Biomedical subjects

Kenji Ikeda

Publications and source records attributed to Kenji Ikeda.

At least 37 records · Page 2Linked to original sources

PubMed2006

Anticarcinogenic impact of interferon on patients with chronic hepatitis C: a large-scale long-term study in a single center.

BACKGROUND: The anticarcinogenic capacity of interferon (IFN) was assessed in a cohort of Japanese patients with chronic hepatitis C en masse. PATIENTS AND METHODS: The rate of hepatocarcinogenesis was analyzed in 2,166 patients with chronic hepatitis C, of whom 1,654 had received IFN therapy while 512 had not. RESULTS: Crude rates of hepatocarcinogenesis in treated and untreated patients were 2.6 and 4.6% at the end of the 5th year, 5.8 and 12.7% at the 10th year and 13.9 and 23.9% at the 15th year (after completion of IFN therapy for those treated) (p < 0.001). IFN decreased the hazard ratio of carcinogenesis to 0.42 (p < 0.001) in multivariate analysis with adjustments for significant covariates including fibrotic stage, gamma-glutamyl transpeptidase level, gender, platelet count and age. Among the 1,654 patients treated with IFN, 606 (36.6%) achieved persistent loss of hepatitis C virus (HCV) RNA and an additional 266 (16.1%) gained normal levels of alanine aminotransferase without loss of HCV RNA for 6 months or longer after the completion of IFN therapy. Cumulative rates of hepatocarcinogenesis in sustained virological responders and biochemical responders were 1.4 and 2.0% at the end of the 5th year, 1.9 and 3.6% at the 10th year and 1.9 and 7.5% at the 15th year, respectively. The hazard ratio of sustained virological response was 0.10 (p < 0.001), and that of biochemical response was 0.12 (p < 0.001). Normalization of aminotransferase levels after IFN therapy without loss of serum HCV RNA decreased hepatocarcinogenesis. CONCLUSION: IFN significantly decreased the rate of hepatocarcinogenesis in patients with chronic hepatitis C as a whole in Japan, even in those who fail to clear HCV RNA from serum.

Adolescent↗

PubMed2006

Efficacy of interferon therapy in elderly patients with chronic hepatitis C.

OBJECTIVE: We assessed the efficacy and safety of interferon (IFN) monotherapy in 84 elderly patients aged > or =65 years with chronic hepatitis C in a retrospective cohort study. METHODS: Twenty-two of the 84 elderly patients were treated with IFN at a dose of 6 million units daily for 6-8 weeks, 18 patients were treated 2-3 times a week for 24 weeks and 44 patients were treated daily for 2-8 weeks and 2-3 times a week for 16-24 weeks. RESULTS: A sustained virological response (SVR) occurred in 35.7% (30/84) of the patients by intention-to-treat analysis. Multivariate analysis showed that patients achieved a significant SVR when: (1) serum HCV-RNA level before IFN therapy was <100 KIU/ml (p < 0.0001) and (2) staging of liver fibrosis was mild (p = 0.040). Eleven (13.1%) patients discontinued the IFN regimen due to adverse events. Regarding factors predicting discontinuation of IFN, univariate analysis showed that patients aged >70 years were prone to drop out of therapy due to adverse events in IFN therapy (p = 0.009). CONCLUSION: Our results suggest that IFN administration is suitable for 65- to 70-year-old patients with chronic hepatitis C without genotype 1b and high virus load.

Age Factors↗

PubMed2006

Correlation between plasma glucagon-like peptide 2 levels and proliferative makers in small intestinal injury in rats induced by methotrexate administration.

Glucagon-like peptide 2 (GLP-2) is a potent intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We examined whether a relationship exists between plasma level of GLP-2 and the degree of intestinal injury induced by chemotherapeutic agents in the rat. Methotrexate (MTX) was administrated orally for 6 consecutive days at doses of 1.25, 2.5, and 5.0 mg/kg body weight per day. Mucosal samples of rat duodenum, jejunum, and ileum were used for assessment of mucosal weight, DNA and protein content. Plasma GLP-2 levels were measured on day 8. MTX significantly reduced body weight. The values of all indices tended to decrease in all segments with increases in MTX dose. Plasma GLP-2 levels were significantly higher in the MTX 2.5 mg/kg/d group (p<0.05) and the MTX 5.0 mg/kg/d group (p<0.01) than in the control group. Correlations were found between plasma GLP-2 levels and mucosal weight, DNA and protein content. We concluded that plasma GLP-2 levels reflect the degree of intestinal injury following MTX administration in this preclinical model.

Administration, Oral↗

PubMed2005

Cost-effectiveness of radiofrequency ablation and surgical therapy for small hepatocellular carcinoma of 3cm or less in diameter.

BACKGROUND: Cost-effectiveness of radiofrequency ablation (RFA) was assessed in treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: During 5 years, 153 patients with HCC of 3cm or less received RFA, and 60 underwent surgery. Judgment after RFA therapy was classified into three grades: residual tumor (grade 1), necrotic area with a less safety margin of 5mm (grade 2), and necrosis with a safety margin of 5mm in all directions (grade 3). RESULTS: Local recurrence rates after RFA and surgery were 7.9% and 0% at the third year. The rates in patients with grades 2 and 3 after RFA were 18.7% and 1.2% at the third year, respectively (P=0.0005). Among 91 patients with grades 1 and 2 necrosis after initial therapy, 52 received additional ablation. Although local recurrence rate was 24.9% in 39 patients without additional therapy, the rates after therapy repetition were 10.9% in 21 patients with eventual grade 2 necrosis, and 0% in 31 patients with grade 3 (P=0.038). Median costs of single RFA, repeated RFA, and surgery were yen849,900, yen1,086,000, and yen1,745,100, respectively. Additional ablation reduced local recurrence by 20.7% at the cost of yen236,100. CONCLUSION: Cost-effectiveness of RFA in the treatment of small HCC was superior to that of surgery.

Journal Article↗

PubMed2005

Early viral kinetics and treatment outcome in combination of high-dose interferon induction vs. pegylated interferon plus ribavirin for naive patients infected with hepatitis C virus of genotype 1b and high viral load.

An investigation was carried out to determine whether early viral monitoring could predict efficiently the virological response to combination therapy of two different regimens in treatment-naive chronic hepatitis C patients infected with genotype 1b with high baseline viral load. Patients were randomly assigned to receive interferon (IFN) alpha-2b induction (6 MU daily for 2 weeks) followed by 6 MU thrice weekly for 46 weeks (IFN/R group; n = 20), or pegylated IFN alpha-2b (1.5 microg/kg) weekly for 48 weeks (PEG/R group; n = 28), in combination with ribavirin (600-1,000 mg daily). Serum HCV RNA was quantitated at 0, 6, 12, 24, and 48 hr post-dose, weekly during the first 4 weeks, and thereafter viral kinetics were assessed every 4 weeks. The sustained virological response rates in the IFN/R and PEG/R groups were 40% (8/20) and 43% (12/28), respectively. The non-virological response rates were 40% (8/20) and 39% (11/28), respectively. The cumulative virological response rates were similar in both groups. Multivariate analyses identified no independent baseline variables linked to sustained virological or non-virological response. Early log viral load changes from baseline in both groups were significantly greater at all time-points after 24 hr in virological response patients than in non-virological response patients (P < 0.001 for all). On the receiver operating characteristics curves for prediction of non-virological response, the area under the curves (0.951-1.000), sensitivity (90%-100%), and negative predictive value (96%- 100%) were similar at any time-points after 24 hr. For prediction of sustained virological response, sensitivity of 80% with 86% negative predictive value was observed for negative HCV RNA at week 12, with the highest area under the curves value of 0.919. The results suggest that early monitoring of viral kinetics is a useful measure to predict virological response, and might facilitate development of rational and effective therapeutic strategies.

Adult↗

PubMed2005

Clinical and virological characteristics of untreated patients with chronic hepatitis C who develop serum alanine aminotransferase flare-up.

Among patients with chronic hepatitis C virus (HCV) infection, serum alanine aminotransferase (ALT) rarely increases above 500 IU/L. We examined the clinical and virological features of untreated patients with serum ALT > or = 500 IU/L. One thousand seven hundred and sixty adult patients with chronic HCV infection were followed-up. Among these patients, 22 developed ALT flare-up (M:F=13:9, median age, 50.5 years). We evaluated liver function tests, genotype, and viral titer in these patients and 44 randomly selected age- and sex-matched control without ALT flare-up. In four patients with ALT flare-up, we examined changes in viral loads and sequential changes in amino acid sequences of the core region, hypervariable region 1 (HVR1), and interferon sensitivity determining region (ISDR) before and after ALT flare-up. Multivariate analysis identified genotype 2 as the only significant determinant of ALT flare-up. ALT flare-up occurred in three of four patients without increase in viral load. Several alterations in amino acids were noted in HVR1 before and within 6 months of ALT flare-up. One or two alterations in the core region and many alterations in HVR1 were noted after ALT flare-up in some patients. Genotype 2 is an important factor for ALT flare-up. However, we could not directly relate ALT flare-up to these alterations in amino acids of the core region, HVR1, and ISDR.

Adult↗

PubMed2005

Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN-resistant cases with hepatocyte steatosis.

The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear, especially in patients infected with hepatitis C virus (HCV) genotype 2a. The present study was conducted in 364 consecutive non-cirrhotic naive patients infected with genotype 2a, who were evaluated for the severity of steatosis and response to IFN monotherapy after a 24-week median duration of therapy. The patients were examined for factors associated with steatosis and treatment efficacy according to the grade of steatosis. Early viral kinetics was also evaluated in 64 patients for predictors of response to therapy. Nine IFN-resistant patients were assessed for the relationship between amino acid sequence of HCV core region/NS5A and severity of steatosis. Multivariate analysis identified two independent factors associated with steatosis; serum ferritin > or =200 microg/l and body mass index > or =25.0 kg/m(2). The sustained virological response rate in patients with high-grade steatosis was significantly lower than in the low-grade group. Study of early viral kinetics showed a significantly lower cumulative HCV-RNA negative rate for the high-grade than low-grade steatosis group. Sequence analysis of HCV core region/NS5A in IFN-resistant patients with or without steatosis failed to identify steatosis-specific amino acid substitutions associated with resistance. This study of HCV genotype 2a suggested that steatosis is associated with excess iron storage, and that it is an important predictor of efficacy of IFN monotherapy. Further large-scale studies are warranted to examine the role of amino acid substitutions on IFN resistance specific for steatosis.

Adolescent↗

PubMed2005

Favorable efficacy of long-term lamivudine therapy in patients with chronic hepatitis B: an 8-year follow-up study.

The long-term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7-8.7 years). The rates of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow-up. Our results suggest that long-term lamivudine therapy improves long-term prognosis, especially when additional treatment for breakthrough hepatitis is used.

Adult↗

PubMed2005

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan.

Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts. The baseline HBV DNA level was higher in the seven (23%) patients in whom infection with HBV genotype A persisted than the remaining 24 (77%) with spontaneous resolution (median: >8.7 vs. 6.0 log genome equivalents/ml, P = 0.004). Persistent infection was more frequent in patients with maximum alanine aminotransferase <500 IU/L than > or =500 IU/L (83% [5/6] vs. 4% [1/25], P = 0.0001). Of the six patients with persistent HBV genotype A infection who received interferon and/or lamivuidine for treatment of chronic active hepatitis, three (50%) responded with the loss of hepatitis B e antigen (HBeAg); hepatitis B surface antigen (HBsAg) was cleared from serum in one patient who received interferon and lamivudine in sequence. HBV genotype A persisted along with HBeAg in the remaining three patients given antiviral therapy as well as another who was not treated. In conclusion, infection with HBV genotype A prevails in patients with acute hepatitis B in Japan where genotypes B and C are common, is often contracted sexually (16/31 [52%]) and tends to persist (7/31 [23%]). Infection was cleared in only one of the six (17%) patients who received antiviral therapy.

Adult↗

PubMed2005

Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection.

BACKGROUND: Phlebotomy is performed to reduce excessive iron accumulation in hepatic tissue. We studied serum alanine aminotransferase (ALT) normalization rates and 50% reduction in initial serum ALT (ALT(50%) reduction rate) in patients with hepatitis C viral (HCV) infection and investigated the factors that influenced the response to phlebotomy therapy. METHODS: We evaluated 23 consecutive patients with HCV infection who underwent phlebotomy. Phlebotomy was performed a few times per week, then a few times per month, and 200-400 ml of blood was removed at each session, depending on the clinical response. During the course of therapy, hemoglobin (Hb), serum ALT, and ferritin levels were assessed monthly. RESULTS: In patients with Hb of less than 11 g/dl, the ALT(50%) reduction rate was 87.5%. In patients with a serum ferritin level of less than 10 g/dl the ALT(50%) reduction rate was 83.3%. In patients with Hb of less than 11 g/dl, the ALT normalization rate was 50%, and in those with a serum ferritin level of less than 10 g/dl, the ALT normalization rate was 41.7%. Multivariate analysis identified ALT less than 100 IU/l at the start of phlebotomy as an independent factor associated with ALT normalization. Of the 7 patients who showed no response to phlebotomy, 85.7% were obese (body mass index > or =25 kg/m(2)), and 40% showed more than 30% steatosis on liver histology. The cumulative ALT normalization rate in relation to the total volume of blood loss was 43.9% with a blood less or more than 3 l, and thus was optimal above 3 l. CONCLUSIONS: Although the sample number was relatively small, the results of our study suggest that phlebotomy is effective therapy for HCV patients who are nonobese, show little or no steatosis on liver histology, and have a baseline serum ALT level of less than 100 IU/l.

Adult↗

PubMed2005

Long-term follow-up of interferon monotherapy in 454 consecutive naive patients infected with hepatitis C virus: multi-course interferon therapy may reduce the risk of hepatocellular carcinoma and increase survival.

OBJECTIVE: The long-term effects of multi-course interferon (IFN) monotherapy in patients infected with hepatitis C virus (HCV) are still unclear. MATERIAL AND METHODS: To evaluate the effects of multi-course IFN on hepatocarcinogenesis and survival, a follow-up study was conducted comprising 454 consecutively recruited non-cirrhotic naive patients infected with HCV, who had received IFN monotherapy between 1987 and 1992. The median follow-up was 11.3 years. RESULTS: A sustained response (SR) after the first IFN was achieved by 152 patients (33.5%) (Group A). Of 302 patients (66.5%) with non-SR after the first IFN, 130 patients (28.6%) did not receive additional IFN (Group B), and the remaining 172 patients (37.9%) received multi-course IFN monotherapy (Group C). With regard to hepatocarcinogenesis and survival rates for liver-related deaths, Groups A and C both showed significantly better long-term clinical outcome than Group B (p < 0.001; log-rank test). Three independent factors were identified by multivariate analyses (fibrosis stage 3, Group B, and age > or = 50) for all patients and two factors (fibrosis stage 3 and age > or = 50) for Group C associated with hepatocarcinogenesis. With regard to hepatocarcinogenesis rates according to the mean alanine aminotransferase (ALAT) levels during the IFN-free period in Group C, significantly higher rates were noted in patients with ALAT levels above 1.5 x the upper normal limit (17.6%) than those below the limit (0%) (p < 0.05). CONCLUSIONS: Multi-course IFN monotherapy reduces the risk of hepatocarcinogenesis and increases survival, and low ALAT levels during the IFN-free period are associated with lower hepatocarcinogenesis rates in multi-course IFN.

Adolescent↗

PubMed2005

Tau-positive fine granules in the cerebral white matter: a novel finding among the tauopathies exclusive to parkinsonism-dementia complex of Guam.

We examined the autopsied brains of cases of 6 types of tauopathy: parkinsonism-dementia complex of Guam (PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick disease, Alzheimer disease (AD), and myotonic dystrophy together with Guamanian controls. Light microscopy sections of these brains were examined using anti-tau antibodies. Tau-positive fine granules (TFGs) were globe-shaped, and 3 to 6 mum in diameter, were observed predominantly in the frontal white matter in 30 of the 35 patients with PDC. However, no TFGs were found in association with PSP, myotonic dystrophy, Pick disease, AD, or CBD. Western blot analysis of frozen brain tissue taken from the PDC cases revealed that the frontal cortex was hyperphosphorylated and contained 6 tau isoforms (3R+4R tau). However, in the present study, it was revealed that the novel TFGs in the white matter of patients with PDC was composed of 4R tau. Western blot analysis of sarkosyl-insoluble tau from the white matter of the PDC cases showed 2 major bands of 60 and 64 kDa and one minor band of 67 kDa. After dephosphorylation, these bands resolved into one major band of 4-repeat (4R) tau isoform and 3 minor bands of 3-repeat (3R) and 4R tau isoforms. Moreover, the TFGs observed in cases in which the number of neurofibrillary tangles (NFTs) was higher than the threshold level were not correlated with the presence of cortical NFTs. In conclusion, these novel TFGs were found almost exclusively in PDC brains and could therefore be considered as a characteristic neuropathologic marker of this particular tauopathy. The TFGs were hyperphosphorylated tau-positive structures that may be formed by a different mechanism from that used to produce cortical NFTs.

Aged↗

PubMed2005

Significance of hepatitis B virus DNA clearance and early prediction of hepatocellular carcinogenesis in patients with cirrhosis undergoing interferon therapy: long-term follow up of a pilot study.

BACKGROUND AND AIM: Because the anti-carcinogenic effect and mechanism of interferon (IFN) in patients with hepatitis B virus (HBV)-related cirrhosis have not been elucidated, quantitative analysis of HBV-DNA concentration was carried out sequentially. METHOD: Of 60 consecutive patients with cirrhosis who began IFN therapy between 1986 and 1990, 57 patients were completely observed for the appearance of hepatocellular carcinoma (HCC). All patients underwent intermittent administration of IFN for a median period of 18 months. HBV-DNA was quantified using transcription mediated amplification and hybridization protection assay. A HBV-DNA count <3.7 log-genome equivalent (LGE)/mL (equivalent to 10(3.7) or 5000 copies/mL) was considered to be a negative value. RESULTS: Of 25 patients who had HBV-DNA loss after IFN therapy, nine lost HBV-DNA during the therapy and 16 lost HBV-DNA after cessation of the therapy. The other nine patients showed a transient loss of HBV-DNA, and the remaining 23 retained persistently positive HBV-DNA during and after therapy. Although HCC developed in two (8.0%) of the 25 patients with HBV-DNA loss, carcinogenesis was found in 11 (34.4%) of 32 patients without HBV-DNA loss (Fisher's exact test, P = 0.026). In the two exceptional patients, HCC was detected at 1.2 and 3.6 years after loss of HBV-DNA, respectively. When the HBV-DNA concentration decreased by 2 LGE/mL (decrease to 1/100) at 6 months after initiation of interferon, HBV-DNA became negative eventually in 15 (60.0%) of 25 patients. CONCLUSION: A significant decrease or loss of serum HBV-DNA prevents development of HCC, and sequential analysis of HBV-DNA could be very useful in both the prediction and the early detection of small HCC.

Adult↗

PubMed2005

Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B.

BACKGROUND: Severe acute exacerbations of chronic hepatitis B virus (HBV) infection can spontaneously occur and rapidly progress to fatal hepatic failure. The purpose of the present paper was to identify factors that could influence the rapid progression of liver disease to hepatic failure, and assess the effects of lamivudine on serious disease. METHODS: Twenty-five patients with spontaneous severe acute exacerbation (accompanied by jaundice and coagulopathy) were consecutively treated with lamivudine. Their clinical outcomes were compared with those of 25 lamivudine-untreated patients, as historical controls. RESULTS: Six lamivudine-treated patients (24%)and seven controls (28%) rapidly developed hepatic failure. Lamivudine monotherapy did not significantly prevent progression to hepatic failure. Multivariate analysis identified baseline serum bilirubin >/=6 mg/dL (odds ratio [OR]: 5.61; 95% confidence interval [CI]: 1.66-21.61; P = 0.018), pre-existing cirrhosis (OR: 4.52; 95%CI: 1.26-30.42; P = 0.034), and baseline prothrombin time <40% (OR: 3.75; 95%CI: 1.03-43.86; P = 0.045) as independent determinants of the event. Of the aforementioned patients with hepatic failure, three lamivudine-treated patients (50%) and two controls (29%) survived (P > 0.15). However, lamivudine induced a sustained normalization of liver function and inhibited the development of cirrhosis in survivors. CONCLUSIONS: Lamivudine monotherapy conferred no significant protection against rapid progression of the disease to hepatic failure, but it resulted in long-term benefits. Lamivudine combined with other drugs could be more beneficial for patients with the aforementioned risk factors.

Acute Disease↗

PubMed2005

Virological differences between patients infected with subtypes Ba and Bj of hepatitis B virus genotype B.

BACKGROUND: Hepatitis B virus (HBV) genotype B is classified into subtype Ba with the recombination with genotype C in the precore region plus core gene and subtype Bj without recombination. Virological and clinical differences between infections with subtypes Ba and Bj, however, are yet to be determined. METHODS: During 1976 through 2001, 224 patients visited Toranomon Hospital in Tokyo, Japan who were infected with HBV genotype B. Subtypes of genotype B were determined by sequencing HBV-DNA recovered from sera for detecting recombination with genotype C. RESULTS: Subtype Ba was detected in 53 patients (24%) and Bj in 167 (75%); subtypes were not able to be determined in the remaining four (1%). The only virological difference was that detection of hepatitis B e antigen at the presentation was more frequent in the patients infected with subtype Ba than those with Bj (63% vs 33%, P = 0.016). There were no differences in the distribution of liver disease of various forms between the patients infected with subtypes Ba and Bj at presentation. No differences were noted, either, in the development of liver cirrhosis or hepatocellular carcinoma, or the loss of hepatitis B surface antigen from serum, between the patients infected with subtypes Ba and Bj during follow up of up to 26 years. CONCLUSIONS: Although there were some virological differences between the patients infected with subtypes Ba and Bj of HBV genotype B, they do not seem to influence the long-term clinical outcome.

Adult↗

PubMed2005

Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C.

OBJECTIVE: The purpose of this clinical retrospective cohort study was to determine the most suitable ribavirin concentration on combination therapy of interferon (IFN)-ribavirin. METHODS: Entry criteria were serum HCV-RNA level >/=100 KIU/ml, HCV-genotype 1b, chronic hepatitis, and initial combination treatment of IFN-alpha-2b (6 million units daily for 2 weeks and then 3 times weekly for 6 weeks) and ribavirin (600-800 mg/day) for 8 weeks without stopping or decreasing the dosage of IFN and/or ribavirin. Sixty-eight consecutive patients who satisfied the above criteria were given maintenance therapy for another 16 weeks. RESULTS: A sustained virological response (SVR) rate of 25.0% (17/68) was seen in all subjects. The SVR rate was 44.0% (11/25) in the high ribavirin group with a serum ribavirin concentration of >/=3,000 ng/ml at 8 weeks after initiation of combination therapy. SVR was significantly dependent at a serum ribavirin level of >/=3,000 ng/ml (p = 0.005). The incidence of discontinuations and dose modifications for combination therapy in patients having a serum ribavirin concentration of >/=3,500 ng/ml 8 weeks after initiation of therapy was 57.1% (4/7). This value was statistically higher than that in patents with <3,500 ng/ml (p = 0.033). CONCLUSION: Our results showed that the most suitable serum ribavirin concentrations are from 3,000 to 3,500 ng/ml 8 weeks after initiation of combination therapy.

Adult↗

PubMed2005

Virological and biochemical relapse after discontinuation of lamivudine monotherapy for chronic hepatitis B in Japan: comparison with breakthrough hepatitis during long-term treatment.

OBJECTIVE: Comparison of virological and biochemical relapse in patients with chronic hepatitis B, based on continuation or discontinuation of lamivudine monotherapy. METHODS: In Japanese genotype C-dominant hepatitis B patients, 25 patients who stopped treatment at normal levels of alanine transferase (ALT) were retrospectively compared with 75 patients who continued treatment. Both groups were matched for age, sex, and observation period after start of treatment. We investigated the relapse rates, and evaluated predictive factors for relapse and efficacy of retreatment of the discontinuous group. RESULTS: Virological and biochemical relapse occurred significantly earlier in the discontinuous than continuous group, and the peak levels and ratios of peak to pretreatment levels of serum bilirubin and ALT after relapse were not significantly different between the two groups. Multivariate analysis identified three independent factors at discontinuation of treatment associated with early biochemical relapse: HBeAg positivity, presence of liver cirrhosis, detection of basic core promoter mutant. Normalization of ALT levels with retreatment occurred in 62.5% of patients, but 2 HBeAg-positive patients retreated after the emergence of YMDD motif mutant developed severe relapse with hyperbilirubinemia. CONCLUSION: Our results in Japanese patients with genotype C-dominant hepatitis B suggest that discontinuation of lamivudine monotherapy, and retreatment after the emergence of YMDD mutant should be given attention.

Adult↗

PubMed2005

Hepatitis B virus-related hepatocellular carcinogenesis and its prevention.

To elucidate the influence of serum hepatitis B virus (HBV) load on hepatocellular carcinogenesis in cirrhotic patients, HBV-DNA was sequentially measured. In a nested, case-control study using 96 patients without antiviral therapy, high HBV-DNA (> or =10(3.7) copies/ml) in the last 3 years was significantly associated with carcinogenesis (a patient group without hepatocellular carcinoma (HCC) development; 0/48 vs. a patient group with eventual HCC development; 22/48, p < 0.0001). No patient with a continuously low HBV-DNA for the last 3 years developed HCC. Persistence of high HBV-DNA concentration suggested an increased risk of carcinogenesis. In a retrospective cohort study using 57 patients with interferon therapy, HCC developed in 2 (8.0%) of the 25 patients with HBV-DNA loss, while carcinogenesis was found in 11 (34.4%) of 32 patients without HBV-DNA loss (Fisher's exact test, p = 0.026). A significant decrease or loss of serum HBV-DNA stops HCC development, and its sequential analysis could be very useful both in the prediction and early detection of small HCC.

Adult↗