN: 1437-7772
    Keywords: Key words Hepatocellular carcinoma ; Transcatheter arterial embolization ; Styrene maleic acid neocarzinostatin ; Embolization-resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Hepatocellular carcinoma often shows a resistance to transcatheter arterial embolization in the course of therapy repetition. Methods. Forty-four of 103 consecutive patients with hepatocellular carcinoma showing a resistance to repeated embolization therapy were treated with intra-arterial injection of the high-molecular weight antitumor agent styrene-maleic acid neocarzinostatin (Zinostatin) mixed with Lipiodol (group A). The remaining 59 patients received repeated embolization with epirubicin given in the same way (group B). Results. In group A, computerized tomography scans 3 months after the therapy showed "complete" accumulation of Lipiodol in 2 patients (4.5%), and "good" accumulation (50%–99%) in 11 (25.0%); 10%–49% accumulation was shown in 12 patients (41.9%), and less than 10% in 19 patients (32.6%). In group B, 1 patient (1.7%) showed complete accumulation, 4 (6.8%) showed "good" accumulation, 10 (16.9%) showed 10%–49% accumulation, and 44 (74.6%) showed less than 10%. Multivariate logistic regression analysis showed that factors affecting Lipiodol accumulation after therapy included tumor multiplicity (P 〈 0.0001), use of Zinostatin (P = 0.010), and decompensation of cirrhosis (P = 0.049). In the 44 patients with Zinostatin injection, tumor size was the only factor affecting Lipiodol accumulation. Survival rates in groups A and B were 70.4% and 45.8%, respectively, at the end of the first year, 36.8% and 17.3% at the end of the second year, and 24.5% and 13.0% at the end of the third year (P = 0.0087). Conclusion. Intra-arterial Zinostatin injection therapy increased the Lipiodol accumulation rate and the survival rate in patients with embolization-resistant HCC, and the best candidates for the treatment were patients with smaller liver cancer of 50 mm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101470050045
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  • 6
    Electronic Resource
    Electronic Resource
    Clinical and virological features of chronic hepatitis C carriers with normal alanine aminotransferase levels despite positive serum HCV-RNA after interferon therapy (1999)
    Springer
    Journal of gastroenterology 34 (1999), S. 594-599 
    Details
    ISSN: 1435-5922
    Keywords: Key words: chronic hepatitis C ; interferon ; incomplete response (ICR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Interferon (IFN) is the only drug that induces viral clearance, but in patients with chronic hepatitis C, HCV-RNA clearance is achieved in only 20%–40% of patients treated with IFN for 6 months. The remaining patients have positive serum HCV-RNA, but about 5%–15% of the patients with positive serum HCV-RNA after IFN therapy showed normal alanine animotransferase (ALT) levels (incomplete response; ICR). In these patients, IFN therapy is thought to be related to the suppression of necroinflammatory reaction in the liver. The aim of this study was to evaluate the demographic, clinical, histological, and virological characteristics of patients with an ICR. In this study, ICR was defined as normalization of serum ALT, but positive HCV-RNA by reverse-transcription (RT) nested PCR at two points, 3 and 6 months after cessation of IFN therapy. By multiple logistic regression analysis, the risk ratio for ICR appearance in patients treated with IFN for more than 12 months was 3.06 compared with patients treated with IFN for less than 12 months. In patients with ICR after IFN therapy, serum ALT was often reelevated during the follow-up period. The incidence of ALT re-elevation was about 10% per year in the patients treated with IFN for less than 12 months, while the incidence of ALT reelevation in the patients treated with IFN for 12 months and more was significantly lower (P = 0.0176) by the log rank test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350050378
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  • 7
    Electronic Resource
    Electronic Resource
    A randomized, double-blind, controlled trial of natural interferon-β therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels (1996)
    Springer
    Journal of gastroenterology 31 (1996), S. 559-564 
    Details
    ISSN: 1435-5922
    Keywords: chronic hepatitis B ; e-antigen negative ; interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intermittent interferon (IFN) therapy appears to be effective for patients with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-β in a prospective, randomized, double-blind, controlled trial in 36 patients with e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1;n=12), 1 MIU (group 2;n=12), or 3 MIU (group 3;n=12), administered twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA tested negative for 6 months after the initiation of the therapy. According to this criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the efficacy rate in group 3 being significantly higher than that in the other two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IFN therapy. Although IFN was effective in controling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited abnormal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02355057
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  • 8
    Electronic Resource
    Electronic Resource
    Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype (1998)
    Springer
    Journal of gastroenterology 33 (1998), S. 223-228 
    Details
    ISSN: 1435-5922
    Keywords: Key words: HCV bDNA-probe ; HCV-RNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350050074
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  • 9
    Electronic Resource
    Electronic Resource
    Hepatic vascular side effects of styrene maleic acid neocarzinostatin in the treatment of hepatocellular carcinoma (2000)
    Springer
    Journal of gastroenterology 35 (2000), S. 353-360 
    Details
    ISSN: 1435-5922
    Keywords: Key words: hepatocellular carcinoma ; styrene maleic acid neocarzinostatin ; side effect ; hepatic artery obstruction ; arterio-portal shunt ; hepatic atrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Styrene-maleic acid neocarzinostatin (SMANCS) sometimes causes hepatic vascular side effects, including arterial stricture, obstruction, and arterio-portal shunt. A total of 128 intra-arterial SMANCS injection treatments, performed for 89 patients with hepatocellular carcinoma, were analyzed to determine the relationship between angiographic findings and subsequent hepatic vascular injuries. After SMANCS therapy, hepatic arterial stricture or obstruction occurred in 5 patients (5/128; 3.9%), arterio-portal shunting in 12 (12/128; 9.4%), liver shrinkage in 4 (4/128; 3.1%), and cholangitis or biloma in 2 (2/128; 1.6%). Among 23 patients whose plain abdominal X-ray films just after SMANCS injection showed Lipiodol retention in the hepatic artery, 5 patients developed arterial obstruction, 10 developed arterio-portal shunt, and 2, cholangitis or biloma. Among 26 patients with Lipiodol retention in the portal vein, 4 developed hepatic lobe atrophy with aggravation of liver function. Among 3 patients with Lipiodol retention in both the hepatic artery and the portal vein, 1 developed arterio-portal shunt. In 76 treatments without excessive Lipiodol retention, only 1 of the patients developed arterio-portal shunt. Excessive retention of Lipiodol in hepatic vascular beds just after SMANCS therapy was significantly associated with future vascular side effects (22/52 vs 1/76; P 〈 0.0001). Lipiodol retention in arteries just after SMANCS injection was closely associated with subsequent arterial obstruction or arterio-portal shunt, and Lipiodol retention in the portal vein was related to subsequent hepatic lobe atrophy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350050360
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  • 10
    Electronic Resource
    Electronic Resource
    Increased response rate to interferon therapy after a second course in hepatitis C patients who show relapse after the initial course (2000)
    Springer
    Journal of gastroenterology 35 (2000), S. 607-612 
    Details
    ISSN: 1435-5922
    Keywords: Key words: chronic hepatitis-C ; HCV-RNA ; relapse ; interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Some patients with chronic hepatitis C become HCV-RNA seronegative during interferon (IFN) therapy. However, about one-half of these patients show a relapse, evident by high serum alanine aminotransferase (ALT) level. In some patients with biochemical relapse, the serum HCV-RNA level becomes low immediately after the ALT relapse. Here, we assessed the changes in serum HCV-RNA level in patients with ALT relapse after IFN therapy, and evaluated the efficacy of a second course of IFN, started at the recovery stage after ALT relapse. Two hundred and seventy-seven patients who showed HCV-RNA seronegativity by reverse transcription nested-polymerase chain reaction (RT nested-PCR) and normalization of ALT during the initial IFN therapy, and had positive HCV-RNA with ALT relapse (〉 100 IU/l) within 3 months after completion of the initial IFN course were enrolled in this retrospective study. Two hundred and sixty patients were followed-up without further IFN retreatment after the ALT relapse (group 1), and 17 patients received another 6-month course of IFN after the ALT relapse (group 2). The median level of serum HCV-RNA, determined with a branched DNA probe assay (version 1; Chiron-Dai-ichi Kagaku Tokyo, Japan), in group 1 was 3.1 Meq/ml before IFN therapy, 1.3 Meq/ml at the time point of the ALT peak after the completion of IFN therapy, and 0.7 and 2.6 Meq/ml at 2–4 and 6–8 weeks after the ALT peak, respectively. The serum HCV-RNA level at 2–4 weeks after the ALT peak was lower than that before IFN therapy. The eradication rate of HCV-RNA (complete response; CR) in group 2 (47.1%; 8/17) was significantly higher than that in group 1 (1.5%; 4/260; P 〈 0.001). In conclusion, our data suggested that: (1) patients who showed biochemical relapse after initial IFN therapy had a significantly lower serum HCV-RNA level at recovery after ALT relapse compared with that before initial IFN therapy. (2) A high response rate was noted after a second course of IFN administered at the recovery stage of the ALT relapse, compared with patients without IFN retreatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350070060
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