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Hidenori Toyoda

Publications and source records attributed to Hidenori Toyoda.

At least 19 recordsLinked to original sources
PubMed2025

Long-Term Effectiveness of Tenofovir Alafenamide Versus Entecavir in Treatment-Naive Chronic Hepatitis B: A Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus.

INTRODUCTION: Although both tenofovir alafenamide (TAF) and entecavir (ETV) are recommended first-line treatments for chronic hepatitis B, comparative data on their effectiveness remain limited. We aim to compare their virologic (VR), biochemical (BR), and complete (CR) response rates. METHODS: This retrospective study enrolled treatment-naive chronic hepatitis B patients who initiated either TAF or ETV in 2016 or after across 22 international centers and evaluated their treatment response after balancing their characteristics using inverse probability treatment weighting and through Fine-Gray competing-risks analysis of the balanced cohort. RESULTS: The study included 1,605 patients (784 TAF and 821 ETV patients with significant background differences) of whom 1,553 (96.8%) were from Asia. Inverse probability treatment-weighting analysis yielded a total weighted cohort of 1,660 (822 TAF and 838 ETV patients with balanced characteristics). The 5-year cumulative VRs were high in both groups with a slightly higher rate in TAF patients (98.0% vs 93.9%, P < 0.001), and similar findings were found in a subgroup analysis by median hepatitis B virus (HBV) DNA (5.5 log IU/mL). However, there was no significant difference in the 5-year BR rates overall (93.7 vs 92.8%, P = 0.484) or by alanine aminotransferase (ALT) cutoff of 2&#xd7; upper limit of normal. TAF patients had a slightly higher 5-year cumulative CR overall (94.9% vs 89.4%, P = 0.001) and in high HBV DNA (96.9% vs 87.9%, P < 0.001) or ALT &#x2265;2&#xd7; upper limit of normal patients (97.3% vs 90.6%, P < 0.001), but not in those with lower HBV DNA or ALT. DISCUSSION: BR rates were similar with ETV and TAF, while VR and CR were higher with TAF, although the difference was modest (<5% overall, 7%-9% in high HBV DNA or ALT groups). Antiviral selection between TAF vs ETV should be based mainly on cost, side effect profile, and patient preference.

Adult↗
PubMed2006

Impact of surveillance on survival of patients with initial hepatocellular carcinoma: a study from Japan.

BACKGROUND & AIMS: We investigated trends in the prediagnostic surveillance of patients in whom hepatocellular carcinoma (HCC) was diagnosed, and evaluated the impact of these trends on early detection of HCC and on patient survival. METHODS: We evaluated 1641 patients in whom HCC initially was diagnosed during the period of 1968 to 2004. Patients were grouped by the year of diagnosis: 1968-1980 (n = 151), 1981-1990 (n = 409), 1991-2000 (n = 754), and 2001-2004 (n = 324). They also were classified according to whether they were in surveillance and its context before the diagnosis of HCC: patients undergoing follow-up evaluation in our center (group A), those followed up and referred by a primary care physician (group B), and those not in surveillance (group C). RESULTS: The percentage of patients in groups A and B increased markedly over time. Early stage HCC was significantly more prevalent in groups A and B than in group C, and the frequency of early stage HCC increased sequentially. The patient survival rate was highest in group A, followed by that in groups B and C in that order; patient survival improved sequentially. CONCLUSIONS: The percentage of patients undergoing in-center surveillance or referred by a primary care physician increased, resulting in increased early detection of HCC and improved patient survival.

Adult↗
PubMed2006

Conserved balance of hepatocyte nuclear DNA content in mononuclear and binuclear hepatocyte populations during the course of chronic viral hepatitis.

AIM: To analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid (4n) and octoploid (8n) nuclei, and then compared mononuclear and binuclear hepatocyte populations. METHODS: The percentages of mononuclear diploid (2n), 4n, and 8n hepatocytes and those of binuclear 2 x 2n, 2 x 4n, and 2 x 8n hepatocytes were determined with a method that can simultaneously measure hepatocyte nuclear DNA content and binuclearity in 62 patients with chronic hepatitis B or C. The percentage of 4n and 8n hepatocytes in the mononuclear hepatocyte population was compared with the percentage of 2 x 4n and 2 x 8n hepatocytes in the binuclear hepatocyte population. RESULTS: The percentages of 4n and 8n hepatocytes in mononuclear hepatocytes and 2 x 4n and 2 x 8n hepatocytes in binuclear hepatocytes were similar, regardless of the activity or fibrosis grade of chronic hepatitis and regardless of the infecting virus. CONCLUSION: The distribution of nuclear DNA content within mononuclear and binuclear hepatocyte populations was conserved during the course of chronic viral hepatitis.

Adult↗
PubMed2006

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen.

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.

Adult↗
PubMed2006

Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers.

BACKGROUND & AIMS: Previously proposed staging systems for hepatocellular carcinoma (HCC) involve clinical, imaging, or pathologic factors in the evaluation. We established and validated a novel staging system for HCC that is based on simply serum markers. METHODS: The new scoring system is based on 5 serum markers: bilirubin, albumin, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) and thus is termed the BALAD score. The system was validated in 2600 HCC patients from 5 institutions. The power of our system to predict patient survival and its discriminative ability were compared with those of previously reported staging systems. RESULTS: The best tumor marker cutoff values were 400 ng/dL for AFP, 15% for AFP-L3, and 100 milli-arbitrary unit/mL for DCP. The patients were classified into 6 categories on the basis of 5 laboratory values. The categories reflected patient survival well. The discriminative ability was comparable to that of previously reported staging systems. CONCLUSIONS: The new staging system for HCC combining serum albumin, serum bilirubin, and 3 tumor markers predicts patient outcomes with excellent discriminative ability. The system is easy to use and objective. In addition, stage can be evaluated with the use of only 1 serum sample. It also allows global comparison of patients with HCC or comparison of patients from different time periods with the same standard.

Aged↗
PubMed2006

Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

Adult↗
PubMed2006

Treatment of chronic hepatitis C with interferon alone or combined with ribavirin in Japan.

We treated 665 patients with chronic hepatitis C with interferon (IFN) monotherapy and 288 with combined IFN and ribavirin. At the baseline, age (53.8 +/- 11.1 vs. 49.7 +/- 10.5 years, p < 0.0001) and activity (p = 0.0207) as well as fibrosis (p = 0.0270) were higher in patients who received combination therapy than in those receiving monotherapy. Compliance to treatment (64.2 vs. 62.1%, p < 0.0001) and discontinuation were more frequent (18.1 vs. 14.5%, p < 0.0001) in patients with combination therapy than in those with monotherapy. Patients with combination therapy with genotype 2 infection achieved sustained viral response (SVR) at a rate of 77.0%, regardless of viral loads, in contrast to those with genotype 1 infection, of whom only 24.4% gained SVR. Of patients with combination therapy, reduction (42.6 vs. 29.0%, p = 0.0453) and discontinuation (34.0 vs. 21.6%, p = 0.0414) of ribavirin were more frequently required in the 47 patients > or =65 years than in the 241 patients <65 years. Although a trend for higher SVR to combination therapy was observed in patients aged < 65 than in those aged > or =65 years (39.4 vs. 25.2%), the difference was not significant (p = 0.0819). In patients with genotype 1 infection, IFN monotherapy in addition to the 24-week combination therapy increased the SVR rate (18.3 vs. 42.6%, p = 0.0003). A decrease in SVR was observed with an increased body mass index in patients who received combination therapy.

Aged↗
PubMed2005

Attenuated phosphorylation of heat shock protein 27 correlates with tumor progression in patients with hepatocellular carcinoma.

Heat shock protein 27 (HSP27) is expressed at high levels in human hepatocellular carcinoma (HCC). We examined correlations of total HSP27 and serine phosphorylated (Ser-15, Ser-78, and Ser-82) HSP27 levels in HCC tissues with clinical and pathologic characteristics in 48 resected HCC specimens. The levels of total and Ser-phosphorylated HSP27 were evaluated by Western blot analysis. Immunohistochemical analysis of HSP27 expression was also performed on some samples. Phosphorylation of HSP27 was detected in all 48 HCC tissues. Levels of phosphorylated HSP27 were correlated inversely with tumor size, microvascular invasion of HCC, and tumor stage by TNM classification. In contrast, only microvascular invasion showed an inverse correlation with total HSP27 levels. The decrease in phosphorylated HSP27 in progressed HCC was also observed by immunohistochemistry. Levels of phosphorylated HSP27 gradually decreased in parallel with HCC progression. Our findings suggest that phosphorylated HSP27 may have a suppressive role in progression of human HCC.

Aged↗
PubMed2005

Changes in hepatitis C virus (HCV) antibody status in patients with chronic hepatitis C after eradication of HCV infection by interferon therapy.

BACKGROUND: Changes in hepatitis C virus (HCV) antibody status were followed for 10 years after the eradication of HCV by interferon (IFN) therapy in 30 patients with chronic hepatitis C who showed a sustained virological response. METHODS: HCV core antibody titer, third-generation HCV recombinant immunoblot assay (RIBA) grade (measuring the presence of antibodies for core, NS3, NS4, and NS5 antigens), and genotype-specific antibodies to the HCV NS4 region were measured annually with commercially available kits for these antibodies. RESULTS: For grade of HCV antibody determined by RIBA, the most significant decrease was observed with anti-NS5 antibody, followed by anti-NS4, anti-NS3, and anti-core antibodies, in that order. Tests for anti-NS5 and anti-NS4 antibodies had negative results in almost 50% of patients 10 years after eradication of HCV. In contrast, the results of tests for anti-core antibody were still markedly positive in most patients. However, anti-core antibody titer decreased continuously during the 10-year follow-up period. Antibodies to the NS4 region specific for HCV genotypes 1 and 2 also decreased during the follow-up period. Differences in the rate at which antibody titers decreased were observed between antibodies for genotypes 1 and 2; as a consequence, the serological type of HCV changed during the follow-up period in some patients. CONCLUSIONS: HCV antibody titer appears to continue to decrease during the 10 years after eradication of HCV by IFN therapy.

Adult↗
PubMed2005

Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma.

AIM: We investigated pathological features of Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3. METHODS: A total of 111 patients with HCC < or =5 cm in diameter who underwent hepatic resection were studied. Serum AFP-L3 concentration was measured within a month prior to surgery by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP-L3-positive and negative HCC specimens. RESULTS: Thirty-three (29.7%) were positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP-L3-positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor. CONCLUSIONS: AFP-L3-positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP-L3 as an indicator of poor prognosis of HCC.

Adult↗
PubMed2005

Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan.

OBJECTIVES: We retrospectively compared the usefulness of three different staging systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC) classification system, and the Japan Integrated Staging (JIS) system, in terms of patient distribution and survival rates. METHODS: Subjects were 1,508 patients diagnosed as having initial HCC during the period of 1976-2003. The disease was staged in all patients by means of the three staging systems, and the distribution of patients across stages and associated survival rates were compared between systems. In addition, comparisons were made on the basis of the time of diagnosis: 1976-1990 (n = 497) and 1991-2003 (n = 1,011). RESULTS: Patients were evenly distributed across stages within each staging system, and survival rates differed between stages except for BCLC C and D. During the period 1991-2003, when HCCs were smaller at diagnosis, JIS system is in particular yielded even distribution of patient across stages and marked differences in survival rates. CONCLUSIONS: Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.

Adult↗
PubMed2005

Comparison of IV contrast-enhanced sonography and histopathology of pancreatic cancer.

OBJECTIVE: We compared contrast-enhanced sonography findings with pathologic findings in pancreatic cancer to evaluate the ability of contrast-enhanced sonography to depict the pathologic changes associated with pancreatic cancer. SUBJECTS AND METHODS: Thirty-four patients with pancreatic cancer who underwent surgery were investigated. Sonography was performed with contrast material (Levovist) for all patients before surgery. Pathologic findings were evaluated on the basis of the resected cancer specimens. We compared contrast-enhanced sonography findings with pathologic findings. RESULTS: All tumors that were hyperechoic on contrast-enhanced sonography were papillary adenocarcinoma, and all tumors that were hypoechoic on contrast-enhanced sonography were ductal adenocarcinoma. Among ductal adenocarcinomas, five (71.4%) of seven tumors for which the size of the hypoechoic area was unchanged on contrast-enhanced sonography had clear tumor margins with no infiltration or inflammation in the margin. In contrast, all tumors for which the size of the hypoechoic area was reduced on contrast-enhanced sonography had unclear tumor margins with infiltration of cancerous cells and inflammation. Nine (90%) of 10 tumors that showed partial contrast enhancement or a vascular shadow in a hypoechoic area had large or medium-sized vessels within a tumor at pathology. In contrast, only one (4.8%) of 21 tumors that did not show the vascular shadow in a hypoechoic area had no large or medium-sized vessels in a tumor. CONCLUSION: Contrast-enhanced sonography well reflects the pathologic changes of pancreatic cancer and will provide useful information in a pretreatment evaluation. Further studies with a large number of patients will be required to confirm this finding.

Adenocarcinoma↗
PubMed2004

Changes in the characteristics and survival rate of hepatocellular carcinoma from 1976 to 2000: analysis of 1365 patients in a single institution in Japan.

BACKGROUND: The authors analyzed changes in the characteristics and survival rate of patients with hepatocellular carcinoma (HCC) in the past 25 years. METHODS: Trends in clinical characteristics and survival rate of patients with HCC were evaluated retrospectively based on data from 1365 patients who were diagnosed, treated, and followed between 1976 and 2000. RESULTS: Between 1976-1995, the number of patients with smaller tumors, a less advanced tumor stage, and with a lower Child-Pugh class increased markedly. No differences were observed in the distributions of these three factors between the periods 1991-1995 and 1996-2000. The year of HCC diagnosis, tumor size, tumor stage, Child-Pugh class, and the kind of initial treatment received correlated significantly with patient survival rates by multivariate analysis. The year of HCC diagnosis was found to contribute independently to the improvement in patient survival rates. Using the Kaplan-Meier comparison, the time periods during which the highest patient survival rates occurred were found to be 1991-1995/1996-2000, 1986-1990, and 1976-1985, in that order. The authors did not observe a difference with regard to survival rates between patients in the 1991-1995 and 1996-2000 groups. CONCLUSIONS: The characteristics of patients with HCC changed dramatically from 1976 to 1995 (but not in the past 10 years) toward the earlier detection of HCC. This contributed to the improvement noted in patient survival rates during this period. The year of HCC diagnosis was found to be an independent factor for the improved survival rates by multivariate analysis. This indicated that the progress of treatment and care for patients with HCC contributed to the annual improvement in patient survival rates.

Carcinoma, Hepatocellular↗
PubMed2004

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan.

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.

Adult↗