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Hiromitsu Kumada

Publications and source records attributed to Hiromitsu Kumada.

At least 73 records · Page 4Linked to original sources
PubMed2004

Peripheral CD8+/CD25+ lymphocytes may be implicated in hepatocellular injuries in patients with acute-onset autoimmune hepatitis.

BACKGROUND: The mechanism of liver injuries in autoimmune hepatitis (AIH) is not fully understood, especially because the onset is insidious and the clinical courses fluctuate with spontaneous exacerbation and improvement even without immunosuppressive therapies. METHODS: Eleven patients with acute-onset AIH, some of whom were without hypergammaglobulinemia or anti-nuclear antibodies, and 41 patients with chronic AIH were compared serologically, biochemically, and histologically to determine differences in liver injuries between patients with acute-onset and chronic AIH. All patients fulfilled the diagnostic criteria according to a scoring system proposed in 1999. RESULTS: Lymphocytes with CD8+/CD25+ markers in pretreatment blood were significantly more prevalent in acute-onset than chronic AIH patients (24% vs 14%; P < 0.05). After treatment, however, CD8+/CD25+ lymphocytes were fewer in patients with acute-onset than in those with chronic AIH at 1 and 2 weeks ( P = 0.0001). No other differences were noted in clinical characteristics or immunological parameters between patients with acute-onset and those with chronic AIH. In a patient with typical acute-onset AIH, CD8+/CD25+ lymphocytes increased and decreased in parallel with the activity of liver disease. CONCLUSIONS: Activated CD8+ T lymphocytes with CD25 markers may be implicated in the development of acute-onset AIH.

Acute Disease↗
PubMed2004

Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C.

BACKGROUND: Recent studies indicate that combination therapy with ribavirin and interferon alfa2b (IFNAlpha2b) is effective for chronic hepatitis C virus (HCV) infection. However, reversible hemolytic anemia is a common side effect of this therapy. METHODS: We determined those factors that contribute to ribavirin dose reduction due to anemia during this treatment by using multiple logistic regression analysis in Japanese patients. The study included 123 patients with chronic hepatitis C (85 male, 38 female; mean age, 50 years; range, 20-70 years), who received 24-week combination therapy. All patients were treated with IFNAlpha2b daily for 2 weeks, followed by three times weekly dosing for 22 weeks, with oral ribavirin twice daily, at a total daily dose of 600 or 800 mg. RESULTS: Of the 123 patients, 34 patients required dose reduction of ribavirin, and 78 patients required no dose reduction. Overall, 20 patients discontinued. On univariate analysis, reduction of the ribavirin dose correlated significantly with pretreatment hemoglobin (Hb) levels of less than 14 g/dl, female sex, and patient age 55 years or older. On multivariate analysis, pretreatment Hb of less than 14 g/dl level and age 55 years or older were significantly associated with ribavirin dose reduction. The hazard ratios were 3.56 (95% confidence interval [CI], 1.48-8.53) for pretreatment Hb levels of less than 14 g/dl, and 2.50 (95% CI, 1.05-5.94) for age 55 years or more. CONCLUSIONS: Because patient age of 55 years or more, and Hb levels of less than 14 g/dl are significant factors that influence ribavirin-induced hemolytic anemia, more careful monitoring is necessary during combination therapy for patients with these risk factors.

Adult↗
PubMed2004

Interferon monotherapy for patients with chronic hepatitis C and normal serum aminotransferase levels at commencement of treatment.

BACKGROUND: Approximately 30% of patients with chronic hepatitis C have normal serum alanine amino transferase (ALT) levels. While interferon (IFN) monotherapy is approved for patients with chronic hepatitis C infection, the effectiveness of such therapy for chronic hepatitis C patients with normal ALT levels at commencement of treatment remains poorly understood. METHODS: Ninety-four individuals (M/F, 54 : 40; median age, 46 years) with normal ALT levels (< 50 IU/l) at the commencement of treatment who were positive for both anti-hepatitis C virus (HCV) and serum HCV-RNA were studied. Among this group, 18 individuals (M/F, 9 : 9; median age, 50 years) had had persistently normal ALT levels for at least 3 months prior to treatment. All patients received their first course of IFN therapy in this study. RESULTS: Forty-three (45.7%) of 94 individuals had lost serum HCV-RNA at 6 months after cessation of therapy (complete response; CR). The proportion of patients with genotype 2a and HCV-RNA level over 1 Meq/ml who showed CR was significantly lower in those with normal ALT levels than in those with elevated ALT levels (23.8% vs 55.6%; P = 0.0189). Two patients who had persistently normal ALT levels and HCV-RNA level over 1 Meq/ml were nonresponders (NR) and had ALT flare-ups after IFN therapy. Patients with HCV-RNA levels of less than 1 Meq/ml did not show differential responses based on ALT levels. CONCLUSIONS: Our data suggest that IFN therapy is effective for patients with normal ALT levels and less than 1 Meq/ml HCV-RNA. Thus, such patients should be considered for curative IFN therapy.

Adolescent↗
PubMed2004

Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through 2001.

BACKGROUND: Because genotype A of hepatitis B virus (HBV) is not indigenous, there have been only few data on infection with it in Japan. METHODS: We examined clinical and virological features of the 66 Japanese patients who admitted Toranomon Hospital in Tokyo, Japan, between 1976 and 2001, who were found to have HBV/A infection. HBV genotype A was classified into subtype A (European type) and A' (South African type) by phylogenetic analysis of the preS1 and preS2 regions, and the S gene sequences. RESULTS: Of the 66 patients infected with HBV/A, 14 (21%) were asymptomatic carriers, 26 (39%) presented with acute hepatitis, 22 (33%) with chronic hepatitis, and 4 (6%) with liver cirrhosis. HBV/A infection persisted for more than 6 months in 5 of the 26 (19%) patients with acute hepatitis. The frequency of acute hepatitis in patients infected with HBV/A was higher after than before 1991 (2/22 [9%] vs 24/44 [55%]; P < 0.0001). The frequency of nucleotide 1858 of T was higher in asymptomatic carriers than in patients with acute hepatitis in whom infection was resolved (5/14 [36%] vs 0/21 [0%]; P = 0.008). Of the 57 patients for whom subtypes of genotype A were determined, subtype A was identified in 53 (93%) and subtype A' in only 4 (7%). All patients infected with subtype A' were persistently infected with HBV. CONCLUSIONS: HBV/A infection has become more frequent during recent years, predominantly presenting as acute hepatitis, and subtype A' is uncommon in the Tokyo metropolitan area.

Adolescent↗
PubMed2004

Efficacy of 6-month interferon therapy in chronic hepatitis B virus infection in Japan.

BACKGROUND: In Japan, there are few studies of long-term (more than 1 month) interferon (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we investigated the efficacy and predictors of response to 6-month IFN therapy. METHODS: We analyzed 66 Japanese patients with CHB who were treated with IFN for 6 months. They comprised patients who were hepatitis B e antigen (HBeAg)-positive (n=45) and -negative (n=21). One (2%), 8 (12%), and 51 (77%) patients were infected with hepatitis B virus (HBV) genotypes A, B, and C, respectively. Responders in patients positive for HBeAg were defined as those who showed normalization of serum alanine aminotransferase (ALT) level, HBeAg loss, and HBV DNA negativity at 6 months after completion of IFN therapy. In patients negative for HBeAg, responders were defined as those patients who showed normalization of ALT level and HBV DNA negativity at the same 6-month time point. RESULTS: Of the 45 patients with HBeAg at the commencement of IFN therapy, 9 (20%) were responders. Young patients, especially those with a high serum ALT level, were significantly more likely to respond to IFN therapy. Of the 21 patients negative for HBeAg, 13 (62%) were responders. There were no significant differences in clinical characteristics between responders and nonresponders among patients negative for HBeAg. Multivariate analyses identified HBeAg negativity and young age as independent factors associated with a positive response to 6-month IFN therapy. However, long-term follow-up of the treated patients showed a fall in the response rate. CONCLUSIONS: The response rate to 6-month IFN therapy among HBeAg-positive patients was low. However, young patients may require long-term IFN therapy.

Adult↗
PubMed2004

Efficacy of lamivudine treatment in Japanese patients with hepatitis B virus-related cirrhosis.

BACKGROUND: Several clinical trials have suggested that lamivudine therapy is effective in patients with hepatitis B virus (HBV)-related cirrhosis. However, there are few studies of lamivudine therapy in Japanese patients with HBV cirrhosis. The aim of this study was to evaluate the efficacy of lamivudine therapy in Japanese patients with cirrhosis, and to evaluate the clinical course after the emergence of YMDD mutants. METHODS: Fifty-four consecutive adult Japanese patients with HBV-related cirrhosis were enrolled and continuously treated with lamivudine, daily for 6-35 months (median, 25 months). Twelve of the 54 patients were hepatitis B envelope antigen (HBeAg)-positive. The clinical courses of 21 of the patients were evaluated using the Child-Pugh-Turcott (CPT) score. RESULTS: Lamivudine suppressed serum HBV-DNA to undetectable levels (<3.7 LGE/ml) in 77.8% of patients at 12 months and in 61.3% at 24 months. Before the emergence of YMDD mutants, clinical improvement, defined as a decrease in the CPT score of 2 points or more, was apparent in 6 of 21 (29%) patients. No change in CPT score was evident in 14 of 21 patients (67%). YMDD mutants emerged in 19 of 54 (35%) patients. The cumulative emergence rates increased each year. The emergence rate of YMDD mutants in patients with HBV cirrhosis was higher than that in patients with chronic hepatitis. After the emergence of YMDD mutants, 3 of 12 (25%) patients with YMDD mutants showed CPT score increases of 2 points or more. CONCLUSIONS: Lamivudine therapy improved the clinical course in some cirrhotic patients. However, in patients with Child's B and C cirrhosis, the emergence of YMDD mutants sometimes led to deterioration of liver function.

Female↗
PubMed2004

Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C.

BACKGROUND: Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin-related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy. METHODS: Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus load, and received 24-week combination therapy developed anemia with hemoglobin level <10 g/dl or anemia-related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200 mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their <8.5 g/dl hemoglobin values decreased to or anemia-related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B. RESULTS: A sustained virological response (SVR) was 29.6% (8/27) in group A and 10% (1/10) in group B, respectively. A 34.4% (12/27) of SVR + biological response in group A was higher than 10% (1/10) in group B ( P = 0.051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with > or =10 g/dl hemoglobin was higher than that in patients with <10 g/dl ( P = 0.036). CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or =10 g/dl is suitable in terms of efficacy and side effects.

Anemia, Hemolytic↗
PubMed2004

Prediction of treatment outcome with daily high-dose IFN alpha-2b plus ribavirin in patients with chronic hepatitis C with genotype 1b and high HCV RNA levels: relationship of baseline viral levels and viral dynamics during and after therapy.

Data on 334 patients with HCV genotype 1b and high viral levels were extracted from two multicenter double-blind studies conducted in Japan comparing IFN alpha-2b plus ribavirin (n = 209) with IFN alpha-2b alone (n = 125) for 24 weeks. HCV RNA assay was conducted before and 4, 12, and 24 weeks after the start and 4, 12, and 24 weeks after the end of treatment. Both sustained viral response (SVR) rate and relapse rate after the end of treatment were analyzed in relation to baseline viral levels and the time of first disappearance of virus. In the combination treatment group, the percentage of patients who were HCV RNA-negative within 4 weeks decreased with increase in baseline viral levels (i.e. 42%, 15%, and 11% were HCV RNA-negative in the groups exhibiting <500, 500 to <850, and >/=850kcopies/mL, respectively). In the IFN monotherapy group, the response rates were lower at 13%, 15%, and 1%, respectively. Disappearance of virus within 12 weeks after the start of combination treatment was indicative of higher probability of SVR. The risk of relapse was more highly correlated with the timing of initial viral disappearance than with baseline HCV levels; it was 4.8 and 10.3 times higher in patients who became HCV-negative at 4-12 and 13-24 weeks compared with in those who were HCV-negative within 4 weeks.

Journal Article↗
PubMed2004

Effect of acute self-limited hepatitis C virus (HCV) superinfection on hepatitis B virus (HBV)-related cirrhosis. Virological features of HBV-HCV dual infection.

We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]), fluctuations of HBV DNA and HBeAg state were accompanied by mutations of the BCP and PreC. In Case 2 (HBeAg-negative; mutant type of the BCP and PreC), changes in HBV DNA levels were associated with mutations of PreC. In both cases, mutant PreC changed to the wild type upon HCV resolution, and no nucleotide A insertion at position 193 of the HCV 5'-untranslated region, which influences HCV spontaneous clearance, was detected. The putative DNA-binding motif in the HCV core was SPRG (amino acids 99-102). HCV infection was associated with changes in the nucleotide sequences of the binding site for the nuclear receptor family in HBV enhancer 2 (Enh2) including the BCP rather than Enh1. Our results suggest that the impact of acute HCV infection on chronic HBV infection varies according to HBV virological state.

5' Untranslated Regions↗
PubMed2004

Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A.

Complete nucleotide sequences of 19 hepatitis B virus (HBV) isolates of genotype A (HBV/A) were determined and analysed along with those of 20 previously reported HBV/A isolates. Of the 19 HBV/A isolates, six including three from Japan and three from the USA clustered with the 14 HBV/A isolates from Western countries. The remaining 13 isolates including four from The Philippines, two from India, three from Nepal and four from Bangladesh clustered with the six HBV/A isolates reported from The Philippines, South Africa and Malawi. Due to distinct epidemiological distributions, genotype A in the 20 HBV isolates was classified into subtype Ae (e for Europe), and that in the other 19 into subtype Aa (a for Asia and Africa) provisionally. The 19 HBV/Aa isolates had a sequence variation significantly greater than that of the 20 HBV/Ae isolates (2.5+/-0.3 % vs 1.1+/-0.6 %, P<0.0001); they differed by 5.0+/-0.4 % (4.1-6.4 %). The double mutation (T1762/A1764) in the core promoter was significantly more frequent in HBV/Aa isolates than in HBV/Ae isolates (11/19 or 58 % vs 5/20 or 25 %, P<0.01). In the pregenome encapsidation (epsilon) signal, a point mutation from G to A or T at nt 1862 was detected in 16 of the 19 (84 %) HBV/Aa isolates but not in any of the 20 HBV/Ae isolates, which may affect virus replication and translation of hepatitis B e antigen. Subtypes Aa and Ae of genotype A deserve evaluation for any clinical differences between them, with a special reference to hepatocellular carcinoma prevalent in Africa.

Africa↗
PubMed2004

Clinical and pathological characteristics of the autoimmune hepatitis and primary biliary cirrhosis overlap syndrome.

BACKGROUND AND AIMS: The defining of the autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) overlap syndrome as a separate clinicopathological entity has been controversial and temporally and geographically subjective. METHODS: From 1979 until 2000, 227 patients diagnosed with AIH, PBC or the overlap thereof were treated. Cases with genuine AIH/PBC overlap syndrome were sorted out using close clinical follow up and serial liver biopsies. RESULTS: Of the 227 patients, 19 (8.4%) were diagnosed with the AIH/PBC overlap syndrome. They all cleared a score >10 for the diagnosis of AIH, and tested positive for antimitochondrial antibodies during their courses. Long-term follow up with frequent histological examinations, however, established the diagnosis of AIH/PBC overlap syndrome in only two (0.8%) patients. The most powerful factor distinguishing AIH from PBC was acidophilic bodies in lobules that were detected significantly more frequently in patients with AIH than PBC or spurious overlap syndrome (39/46 [85%]vs 3/85 [4%], P < 0.001). It was more reliable than bile-duct lesions for the distinction of PBC from AIH. CONCLUSIONS: Although AIH/PBC overlap syndrome does exist, it is infrequent and needs to be diagnosed carefully using close clinical and histological follow up to enable timely and effective treatment.

Adult↗
PubMed2004

Sustained negativity for HCV-RNA over 24 or more months by long-term interferon therapy correlates with eradication of HCV in patients with hepatitis C virus genotype 1b and high viral load.

OBJECTIVE: We assessed whether sustained negativity for HCV-RNA over 24 or more months by long-term interferon (IFN) therapy correlates with eradication of HCV in patients with hepatitis C virus genotype 1b and high viral load or not. METHODS: The number of patients with HCV-genotype 1b and high viral load exceeding 1 Meq/ml who received 6 MU of natural IFN-alpha daily for 2-8 weeks, followed by three times/week for 16-22 weeks and negativity for HCV-RNA during IFN administration was 403. Forty-one of 403 patients received 6 MU of natural IFN-alpha three times/week for more than 18 months after the initial IFN therapy (long-term-IFN-group). Three hundred and two patients did not receive any IFN treatment for 6 months after the termination of the 6-month course (6-month-IFN-group). Sustained virological response (SVR) was defined as negative HCV-RNA at both 3 and 6 months after the completion of IFN therapy. RESULTS: SVR was noted in 73.2% (30/41) of long-term-IFN-group and 18.2% (55/302) of 6-month-IFN-group. Multivariate analysis showed that long-term IFN therapy was the most significant contributor to SVR (p < 0.0001). CONCLUSION: Sustained negativity of HCV-RNA for 24 or more months by long-term IFN therapy correlated with SVR in patients with genotype 1b and high viral load.

Adult↗
PubMed2004

Benefit of lamivudine therapy and factors associated with clinical outcome in spontaneous severe acute exacerbation of chronic hepatitis B virus infection.

OBJECTIVE: During the course of chronic hepatitis B virus (HBV) infection, severe acute exacerbations of the infection often occur spontaneously and follow a fulminating progression to fatal hepatic failure. The aim of this study was to clarify potential factors, including benefit of lamivudine therapy, which could influence clinical course of the serious disease in an area of intermediate HBV endemicity. METHODS AND RESULTS: Using a database of 3,163 chronically HBV-infected patients, 418 (13.2%) developed acute exacerbation of hepatitis B. Of the 418 patients, 52 (12.4%) spontaneously developed severe acute exacerbation and were included in this study. Of the 52 patients, 23 were treated with lamivudine. In multivariate analyses, fulminating progression to hepatic failure (odds ratio, 15.45; 95% confidence interval, 3.71-64.41; p = 0.0002) was a significantly independent predictor of patient survival. Three variables were independently associated with fulminating development of hepatic failure: presence of cirrhosis (29.06, 1.74-85.56, 0.019, respectively), higher baseline bilirubin level (14.89, 1.31-52.91, 0.029, respectively), and genotype B (22.14, 1.59-29.68, 0.021, respectively). Treatment lacking lamivudine was a significant factor that contributed to shorter survival time, development of hepatic failure, and progression to cirrhosis in univariate analyses (p = 0.014, 0.012 and 0.0030, respectively). CONCLUSION: In an area of intermediate HBV endemicity, certain proportion of chronic hepatitis B patients could spontaneously develop the serious disease. Factors influencing clinical course of the disease should be identified to improve prognosis and establish more rational and effective therapeutic strategies. Lamivudine therapy could potentially benefit the serious disease, although larger series of patients and longer follow-up periods are needed.

Acute Disease↗
PubMed2004

Interferon therapy for 2 years or longer reduces the incidence of hepatocarcinogenesis in patients with chronic hepatitis C viral infection.

OBJECTIVE: The purpose of this clinical study was to determine the effect of long-term interferon (IFN) administration on the incidence of hepatocellular carcinomas (HCC) in chronic hepatitis C patients, without eradication of hepatitis C virus (HCV) by IFN therapy. METHODS: The number of patients with biopsy-proven chronic hepatitis with moderate or severe staging, HCV genotype 1b, a high viral load exceeding 1 MEq/ml (mega equivalents per milliliter), who received 6 MU of natural IFN-alpha daily for 2-8 weeks, followed by three times/week for 16-22 weeks, as initial IFN therapy, and positivity for HCV RNA during IFN administration was 131. 47 of the 131 patients continued to be treated with IFN (long-term IFN group, dose 3 or 6 MU twice or three times weekly for 1.5-10.5 years, median 4.0 years) after initial IFN therapy, while 84 patients did not receive any IFN therapy apart from the initial 6-month course (no-add-IFN group). The patients were prospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. RESULTS: The 5- and 10-year cumulative rates of HCC were 1.9 and 6.4% and 1.9 and 26.8% for long-term IFN and no-add-IFN groups, respectively. Cox regression analysis indicated that the relative risk of HCC in the patients of the no-add-IFN group was 8.72 times of that in patients of the long-term IFN group. CONCLUSION: Long-term IFN therapy in patients with chronic HCV infection is effective in preventing hepatocarcinogenesis.

Adult↗
PubMed2004

Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine-resistant mutants of hepatitis B virus.

OBJECTIVE: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants. METHODS: Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis. RESULTS: At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and -22.3 times the ULN in the ADV + IFN group. CONCLUSIONS: Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.

Adenine↗