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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 109 records · Page 6Linked to original sources
PubMed2000

Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein.

BACKGROUND: Although the importance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the clinical treatment of hepatocellular carcinoma (HCC) has been studied extensively, the authors examined the clinical picture of HCC with regard to the state of these two tumor markers. METHODS: The authors categorized 237 HCC cases into 4 groups according to levels of AFP and DCP: high levels of AFP with low DCP levels, high DCP levels with low AFP levels, high levels of both tumor markers, and low levels of both tumor markers. Comparisons of survival rates were made among these groups using the Kaplan-Meier product limit method, and for other comparisons of clinical parameters the Fisher PSLD test was used. Prognostic significance was tested with the Cox proportional hazards model. RESULTS: The cutoff values were set at 100 ng/mL for AFP and 0.0625 AU/mL for DCP. Forty-eight patients (20.7%) had high levels of AFP and low levels of DCP, 22 (9.3%) had high DCP levels and low levels of AFP, 12 (4.6%) had high levels of both AFP and DCP, and 155 (65.4%) had low levels of both DCP and AFP. Patients with high levels of DCP but low levels of AFP were predominantly male and had large lesions but few nodules. Patients with high levels of both tumor markers had the most discouraging outcome observed in this study (death within 3 years). CONCLUSIONS: Patients with high levels of DCP and low levels of AFP exhibited the unique clinical characteristic of large HCC nodules that were few in number. In addition, it was observed that measurement of both AFP and DCP can predict the survival of patients.

Adult↗
PubMed2000

Assessment of gastric carcinoma risk associated with Helicobacter pylori may vary depending on the antigen used: CagA specific enzyme-linked immunoadsorbent assay (ELISA) versus commercially available H. pylori ELISAs.

BACKGROUND: Previous epidemiologic studies produced inconsistent results when examining the relation between Helicobacter pylori infection and the risk of gastric carcinoma by measuring various anti-H. pylori antibodies. This study investigated the increased risk of cancer by examining different antibodies, including the specific anti-CagA antibody and antibodies from two commercially available kits. METHODS: An ELISA for the detection of serum anti-CagA was established using a recombinant CagA protein that the authors previously reported. Serum anti-CagA titer was determined for 80 patients with gastric carcinoma and 80 gender- and age-matched controls. Two anti-H. pylori antibodies from the commercially available kits HEL-p (Amrad, Kew Vic, Australia) and HM-CAP (Enteric Product Inc., Westbury, NY) were also evaluated. RESULTS: Anti-CagA seropositivity differed significantly between gastric carcinoma patients and controls (92.5% vs. 55.0%; P = 0. 0001), showing an odds ratio of 10.4 (95% confidence interval [CI]: 4.23-29.74). The difference was less prominent for the seropositivity of HEL-p (77.5% vs. 58.8%; P = 0.0139; odds ratio: 2. 38; 95% CI: 1.20-4.82) and insignificant for that of HM-CAP (65.0% vs. 57.5%; P = 0.4325; odds ratio: 1.30; 95% CI: 0.68-2.49). CONCLUSIONS: The current study revealed that the antibody assay system used could be one important factor in the assessment of gastric carcinoma risk for patients with H. pylori.

Adult↗
PubMed2000

Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells.

Attachment of Helicobacter pylori to gastric epithelial cells induces various cellular responses, including the tyrosine phosphorylation of an unknown 145-kD protein and interleukin 8 production. Here we show that this 145-kD protein is the cagA product of H. pylori, an immunodominant, cytotoxin-associated antigen. Epithelial cells infected with various H. pylori clinical isolates resulted in generation of tyrosine-phosphorylated proteins ranging from 130 to 145 kD in size that were also induced in vitro by mixing host cell lysate with bacterial lysate. When epithelial cells were infected with [(35)S]methionine-labeled H. pylori, a radioactive 145-kD protein was detected in the immunoprecipitates with antiphosphotyrosine antibody or anti-CagA (cytotoxin-associated gene A) antibody. Consistently, the 145-kD protein recognized by the anti-CagA and antiphosphotyrosine antibodies was induced in epithelial cells after infection of wild-type H. pylori but not the cagA::Km mutant. Furthermore, the amino acid sequence of the phosphorylated 145-kD protein induced by H. pylori infection was identical to the H. pylori CagA sequence. These results reveal that the tyrosine-phosphorylated 145-kD protein is H. pylori CagA protein, which may be delivered from attached bacteria into the host cytoplasm. The identification of the tyrosine-phosphorylated protein will thus provide further insights into understanding the precise roles of CagA protein in H. pylori pathogenesis.

Amino Acid Sequence↗
PubMed2000

Reentry into the cell cycle of contact-inhibited vascular endothelial cells by a phosphatase inhibitor. Possible involvement of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.

Vascular endothelial cells are unique in that they exit from the cell cycle when they come into contact with each other. Although the phenomenon is called "contact inhibition," little is known about the cellular mechanisms involved. Here we show that the phosphatase inhibitor sodium orthovanadate (SOV) induced the reentry of contact-inhibited human umbilical vascular endothelial cells (HUVECs) into the cell cycle and that reentry was associated with activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-K)/Akt pathways. SOV stimulated [(3)H]thymidine uptake of contact-inhibited HUVECs in a time- and dose-dependent manner. SOV-induced increase in [(3)H]thymidine uptake was significantly inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 and by the PI 3-K inhibitor LY294002. SOV also stimulated the expression of cyclin D1, cyclin E, and cyclin A, and the activity of CDK2 kinase, whereas it decreased the expression of p27(kip1). In marked contrast, growth media alone did not induce these changes. Furthermore, these SOV-induced changes were abolished by pretreatment with PD98059 and LY294002. SOV stimulated phosphorylation of ERK and Akt in contact-inhibited HUVECs, while growth media alone did not. This phosphorylation was associated with inhibition of phosphatase activity in the cells. Finally, overexpression of high cell density-enhanced protein tyrosine phosphatase 1 inhibited c-fos and cyclin A promoter activity. Taken together, our results suggest that in contact-inhibited HUVECs, increased phosphatase activity suppressed the ERK and PI 3-K/Akt pathways, resulting in exit from the cell cycle by down-regulation of cyclin D1, cyclin E, and cyclin A and by up-regulation of p27(kip1).

Animals↗
PubMed2000

Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination.

We found previously that overexpression of an F-box protein betaTrCP1 and the structurally related betaTrCP2 augments ubiquitination of phosphorylated IkappaBalpha (pIkappaBalpha) induced by tumor necrosis factor-alpha (TNF-alpha), but the relationship of the two homologous betaTrCP proteins remains unknown. Herein we reveal that deletion mutants of betaTrCP1 and betaTrCP2 lacking the F-box domain suppressed ubiquitination and destruction of pIkappaBalpha as well as transcriptional activation of NF-kappaB. The ectopically expressed betaTrCP1 and betaTrCP2 formed both homodimer and heterodimer complexes without displaying the trimer complex. Dimerization of betaTrCP1 and/or betaTrCP2 takes place at their conserved NH(2)-terminal regions, termed a "D-domain" (for dimerization domain), located upstream of the F-box domain. The D-domain was necessary and sufficient for the dimer formation. Intriguingly, the betaTrCP homodimer, but not the heterodimer, was selectively recruited to pIkappaBalpha induced by TNF-alpha. These results indicate that not only betaTrCP1 but also betaTrCP2 participates in the ubiquitination-dependent destruction of IkappaBalpha by forming SCF(betaTrCP1-betaTrCP1) and SCF(betaTrCP2-betaTrCP2) ubiquitin-ligase complexes.

Base Sequence↗
PubMed2000

Molecular cloning of neonate/infant-specific pepsinogens from rat stomach mucosa and their expressional change during development.

To clarify the nature of rat neonate/infant-specific pepsinogens, we carried out their purification and molecular cloning. Prochymosin was found to be the major neonatal pepsinogen. The general proteolytic activity of its active form, chymosin, was, however, lower than those of pepsins A and C which are predominant in adult animals. Molecular cloning of rat prochymosin cDNA was achieved along with cDNA for another neonate-specific pepsinogen, pepsinogen F, although determination of pepsinogen F in neonatal gastric mucosa was unsuccessful, presumably due to its lack of proteolytic activity or different proteolytic specificity. Northern blot analysis confirmed that genes for prochymosin and pepsinogen F are expressed only at neonatal/infant stages and the switching of gene expression to that of pepsinogen C occurred at late infant stages. A phylogenetic tree based on nucleotide sequences showed clearly that pepsinogens fall into four major groups, namely prochymosin and pepsinogen F of the neonate/infant and pepsinogens A and C of adult animals. Although, to date, prochymosin and pepsinogen F were believed to be expressed in only a limited number of mammals, the present results suggest that they might be expressed at the neonatal/infant stage in a variety of mammals.

Aging↗
PubMed2000

A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.

Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vascular remodeling. Several models of arterial injury have been proposed to analyze transgenic/knock-out mice, but many questions have been raised about their reproducibility and physiological significance. Here, we report a new mouse model of vascular injury that resembles balloon-angioplasty. A straight spring wire was inserted into the femoral artery via arterioctomy in a small muscular branch. The wire was left in place for one minute to denude and dilate the artery. After the wire was removed, the muscular branch was tied off and the blood flow of the femoral artery was restored. The lumen was enlarged with rapid onset of medial cell apoptosis. While the circumference of the external elastic lamina remained enlarged, the lumen was gradually narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reproducibly in the region where the wire had been inserted. Similar exuberant hyperplasia could be induced in all strains examined (C57BL/6J, C3H/HeJ, BALB/c, and 129/SVj). This model may be widely used to study the molecular mechanism of post-angioplasty restenosis at the genetic level.

Angioplasty, Balloon↗
PubMed2000

Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction.

It was previously reported that inhibition of carnitine synthesis by 3-(2,2,2-trimethyl-hydrazinium) propionate (MET-88) restores left ventricular (LV) systolic and diastolic function in rats with myocardial infarction (MI). Preservation of the calcium uptake function of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) is one of the possible mechanisms by which MET-88 alleviates hemodynamic dysfunction. To test this hypothesis, the effects of MET-88 on protein content of SERCA2 were evaluated using the same rat model of heart failure. Myocardial protein content of hexokinase, which is one of the key enzymes of glucose utilization, was also measured. Either MET-88 (MET-88 group) or a placebo (MI group) was administered for 20 days to rats with MI induced by coronary artery ligation. The control group underwent sham surgery (no ligation) and received placebo. In LV myocardial homogenates, the myocardial SERCA2 protein content was 32% lower (p<0.05) in the MI group than in the control group. However, in the MET-88 group myocardial SERCA2 content was the same as in the control group. Hexokinase I protein content was 29 % lower (p<0.05) in the MI group compared with the control. In contrast, hexokinase II protein content did not differ significantly among the three groups. Consequently, inhibition of carnitine synthesis ameliorates depression of SERCA2 and hexokinase I protein content which may reduce tissue damage caused by MI.

Animals↗
PubMed2000

Tacrolimus in corticosteroid-resistant ulcerative colitis.

We report a case of refractory ulcerative colitis treated with tacrolimus. The patient was a 73-year-old woman with a 45-year history of ulcerative colitis. An attack unresponsive to intravenous corticosteroid therapy occurred when she was age 73. Leukocytapheresis therapy was attempted, but was discontinued because of the patient's poor general condition. Cyclosporine A therapy brought about fair control of the disease. A liver injury that was suspected to be associated with this agent, however, occurred within 5 weeks of its initiation. At that time, the cyclosporine A was discontinued and azathioprine treatment was started. Within 6 weeks, signs of exacerbation of the ulcerative colitis became apparent. Tacrolimus administered at that time brought about remission of the disease, and the corticosteroid dose was then reduced. Tacrolimus, like cyclosporine A, appears to be effective for the treatment of attacks of ulcerative colitis.

Aged↗
PubMed2000

A possible novel src-related tyrosine kinase in cancer cells of LEC rats that develop hepatocellular carcinoma.

BACKGROUNDS/AIMS: Src-related protein tyrosine kinase is known to be related to cell transformation. In this study, we report a possible novel src-related tyrosine kinase of 100 kDa specifically expressed in the nuclei of hepatocytes and/or cancer cells in Long-Evans Cinnamon rats, one of the experimental models of hepatocellular carcinoma. METHODS: Src-related protein tyrosine kinase in hepatocytes of Long-Evans Cinnamon rats was analyzed by using immunohistochemistry and Western blot and in vitro tyrosine kinase assay using a specific antibody (src antibody) against a synthetic peptide corresponding to the conserved autophosphorylation site of src family tyrosine kinases. RESULTS: Src-related protein was found to be expressed in the nuclei of hepatocytes and/or cancer cells in Long-Evans Cinnamon rat liver, exhibiting tyrosine kinase activity, and migrated to the position of 100 kDa. The protein quantity and activity of this 100-kDa src-related protein tyrosine kinase significantly increased with the progress of chronic hepatitis to hepatocellular carcinoma, especially in the tumorous portion of the liver. On the other hand, the 100-kDa src-protein tyrosine kinase was not observed in the nuclei of hepatocytes and/or cancer cells in normal age-matched control Wistar rats. CONCLUSIONS: Since the src-family tyrosine kinases have been observed at a molecular weight of 55 to 62 kDa and located in the hepatocellular membrane and/or cytoplasm, the 100-kDa src-related protein tyrosine kinase observed in the present study may be novel, and closely related to the pre-cancerous and cancerous process in Long-Evans Cinnamon rat liver.

Animals↗
PubMed2000

Decrease of wild-type and precore mutant duck hepatitis B virus replication during lamivudine treatment in white Pekin ducks infected with the viruses.

BACKGROUND/AIMS: Lamivudine, an antiviral agent, has been used in the treatment of chronic hepatitis B, but little is known about its effect on intrahepatic replication of hepatitis B virus. We investigated the effect of lamivudine on the replication of wild-type and precore mutant duck hepatitis B virus (DHBV) in the liver and serum of DHBV carrier ducks. METHODS: Chronic carrier ducks with either wild-type or precore mutant DHBV were treated for 2 weeks with either low-dose (20 mg/kg, p.o., b.i.d.) or high-dose lamivudine (100 mg/kg, p.o., b.i.d.) or were untreated. Serum levels of DHBV DNA were examined serially by slot-blot hybridization. A second group of chronic carrier ducks was treated for 12 weeks with lamivudine (100 mg/kg, p.o., b.i.d.) or was untreated. The amount of DHBV DNA in serum and its various replicative intermediates in the liver were serially examined by slot-, Southern, and Northern blot methods. RESULTS: In the 2-week treatment study, concentration of DHBV DNA in serum treated with low- and high-dose lamivudine was reduced to 10.8% and 1.1% of the control level in wild-type DHBV carriers, and to 2.3% and 0.48% in precore mutant DHBV carriers, respectively. In the 12-week treatment study, concentration of DHBV DNA in serum at the end of treatment was reduced to <0.65% and <5.36% in wild-type and precore mutant DHBV carriers, respectively. Southern and Northern blot analyses revealed that the various replicative forms of DHBV DNA in the liver were decreased in all treated ducks, but, covalently closed circular DNA and RNA intermediates tended to remain unchanged. CONCLUSIONS: Our results showed that lamivudine could reduce both wild-type and precore mutant DHBV levels in the liver through inhibition of the reverse transcription step, but complete elimination of the viruses from liver is difficult even by relatively long-term lamivudine monotherapy, suggesting a need for some additional therapy to obtain complete clearance.

Animals↗
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

End-tidal CO2 pressure decreases during exercise in cardiac patients: association with severity of heart failure and cardiac output reserve.

OBJECTIVES: We measured end-tidal CO2 pressure (PETCO2) during exercise and investigated the relationship between PETCO2 and exercise capacity, ventilatory parameters and cardiac output to determine the mechanism(s) of changes in this parameter. BACKGROUND: It is unclear whether PETCO2 is abnormal at rest and during exercise in cardiac patients. METHODS: Cardiac patients (n = 112) and normal individuals (n = 29) performed exercise tests with breath-by-breath gas analysis, and measurement of cardiac output and arterial blood gases. RESULTS: PETCO2 was lower in patients than in normal subjects at rest and decreased as the New York Heart Association class increased, whereas the partial pressure of arterial CO2 did not differ among groups. Although PETCO2 increased during exercise in patients, it remained lower than in normal subjects. PETCO2 in relation to cardiac output was similar in patients and normal subjects. PETCO2 at the respiratory compensation point was positively correlated with the O2 uptake (r = 0.583, p < 0.0001) and the cardiac index at peak exercise (r = 0.582, p < 0.0001), and was negatively correlated with the ratio of physiological dead space to the tidal volume. The sensitivity and specificity of PETCO2 to predict an inadequate cardiac output were 76.6% and 75%, respectively, when PETCO2 at respiratory compensation point and a cardiac index at peak exercise that were less than the respective control mean-2 SD values were considered to be abnormal. CONCLUSIONS: PETCO2 was below normal in cardiac patients at rest and during exercise. PETCO2 was correlated with exercise capacity and cardiac output during exercise, and the sensitivity and specificity of PETCO2 regarding decreased cardiac output were good. PETCO2 may be a new ventilatory abnormality marker that reflects impaired cardiac output response to exercise in cardiac patients diagnosed with heart failure.

Anaerobic Threshold↗
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

High viral eradication with a daily 12-week natural interferon-beta treatment regimen in chronic hepatitis C patients with low viral load. IFN-beta Research Group.

Virological sustained response (SR) is achieved in 31-49% of patients with chronic hepatitis C with combination therapy using interferon (IFN)-alpha and ribavirin for 24-48 weeks. However, as a period of 24-48 weeks is a burden for patients, we investigated the effect of daily intravenous administration of natural IFN-beta for 12 weeks in this study. In all, 112 patients were enrolled and received a daily administration of 6 MU of natural IFN-beta intravenously for 12 weeks. Serum HCV-RNA before treatment was assessed by the competitive reverse-transcription polymerase chain reaction assay. The patients were divided into two groups according to pretreatment viral load: the low viral load group (N = 25, <6.3 x 10(5) copies/ml), and the high viral load group (N = 87, > or =6.3 x 10(5) copies/ml) who were additionally administered IFN-beta thrice weekly for subsequent 14 weeks at the patients' request. Virological SR was obtained in 37% (41/112) of all the patients; 88% of those with a low viral load, and 22% of patients with a high viral load. Virological SR was attained in 21% of patients with HCV subtype 1, and in 67% of those with subtype 2a. In patients with HCV subtype 1b, virological SR was obtained in patients with the mutant-type (> or =4 amino acid mutations in the NSSA2209-48) having a low viral load (4/4), but not in those having a high viral load (0/3). The results suggest that a daily intravenous administration of natural IFN-beta for 12 weeks showed high therapeutic efficacy in patients with a low viral load despite the shorter treatment period and that the therapeutic efficacy depends on viral load rather than on the number of NS5A2209-48 amino acid mutations.

Adolescent↗
PubMed2000

Poor association of TT virus viremia with hepatocellular carcinoma.

AIM: The aim of this study was to clarify the relationship between TT virus (TTV) infection and the development of hepatocellular carcinoma. METHODS: TTV from serum was examined in 224 patients with hepatocellular carcinoma (HCC) and 106 patients with chronic liver disease (CLD) but without HCC who were admitted to our hospital between 1995-1997. As controls, 48 patients without liver disease were also examined. TTV DNA was detected using nested PCR method after extraction of DNA from serum. RESULTS: TTV DNA was detected in 29/224 (13%) of patients with HCC; in 14% (4/28) of HCC patients negative for both hepatitis B virus surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV), in 9% (2/22) of HCC patients positive for HBsAg, and in 12% (21/170) of HCC patients positive for anti-HCV. The prevalence of TTV DNA in HCC patients (13%) was not significantly higher than in CLD patients (22%). There were no significant differences in age, gender, liver function, tumor biology (size, TNM classification), other viral markers, or amount of alcohol intake between TTV-positive and -negative HCC patients. Only a history of blood transfusion was significantly more frequent in TTV-positive HCC patients than in TTV-negative cases (p= 0.02). Coinfection with TTV did not correlate with the severity of HCV-positive liver disease. There was no significant difference in prognosis between TTV-positive and -negative HCC patients. CONCLUSIONS: TTV does not seem to contribute to the development of HCC from chronic liver disease and is not correlated with severity of liver disease.

Aged↗
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↗