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2.
QJM ; 111(9): 657-658, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-29534208
3.
J Viral Hepat ; 25(5): 608-611, 2018 05.
Article in English | MEDLINE | ID: mdl-29194858

ABSTRACT

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.


Subject(s)
Antiviral Agents/administration & dosage , Hepatitis B/pathology , Hepatitis B/virology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Virus Activation , Aged , DNA, Viral/blood , Female , Humans , Incidence , Male , Middle Aged
4.
J Viral Hepat ; 23(12): 977-984, 2016 12.
Article in English | MEDLINE | ID: mdl-27476460

ABSTRACT

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA+ -M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA+ -M2BP had the highest correlation coefficient (rs =.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest rs value (.415) in the hepatitis B group. Although WFA+ -M2BP could be a useful indicator of liver fibrosis, WFA+ -M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut-off values in each aetiology for the degree of fibrosis should be determined.


Subject(s)
Antigens, Neoplasm/blood , Antigens, Neoplasm/metabolism , Hepatitis B, Chronic/pathology , Hepatitis C, Chronic/pathology , Membrane Glycoproteins/blood , Membrane Glycoproteins/metabolism , Plant Lectins/metabolism , Receptors, N-Acetylglucosamine/metabolism , Serum/chemistry , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Protein Binding , Young Adult
5.
Clin Exp Obstet Gynecol ; 43(2): 192-7, 2016.
Article in English | MEDLINE | ID: mdl-27132408

ABSTRACT

PURPOSE: To investigate the relationship between the change of daily step counts and low back pain (LBP) during pregnancy. Materials and METHODS: Pregnant women at less than eight weeks of gestation (WG) were recruited. Daily step counts were measured with a pedometer. To assess LBP, the Oswestry disability index (ODI) score was recorded. Thirty-six individuals were divided into the LBP and non-LBP groups. The effect of step counts on LBP between the two groups was analyzed. RESULTS: At 16-19 WG, step counts were not considerably changed in the non-LBP group but were significantly increased in the LBP group. At 24-27 and 32-35 WG, step counts were increased in the non-LBP group but were significantly decreased in the LBP group. CONCLUSIONS: Acute increase of daily step counts in early pregnancy is a risk for LBP, and gradual increases of step counts after mid-pregnancy is recommended for women.


Subject(s)
Low Back Pain/epidemiology , Motor Activity , Pregnancy Complications/epidemiology , Walking , Actigraphy , Adult , Cohort Studies , Female , Humans , Pregnancy , Prospective Studies
6.
J Viral Hepat ; 23(10): 780-8, 2016 10.
Article in English | MEDLINE | ID: mdl-27196675

ABSTRACT

High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) ±ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had ≥1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks.


Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Drug Resistance, Viral , Fluorenes/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Sofosbuvir/therapeutic use , Uridine Monophosphate/analogs & derivatives , Amino Acid Substitution , Antiviral Agents/pharmacology , Benzimidazoles/pharmacology , Clinical Trials, Phase III as Topic , Fluorenes/pharmacology , Genotype , Hepacivirus/genetics , High-Throughput Nucleotide Sequencing , Humans , Japan , Sequence Analysis, DNA , Sofosbuvir/pharmacology , Treatment Outcome , Uridine Monophosphate/pharmacology , Uridine Monophosphate/therapeutic use , Viral Nonstructural Proteins/genetics
7.
Methods Inf Med ; 55(1): 65-9, 2016.
Article in English | MEDLINE | ID: mdl-26391694

ABSTRACT

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". BACKGROUND: Rheumatoid arthritis (RA) is a progressive inflammatory disease that causes damage to multiple joints, decline in functional status, and premature mortality. Thus, effective and frequent objective assessments are necessary. Then, we developed a self-assessment system for RA patients based on a smartphone application. OBJECTIVE: The purpose of this study was to investigate the feasibility of a self-assessment system for RA patients using a smartphone application. METHODS: We measured daily disease activity in nine RA patients who used the smartphone application for a period of three months. A disease activity score (DAS28) predictive model was used and feedback comments relating to disease activity were shown to patients via the smartphone application each day. To assess participants' RA disease activity, the DAS28 based on the C-reactive protein level was measured by a rheumatologist during monthly clinical visits. RESULTS: The disease activity measured by the application correlated well with the patients' actual disease activity during the 3-month period, as assessed by clinical examination. Furthermore, most participants gave favourable responses to a questionnaire administered at the end of the 3-month period containing questions relating to the ease of use and usefulness of the system. CONCLUSIONS: The results of this feasibility study indicated that the DAS28 predictive model can longitudinally predict DAS28 and may be an acceptable and useful tool for assessment of RA disease activity for both patients and healthcare providers.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Diagnosis, Computer-Assisted/methods , Diagnostic Self Evaluation , Mobile Applications , Smartphone , Activities of Daily Living , Adult , Aged , Arthralgia/diagnosis , C-Reactive Protein/chemistry , Computer Simulation , Feasibility Studies , Female , Humans , Male , Middle Aged , Psychometrics/methods , Rheumatology/methods , Software , Surveys and Questionnaires , User-Computer Interface
8.
J Viral Hepat ; 19(10): 694-703, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22967100

ABSTRACT

Pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20-50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti-IFN-α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN-α as a standard. We studied 129 PEG-IFN-α/RBV-treated patients. In the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG-IFN-α treatment, and detected 12 with NAbs. Patients with good IFN-responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN-ß (nIFN-ß) and re-treatement of patients with NAbs with nIFN-ß/RBV achieved SVR. Our analyses revealed that the emergence of anti-IFN-α NAbs was a candidate causal factor of PEG-IFN-α-treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG-IFN-α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti-IFN-α NAbs, should be considered.


Subject(s)
Antibodies, Neutralizing/blood , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Interferon-alpha/immunology , Ribavirin/administration & dosage , Adult , Aged , Female , Humans , Male , Middle Aged , Neutralization Tests , Treatment Outcome
9.
Vox Sang ; 102(4): 285-93, 2012 May.
Article in English | MEDLINE | ID: mdl-22082342

ABSTRACT

BACKGROUND: The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. STUDY DESIGN AND METHODS: Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. RESULTS: Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). CONCLUSION: This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.


Subject(s)
Blood Donors , Hepatitis B , Hepatitis C , Transfusion Reaction , Virus Diseases/transmission , HIV Infections/transmission , Hepatitis B/transmission , Hepatitis B Antibodies/blood , Hepatitis C/transmission , Humans , Prospective Studies , Risk
10.
J Frailty Aging ; 1(1): 39-44, 2012.
Article in English | MEDLINE | ID: mdl-27092936

ABSTRACT

BACKGROUND: Recent studies suggested that pedometer-based walking programs are applicable to older adults. OBJECTIVES: The purpose of this study was to evaluate the use of pedometer in sedentary older adults to improve physical activity, fear of falling, physical performance, and leg muscle mass. DESIGN: This was a pilot randomized controlled trial (RCT). SETTING AND PARTICIPANTS: Eighty-seven community dwelling sedentary older adults living in Japan. INTERVENTION: The intervention group (n=43) received a pedometer-based behavioural change program for 6 months, while the control group (n=44) did not. The participants in the intervention group were instructed to increase their mean daily steps by 10% each month. Thus, at the end of 6 months, participants in the intervention group were expected to have 77 % more daily steps than their baseline step counts. Written activity logs were monthly averaged to determine whether the participants were achieving their goal. MEASUREMENTS: Outcome measures were physical activity, fear of falling, physical performances, and leg muscle mass. RESULTS: In this 6-month trial 40 older adults (93%) completed the pedometer protocol with good adherence. In the intervention group, average daily steps were increased by 83.4% (from 20311323 to 3726 1607) during the study period, but not in the control group (from 20471698 to 22671837). The pedometer-based behavioral change program was more effective to improve their physical activity, fear of falling, locomotive function, and leg muscle mass than control (P<0.05). CONCLUSION: These results suggested that the pedometer-based behavioral change program can effectively improve the physical activity, fear of falling, physical performance, and leg muscle mass in sedentary older adults.

11.
J Frailty Aging ; 1(2): 64-70, 2012.
Article in English | MEDLINE | ID: mdl-27093042

ABSTRACT

OBJECTIVE: Sarcopenia, the age-related loss of skeletal muscle mass, is highly prevalent in older adults. The aim of this study was to investigate the effects of the combination of resistance training and multinutrients supplementation (including vitamin D and protein) on muscle mass and physical performance in frail older adults. METHODS: This trial was conducted in Japanese frail older adults (n=77), which underwent a standardized protocol of a 3-month physical exercise intervention. The sample population was divided into two groups, according to the adoption (S/Ex: n = 38) or not (Ex: n = 39) of the additional multinutrient supplementation. The outcome measures of interest for the present analyses were the skeletal muscle mass index (SMI) and several physical performance tests. RESULTS: Participants in S/Ex group had significant improvements for the outcome measures, including SMI and maximum walking time (P<0.05), compared to those in Ex group. The prevalence of sarcopenia decreased from 65.7% to 42.9% in S/Ex group, while that in Ex group remained unchanged (68.6% to 68.6%) (relative risk = 1.60, 95% CI: 1.03-2.49). CONCLUSION: The results of this study suggest that the combination of resistance training and multinutritional supplementation may be more effective at improving muscle mass and walking speed than an intervention only based on resistance training.

12.
J Environ Qual ; 37(1): 207-18, 2008.
Article in English | MEDLINE | ID: mdl-18178894

ABSTRACT

Herbicide-tolerant Zoysia grass (Zoysia japonica Steud.) has been generated previously through Agrobacterium tumefaciens-mediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1.2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.


Subject(s)
Herbicide Resistance , Plants, Genetically Modified/physiology , Poaceae/physiology , Adult , Antigens, Plant/immunology , Female , Gene Flow , Humans , Hybridization, Genetic , Hypersensitivity/etiology , Hypersensitivity/immunology , Korea , Male , Phenotype , Plants, Genetically Modified/anatomy & histology , Poaceae/anatomy & histology , Pollen/immunology , Pollination , Risk Assessment , Skin Tests , Wind
13.
Liver Int ; 27(2): 186-91, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17311612

ABSTRACT

BACKGROUND: Interferon (IFN) improves hepatic inflammation/fibrosis and reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CH-C). However, HCC develops in some patients who have a sustained virological response (SVR) to IFN therapy. We designed this study to establish a follow-up protocol for patients with CH-C who have SVR to IFN therapy. METHODS: We retrospectively studied 1124 patients with CH-C who received IFN. RESULTS: HCC developed in 3.5% of patients with SVR to IFN. As compared with SVR patients without HCC, SVR patients with HCC were predominantly male (P=0.003), older at the initiation of IFN therapy (P=0.002), and at a more advanced histologic stage of disease (P<0.001). However, three of the 13 SVR HCC patients had mild fibrosis. The mean interval from IFN therapy to the detection of HCC in SVR HCC patients was 5.8 years and did not differ significantly from that in non-SVR HCC patients (P=0.304). Although most patients with HCC received curative therapy, the prognosis of some SVR HCC patients was poor, probably because of insufficient follow-up, resulting in delayed detection of HCC. CONCLUSIONS: SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/virology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Interferons/therapeutic use , Liver Neoplasms/virology , Adolescent , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
15.
J Viral Hepat ; 12(5): 494-8, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16108764

ABSTRACT

SUMMARY: We recently reported that the genetic instability resulting in the high rate of mitochondrial DNA (mtDNA) mutation in noncancerous liver tissue is consistent with the multicentric hepatocarcinogenesis detected clinically. Interferon (IFN) has been reported to reduce hepatocarcinogenesis in individuals with hepatitis virus infection. Liver biopsy specimens were obtained from 26 patients with chronic hepatitis C virus (HCV) infection before and after IFN therapy (total dose: 252 million units). The mean (+/-SD) age of the study population was 45 +/- 9 years and 13 (50%) were male [mode of acquisition: blood transfusion (27%), unknown (73%); viral load: 5.2 +/- 1.1 k copies/mL; duration of infection: 17 +/- 9 years (65%), unknown (35%); genotype: I (4%), II (80%), III (8%), IV (8%); alcohol intake: positive (31%), negative (69%)]. DNA samples were extracted from the specimens and subjected to direct sequencing. The mtDNA mutation frequency in the D-loop was increased in liver specimens from individuals with HCV infection compared with 21 controls (2.5 vs 0.6, P < 0.001). IFN therapy decreased the mtDNA mutation (mean difference = 0.7, P < 0.001) and the decreased number of mtDNA mutations was positively correlated with suppression of the total histological activity index score (mean difference = 1.3, P < 0.01). These results clearly indicate that the mutational rate of mtDNA is strongly associated with IFN therapy. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation of the effect of IFN, and may be useful for the prediction of risk of carcinogenesis.


Subject(s)
Antiviral Agents/administration & dosage , DNA, Mitochondrial/drug effects , Interferons/pharmacology , Mutation , Adult , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/prevention & control , DNA, Mitochondrial/genetics , Female , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Humans , Interferons/therapeutic use , Liver Neoplasms/etiology , Liver Neoplasms/prevention & control , Male , Polymerase Chain Reaction , RNA, Viral/blood
16.
J Viral Hepat ; 11(5): 448-54, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15357651

ABSTRACT

This study aimed to find how ribavirin increases viral disappearance in patients with hepatitis C virus (HCV) of genotype 1 and high baseline viral loads (>5.0 x 10(5) copies/mL) when given with interferon (IFN). Using the real-time quantitative polymerase chain reaction, we measured serum HCV in 20 patients during the first 12 weeks of therapy with IFN-alpha 2b and ribavirin. Controls were 10 similar patients given IFN-alpha 2b alone. IFN-alpha 2b was given at 6 MU daily for 2 weeks, and then three times weekly. Ribavirin was given at 600 or 800 mg daily. Serum HCV RNA decreased rapidly in the first phase, during the first 24 h of therapy (day 0), and more slowly in the early second phase (days 1-14). The median decrease was by 1.41 and 0.078 log 10/day in these two phases in the combination therapy group, and 0.90 and 0.081 log 10/day in the monotherapy group. The difference between groups in the first phase was not significant (P = 0.24), nor was that in the next phase (P = 0.68). Later in the second phase, between days 14 and 84, the median decrease was larger in the combination therapy group (0.030 log 10/day) than in the monotherapy group (0.015 log 10/day, P = 0.035). In patients with HCV genotype 1 and high viral loads, the effects of ribavirin with IFN-alpha appeared slowly, after the earliest days of treatment. A long-term favourable outcome of combination therapy may be associated with a rapid viral decline in this later phase of therapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/physiology , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Ribavirin/therapeutic use , Viral Load , Adult , Aged , Antiviral Agents/administration & dosage , Drug Therapy, Combination , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/administration & dosage , Kinetics , Male , Middle Aged , RNA, Viral/blood , Recombinant Proteins , Ribavirin/administration & dosage , Treatment Outcome
17.
Gut ; 53(3): 425-30, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14960528

ABSTRACT

BACKGROUND: An increase in the incidence of hepatocellular carcinoma (HCC) in Japan since the 1980s suggests an imminent outbreak in other countries where viral spread occurred more recently. Interferon therapy for chronic hepatitis C, in general, has been shown to prevent HCC. AIMS: To determine the scale of benefit in individual patients. SUBJECTS: Histologically proven chronic hepatitis C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT) cohort (Ann Intern Med 1999;131:174), as updated in March 2003. METHODS: The lifetime risk for HCC was calculated based on HCC incidence rates, stratified by sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free survival was defined as the difference between expected HCC free survival with sustained virological response and that without. RESULTS: The gain in HCC free survival was greater when a patient was younger and fibrosis was more advanced. For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining sustained response while a patient with F1 fibrosis older than 60 years gained less than one year. For a treatment protocol with a given sustained response rate, prior estimation of the gain can be obtained by multiplying the calculated HCC free survival for responders by the response rate. CONCLUSIONS: The gain in HCC free survival may serve as an indicator of the benefit of interferon therapy in terms of HCC prevention and be useful in the consideration of indication and selection of treatment protocol for individual patients.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/prevention & control , Hepatitis C, Chronic/drug therapy , Interferons/therapeutic use , Liver Neoplasms/prevention & control , Adult , Age Distribution , Age Factors , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Disease-Free Survival , Female , Hepatitis C, Chronic/complications , Humans , Incidence , Japan/epidemiology , Liver Neoplasms/epidemiology , Liver Neoplasms/virology , Male , Middle Aged , Proportional Hazards Models , Risk Assessment , Sex Distribution
18.
Br J Cancer ; 88(12): 1894-9, 2003 Jun 16.
Article in English | MEDLINE | ID: mdl-12799633

ABSTRACT

Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were measured in sera from 187 patients with primary liver cancer (164 with hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC)) and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U-test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)), CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%), and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1 represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA 21-1 reflected differences in tumour burden, suggesting applicability to staging and follow-up.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Liver Neoplasms/diagnosis , Adult , Aged , CA-19-9 Antigen/blood , Carcinoma, Hepatocellular/diagnosis , Cholangiocarcinoma/diagnosis , Humans , Keratin-19 , Keratins , Liver Diseases/diagnosis , Liver Neoplasms/pathology , Male , Middle Aged , Sensitivity and Specificity , alpha-Fetoproteins/analysis
19.
Neuroscience ; 119(2): 421-32, 2003.
Article in English | MEDLINE | ID: mdl-12770556

ABSTRACT

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.


Subject(s)
DNA-Binding Proteins/metabolism , Epilepsy/physiopathology , High Mobility Group Proteins/metabolism , Olfactory Pathways/abnormalities , Prosencephalon/abnormalities , Animals , Animals, Newborn , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Disease Models, Animal , Electroencephalography/methods , Embryo, Mammalian , Epilepsy/genetics , Epilepsy/metabolism , Female , High Mobility Group Proteins/deficiency , High Mobility Group Proteins/genetics , In Vitro Techniques , Male , Matched-Pair Analysis , Membrane Potentials , Mice , Mice, Mutant Strains , Neural Conduction , Neurons/metabolism , Patch-Clamp Techniques/methods , Prosencephalon/embryology , Prosencephalon/growth & development , SOXB1 Transcription Factors , Synaptic Transmission
20.
Br J Surg ; 89(4): 418-22, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11952580

ABSTRACT

BACKGROUND: Interferon therapy seems to decrease the incidence of recurrence after resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Effects of postoperative interferon therapy on the survival rate after resection of such HCC are still unclear. METHODS: A prospective randomized clinical trial of postoperative interferon therapy was performed. Thirty men were allocated randomly after liver resection to an interferon-alpha group (15 patients) or a control group. Patients in the interferon group received interferon-alpha 6 MIU intramuscularly every day for 2 weeks, then three times a week for 14 weeks and finally twice a week for 88 weeks. RESULTS: The response to interferon was complete in two patients, there was a biochemical response in six patients and no response in seven patients. Interferon administration was not completed in three patients because of adverse events. Liver function did not change or worsened after operation in the control group, and did not change or improved in the interferon group. The cumulative survival rate was higher in the interferon group than in the control group (P = 0.041). CONCLUSION: Postoperative interferon therapy seems to improve the outcome after resection of HCV-related HCC.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/prevention & control , Hepatitis C/complications , Interferon-alpha/therapeutic use , Liver Neoplasms/prevention & control , Neoplasm Recurrence, Local/prevention & control , Postoperative Care/methods , Aged , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/virology , Female , Follow-Up Studies , Hepatitis C/blood , Hepatitis C/drug therapy , Humans , Liver Neoplasms/surgery , Liver Neoplasms/virology , Male , Neoplasm Recurrence, Local/virology , Recurrence , Serum Albumin/analysis , Survival Analysis , Treatment Outcome
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