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1.
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
2.
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
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.
Esophagus ; 18(3): 669-675, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33221955

RESUMO

BACKGROUND: The study aimed to investigate the efficacy of vonoprazan 10 mg compared with 20 mg in patients with erosive esophagitis. METHOD: Seventy-three patients with erosive esophagitis were randomly divided into two groups either vonoprazan 20 mg (n = 37) or 10 mg (n = 36). They were administered each dose for 4 weeks as the initial treatment followed by maintenance treatment with 10 mg for 8 weeks. The primary endpoints were mucosal healing rate and symptom relief at 4 weeks. The secondary endpoint was symptom relief at 12 weeks after the maintenance treatment. Mucosal healing was assessed endoscopically, and symptom relief was assessed using the FSSG score. RESULTS: At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients. CONCLUSION: Our findings suggest that initial treatment with vonoprazan 10 mg might be useful especially in patients with mild erosive esophagitis. Large controlled studies are warranted to confirm our investigation.

5.
Cancer Treat Res Commun ; 26: 100270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33338849

RESUMO

Atezolizumab is an immune checkpoint inhibitor that is a key drug in non-small-cell lung cancer treatment. However, it can cause immune-related adverse events, including liver injury. Several patterns of liver injury associated with immune checkpoint inhibitor therapy have been reported; however, not much is known about sclerosing cholangitis. We present here a case of lung adenocarcinoma with atezolizumab-induced secondary sclerosing cholangitis diagnosed using needle biopsy of the liver. A 77-year-old woman with lung adenocarcinoma, cT3N2M0, stage IIIA, was treated with concurrent chemoradiotherapy involving carboplatin and paclitaxel, which markedly reduced the tumor diameter. However, 5 months later, the lesion regrew, and she underwent 39 cycles of pemetrexed monotherapy. As pulmonary metastasis progressed, she was treated with atezolizumab. After 13 cycles of atezolizumab therapy, she complained of nausea. Laboratory tests showed elevated levels of the biliary tract and hepatic enzymes. Nevertheless, abdominal computed tomography and ultrasonography revealed no underlying related cause. Ultrasound-guided needle biopsy of the liver was performed, and histopathological analysis of biopsy samples showed features of sclerosing cholangitis. Further examinations were performed, and a diagnosis of atezolizumab-induced secondary sclerosing cholangitis without strictures and dilatations of the large bile ducts was established. Prednisolone was administered orally, after which the biliary tract and hepatic enzyme levels improved immediately. In patients presenting with a hepatic injury during immune checkpoint inhibitor therapy, clinicians should be aware of the possibility of immune checkpoint inhibitor-induced sclerosing cholangitis, even if the large bile ducts have no strictures and dilatations.

6.
Hepatol Res ; 50(11): 1234-1243, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32914512

RESUMO

AIM: Combination therapy with sofosbuvir (SOF) plus velpatasvir (VEL) is approved for patients with hepatitis C virus (HCV)-related decompensated cirrhosis. We analyzed the real-world efficacy of SOF/VEL therapy. METHODS: Thirty-three patients with HCV-related decompensated cirrhosis (25 and eight patients with Child B and C, respectively) were treated with SOF/VEL for 12 weeks. The HCV non-structural protein (NS)5A and NS5B drug resistance-associated substitutions (RASs) were determined by direct sequencing. RESULT: Thirty-two of 33 patients completed the treatment, but the remaining patient discontinued the therapy during third week of the treatment due to aggravation of hepatic encephalopathy. Serum HCV-RNA became negative during the treatment in all patients but relapsed after the end of therapy in five patients. In total, 28 out of 33 patients (85%) achieved sustained virological response 12 weeks following completion of treatment (SVR12). The SVR12 rate was 96% in patients with Child B, but significantly lower, at 50%, in patients with Child C (P < 0.05). In genotype 1b HCV-infected patients, all eight patients without baseline NS5A RASs, but only three of seven patients with RASs, achieved SVR12. Multivariate analysis identified Child B (odds ratio, 35.8 for Child C; P = 0.045) as an independent predictor of SVR12. Median serum albumin levels significantly increased only in patients who achieved SVR12. Child-Pugh scores improved in 16 of 28 patients (57%) following achievement of SVR12. CONCLUSION: The effect of SOF/VEL therapy is lower for patients with Child C. Improvement of hepatic function is expected after viral eradication with SOF/VEL therapy in patients with decompensated cirrhosis.

7.
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
8.
Clin J Gastroenterol ; 13(6): 1233-1238, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32656649

RESUMO

The hepatitis C virus (HCV) NS5A-P32 deletion (P32del) confers potent resistance to NS5A inhibitors. Chronic hepatitis C patients in whom NS5A-P32del variants had emerged during prior direct-acting antiviral (DAA) therapy with an NS5A inhibitor show poor response to DAA retreatment. Here, we report three patients with HCV NS5A-P32del infection who were treated with sofosbuvir, velpatasvir plus ribavirin (SOF/VEL + RBV) in a real-world setting. The patients developed HCV NS5A-P32del, L31F + P32del, or L31V + P32del variants following failure of daclatasvir plus asunaprevir (DCV/ASV) therapy. One of the patients failed to respond to subsequent DCV/ASV and beclabuvir therapy, and the remaining two patients failed to respond to subsequent glecaprevir and pibrentasvir therapy. All three patients completed 24-week SOF/VEL + RBV therapy. Serum HCV RNA became negative at the end of the therapy in all three patients. Two patients with NS5A-P32del and NS5A-L31F + P32del achieved sustained virological response 12 weeks after completion of treatment (SVR12), but HCV relapsed in the remaining NS5A-L13V + P32del patient. Direct sequence analysis detected no additional variants within either the NS5A or NS5B regions at the time of relapse. In conclusion, three patients with prior NS5A-P32del-associated DAA treatment failure received 24 weeks of SOF/VEL + RBV therapy, and two of the patients achieved SVR12.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Carbamatos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento
9.
Liver Cancer ; 9(1): 50-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32071909

RESUMO

Introduction: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered a safe and minimally invasive procedure. We previously reported that the mortality and complication rates for RFA were 0.038% (5/13,283 patients) and 3.54% (579 complications/16,346 procedures), respectively, from 1999 to 2010 (previous period). In this study, we investigated the clinical criteria for RFA and the mortality and complication rates from 2011 to 2015 (recent period). Methods: Data were collected from 25 centers by using a questionnaire developed by the Chugoku-Shikoku Society for Local Ablation Therapy of HCC. The criteria for RFA, RFA modification, use of image-guidance modalities, mortality, and complications during the previous and recent periods were compared. Results: We evaluated 11,298 procedures for 9,411 patients, including those that involved new devices (bipolar RFA and internally adjustable electrode system). The criterion of hepatic function for RFA increased from a Child-Pugh score ≤8 during the previous period to ≤9 during the recent period. The criteria regarding the tumor location and other risk factors have been expanded recently because of the increased use of several modifications of the RFA procedure and image-guidance modalities. The mortality rate was 0.064% (6/9,411 patients), and the complication rate was 2.92% (330 complications/11,298 procedures). There was no difference in mortality rates between the 2 periods (p = 0.38), but the complication rates was significantly lower during the recent period (p = 0.038). Discussion and Conclusions: Our findings confirmed that RFA, including the use of new devices, is a low-risk procedure for HCC, despite the expansion of the criteria for RFA during the recent period.

10.
Mol Clin Oncol ; 12(1): 60-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814977

RESUMO

Although sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), the predictive factors sorafenib tolerance in intermediate-stage HCC cannot be accurately determined. The aim of the current study was to identify the predictive characteristics for the continuation of sorafenib treatment (≥400 mg) in patients with transarterial chemoembolization (TACE)-refractory intermediate HCC and to identify candidates for second-line sorafenib treatment. A total of 33 TACE-refractory intermediate patients with HCC that were treated with sorafenib, and who had reached progressive disease (PD), were analyzed in the present retrospective study. Of 33 patients, 6 patients (18.1%) were able to continue sorafenib treatment (≥400 mg) until PD, however, a total of 27 patients (71.9%) were unable to continue treatment (<400 mg). The current study compared the baseline characteristics parameters to sorafenib ≥400 mg and <400 mg using a logistic regression model. The overall survival (OS) of patients receiving sorafenib ≥400 mg treatment was significantly increased compared with patients receiving sorafenib treatment <400 mg [554.5 days (228-674) vs. 219 days (134-369); P=0.0315). A univariate analysis was performed and indicated that Age (<75 years; P=0.021), total cholesterol (>180 mg/dl; P=0.026) and cholinesterase (ChE; ≥220 U/l; P=0.024) were significant factors, and a multivariate analysis indicated that ChE (≥220 U/l) was a significant prognostic factor (HR: 11.9; 95% CI: 1.19-118.0; P=0.004). Both progression-free survival [279 (204-403) vs. 117.5 (63-197) days; P=0.0136] and OS [470 (277-679) vs. 171.5 (80-236) days; P=0.0004] were significantly increased in patients with ChE levels ≥220 U/l compared with patients exhibiting ChE levels <220 U/l. Baseline high value of ChE in intermediate-stage HCC predicts the ability to continue sorafenib treatment at ≥400 mg.

12.
Nihon Shokakibyo Gakkai Zasshi ; 116(12): 1030-1038, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31827043

RESUMO

A 77-year-old Japanese man with a gastrointestinal stromal tumor (GIST) had undergone a duodenectomy 11 years prior. At that time, he had an incidentally detected left renal cell carcinoma, for which he underwent a nephrectomy and was followed-up at our institution. Twenty-four months after the nephrectomy, a 13-mm low-density mass was found on abdominal computed tomography (CT). Contrast-enhanced ultrasonography indicated an irregular hyperenhancement in the vascular phase and a defect on the post-vascular image. A tumor biopsy for differential diagnosis revealed that the tumor was a GIST. Since positron emission tomography-CT and capsule endoscopy revealed no evidence of a primary lesion, we performed a partial hepatectomy without adjuvant treatment. Microscopic examination revealed that the tumor consisted of uniform spindle cells with a fascicular growth pattern. Immunohistochemical examination revealed c-kit and CD34 expressions, similar to those found in the resected duodenal GIST specimen 11 years prior. We diagnosed metastatic liver tumor from the duodenal GIST resected 11 years prior. The patient remains alive without disease recurrence 24 months after the hepatectomy. Long-term surveillance is required after resection of a high-risk primary GIST.


Assuntos
Duodeno , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Idoso , Hepatectomia , Humanos , Masculino , Recidiva Local de Neoplasia
13.
J Gastroenterol ; 54(8): 742-751, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30848363

RESUMO

BACKGROUND: The virological efficacy and safety of the direct-acting antiviral (DAA) regimen consisting of daclatasvir, asunaprevir, and beclabuvir (DCV/ASV/BCV) for patients chronically infected with hepatitis C virus (HCV) genotype 1 have not been previously evaluated in Japanese real-world settings. METHODS: In a Japanese nationwide multicenter study, the rate of sustained virologic response (SVR) and safety were analyzed in 91 patients who started the DCV/ASV/BCV regimen between November 2016 and July 2017. SVR rates were compared based on baseline patient characteristics. RESULTS: More than 60% of patients had a history of failure to achieve SVR with interferon (IFN)-free DAA therapy. Overall, 50 of 91 patients (54.9%) achieved SVR. Multivariate analysis identified a history of failure with IFN-free DAA therapy and pretreatment HCV RNA levels as factors significantly associated with treatment failure. Whereas the SVR rate in patients without a history of IFN-free DAA therapy was 91.7% (33 of 36 patients), it was only 30.9% (17 of 55 patients) among patients with a history of IFN-free DAA therapy. The rate of discontinuation due to an adverse event was 4.4%. CONCLUSIONS: Many patients treated with the DCV/ASV/BCV regimen have a history of a failure to achieve SVR with previous IFN-free DAA therapy. SVR rate was not as high as that in pre-approval clinical trial of this regimen in IFN-free DAA-naïve patients. In addition, most patients with a history of failure with IFN-free DAA therapy, particularly the DCV/ASV regimen, showed resistance to this regimen.


Assuntos
Antivirais/administração & dosagem , Benzazepinas/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Indóis/administração & dosagem , Isoquinolinas/administração & dosagem , Sulfonamidas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Benzazepinas/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Indóis/efeitos adversos , Isoquinolinas/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
14.
Nihon Shokakibyo Gakkai Zasshi ; 115(5): 485-493, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29743457

RESUMO

An 83-year-old woman was admitted to our hospital because of a space-occupying lesion (SOL) in the liver. Enhanced computed tomography (CT) showed a nodule measuring 20mm in size in the posterosuperior segment of the right hepatic lobe (S7) and another nodule measuring 14mm in size in the anterosuperior segment of the right hepatic lobe (S8). The margins of these nodules showed faint enhancement in the arterial phase and presented as low-density areas in the equilibrium phase. The S8 SOL could not be easily identified using ultrasonography (US). However, the S7 SOL could be clearly identified as a nodule accompanying the marginal enhancement in the early vascular phase and a defect in the late vascular phase using contrast-enhanced US. On gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, both nodules were described as low-intensity lesions in the T1 phase, high-intensity lesions in the T2 phase, faint high-intensity diffusion-weighted images, and clear low-intensity lesions in the hepatobiliary phase. On positron-emission CT, there was no uptake of 18F-fluorodeoxyglucose in these nodules. Hepatectomy was performed because we were unable to rule out a malignant tumor. Histopathologically, these lesions demonstrated collapsed vascular spaces against a background of rich paucicellular fibrous stroma and were diagnosed as sclerosed hemangiomas. The occurrence of multiple sclerosed hemangiomas is rare and often difficult to diagnose because of variable findings on imaging studies. We report a case of multiple hepatic sclerosed hemangiomas, which was difficult to diagnose preoperatively. Moreover, we have reviewed the literature, particularly with respect to the relevant imaging findings.


Assuntos
Hemangioma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética
15.
J Gastroenterol ; 53(10): 1142-1150, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29626296

RESUMO

BACKGROUND: We aimed to describe the real-world efficacy and safety of combination therapy with ledipasvir and sofosbuvir (LDV/SOF) for chronic hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS: This retrospective analysis of a prospective, nationwide, multicenter registry included GT1-infected patients treated with LDV/SOF for 12 weeks. We assessed the rate of sustained virological response at 12 weeks post-treatment (SVR12), incidence of adverse events, and serum markers of hepatocellular carcinoma (HCC). RESULTS: Among the 1461 patients included (mean age, 69 years; 29.5% aged > 75 years; cirrhosis, 23.8%; history of treatment for HCC, 10.9%), the overall SVR12 rate was 98.4% (1438/1461). Factors associated with treatment failure were cirrhosis (odds ratio, 4.19; p = 0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p = 0.0004). The SVR12 rate in patients with cirrhosis and NS5A RASs was 93.0% compared to 100% in patients without cirrhosis or NS5A RASs. In patients with SVR, the levels of alpha-fetoprotein (AFP), AFP-L3, and Mac-2 binding protein glycosylation isomer (M2BPGi) decreased from baseline to end of treatment (from 13.4 ± 37.6 to 6.0 ± 10.6 ng/mL, p < 0.0001; from 2.2 ± 4.9 to 1.5 ± 6.3%, p < 0.005; and from 3.6 ± 3.7 to 2.0 ± 3.5 cut-off index, p < 0.0001; respectively). Adverse events were rare and not associated with age. No decrease in estimated glomerular filtration rate was observed in patients with baseline chronic kidney disease stage 3. CONCLUSIONS: LDV/SOF therapy is highly effective and safe in elderly Japanese patients with HCV GT1, even in the presence of cirrhosis or NS5A RASs. Patients with SVR may have a lower risk of HCC.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/etiologia , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Japão/epidemiologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Cruz Vermelha , Estudos Retrospectivos , Risco , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Falha de Tratamento , Proteínas não Estruturais Virais/análise , Adulto Jovem , alfa-Fetoproteínas/análise
16.
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
17.
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
18.
J Gastroenterol ; 53(4): 548-556, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28815329

RESUMO

BACKGROUND: In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy. METHODS: Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined. RESULTS: The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log10 HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed. CONCLUSION: Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Ribavirina/uso terapêutico , Uridina Monofosfato/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral/sangue , Retratamento/efeitos adversos , Retratamento/métodos , Ribavirina/efeitos adversos , Sofosbuvir , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Falha de Tratamento , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico
19.
Infect Genet Evol ; 55: 343-349, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28987806

RESUMO

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans worldwide and can be transmitted via the fecal-oral route. Four HEV strains (HE-JA14-2173, HE-JA15-1335, HE-JA15-1920 and HE-JA16-0610) obtained from patients with imported (from Pakistan or India) or autochthonous acute hepatitis E in Japan were most closely related to the Nepalese and Mongolian genotype 1 HEV strains of unassigned subtype within the partial ORF2 sequence. To investigate whether a putative novel subtype (1g) of genotype 1 can be assigned, full-length genomic sequences were determined for the four HEV strains. They shared 95.4-99.2% nucleotide identity over the entire genome, and differed by 6.3-11.7% from the reported HEV strains of subtypes 1a-1f and by only 0.6-4.7% from a Mongolian genotype 1 HEV strain (MNE15-072) of unassigned subtype. A phylogenetic analysis showed that the four HEV strains obtained in the present study formed a cluster with MNE15-072, with a bootstrap value of 100%. Although the p-distance between subtypes 1a and 1f was 0.048-0.083, these five strains showed a higher nucleotide p-distance value of 0.068-0.138 with the genotype 1 HEV strains of subtypes 1a-1f. A BLAST search revealed the presence of candidate members of subtype 1g HEV in at least five other countries, including France, Israel, the Netherlands, Portugal, and the UK, sharing identities of 95.4-99.6% with the HE-JA16-0610 strain within the common sequence of 294-867 nucleotides. These results support the assignment of a new subtype 1g within genotype 1 and suggest a global distribution of subtype 1g strains. Subtype 1g strains found in Europe can be imported from Asia. Further studies are needed to confirm the global distribution of HEV subtype 1g.


Assuntos
Genoma Viral , Genômica , Vírus da Hepatite E/classificação , Vírus da Hepatite E/genética , Hepatite E/epidemiologia , Hepatite E/virologia , Adolescente , Adulto , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/virologia , Genômica/métodos , Hepatite E/imunologia , Vírus da Hepatite E/imunologia , Humanos , Japão/epidemiologia , Masculino , Filogenia , Estudos Soroepidemiológicos , Sequenciamento Completo do Genoma , Adulto Jovem
20.
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
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