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1.
Hepatol Commun ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676692

RESUMO

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.

2.
J Med Virol ; 93(11): 6247-6256, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34170517

RESUMO

The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child-Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV-related decompensated cirrhosis.

3.
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
4.
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
5.
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
6.
Clin Infect Dis ; 73(9): e3349-e3354, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33544129

RESUMO

BACKGROUND: It is unclear whether the fibrosis 4 index (FIB-4), a marker of liver fibrosis, at baseline and change in FIB-4 after sustained virological response (SVR) is associated with incident hepatocellular carcinoma (HCC) risk. In this study, we examined the association of incident HCC risk with baseline FIB-4 and sustained high FIB-4 (>3.25) at any time point after SVR. METHODS: A total of 3823 patients who received direct-acting antiviral treatment and achieved SVR were enrolled. The FIB-4 was measured 24 weeks after the end of direct-acting antiviral treatment and achievement of SVR (SVR24), and 1, 2, and 3 years after SVR24, after which subsequent HCC development was investigated. RESULTS: In patients with an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years after SVR24, subsequent HCC development was significantly higher than in those with an FIB-4 ≤3.25 at each point. The rates of HCC development 1, 2, 3, and 4 years after SVR24 were significantly higher in patients with sustained FIB-4 >3.25 than in those whose FIB-4 decreased to ≤3.25 (5.4%, 9.2%, 11.7%, and 16.0%, respectively, vs 2.2%, 3.1%, 3.7%, and 4.4%; P < .001). The adjusted hazard ratios (95% confidence intervals) for an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years later were 3.38 (2.4-4.8), 2.95 (1.9-4.7), 2.62 (1.3-5.1), and 3.37 (1.4-9.8), respectively. CONCLUSIONS: The FIB-4 could be used to assess HCC development risk at any time after SVR, and changes in FIB-4 were associated with changes in the HCC development risk. Repeated assessments of FIB-4 could serve as a prognostic indicator of a high-risk HCC cohort that may require more intensive HCC surveillance strategy.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Fatores de Risco , Resposta Viral Sustentada
7.
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.

8.
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.

9.
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
10.
Metabolites ; 10(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878279

RESUMO

Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers. We identified 463 lipids and compared their levels between the acute and recovery phases of the three types of DILI patients. Mixed and cholestatic types demonstrated specific plasma lipid alterations between the phases, but the hepatocellular type did not. Moreover, as specific indicators of mixed-type DILI, levels of several ceramides increased in the acute phase, while those of arachidonic acid-containing ether-linked phosphoglycerolipids decreased. In contrast, as specific indicators of cholestatic-type DILI, levels of palmitic acid-containing saturated or monounsaturated phosphatidylcholines increased in the acute phase, while those of arachidonic acid- or docosahexaenoic acid-containing ether-linked phosphoglycerolipids and phosphatidylinositols decreased. We also identified lipids with a relatively high capacity to discriminate the acute phase from the recovery phase and healthy subjects. These findings may help with understanding the pathophysiology of different DILI types and identify candidate biomarkers.

11.
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
12.
J Clin Invest ; 130(6): 3205-3220, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32163375

RESUMO

In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.


Assuntos
Coinfecção/imunologia , Hepacivirus/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite B/imunologia , Hepatite C/imunologia , Interferons/imunologia , Ativação Viral/imunologia , Animais , Quimiocina CCL5/imunologia , Quimiocina CXCL10/imunologia , Coinfecção/patologia , Coinfecção/virologia , Hepatite B/patologia , Hepatite B/virologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Camundongos
13.
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.

15.
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
16.
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
17.
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
18.
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
19.
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
20.
J Gastroenterol ; 53(1): 119-128, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28560477

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). METHODS: Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. RESULTS: Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12. CONCLUSIONS: This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Isoquinolinas/administração & dosagem , Diálise Renal , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Antivirais/farmacologia , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Imidazóis/farmacologia , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacologia , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia , Resposta Viral Sustentada , Resultado do Tratamento
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