Biomedical subjects

Kenji Ikeda

Publications and source records attributed to Kenji Ikeda.

At least 73 records · Page 4Linked to original sources

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

Distribution of neuropeptide Y interneurons in the dorsal prefrontal cortex of schizophrenia.

The distribution of neuropeptide Y (NPY) containing neurons was investigated in the dorsal prefrontal region in the brains of the schizophrenic patients and compared to those of normal control. Proportional comparison of NPY neurons in four compartments, upper cortical layers, lower cortical layers, subcortical white matter and deep white matter, demonstrated differential distribution between schizophrenic brains and controls. The proportion of NPY neurons in the upper cortical layers was low in disorganized form and subsequently in paranoid form in comparison to controls. The proportion of NPY neurons in the deep white matter was, conversely, high in the disorganized form and subsequently in the paranoid form. These results indicate that there may be a gamma-aminobutyric acid (GABA)-ergic deficit in schizophrenic patients, especially, in the disorganized form. These results also support the hypothesis of neurodevelopmental dysfunction of schizophrenia.

Adult↗

PubMed2004

Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia.

Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n = 17), normal controls (n = 22), and cases of Alzheimer's disease (AD) as a positive control (n = 17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Abeta load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.

Aged↗

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

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

Coexistence of CJD and Alzheimer's disease: an autopsy case showing typical clinical features of CJD.

The present report concerns an autopsy case of CJD showing typical clinical features of CJD. The patient was a Japanese woman without hereditary burden or dementing disorder anamnesis who was 70-years-old at the time of death. She developed gait disturbance at age 68, followed by memory impairment, visual disturbance, and myoclonus. A neurological examination approximately 2 months after the disease onset revealed akinetic mutism, in addition to periodic synchronous discharges on electroencephalogram. Serial neuroradiological examinations disclosed progressive atrophy of the brain. She died of bronchopneumonia 25 months after the disease onset. The brain weighed 560 g (cerebrum 490 g, brainstem with cerebellum 70 g). Macroscopically, neuropathological examination showed prominent atrophy of the cerebrum, caudate nucleus, and cerebellum, in addition to necrosis of the cerebral white matter, compatible with panencephalopathic CJD. Histologically, there was neuronal loss with or without spongiform change in the cerebral cortex, parahippocampal gyrus, amygdala, striatum, pallidum, thalamus, pontine nucleus, and cerebellar granule cells, in addition to diffuse synaptic-type prion staining in the cerebrum and cerebellum. Furthermore, senile plaques, compatible with definite Consortium to establish a registry for Alzheimer's disease rank Alzheimer's disease, and neurofibrillary changes of the limbic system, consistent with stage IV of Braak's classification, were found. Based on these clinicopathological findings and a review of the published literature, it is concluded that there were two forms of coexistence of CJD and Alzheimer's disease in the same patient.

Aged↗

PubMed2004

Motor neuron disease group accompanied by inclusions of unidentified protein signaled by ubiquitin.

Peculiar tau-negative, ubiquitin-positive inclusions appear in dementia with ALS (ALS-D), the majority of lobar atrophy (Pick's disease) without Pick body and a small portion of ALS. Another common neuropathological lesion in these diseases is the motor neuron involvement with the degenerative processes. The lower motor neuron is predominantly involved in ALS and ALS-D the upper motor neuron is predominantly involved, but in varying degrees in a considerable number of patients with lobar atrophy that lack Pick bodies. There are, however, some points that have yet to be elucidated. The boundary between these diseases is not always clear and a significant number of cases are considered to be the transitional form. Lobar atrophy without Pick body seems to be a heterogeneous disease group. The nature of ubiquitin inclusions also needs to be clarified. Nevertheless, we postulate that these diseases are grouped with the concept of motor neuron disease-inclusion dementia.

Brain↗

PubMed2004

Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists: additional autopsy case with a clinical course of 19 years.

This report concerns an autopsy case of sporadic amyotrophic lateral sclerosis (ALS) clinically diagnosed as having spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness in the distal part of the right upper extremity at age 52, followed by muscle weakness in the left upper extremity and lower extremities at age 54 and 64, respectively. At age 66 she could not walk, even with assistance. Fasciculation and atrophy of the tongue appeared at age 68, followed by dysphagia and dysarthria at age 70. She died of respiratory disturbance at age 71. During the clinical course, neurological examination revealed neither Babinski sign nor hyperreflexia. No respirator administration was performed throughout the clinical course. Neuropathological examination disclosed not only neuronal loss with gliosis in the hypoglossal nucleus and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tract. Based on these clinicopathological findings and a literature review of sporadic autopsy cases of ALS with long clinical course (10 years or more), including four cases without pyramidal signs, we believe that sporadic ALS of long clinical course mimicking SPMA exists.

Aged↗

PubMed2004

Ubiquitin and ubiquitin-related proteins in the brains of patients with atypical Pick's disease without Pick bodies and dementia with motor neuron disease.

Nine cases of atypical Pick's disease without Pick bodies (aPiD) and seven cases of dementia with motor neuron diseases (D-MND) were compared using immunohistochemistry of ubiquitin (ub) and ub-related proteins. All cases showed rostral-dominant atrophy in the temporal and frontal lobes, although the degree of atrophy with neuronal loss was much more severe in the aPiD cases. In both aPiD and D-MND cases, ub-positive and tau-negative structures were found mainly in the hippocampal dentate gyrus and cerebral cortex. Granular cells of the dentate gyrus showed similar ub-positive intraneuronal inclusions in both cases. In the aPiD cases, most of the ub-positive cortical structures were ub-positive dendrites in layers II-IIIab and layers V-VI, although some neurons also showed diffuse ub-positive staining in the cytoplasm. In the D-MND cases, some neurons showed ub-positive inclusions in layers II-IIIab, and ub-positive dendrites were unremarkable. The number of ub-positive neurons and dendrites in relation to the degree of neuronal loss in the cerebral cortex were then evaluated. The number of ub-positive neurons in the regions showing very mild to mild neuronal loss was significantly greater in the D-MND cases than in the aPiD cases. However, in the aPiD cases, the number of ub-positive neurons was significantly greater in the regions showing moderate neuronal loss. When double-immunostained, almost all ub-positive structures were positive for ub-binding protein p62. Some ub-positive or negative neurons in the cerebral cortex were immunostained with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase (UCH-L1) antibodies. Granular cells of the dentate gyrus were weakly positive for UCH-L1. There could be some differences in the mechanism by which neurons in the cerebral cortex accumulate ub between aPiD and D-MND.

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↗