Biomedical subjects

F Imazeki

Publications and source records attributed to F Imazeki.

At least 19 recordsLinked to original sources

PubMed2004

Hepatitis B virus X protein (HBx)-induced apoptosis in HuH-7 cells: influence of HBV genotype and basal core promoter mutations.

BACKGROUND: Hepatitis B virus (HBV) infection is a serious, world-wide problem. HBV genotype and basal core promoter (BCP) mutations affect the clinical course of HBV-infected patients. BCP mutations also lead to mutations at HBV X protein (HBx) codons 130/131. The functional significance of naturally occurring variants of human HBx remains largely unknown. The purpose of the study was to investigate whether HBV genotypes or double mutations affect HBx-induced apoptosis. METHODS: We constructed genotype A, B, C, and D HBx expression vectors and HBx expression vectors with double mutations at HBx codons 130K and 131V or positions 130M and 131I using site-directed mutagenesis. A transient expression system in HuH-7 cells was established and this model was utilized to address the effect of HBx on cell viability. RESULTS: HBx-transfected cells showed a dose-dependent decrease in cell viability by MTS assay. A subset of cells expressing HBx underwent apoptosis according to terminal transferase enzyme-mediated end labeling of DNA and caspase-3 activity. This study demonstrated that HBx can induce cell death by apoptosis in a dose-dependent manner and that HBV genotypes and double mutations did not affect HBx-induced apoptosis. CONCLUSIONS: HBV genotypes and mutation of two amino acids directly adjacent to the conserved Kunitz domain essential for transcription activating activity of HBx did not change the pro-apoptotic activity of HBx. Further study is needed to determine whether HBV genotypes and double mutations have any effect on the function of HBx.

Apoptosis↗

PubMed2004

Inhibition of subgenomic hepatitis C virus RNA in Huh-7 cells: ribavirin induces mutagenesis in HCV RNA.

Hepatitis C virus (HCV) infection is a major problem throughout the world. Combination therapy of interferon (IFN) and ribavirin is the best treatment for eradication at present, but the mechanism is not completely understood. We used the HCV replicon system to investigate this mechanism. The effects of six drugs (UDCA, glycyrrhizin, TJ-9, bezafibrate, ribavirin, and alpha-IFN 2b) on HCV subgenomic RNA (genotype 1b, NS5B 415Y) were examined by reverse transcription polymerase chain reaction, cloning and sequencing. The HCV replication was inhibited by alpha-IFN 2b (7.39-13.2% at 10 U/mL, 3.29-6.12% at 100 U/mL, 1.3-4.86% at 1000 U/mL) and by ribavirin (4.36-13.9% at 100 microg/mL), but not by the other drugs at 24-72 h after treatment. Furthermore, the combination treatment was superior to IFN monotherapy and to ribavirin monotherapy at 72 h post-treatment. Sequence analyses of the double-stranded RNA-activated protein kinase (PKR)-binding domain and flanking regions within the HCV NS5A region revealed that the total numbers of substitutions caused by ribavirin (n = 36) or combination treatment (n = 57) were more than those of IFN alone (n = 5) and controls (n = 6). The HCV replicon system is the most efficient system for HCV replication and is an excellent choice for testing anti-HCV drugs and disinfectants. Our results further suggested that the combination of alpha-IFN 2b and ribavirin might induce mutations, and inhibit HCV RNA synthesis in hepatocytes to a greater extent than ribavirin monotherapy.

Amino Acid Substitution↗

PubMed2003

Hepatitis A virus VP3 may activate serum response element associated transcription.

BACKGROUND: Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways. METHODS: Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant. RESULTS: VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways. CONCLUSIONS: HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.

Blotting, Western↗

PubMed2003

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan.

BACKGROUND: Although it has been reported that different hepatitis B virus (HBV) genotypes induce different clinical characteristics in patients with chronic liver diseases (CLD), there have been few reports that have detailed the distribution of HBV genotypes in acute forms of liver disease. METHODS: HBV genotypes were determined in 61 patients who had acute forms of liver disease (45 had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in 531 patients with CLD, including 19 patients with severe acute exacerbation of CLD. We also analysed the enhancer II, core promoter, and precore region sequences for the presence of mutations. RESULTS: Expression of genotype B in patients with acute forms of liver disease was significantly greater than in those with CLD (39.3% v 11.7%, respectively; p<0.001). Furthermore, expression of genotype B was significantly greater in patients with FH than in those with AH (62.5% v 31.1%, respectively; p=0.027). The precore mutation A1896 and the core promoter mutation at nt 1753 and 1754 were found more frequently in FH than in AH, and genotype B was predominant in FH regardless of the presence of these mutations. CONCLUSIONS: HBV genotype B was found more frequently in patients with acute forms of liver disease than in patients with CLD, and more frequently in patients with FH than in those with AH. These results suggest that this HBV genotype may induce more severe liver damage than other viral genotypes, at least in patients from Chiba, Japan.

Acute Disease↗

PubMed2001

State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma: existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA PCR and conventional HBV PCR.

The role of hepatitis B virus (HBV) in carcinogenesis of hepatitis B surface antigen (HBsAg)-negative, anti-hepatitis C virus (anti-HCV)-positive hepatocellular carcinoma (HCC) remains unknown. To investigate the state of HBV DNA in such HCC, HBV DNA was examined by polymerase chain reaction (PCR) between HBV DNA and human Alu sequence (HBV-Alu PCR), which could detect integrated form of HBV DNA only, and by conventional HBV PCR, which could detect both integrated and episomal forms of HBV DNA. In all the 17 HBsAg-positive HCC, HBV DNA was detected by both HBV-Alu PCR method and conventional HBV PCR method. By contrast, in HBsAg-negative, anti-HCV-positive cases, HBV DNA was detected in 10 of 21 (47.6%) by conventional HBV PCR and in none of 21 (0%) by HBV-Alu PCR method. Thus, integrated form of HBV DNA was not found in most HbsAg-negative, anti-HCV-positive HCC in the current study. The role of episomal form of HBV DNA requires further investigation of its involvement in the process of the development of HBsAg-negative, anti-HCV-positive HCC.

Adult↗

PubMed2001

Analysis of full-length hepatitis A virus genome in sera from patients with fulminant and self-limited acute type A hepatitis.

BACKGROUND/AIMS: Type A hepatitis still poses a considerable problem worldwide. Why some patients progress to fulminant type A hepatitis and others do not is still unknown. To examine whether genomic differences of hepatitis A virus (HAV) are responsible for the severity of the disease, we analyzed the whole HAV genomes from patients with fulminant and self-limited acute type A hepatitis. METHODS: Sera from three patients with sporadic type A fulminant hepatitis (FH) and three patients with acute hepatitis (AH) were examined for HAV RNA. Full-length nucleotide sequences were determined using long reverse transcription polymerase chain reaction, 5' and 3' rapid amplification of cDNA ends methods, and direct sequencing. The amino acid sequences were deduced from the nucleotide sequences. RESULTS: HAV RNA was detected in all six patients examined. From the sequence of viral protein 1/2A, all cases were revealed to be genotype IA. By comparing with genotype IA, wild-type HAV strain GBM, the analysis of whole genomes from the six cases showed no specific substitutions between FH and AH. Completely identical nucleotide sequences were observed at 3' non-translated region (NTR) in all six cases. In 5'NTR, less nucleotide substitutions were found in FH than in AH, and in the non-structural protein 2B region, a little more amino acid substitutions seemed to be found in FH than in AH. CONCLUSIONS: This study showed that full-length HAV could be analyzed from serum samples. Although there were no unique nucleotide or amino acid substitutions, possible associations were suggested between the severity of type A hepatitis and the nucleotide substitutions in 5'NTR and the amino acid substitutions in 2B.

3' Untranslated Regions↗

PubMed2001

Roles of TT virus infection in various types of chronic hepatitis.

An unenveloped single-stranded virus, which might be a causative agent for posttransfusion non-A-G hepatitis, was recently found and named "TT virus" (TTV). There is still controversy over the role of TTV in chronic hepatitis. Therefore, we have examined the prevalence of TTV in various types of chronic hepatitis in Japan. TTV DNA was detected in 11 of 40 patients (27.5%) with non-B, non-C chronic hepatitis, 13 of 46 patients (28.3%) with type B chronic hepatitis, 21 of 55 patients (38.2%) with type C chronic hepatitis, and 41 of 131 subjects (31.3%) with normal liver function tests. The positivity rate for TTV DNA tended to increase with age. The detection rate did not differ statistically between non-B, non-C chronic hepatitis and type B or type C chronic hepatitis, or normal subjects. The distribution of TTV genotypes was not significantly different among them. Clinical characteristics of the chronic illness were similar for patients with or without TTV in all hepatitis groups. The etiologic role of TTV in chronic hepatitis is not confirmed from the statistical and clinical standpoint.

Adult↗

PubMed2000

The prevalence of TT virus infection in renal transplant recipients in Brazil.

BACKGROUND: Recently, TT virus (TTV) was discovered as a potential causative agent for non-A-E hepatitis. Little is known about the prevalence of TTV infection in renal transplant recipients. METHODS: One hundred and seventeen Brazilian renal transplant recipients and 100 normal subjects were examined to determine the prevalence of TTV infection. The TTV DNA in serum and its genotype were examined using polymerase chain reaction and restriction enzyme length polymorphism, respectively. RESULTS: TTV DNA was detected in 63/117 (53.8%) renal transplant recipients in contrast to its detection in 10/100 (10%) normal subjects (P<0.001). There was no statistical difference in the distribution of TTV genotypes between these groups. There was no significant difference in clinical backgrounds between TTV positive and negative patients. CONCLUSIONS: These results indicate a risk for TTV infection in renal transplant recipients in Brazil. They also indicate that TTV itself might not have a strong correlation with the pathogenicity of liver diseases.

Adolescent↗

PubMed2000

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy.

BACKGROUND: Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear. OBJECTIVE: To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C. DESIGN: Retrospective cohort study. SETTING: 7 university hospitals and 1 national hospital in Japan. PATIENTS: 593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated. INTERVENTION: Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy. MEASUREMENTS: Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated. RESULTS: 183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (+/-SE) reduction in fibrosis score of -0.60+/-0.07 at less than 3 years of follow-up and -0.88+/-0.08 at 3 years or more of follow-up. The rate of fibrosis progression was -0.28+/-0.03 unit/y (regression) in patients with sustained response, 0.02+/-0.02 unit/y in patients with nonsustained response (P< 0.001), and 0.10+/-0.02 unit/y in untreated patients. CONCLUSION: Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.

Adult↗

PubMed2000

Emergence of YMDD motif mutants of hepatitis B virus during lamivudine treatment of immunocompetent type B hepatitis patients.

Lamivudine is an effective antiviral agent for the treatment of chronic type B hepatitis. Recent studies have shown the appearance of lamivudine resistant viruses with mutations at the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the viral polymerase in hepatitis B virus (HBV) infected patients who received orthotopic liver transplantation. In order to confirm the appearance of such mutant HBV in immunocompetent patients, the HBV sequences in and around the YMDD motif of HBV DNA polymerase were examined in the sera from 16 lamivudine treated and 10 untreated control patients. Approximately 200 bases including the YMDD motif of HBV DNA polymerase were amplified by polymerase chain reaction (PCR) and sequenced directly by an automated sequencer. Of the 16 patients receiving lamivudine, mutant viruses with mutations in the YMDD motif were found in 3 of 8 patients treated with lamivudine for 52 weeks. However, this mutation was not found in any of the 8 patients treated for 32 weeks or a shorter period. Mutant viruses appeared after 40 weeks of treatment and were undetectable within 12 weeks after the cessation of the treatment. Such mutant viruses were not detected in any of the 10 untreated patients. This study confirms the emergence of YMDD mutant viruses during long-term lamivudine treatment in immunocompetent type B hepatitis patients. The results from this study suggest the need for combination therapies to reduce the levels of such mutant viruses in some patients.

Adult↗

PubMed2000

Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.

BACKGROUND/AIM: Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS: Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS: Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day. CONCLUSION: The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.

Adult↗

PubMed2000

Sustained viral response is rarely achieved in patients with high viral load of HCV RNA by excessive interferon therapy.

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50-94% of patients with < or =2 x 10(4) copies/ml (competitive RT-PCR) or <100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients with > or =2 x 10(5.5) copies/ml (competitive RT-PCR) or >200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that with < or =900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100-200 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with <100, 100-200, and >200 x 10(3) copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 x 10(3) copies/ml of HCV RNA.

Adolescent↗

PubMed2000

PCR-SSCP analysis of 5'-nontranslated region of hepatitis A viral RNA: comparison with clinicopathological features of hepatitis A.

The recent development of the sensitive reverse transcription-polymerase chain reaction (RT-PCR) method allowed us to detect the presence of hepatitis A virus (HAV) RNA in sera from hepatitis A patients. To determine whether differences in HAV are related to the wide range of clinical severity, we used PCR-single strand conformation polymorphism (SSCP) to analyze the amplified product of the 5'-nontranslated region (5'NTR), where relatively homologous sequences are reported and the internal ribosomal entry site is considered to exist, from these various levels of hepatitis A. Twenty-seven patients admitted to Chiba University Hospital (between 1988 and 1997) were examined for HAV RNA in their sera by RT-PCR with primers located at 5'NTR of HAV RNA. The nucleotide (nt) sequence of a central part (nt 277-551) of 5'NTR was amplified and the product was examined by PCR-SSCP. HAV RNA was detected in all 27 hepatitis A patients examined: in 3 with fulminant hepatitis, 2 with severe acute hepatitis, and 22 with self-limited acute hepatitits. The amplified sequence revealed by PCR-SSCP showed that samples from fulminant and severe acute hepatitis patients had similar mobility in the gel, whereas that from acute hepatitis patients demonstrated a considerable variety in mobility patterns. From the analysis of the amplified product of 5'NTR of HAV, the bands are likely to be similar in the more severe forms of hepatitis A compared to those from uncomplicated self-limited acute hepatitis.

Acute Disease↗

PubMed2000

A prospective study of interferon therapy modified by pre-treatment viral load in cirrhotic patients. Tokyo-Chiba Hepatitis Research Group.

BACKGROUND/AIMS: The relative role of hepatitis C virus (HCV) load and subtype as predictors of the efficacy of interferon therapy has been clarified in patients with chronic hepatitis C, but the effectiveness of interferon therapy in cirrhotic patients is still unclear. METHODS: To resolve this issue, we undertook a multicenter, randomized, and prospective study of 114 cirrhotic patients with hepatitis C virus infection. The patients were selected to undergo two different periods (6 or 12 months) of IFN therapy according to viral load. Patients with "low" viral load (< or = 10(5.8) copies/ml serum) were randomly divided into three groups, receiving 6 or 9 million units (MU) interferon three times a week for 6 months (total dose: 468 or 702 MU), or of a modified regimen using 6MU of IFN over 6 months (total dose 564 MU), while patients with "high" viral load (< or = 10(6.3) copies/ml serum) were also randomly divided into two groups of 6 or 9 MU of IFN three times a week for 12 months (total dose: 936 or 1,404 MU). RESULTS: HCV-RNA negativity rate at the completion of treatment with 6 or 9 MU IFN was 65% in patients with "low" viral load, in contrast to 14% in patients with "high" viral load. Sustained virological response was found in 40% of patients with "low" viral load irrespective of the three different regimens, in contrast to only 1 out of 35 patients (3%) with "high" viral load. Viral eradication was found in approximately 50% of patients having a low virus load (< or = 10(4.3) copies/ml) and with HCV subtype 2a. Univariate and multivariate analysis revealed that pretreatment viral load was a significant factor contributing to efficacy of IFN therapy. CONCLUSIONS: Sustained response was scarcely achieved in cirrhotic patients with high viral loads even after a 12-month course of intensive IFN therapy. This result indicates that there is a certain cut-off level of HCV RNA load which can not be eradicated.

Adult↗

PubMed2000

Sequence-motif analysis of 5'-untranslated region of GB virus-C in Japanese patients.

BACKGROUND: GB Virus C (GBV-C) is considered to belong to the Flaviviridae; however, the structures of the N-terminal end of its putative polyprotein are not well known. The internal ribosomal entry site (IRES) at the 5'-untranslated region of GBV-C and an initiating codon at nucleotides (nt) 552-554 have been proposed. We investigated the validity of this proposal. METHODS: The 5'-untranslated region of GBV-C was amplified from serum samples of 17 Japanese patients. Polymerase chain reaction-amplified products were directly sequenced and the obtained sequences were analysed by comparing them with the IRES structure of other viruses. RESULTS: Fifteen of the 17 (88%) GBV-C strains in our patients were classified as being Asian type. The box-A-like sequence (UUUC) and box-B-like sequence (AUCAUGG) observed in the IRES of picornaviruses were highly conserved in all the strains. Based on pair-wise comparisons with the multiple alignment data, overall sequence divergence for the 5'-terminus was 2.9-12%. When compared with the proposed secondary structure of the IRES model, the sequence divergences of the Asian-type GBV-C were higher at the regions of loop structures and lower at the regions of double-stranded RNA. The AUG codons, except for the one located at nt 552-554, produced truncated polyproteins or were not in-frame with the putative protein. CONCLUSIONS: Our examination of the sequence motif of GBV-C supports the proposal that the GBV-C has common structural motifs for IRES at its 5'-untranslated region and the AUG codon at nt 552-554 may be an initiating codon.

5' Untranslated Regions↗

PubMed1999

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

BACKGROUND: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma. OBJECTIVE: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis. DESIGN: Retrospective cohort study. SETTING: Seven university hospitals and one regional core hospital in Japan. PATIENTS: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated. MEASUREMENTS: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression. RESULTS: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]). CONCLUSIONS: Interferon therapy significantly reducesthe risk for hepatocellular carcinoma, especially among virologic or biochemical responders.

Alanine Transaminase↗

PubMed1999

Quantification of hepatitis C virus by TaqMan PCR: comparison with HCV Amplicor Monitor assay.

The quantitation of serum levels of hepatitis C virus RNA in chronic hepatitis C has been regarded as one of the most important indicators for the outcome of interferon therapy. A new method was used for quantitating the copy number of hepatitis C virus RNA using TaqMan polymerase chain reaction and for comparing the ability and usefulness of this assay with Amplicor Monitor assay in 138 patients. The detection range of hepatitis C virus RNA by TaqMan polymerase chain reaction was from 2 x 10(3) to 2 x 10(8) copies/ml. Hepatitis C virus RNA was detectable in 128 cases (92.8%) and undetectable in 10 cases (7.2%) by this method. The RNA levels measured by Amplicor Monitor assay correlated significantly with those measured by TaqMan polymerase chain reaction assay and the sensitivity of the two assays was almost equal. Thus, TaqMan polymerase chain reaction assay appears sufficiently sensitive for the evaluation of hepatitis C virus RNA and would be useful for the diagnosis and management of hepatitis C virus infection.

Adolescent↗

PubMed1999

The role of TT virus infection in acute viral hepatitis.

Recently, transfusion-transmitted virus (TTV) was discovered to be a potential causative agent for non-A-E hepatitis. Little is known about the relation between TTV and the clinical courses of various types of acute viral hepatitis. One hundred twenty-five patients with acute viral hepatitis who were admitted to the Chiba University Hospital between 1984 and 1998 and 100 persons with normal liver function tests were tested for the presence of TTV in their sera. Serum samples were tested for TTV DNA and genotype by polymerase chain reaction (PCR). TTV DNA was detected in 15 of 35 patients (43%) with non-A-E hepatitis, 14 of 33 patients (42%) with hepatitis C, 8 of 28 patients (29%) with hepatitis A, 7 of 29 patients (24%) with hepatitis B, and 37 of 100 subjects with normal liver function tests (37%). The detection rate did not differ statistically between non-A-E hepatitis and hepatitis A, B, C, or controls. The distribution of TTV genotypes was similar in non-A-E, A, B, C types, and controls. The clinical characteristics of the acute illnesses were similar for patients with or without TTV in hepatitis non-A-E, A, B, or C. Although TTV was detected frequently in non-A-E acute hepatitis, no etiologic role for TTV could be established.

Adult↗