Biomedical subjects

N Kinukawa

Publications and source records attributed to N Kinukawa.

At least 55 records · Page 3Linked to original sources

PubMed2000

The impact of covariate imbalance on the size of the logrank test in randomized clinical trials.

This paper examines the baseline imbalance incidental to stratified random sampling in clinical trials. We assume that patients are randomly sampled from a stratum-specific population and assigned to either treatment or control groups. Prognostic factors not used for the stratification cause within-stratum patient heterogeneity. The patient heterogeneity is investigated with an analysis of the prognostic index, or the log-relative-hazard. An index V, used to measure the degree of baseline imbalance between the groups, is defined using the prognostic index. The degree of baseline imbalance resulting from the stratified random sampling of a population of heterogeneous patients is examined. A method to estimate the exact size of the stratified logrank test is developed and applied to data obtained from a cancer clinical trial.

Adult↗

PubMed2000

Morphometric analysis of regional lymph nodes with and without metastasis from early gastric carcinoma.

BACKGROUND: To the authors' knowledge detailed morphometric changes in lymph nodes with and without metastasis in patients with early gastric carcinoma remain undocumented. METHODS: Histologic slides of 1847 lymph nodes dissected from 115 consecutive patients who underwent gastrectomy for early gastric carcinoma were examined histologically and measured using computer morphometry with the public domain National Institutes of Health Image program. Quantitative data were analyzed in relation to preoperative and intraoperative clinical assessments and postoperative pathologic diagnosis. RESULTS: Metastasis was found in 11 lymph nodes (0.6%) from 8 patients (7.0%). Metastatic lymph nodes showed a mean maximum dimension of 4.8 mm, a mean area of 14.4 mm(2), and a mean ratio of maximum/minimum dimension of 1.36; the corresponding values for nonmetastatic lymph nodes were 4.7 mm (P = 0.45), 13.2 mm(2) (P = 0. 13), and 1.66 (P = 0.10), respectively. The lymph node with a metastasis was not necessarily the largest of the dissected lymph nodes from each patient, and histologically each lymph node with a metastasis showed pericancerous fibrosis in > 10% of its area. The sensitivities of preoperative computed tomography, abdominal ultrasonography (US), endoscopic US, and intraoperative assessments to diagnose metastasis were 0%, 13%, 0%, and 13%, respectively, and the sensitivities of these modalities to detect lymph nodes > 10 mm in dimension were 18%, 10%, 3%, and 10%, respectively. CONCLUSIONS: Digital quantitative analysis is useful and widely applicable to clinicopathologic evaluation. The diagnostic sensitivity of lymph node metastasis in patients with early gastric carcinoma in the current study was very low with preoperative and intraoperative assessments because lymph node metastases were small and showed subtle histologic changes of pericancerous fibrosis.

Adult↗

PubMed2000

Prognostic value of the preserved expression of the E-cadherin and catenin families of adhesion molecules and of beta-catenin mutations in synovial sarcoma.

This study addresses the immunohistochemical expression of the E-cadherin and catenin families and mutations of the beta-catenin gene detected by PCR-SSCP in synovial sarcoma. Immunohistochemical analysis was performed for 72 cases, with follow-up data available on 62. The prognostic value of the expression of these proteins was evaluated. Reduced immunoreactivity for E-cadherin and alpha-catenin was significantly correlated with a poor survival rate (p=0.0040 and 0.0053, respectively). According to multivariate analysis, low AJC stage (stages I and II: p<0.0001), the preservation of alpha-catenin expression (p=0.0001), and a low necrotic rate (<50%: p=0.0139) were independent favourable prognostic factors. Widespread aberrant staining of beta-catenin protein within cytoplasm and/or nuclei was observed in 28 cases (38.9%) and was significantly correlated with poor survival (p=0.0122). In addition, there was a trend towards a correlation between widespread aberrant staining of beta-catenin and the MIB-1 labelling index (p=0.0535). Mutational analysis of exon 3 of the beta-catenin gene was performed for 49 cases. Nucleotide sequencing analysis revealed that four (8.2%) contained point mutations (three in codon 32, GAC to TAC; one in codon 37, TCT to TTT). Survival data were available for three out of four cases with beta-catenin mutations; two of these patients died within 1 year (died of disease at 6 and 11 months, respectively). These results suggest that E-cadherin and alpha-catenin undertake important roles as intercellular adhesion molecules; their preserved expression is associated with a better overall survival rate in synovial sarcoma and may have prognostic value. Abnormal levels of beta-catenin, with or without mutation, could contribute to the development and progression of synovial sarcoma, through increasing the proliferative activity of the tumour cells.

Cadherins↗

PubMed2000

Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma.

The hepatocyte growth factor (HGF)/c-MET signaling system plays an important role in the carcinogenesis of various organs. We investigated the expression of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic parameters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and SYT-SSX fusion gene was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 concordant frozen materials. Twenty-one of 69 (30.4%) tumors showed positive reaction for c-MET, whereas 22 tumors (31.9%) were positive for HGF. In 10 cases, co-expression of HGF and c-MET was observed; however, there was no significant correlation between HGF and c-MET expression. HGF expression was correlated with female patients, large tumors (more than 5 cm), the presence of rhabdoid cells, low frequency of mast cells (<20/10 HPF), high nuclear grade (grade III), and high American Joint Committee (AJC) stage (III and IV). Conversely, c-MET expression was only correlated with large tumors. However, the coexpression of HGF and c-MET was significantly correlated with large tumor size, the existence of rhabdoid cells, and high AJC stage. Both the expression of HGF and the co-expression of HGF and c-MET showed a significantly high MIB-1 LI and were correlated with poor prognosis according to univariate analysis. Multivariate Cox analysis showed that high AJC stage, the expression of HGF, and a high MIB-1 LI (12.0>) independently had a negative impact on overall survival. In 22 frozen material cases evaluated by both IHC and RT-PCR, a statistically significant correlation was found between the 2 techniques. SYT-SSX fusion transcripts were detected in all 22 cases. Three tumors had SYT-SSX2 fusion transcripts, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET paracrine signaling may contribute to tumorigenesis and progression in synovial sarcoma.

Adult↗

PubMed2000

An easily customized, random allocation system using the minimization method for multi-institutional clinical trials.

In a randomized clinical trial, random allocation of patients to treatment groups should be done to balance in the distribution of prognostic factors. Random allocation in a multi-institutional randomized clinical trial is conducted by a coordinating center, independent of the medical institution the attending doctor uses for his/her practice. This study provides a sophisticated system for doing an exact random allocation of patients to treatment groups. The minimization method proposed by Pocock was applied to this system to balance the distribution of prognostic factors between two treatment groups, even when the number of registered patients is relatively small (S.J. Pocock, Allocation of patients to treatment in clinical trial, Biometrics 35 (1979) 183-197). Furthermore, Zelen's method is used to balance the number of patients allocated to the two groups within each institution (M. Zelen, The randomization and stratification of patients to clinical trials, J. Chron. Dis. 27 (1974) 365-375.). This system was created by the 'PERL&RSQUO; language for writing common gateway interface (CGI) script, and can therefore, be easily extended to include data entry function by attending doctors as well as the random allocation function. This system is being used effectively in thirteen multi-institutional randomized clinical trials for stomach, colon-rectum and breast cancers in Japan.

Clinical Trials as Topic↗

PubMed2000

Hepatitis C virus infection in institutionalized psychiatric patients: possible role of transmission by razor sharing.

The objective of this study was to determine if HCV can be transmitted from patient to patient in psychiatric institutions and to determine possible routes of infection. We did a cross-sectional survey of 196 Japanese psychiatric patients tested for HCV and HBV markers and 400 age- and sex-matched controls. Anti-HCV was detected in 10.2% and antibody to hepatitis B core antigen was detected in 44.4% of the patients, a significantly higher prevalence than found among matched controls. A multiple regression logistic analysis was used to identify risk factors that could indicate the route of infection by HCV. Duration of hospitalization, age, razor sharing, and history of surgery proved to be statistically significant independent risk factors associated with positive anti-HCV results [odds ratio (OR), 4.00; 95% confidence interval (CI), CI, 1.74-9.19; OR, 2.19; 95% CI, 1.27-1.3.77; OR, 4.90; 95% CI, 1.29-18.86; OR, 3.35; 95% CI, 0.997-11.3, respectively]. These observations suggest that razor sharing played an important role in the spread of the HCV infection in the institutionalized psychiatric patients we studied.

Adult↗

PubMed2000

Effectiveness of interferon treatment for patients with chronic hepatitis C virus infection and normal aminotransferase levels.

To determine the effects of interferon treatment, we studied 77 Japanese patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase (ALT). Of 77 patients, 37 were given natural interferon-alpha for 24 weeks, and 40 not given interferon acted as controls. Serum samples were tested for HCV RNA and genotypes by polymerase chain reaction (PCR). HCV RNA levels were measured by competitive PCR. Of 37 treated patients, 11 (29.7%) had sustained elimination throughout a six-month follow-up, while HCV RNA was not eliminated in any untreated patients. At 24 months, the number of patients with elevated ALT was not significantly different between treated (13.5%) and untreated patients (15%). Interferon eliminates HCV RNA in patients with normal ALT without severe side effects. The natural history of HCV infection should be clarified so that the interferon treatment regimen can be tailored to the needs of each patient.

Adult↗

PubMed2000

Association between basal serum and leptin levels and changes in abdominal fat distribution during weight loss.

The aim of this study was to evaluate the relationship between changes in abdominal fat areas and the baseline serum leptin levels of Japanese obese women during weight reduction. The study was performed on 100 obese female Japanese volunteers. We measured the BMI and abdominal fat areas (visceral, subcutaneous and total) by magnetic resonance imaging and determined the fasting serum leptin levels before and after a 3 month weight reduction program. We examined whether or not a relationship exists between the baseline leptin levels and the subsequent changes in the abdominal fat areas after a weight reduction program. Multiple linear regression analysis was performed to examine the relationship between the baseline leptin levels and changes in abdominal visceral, subcutaneous, and total fat areas, and demonstrated that the baseline leptin level was a significant predictive factor for changes in the abdominal visceral fat area in both pre and postmenopausal Japanese obese women. We thus concluded the relatively higher baseline leptin levels in Japanese obese women to be associated with a relatively smaller reduction in the amount of abdominal visceral fat after undergoing a weight reduction program.

Abdomen↗

PubMed2000

[A case of proliferative sarcoid retinopathy with sarcoid nodules in tissue obtained during vitrectomy].

BACKGROUND: In previous studies, intraocular proliferative tissues obtained from proliferative sarcoid retinopathy cases during vitrectomy have been examined histopathologically. However, there is no report of identification of sarcoid nodules in examined tissues. We performed vitrectomy for a case of proliferative sarcoid retinopathy with extensive proliferative changes. Histopathologically, sarcoid nodules were identified in the fibrovascular membranes. CASE: A 25-year-old man was treated for sarcoid uveitis in the right eye by his local ophthalmologist. Lens aspiration was performed for complicated cataract. He was referred to our hospital with vitreous opacity and traction retinal detachment which occurred after the surgery. FINDINGS: The vitreous opacity was so severe that details of the fundus were not visible. Traction retinal detachment was suspected from findings of B-mode echography. Vitrectomy was performed, and total retinal detachment due to contraction of the fibrovascular membrane around the optic disc and posterior pole was observed. Sarcoid nodules were identified histopathologically in fibrovascular membranes obtained during vitrectomy. CONCLUSION: In proliferative sarcoid retinopathy cases, sarcoid lesions may be one of the causes of fibrovascular membrane formation.

Adult↗

PubMed2000

Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas.

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often up-regulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-6 mRNA levels and drug resistance are not well understood. Data on 45 patients with colorectal cancer were analyzed. Of the ATP-binding cassette superfamily genes, we asked whether mRNA levels of MDR1, MRP1, MRP2, and MRP3 correlated with drug resistance to anticancer agents. For this analysis, we used quantitative reverse transcription-PCR, and the sensitivity to anticancer agents in surgically resected colon carcinomas was determined using the in vitro succinate dehydrogenase inhibition test. MDR1, MRP1, and MRP3 were highly expressed in normal colorectal mucosa, and the relative mRNA levels of MDR1, MRP1, and MRP3 in cancerous tissues compared with noncancerous tissues were decreased or unchanged. By contrast, MRP2 mRNA expression was low in normal colorectal mucosa and specifically increased in cancer regions compared with noncancerous regions. Of the anticancer agents prescribed for patients with colorectal cancers, including doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, etoposide, and a camptothecin derivative, mRNA expression of MRP2 was significantly associated with resistance to cisplatin. MRP2 may be important for resistance to cisplatin treatment in colorectal cancer.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2000

Neuron-specific enolase in hemophagocytic lymphohistiocytosis: a potential indicator for macrophage activation?

To determine the pathogenesis of hemophagocytic lymphohistiocytosis (HLH), serum levels of neuron-specific enolase (NSE) and cytokine profiles were investigated. Serum concentrations of NSE and several cytokines were measured by immunoassays, and the association was evaluated in 18 HLH patients. Serum NSE levels increased (> 10 ng/mL) in 27/29 samples (93%) during the active febrile phase, the mean level of which (35.9 ng/mL) was much higher than that during the remission phase (11.2 ng/mL) (P = .001). The peak levels of NSE in 11 patients who required cytotoxic agents were higher than those in 7 patients without chemotherapy, 64.6 +/- 49.4 and 17.9 +/- 12.9, respectively (P = .265). The NSE levels correlated positively with the levels of interferon (IFN)-gamma (Pearson's correlation coefficient [r] = 0.408, P = .044), soluble interleukin-2 receptor (sIL-2R) (r = 0.464, P = .048), lactate dehydrogenase (r = 0.830, P < .00001), aspartate aminotransferase (r = 0.531, P = .003), and ferritin (r = 0.715, P < .00001), and correlated negatively with platelet count (r = -0.422, P = .021), but not with other parameters, including tumor necrosis factor-alpha, IL-1 beta, IL-18, soluble Fas ligand and C-reactive protein. Multiple regression analysis indicated that the correlation of NSE with platelet count was independent of other correlations. Sequential NSE changes well reflected the clinical course of patients. Immunohistochemical staining revealed an appreciable number of NSE-positive histiocytes in bone marrow specimens with florid hemophagocytosis. These results suggest that the circulating NSE originated from macrophages stimulated with IFN-gamma/sIL-2R, and partly from the destruction of platelets. Serum NSE level may be a useful marker for predicting the disease progression of HLH.

Adolescent↗

PubMed1999

An early gastric carcinoma treatment strategy based on analysis of lymph node metastasis.

BACKGROUND: Newly developed therapies for early gastric carcinoma attempt to consider patients' quality of life, but the applicability and effectiveness of these treatments remain undetermined. METHODS: Clinicopathologic data of 612 consecutive patients with early gastric carcinoma, all of whom were treated by D1 and D2 gastrectomy, were analyzed. Patients with and without lymph node metastases were compared in relation to age and gender distributions, surgical procedures, histopathology of the tumors, 5-year prognosis, and in reference to the preoperative and intraoperative assessments. RESULTS: The overall incidence of lymph node metastases was 5.7%. Tumor depth and size were related to lymph node metastases judged by univariate and multivariate analyses. Patients with mucosal tumors showed no relation between metastatic rate and tumor size, whereas those with submucosal tumors showed an increasing metastatic rate with tumor size. In all cases but one, lymph node metastases were confined to lymph node stations defined as Group 1 locations. Preoperative endoscopic ultrasonography showed a 55% diagnostic accuracy in determining tumor depth and a 15% sensitivity in diagnosing lymph node metastases. CONCLUSIONS: Patients with early gastric carcinoma may be candidates for endoscopic mucosal resection if their tumor is confined to the mucosa and measures < 1 cm in greatest dimension. Other limited resections including D1 gastrectomy or standard D2 gastrectomy based on tumor depth and size are appropriate. Based on the current study findings, the authors propose a useful algorithm for managing such patients.

Age Factors↗

PubMed1999

Comparison of p53, Ki-67, and CD44v6 expression between primary and matched metastatic lesions in ovarian cancer.

OBJECTIVE: Many studies have demonstrated that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration causes tumor progression which plays a role in metastasis. Therefore, it could be expected that malignant potential in the metastatic site is more aggressive than that in the primary site. Using several immunohistochemical markers (p53, Ki-67, and CD44v6), we investigated an alteration of malignant potential. METHODS: We immunohistochemically examined expression of p53, Ki-67, and CD44 in primary and metastatic lesions of ovarian cancer. Fifty-six samples of primary lesions and matched metastatic sites from 56 patients with primary epithelial ovarian cancers were included in this study. RESULTS: In 16 cases (28%), the histological grade of the metastatic lesion increased. This difference was statistically significant (P = 0.0232). In 16 cases (28%), the expression of p53 increased in the metastatic lesions, in 5 pairs from negative to positive, whereas the case decrease in the metastatic lesions was only 1. This difference was statistically significant (P = 0.0046). There was no significant difference in Ki-67 labeling indices and expression of CD44v6 between the primary and matched metastatic lesions. The degree of p53 expression in the metastatic lesions significantly correlated with disease-free survival (P = 0.0482), whereas that in the primary lesions did not. Moreover, high p53 expression in the metastatic lesions significantly correlated with disease-free survival in multivariate analysis. CONCLUSIONS: The p53 expression in metastatic lesions may reflect an aggressive biologic behavior in ovarian cancer.

Adenocarcinoma↗

PubMed1999

Prognostic significance of epithelial-stromal vascular cuffing and microvessel density in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma. METHODS: One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses. RESULTS: The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P<0.011 and P<0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival. CONCLUSIONS: The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.

Adult↗

PubMed1999

Rapid somatic growth after birth in children with neuroblastoma: A survey of 1718 patients with childhood cancer in Kyushu-Okinawa district.

OBJECTIVE: To evaluate the association of somatic growth from birth through diagnosis with the development of childhood cancer. METHODS: The weights and heights of 1718 children with cancers were determined and converted into standard deviation (SD) scores, both at birth and at diagnosis, by using the means and SD values of the general population. RESULTS: Among patients with neuroblastoma and acute lymphoblastic leukemia, the percentages of children with body weight and height over mean + 2 SDs were significantly higher at diagnosis than the expected value in the general population. The percentage of children with neuroblastoma and body weight over mean + 2 SD increased significantly from birth through diagnosis (P =.04). Although the medians of weight SD scores decreased from birth through diagnosis in patients with representative cancers except for neuroblastoma, the value significantly increased in patients with neuroblastoma diagnosed before 1 year of age (P =.03), especially in those whose cancer was detected by mass screening at 6 months of age (P <.01). CONCLUSIONS: Rapid somatic growth from birth through diagnosis in patients with neuroblastoma diagnosed before 1 year of age suggests a possible involvement of certain growth factors in these patients.

Birth Weight↗

PubMed1999

Cerebrospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis.

OBJECTIVES: cerebrospinal fluid (CSF) levels of interleukin (IL)-1 beta and tumor necrosis factor (TNF) alpha were measured to assess the effect and application of dexamethasone (Dex) therapy for bacterial meningitis. METHODS: associations between clinical findings and CSF parameters were first investigated, and prognosis was compared between 25 patients with Dex and 12 without Dex therapy. RESULTS: patients with the presence of disturbed consciousness showed higher CSF levels of TNF alpha (mean: 3015 pg/ml) or protein (mean: 215 mg/dl) than those without it (both, P < 0.O5). Simultaneous increase of TNF alpha (> 1000 pg/ml) and protein (> 100 g/dl) was observed in 80%, of patients with profoundly disturbed consciousness. Patients with Dex therapy presented higher TNF alpha/protein levels at diagnosis than those without Dex therapy (P < 0.05). Despite worse conditions at diagnosis, only one of 14 Dex-treated patients whose initial CSF TNF alpha levels exceeded 1000 pg/ml developed deafness. On the other hand, two of four patients without Dex therapy who had the same TNF alpha level suffered from psychomotor retardation. The differences in the frequency of sequelae between those with and without Dex therapy were significant in patients showing high TNF alpha level (P < O.05), but not in those showing high CSF levels of IL-1 beta or protein. The logistic regression analysis indicated that high CSF protein level (P < O.0001), or no Dex therapy (P=0.0001) was the independent risk factor for sequelae. CONCLUSIONS: although the study number was small, our observations suggested that CSF TNF alpha/protein levels reflected the neurologic severity, and implied that early Dex therapy might be beneficial for patients with prominently high TNF alpha levels.

Adolescent↗

PubMed1999

Statistical study for sonographic differential diagnosis of tumorous lesions in the parotid gland.

OBJECTIVE: The purpose of this study was to clarify characteristic sonomorphologic features of parotid lesions statistically and to propose new criteria for the differential diagnosis. STUDY DESIGN: Eighty-six tumorous lesions were analyzed with regard to the following sonomorphologic features: boundary, shape, echo intensity level, distribution of internal echoes, and acoustic enhancement. Stepwise polychotomous logistic regression analysis was performed to assess characteristic sonographic features. As dependent variables, we used "pleomorphic adenoma," "Warthin tumor," "malignant tumors" and "other benign lesions"; as predictor variables, we used the aforementioned sonomorphologic features. Proportion of the occurrence of each dependent variable was calculated. RESULTS: Lobular shape and homogeneous internal echoes predicted pleomorphic adenoma. A lesion with multiple anechoic areas would be Warthin tumor with very high sensitivity. Malignant tumors showed either heterogeneous internal echoes without characteristic structures or polygonal shape. CONCLUSIONS: These sonomorphologic features should be observed to make more exact differential diagnoses for operation and therapy planning.

Acoustics↗

PubMed1999

Differences between interferon-alpha and -beta treatment for patients with chronic hepatitis C virus infection.

To compare virological, biochemical, and immune responses to human lymphoblastoid interferon (IFN-alpha) and human fibroblast interferon (IFN-beta) in patients with chronic hepatitis C virus (HCV) infection, 120 patients were randomly assigned to three groups (group A, 60 patients receiving IFN-alpha, 6 million units (MU) once a day, daily for one month and thrice weekly for five months; group B, 40 patients receiving 6 MU IFN-beta once a day daily for two months; and group C, 20 patients receiving 3 MU IFN-beta twice a day (6 MU/day) daily for two months). Serum soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Patients with sustained clearance of serum HCV RNA detected by polymerase chain reaction (PCR) at six months after IFN treatment were defined as having complete response to IFN treatment. A low level of HCV RNA (< or = 10(4) copies/50 microl, measured by competitive PCR) and HCV RNA of genotype 2a were favorable factors for a complete response to both IFNs. Complete response in group A treatment was strongly associated with early HCV RNA clearance, in contrast with group B. A significantly higher HCV RNA negativity at the second week from start of treatment was noted in group C (80.0%), compared with groups A (41.6%) and B (27.5%). sIL-2R levels rose in each group during IFN administration. In group C, alanine aminotransferase (ALT) and IL-6 levels were remarkably elevated. These findings indicate that timing of serum HCV RNA negativity in sustained response differs between IFN-alpha and IFN-beta administrations and that early HCV RNA clearance was induced by twice-a-day IFN-beta treatment.

Antiviral Agents↗