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1.
Oncology ; 99(8): 491-498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34000725

RESUMO

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
2.
Oncology ; 99(8): 507-517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33946070

RESUMO

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Pontuação de Propensão , Quinolinas/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Oncology ; 99(5): 327-335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33677453

RESUMO

INTRODUCTION: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. METHODS: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. RESULTS: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. CONCLUSION: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Quinolinas/administração & dosagem , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Taxa de Sobrevida
4.
Oncology ; 98(11): 787-797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32882687

RESUMO

BACKGROUND: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. METHODS: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. RESULTS: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors. CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Taxa de Sobrevida
5.
J Gastroenterol Hepatol ; 33(10): 1780-1786, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29645345

RESUMO

BACKGROUND AND AIM: Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and HCC refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). Also, hepatic arterial infusion chemotherapy (HAIC) has been used for advanced HCC in Southeast and East Asian countries. However, clearer information is needed for choosing appropriately between these therapies. METHODS: The subjects were 391 HAIC and 431 sorafenibs administered at our hospital and related hospitals. In this case, cases that satisfy the following three conditions were targeted: (i) no extrahepatic metastasis, (ii) Child-Pugh A, and (ii) not having received treatment of both HAIC and sorafenib during the course. As a result, 150 cases of HAIC and 134 cases of sorafenib were analyzed this time. RESULTS: Univariate and multivariate analyses were performed for the HAIC and sorafenib groups. TACE refractory status and MVI were factors contributing to overall survival (OS). Therefore, this study divided all cases according to those variables. The median survival time of MVI-positive and non-TACE refractory cases was significantly better with HAIC (13 months) versus sorafenib (6 months). However, in MVI-negative and TACE refractory cases, the median survival time of HAIC (8 months) was significantly poorer than for sorafenib (20 months). CONCLUSION: Transcatheter arterial chemoembolization refractory status with HAIC and MVI with sorafenib were factors for poor prognosis. In particular, HAIC was significantly better than sorafenib as primary treatment in MVI and non-TACE refractory cases. It is necessary to consider these factors in treatment selection.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Cateterismo Periférico/métodos , Quimioembolização Terapêutica/métodos , Artéria Hepática , Neoplasias Hepáticas/terapia , Microvasos/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Idoso , Carcinoma Hepatocelular/irrigação sanguínea , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Sorafenibe , Resultado do Tratamento
6.
Oncology ; 94(4): 215-222, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29428943

RESUMO

OBJECTIVE: To compare the outcome of hepatic arterial infusion chemotherapy combined with radiotherapy (HAIC + RT) versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombosis (PVTT). METHODS: This retrospective study included 108 HCC patients with PVTT of the main trunk or first branch and Child-Pugh ≤7. Sixty-eight received HAIC + RT and 40 received sorafenib. Patients were then assigned to the HAIC + RT group (n = 36) and the sorafenib group (n = 36) through case-control matching. The decision to treat with HAIC + RT or sorafenib was left to the attending physician. RESULTS: The median overall, progression-free, and postprogression survival were significantly longer in the HAIC + RT group than in the sorafenib group (9.9 vs. 5.3, p = 0.002; 3.9 vs. 2.1, p = 0.048; and 3.7 vs. 1.9 months, p = 0.02, respectively). Multivariate analysis identified HAIC + RT (hazard ratio = 2.02; 95% confidence interval, 1.14-3.57; p = 0.01) as a significant and independent determinant of overall survival. CONCLUSIONS: In patients with advanced HCC and major PVTT, survival was significantly longer in those treated with HAIC + RT than with sorafenib.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Veia Porta/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Interferons/administração & dosagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida
7.
J Med Virol ; 89(11): 1963-1972, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28657143

RESUMO

Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (<25%) of baseline NS5A RAVs, but 82.8% for patients with high frequency (>75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency <75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Farmacorresistência Viral Múltipla/genética , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Lipídeos/sangue , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/uso terapêutico , Carbamatos/uso terapêutico , Quimioterapia Combinada , Feminino , Variação Genética , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Ritonavir/uso terapêutico , Sofosbuvir , Resposta Viral Sustentada , Falha de Tratamento , Uridina Monofosfato/uso terapêutico , Adulto Jovem
8.
J Gastroenterol Hepatol ; 32(3): 645-650, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27513614

RESUMO

BACKGROUND AND AIMS: Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected-patients. However, the real-world efficacy and safety of the therapy for patients with cirrhosis are unknown. METHODS: A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end-of-treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed. RESULT: Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End-of-treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre-treatment NS5A drug resistant-associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment-related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR. CONCLUSION: Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected-patients with compensated cirrhosis.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Isoquinolinas/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Isoquinolinas/efeitos adversos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
9.
Anticancer Res ; 36(7): 3523-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27354618

RESUMO

AIM: To compare the outcome of 5-fluorouracil (FU)-based hepatic arterial infusion chemotherapy (HAIC) with sorafenib monotherapy in patients with hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE). PATIENTS AND METHODS: In this retrospective cohort study, 123 patients with HCC refractory to TACE, with Child-Pugh A and free of extrahepatic metastasis, were divided into two groups: 65 received HAIC and 58 received sorafenib. Since the size of main tumor and portal vein invasion were significantly different between the HAIC and sorafenib groups, we selected 48 patients from the 65 patients of the HAIC group and 48 from the 58 patients of the sorafenib group. The model used one-to-one matching between the two groups using the case-control method matching method. The clinical characteristics of patients of the case-control HAIC (n=48) and sorafenib groups (n=48) were similar. Overall survival, time to progression and time to treatment failure (TTTF) were compared between the two groups. RESULTS: The median survival time and TTTF were significantly longer in the sorafenib group than in the HAIC group (15 and 12.2 months versus 8 and 4.4 months, respectively; p=0.021 and p=0.002, respectively). Multivariate analysis identified male gender (p=0.008), relative tumor size <50% (p=0.012), α-fetoprotein <400 ng/ml (p=0.005), and treatment with sorafenib (p=0.001) as significant and independent determinants of better overall survival. CONCLUSION: In patients with HCC refractory to TACE, overall survival was favorable in those treated with sorafenib rather than HAIC.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática/patologia , Humanos , Infusões Intra-Arteriais , Interferons/administração & dosagem , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sorafenibe , Resultado do Tratamento
10.
Antimicrob Agents Chemother ; 58(4): 2105-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24468783

RESUMO

Direct-acting antivirals (DAAs) are either part of the current standard of care or are in advanced clinical development for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1, but concern exists with respect to the patients who fail these regimens with emergent drug-resistant variants. In the present study, ultradeep sequencing was performed to analyze resistance to daclatasvir (DCV), which is a highly selective nonstructural protein 5A (NS5A) inhibitor. Eight patients with HCV genotype 1b, who were either treatment naive or prior nonresponders to pegylated interferon plus ribavirin (Rebetol; Schering-Plough) (PEG-IFN/RBV) therapy, were treated with DCV combined with PEG-IFN alpha-2b (Pegintron; Schering-Plough, Kenilworth, NJ) and RBV. To identify the cause of viral breakthrough, the preexistence and emergence of DCV-resistant variants at NS5A amino acids were analyzed by ultradeep sequencing. Sustained virological response (SVR) was achieved in 6 of 8 patients (75%), with viral breakthrough occurring in the other 2 patients (25%). DCV-resistant variant Y93H preexisted as a minor population at higher frequencies (0.1% to 0.5%) in patients who achieved SVR. In patients with viral breakthrough, DCV-resistant variant mixtures emerged at NS5A-31 over time that persisted posttreatment with Y93H. Although enrichment of DCV-resistant variants was detected, the preexistence of a minor population of the variant did not appear to be associated with virologic response in patients treated with DCV/PEG-IFN/RBV. Ultradeep sequencing results shed light on the complexity of DCV-resistant quasispecies emerging over time, suggesting that multiple resistance pathways are possible within a patient who does not rapidly respond to a DCV-containing regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT01016912.).


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Imidazóis/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico
11.
Hepatol Res ; 44(10): E273-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24102845

RESUMO

The aim of this study was to evaluate portal vein and bile duct toxicity after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). We retrospectively reviewed 63 patients who were administrated SBRT once for HCC. The prescribed doses were from 48 Gy in four fractions to 60 Gy in eight fractions. Portal vein thrombosis and bile duct stenosis were evaluated. The dose received by 2% of the volume (D2 ) of the portal vein and bile duct was calculated. Portal vein thrombosis was observed in three patients (4.8%). Common points of these patients were Child-Pugh class B and D2 of the portal vein 40 Gy or more (BED3 ≥200 Gy). Bile duct stenosis was observed in one patient (1.6%). The patient had a history of cholangiocarcinoma and left hepatic lobectomy. Portal vein thrombosis may be necessary to be considered when SBRT for HCC is administrated to patients in higher Child-Pugh class with higher D2 of the portal vein.

12.
Biochem Biophys Res Commun ; 441(1): 230-5, 2013 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-24140055

RESUMO

The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs.


Assuntos
Hepatite B/patologia , Hepatite C/patologia , Timidina Quinase/metabolismo , Alanina Transaminase/sangue , Animais , Antivirais/farmacologia , Modelos Animais de Doenças , Ganciclovir/administração & dosagem , Ganciclovir/farmacologia , Hepacivirus/efeitos dos fármacos , Hepatite B/sangue , Hepatite B/enzimologia , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite C/sangue , Hepatite C/enzimologia , Hepatite C/virologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Camundongos , Camundongos SCID , Camundongos Transgênicos , Análise de Sobrevida , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
13.
Hepatol Res ; 43(11): 1182-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23551911

RESUMO

AIM: Steatosis is a common histological feature of chronic liver disease, especially alcoholic and non-alcoholic fatty liver disease, as well as chronic hepatitis C. A recent study showed that evaluating the controlled attenuation parameter (CAP) with transient elastography was an efficient way of non-invasively determining the severity of hepatic steatosis. The objective of this study was to prospectively evaluate the utility of CAP for diagnosing steatosis in patients with chronic liver disease. METHODS: One hundred and fifty-five consecutive patients with suspected chronic liver disease underwent steatosis diagnosis using CAP, blood sample analyses, computed tomography for assessing the liver/spleen ratio and liver biopsy. Steatosis was graded according to the percentage of fat-containing hepatocytes: S0, less than 5%; S1, 5-33%; S2, 34-66%; and S3: more than 66%. RESULTS: The CAP was significantly correlated with steatosis grade, and there were significant differences between the CAP value of the S0 patients and those of the patients with other grades of steatosis. S0 and S1-3 hepatic steatosis were considered to represent mild and significant steatosis, respectively. The CAP values of the patients with mild and significant steatosis were significantly different (P < 0.0001). The area under the receiver-operator curve (AUROC) value of the CAP for diagnosing significant steatosis was 0.878 (95% confidence interval, 0.818-0.939), and the optimal CAP cut-off value for detecting significant steatosis was 232.5 db/m. In multivariate analysis, the CAP (P = 0.0002) and the liver to spleen ratio (P = 0.004) were found to be significantly associated with significant steatosis. CONCLUSION: The CAP is a promising tool for rapidly and non-invasively diagnosing steatosis.

14.
Nihon Shokakibyo Gakkai Zasshi ; 110(3): 456-64, 2013 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-23459541

RESUMO

A 61-year-old man was admitted to our hospital for examination of the cause of rapid growth of a liver cyst. We found a slight dilatation of bile duct in the vicinity of the liver cyst. Then, we underwent ERCP and found a communication between the bile duct and liver cyst. Bile cytodiagnosis revealed a large quantity of clonorchis eggs. The patient like to do eat raw freshwater fish and we suspected that the acute expansion of the cyst was due to clonorchiasis. Following administration of 40mg/kg praziquantel, the blood clonorchis antibody disappeared and the liver cyst also disappeared after 6 months. We encountered a case of clonorchiasis complicated with growth of a liver cyst. Medical interviews should be conducted carefully along with meticulous examinations.


Assuntos
Clonorquíase/complicações , Cistos/complicações , Hepatopatias/complicações , Colangiopancreatografia Retrógrada Endoscópica , Clonorquíase/diagnóstico , Cistos/diagnóstico , Humanos , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade
15.
Hepatol Res ; 43(7): 717-27, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23356835

RESUMO

AIM: To evaluate the dynamic computed tomography (CT) appearance of tumor response after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) and reconsider response evaluation criteria for SBRT that determine treatment outcomes. METHODS: Fifty-nine patients with 67 tumors were included in the study. Of these, 56 patients with 63 tumors underwent transarterial chemoembolization using lipiodol prior to SBRT that was performed using a 3-D conformal method (median, 48 Gy/four fractions). Dynamic CT scans were performed in four phases, and tumor response was evaluated by comparing tumor appearance on CT prior SBRT and at least 6 months after SBRT. The median follow-up time was 12 months. RESULTS: The dynamic CT appearance of tumor response was classified into the following: type 1, continuous lipiodol accumulation without early arterial enhancement (26 lesions, 38.8%); type 2, residual early arterial enhancement within 3 months after SBRT (17 lesions, 25.3%); type 3, residual early arterial enhancement more than 3 months after SBRT (19 lesions, 28.4%); and type 4, shrinking low-density area without early arterial enhancement (five lesions, 7.5%). Only two tumors with residual early arterial enhancement did not demonstrate remission more than 6 months after SBRT. CONCLUSION: The dynamic CT appearance after SBRT for HCC was classified into four types. Residual early arterial enhancement disappeared within 6 months in most type 3 cases; therefore, early assessment within 3 months may result in a misleading response evaluation.

16.
Oncology ; 83(4): 192-200, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22890083

RESUMO

OBJECTIVE: To compare the assessment of response and prognosis of patients to sorafenib treatment by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). METHODS: Sixty-six patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib were enrolled in this retrospective study. The response to treatment was evaluated by RECIST, mRECIST and changes in AFP and DCP. RESULTS: The median survival time of all patients was 8.6 months. The median time to radiological progression was 3.3 months. The response rates [complete response (CR) + partial response (PR)] by RECIST and mRECIST were 3.0 and 9.0%, respectively, while the disease control rates [CR + PR + stable disease (SD)] were 50 and 50%, respectively. Assessment by mRECIST of overall survival provided a better stratification of the patients according to the response to treatment (p = 0.009) than RECIST (p = 0.09). Assessment of overall survival by a change in AFP ratio of ≤ 1 at 8 weeks was better than that of >1 at 8 weeks (p = 0.002). The DCP ratio was not useful for assessment of overall survival. Multivariate analysis identified mRECIST response (CR + PR + SD; p = 0.001), AFP ratio at 8 weeks (≤ 1; p = 0.046) and Child-Pugh A before treatment (p = 0.012) as significant and independent determinants of survival. The combination of AFP ratio at 8 weeks, assessment by mRECIST and Child-Pugh score before treatment allows stratification of prognosis of patients treated with sorafenib. CONCLUSION: The combination of mRECIST and AFP ratio is useful for the assessment of prognosis of patients with advanced HCC treated with sorafenib.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/uso terapêutico , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/análogos & derivados , Avaliação de Resultados em Cuidados de Saúde , Compostos de Fenilureia , Prognóstico , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
17.
Hepatol Res ; 42(4): 368-75, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22151896

RESUMO

AIM: In this study, we evaluated the clinical characteristics of hepatocellular carcinoma (HCC) because the etiology of HCC has been changing recently. METHODS: Consecutive 1374 HCC patients at our institution from 1995 to 2009 were enrolled and clinical characteristics were investigated. RESULTS: Seventeen percent and 67% of HCC were related to hepatitis B virus (HBV-HCC) and hepatitis C virus (HCV-HCC), respectively. Fifteen percent of that was negative for hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (HCVAb) (NBNC-HCC). HCV-HCC tended to decrease and NBNC-HCC tended to increase in recent years. Patients with NBNC-HCC and HCV-HCC were significantly older than those with HBV-HCC. The complication rates of diabetes mellitus (DM), heavy alcohol consumption, hypertension, and hyperlipidemia in NBNC-HCC were significantly higher than those in other groups. Furthermore, the platelet counts and body mass index in NBNC-HCC were significantly higher than those of other groups. Among 209 NBNC-HCC patients, 58 patients underwent hepatic resection in which 29%, 36%, and 35% of those were based on non-alcoholic steatohepatitis (NASH), heavy alcohol consumption, and unknown etiology, respectively. DM was prevalent especially in NASH and heavy alcohol consumption. Cirrhosis was detected in 65%, 81%, and 15% in NASH-HCC, heavy alcohol consumption-HCC, and unknown etiology, respectively. CONCLUSIONS: NBNC-HCC has gradually been increasing in recent years. The present study elucidated that the presence of NASH and metabolic syndrome were important risk factors for NBNC-HCC and suggests that these patients should receive surveillance for HCC development.

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