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1.
BMC Gastroenterol ; 21(1): 489, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930140

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA. METHODS: In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks. RESULTS: At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was -0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]). CONCLUSIONS: In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Humanos , Estudos Prospectivos , Tenofovir/uso terapêutico
2.
Intern Med ; 60(20): 3195-3203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34657905

RESUMO

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.


Assuntos
Hepatopatias , Transtornos do Sono-Vigília , Idoso , Humanos , Hepatopatias/complicações , Hepatopatias/epidemiologia , Masculino , Medição da Dor , Prurido/diagnóstico , Prurido/epidemiologia , Prurido/etiologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Inquéritos e Questionários
3.
BMC Cancer ; 21(1): 699, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126947

RESUMO

BACKGROUND: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. METHODS: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. RESULTS: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. CONCLUSION: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , alfa-Fetoproteínas/metabolismo , Idoso , Antivirais/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Taxa de Filtração Glomerular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco
4.
Cancer Med ; 10(11): 3584-3592, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33960691

RESUMO

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

5.
Liver Cancer ; 10(2): 115-125, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33977088

RESUMO

Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

6.
Gastroenterol Rep (Oxf) ; 9(2): 133-138, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34026220

RESUMO

Background: Lenvatinib is used for unresectable hepatocellular carcinoma (u-HCC) as first-line, as well as second- and third-line therapy in Japan. We evaluated the therapeutic efficacy of newly developed ramucirumab when given after lenvatinib for post-progression treatment. Methods: Of 385 patients with u-HCC and treated with lenvatinib at 16 different institutions in Japan between May 2018 and January 2020, 28 who received ramucirumab as the next treatment were enrolled and therapeutic responses were evaluated in a retrospective manner. Results: The median age of the 28 patients given ramucirumab was 70 years and the median albumin-bilirubin score was -2.19. Of the 28 patients, 23 were male, 21 were classified as Child-Pugh A and 7 as Child-Pugh B, and 25 were Barcelona Clinic Liver Cancer Stage C. Ramucirumab was given as second-line therapy in 14, third-line in 9, and fourth-line in 5. Therapeutic response was obtained in only 26 patients; the objective response rate was 3.8% (1/26) and the disease-control rate was 42.3% (11/26), with a median period to progression of 2.0 months. The reasons for discontinuation of ramucirumab were progression of disease in 16 and Grade 3 adverse events (gastrointestinal bleeding, ascites) in 2. Conclusions: The anticipated therapeutic efficacy of ramucirumab for post-progression treatment following lenvatinib was not seen in our early experience.

7.
Hepatol Res ; 51(8): 880-889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33837620

RESUMO

AIM: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure. METHODS: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting. RESULTS: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment. CONCLUSION: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.

8.
Oncology ; 99(8): 518-527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906189

RESUMO

AIM/BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage hepatocellular carcinoma (HCC). In this study, we investigated the impact of early lenvatinib administration in patients with intermediate-stage HCC, especially those with tumors beyond the up-to-7 criteria. MATERIALS/METHODS: A total of 208 patients with intermediate-stage HCC whose initial treatment was early lenvatinib administration or TACE were enrolled. Multivariate overall survival analysis was performed in this cohort. In addition, the impact of early lenvatinib administration on survival in patients with HCC beyond the up-to-7 criteria was clarified using inverse probability weighting (IPW) analysis. RESULTS: The overall cumulative survival rates at 6, 12, 18, and 24 months were 94.4, 79.9, 65.8, and 50.1%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that HCC treatment with lenvatinib (hazard ratio [HR], 0.199; 95% confidence interval [CI], 0.077-0.517; p < 0.001), α-fetoprotein ≥100 ng/mL (HR, 1.687), Child-Pugh class B disease (HR, 1.825), and beyond the up-to-7 criteria (HR, 2.016) were independently associated with overall survival. The 6-, 12-, 18-, and 24-month cumulative survival rates were 96.0, 90.4, 65.7, and 65.7%, respectively, in patients treated with lenvatinib, and 94.1, 78.5, 65.3, and 48.4%, respectively, in patients who received TACE (p < 0.001). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that lenvatinib therapy was significantly associated with overall survival in patients with HCC beyond the up-to-7 criteria (HR, 0.230; 95% CI, 0.059-0.904; p = 0.035). CONCLUSIONS: Lenvatinib may be a suitable first-line treatment for patients with intermediate-stage HCC beyond the up-to-7 criteria.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Análise Multivariada , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
9.
J Gastroenterol ; 56(1): 90-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33278003

RESUMO

BACKGROUND: The effects of direct-acting antivirals (DAAs) on survival and recurrence rates after curative hepatocellular carcinoma (HCC) treatment in patients with hepatitis C virus (HCV) infection remain controversial. METHODS: This retrospective, multicenter study involved Child-Pugh class A patients within the Milan criteria who had a first diagnosis of HCC and survived 6 months or longer after undergoing hepatectomy or radiofrequency ablation (RFA). The DAA-treated group (DAA group) included 56 patients, and the DAA-untreated group (untreated group) included 261 patients. The study was conducted using the propensity score-matched (1:2) DAA group and untreated group, 56 and 112 patients, respectively. RESULTS: The survival rate at 48 months in the DAA group and the untreated group was 91.0% and 68.7%, respectively, showing significantly better survival in the DAA group (HR: 0.33; 95% CI 0.13-0.84; p = 0.021). The recurrence rate at 48 months was 36.7% and 66.7%, respectively, showing a significantly lower recurrence rate in the DAA group (HR, 0.46; 95% CI 0.27-0.77; p = 0.003). The median albumin-bilirubin (ALBI) score at 3 years post-HCC treatment was - 2.84 in the DAA group and - 2.34 in the untreated group. The ALBI score showed a significant improvement from baseline to 3 years post-HCC treatment (p = 0.001), whereas that in the untreated group showed a significant decline (p = 0.040). CONCLUSIONS: DAAs after HCC treatment prevents deterioration of hepatic functional reserve and significantly improves both recurrence and survival rates.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Ablação por Radiofrequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Seguimentos , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
J Gastroenterol Hepatol ; 36(7): 1812-1819, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33171524

RESUMO

BACKGROUND AND AIM: This study aimed to elucidate the clinical importance of muscle volume loss (pre-sarcopenia) in patients receiving lenvatinib as treatment for unresectable hepatocellular carcinoma (u-HCC). METHODS: Of 437 u-HCC patients treated with lenvatinib at specific institutions in Japan between March 2018 and May 2020, 151 with available computed tomography imaging data from the time of lenvatinib introduction were enrolled. Pre-sarcopenia was diagnosed based on a previously reported cut-off value calculation formula [psoas muscle area at level of middle of third lumbar vertebra (cm2 )/height (m)2 ]. Clinical features and prognostic factors for overall survival (OS) with inverse probability weighting were investigated retrospectively for their relationship with pre-sarcopenia. RESULTS: Cox hazard multivariate analysis showed alpha-fetoprotein (≥400 ng/mL) (hazard ratio [HR] 2.271, P < 0.001), Barcelona Clinic Liver Cancer stage (C and D) (HR 1.625, P = 0.018), and positive for pre-sarcopenia (HR 1.652, P = 0.042) to be significant prognostic factors. OS rates for the pre-sarcopenia group (n = 41) were worse than those for the non-pre-sarcopenia group (n = 110) (0.5-, 1-, and 1.5-year OS: 72.5%, 27.9%, and 7.0% vs 80.7%, 56.7%, and 46.1%, respectively; P < 0.001), as was progression-free survival (P = 0.025). Time to stopping lenvatinib or disease progression was better in the non-pre-sarcopenia group (0.5-, 1-, and 1.5-year OS: 48.0%, 24.5%, and 8.4% vs 20.0%, 10.3%, and 4.2%, respectively; P < 0.001). Also, the frequency of the adverse event appetite loss (any grade) was greater in the pre-sarcopenia group (43.9% vs 18.2%, P = 0.003). CONCLUSION: Pre-sarcopenia was shown to be a significant prognostic factor in patients treated with lenvatinib for u-HCC.

11.
Infect Dis Ther ; 10(1): 269-280, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33141401

RESUMO

INTRODUCTION: The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with ledipasvir (LDV) plus sofosbuvir (SOF) were assessed in patients who were chronically infected with hepatitis C virus (HCV) genotype 2. METHODS: A total of 126 patients with chronic hepatitis C due to HCV genotype 2 infection who were treated with the LDV/SOF regimen were enrolled. The sustained virological response (SVR) rate and safety were analyzed. SVR was assessed in the intention-to-treat (ITT) population as well as in the modified intention-to-treat (mITT) population, which excluded patients with non-virological failure, including those who dropped out before the SVR assessment. RESULTS: The overall SVR rates of the ITT and mITT populations were 87.3% (95% confidence interval [CI] 80.2-92.6) (110/126) and 97.3% (95% CI 92.4-99.4) (110/113), respectively. In the mITT population, the percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 92.9% (95% CI 86.5-96.9) (105/113), 99.1% (95% CI 95.2-100.0) (112/113), and 100.0% (95% CI 97.4-100.0) (113/113), respectively. Subgroup analyses of the mITT population showed no significant differences in SVR rates according to age, sex, HCV genotype (subtype), history of interferon-based therapy, baseline FIB-4 index, or baseline estimated glomerular filtration rate. In all subpopulations, the SVR rates were > 90%. There were no severe adverse events associated with the treatment. CONCLUSION: The LDV/SOF regimen showed high virological efficacy and acceptable safety in patients with HCV genotype 2 infection. TRIAL REGISTRATION: UMIN registration no. 000038604.

12.
Eur J Gastroenterol Hepatol ; 32(2): 261-268, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32282541

RESUMO

OBJECTIVE: Lenvatinib, a newly developed molecularly targeted agent, has become available as a first-line therapy in patients with unresectable hepatocellular carcinoma (HCC). The platelet-to-lymphocyte ratio (PLR) has been associated with poor outcome in various malignancies, including HCC. In this study, we investigated the ability of PLR to predict outcomes in patients with unresectable HCC who received lenvatinib. METHODS: Multivariate survival analysis was performed in 283 patients with unresectable HCC who received lenvatinib. In addition, the utility of PLR for predicting survival was clarified using an inverse probability weighting (IPW) analysis. RESULTS: Cumulative overall survival at 100, 200, 300, 400, and 500 days was 95.2, 83.8, 68.3, 60.3, and 49.9%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that PLR (≥150) [hazard ratio, 1.588; 95% confidence interval (CI), 1.039-2.428; P = 0.033], α-fetoprotein level, and Barcelona clinic liver cancer stage were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high PLR (P = 0.029). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that PLR (≥150) (hazard ratio, 1.396; 95% CI, 1.051-1.855; P = 0.021) was significantly associated with overall survival. Conversely, univariate analysis with Cox proportional hazards modeling adjusted only by IPW showed that PLR (≥150) (hazard ratio, 1.254; 95% CI, 1.016-1.549; P = 0.035) was significantly associated with progression-free survival. PLR values were not independently associated with therapeutic responses before or after IPW-adjusted logistic regression analysis. CONCLUSIONS: PLR predicted overall survival in patients with unresectable HCC who received lenvatinib.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos , Compostos de Fenilureia , Prognóstico , Modelos de Riscos Proporcionais , Quinolinas
13.
Intern Med ; 59(22): 2825-2830, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33191369

RESUMO

Objective There is a paucity of information on whether the hepatitis B virus (HBV) vaccine, derived from HBV genotype C, can prevent mother-to-child transmission of HBV genotype D. The aim of this study was to clarify this issue. Methods The subjects consisted of 25 children (8.5±4.1 years old, 7 males, 18 females), born to 17 mothers who were chronically infected with HBV genotype D. Of these, 20 children were inoculated with the genotype C-derived vaccine, one was inoculated with the genotype A-derived vaccine, and one was inoculated with both the A- and C-derived vaccines. Information on the type of vaccine given to the remaining three children was not available. The serum levels of HB surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HB core (anti-HBc) of the children, as well as HBV markers of the mothers, were examined. Results All mothers were positive for HBsAg (6,563±11,005 IU/mL), negative for HBeAg, and positive for anti-HBe. HBV-DNA levels (log IU/mL) were <3.3 in 7 mothers, 3.3-4.3 in 9 mothers, and >4.3 in one mother. HBsAg and anti-HBc were negative in all children, regardless of the type of vaccine used. Anti-HBs were positive in 13 children and negative in 12. Conclusion All children born to mothers infected with genotype D, including 20 who were inoculated with the genotype C-derived vaccine, were negative for both HBsAg and anti-HBc. These results suggest that the genotype C-derived HB vaccine is effective in preventing mother-to-child transmission from mothers infected with HBV genotype D.


Assuntos
Genótipo , Vacinas contra Hepatite B/imunologia , Hepatite B/genética , Hepatite B/imunologia , Hepatite B/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Criança , Pré-Escolar , DNA Viral/genética , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Japão , Masculino
14.
Clin J Gastroenterol ; 13(5): 891-895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32468502

RESUMO

We treated a 66-year-old Japanese male with unresectable hepatocellular carcinoma (u-HCC) for multiple (>5) liver tumors (maximum 2.6 cm in size, Child-Pugh B score 7) in September 2018. The patient had a history of psoriasis vulgaris and sorafenib (SOR) was introduced (800 mg/day) because of transcatheter arterial chemoembolization (TACE) refractoriness. However, psoriasis vulgaris exacerbation and a high fever were observed 2 weeks later, and the patient was admitted, after which improvement of psoriasis vulgaris was obtained with external medicine administration and SOR intake discontinuation. Few reports have noted exacerbation of psoriasis vulgaris caused by SOR treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Psoríase , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Sorafenibe/efeitos adversos , Resultado do Tratamento
15.
J Med Virol ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374470

RESUMO

Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P = .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P = .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P = .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR = 1.090; 95%CI, 1.024-1.160, P = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.

16.
Nihon Shokakibyo Gakkai Zasshi ; 117(3): 261-269, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32161248

RESUMO

A man in his 40s visited a facility with the chief complaint of abdominal pain;liver dysfunction was detected, and consequently, he was referred to our hospital for further examinations. His medical history was unremarkable. He used to drink alcohol (beer, 1500mL) every day. Magnetic resonance imaging and computed tomography showed stenosis of the distal bile duct and slight dilation of the upstream bile duct. Common bile duct stones and gallbladder stones were not detected. Malignant tumors in the bile duct biopsy were not discovered. The patient underwent subtotal stomach preserving pancreatoduodenectomy. The pathological diagnosis was chronic pancreatitis with amputation neuroma-like neurogenesis of the bile duct.


Assuntos
Neuroma/diagnóstico , Pancreatite Crônica/diagnóstico , Amputação , Ducto Colédoco , Humanos , Masculino , Neurogênese , Neuroma/cirurgia
17.
Liver Cancer ; 9(1): 73-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32071911

RESUMO

Background/Aim: Post-progression treatment following tyrosine-kinase inhibitor (TKI) failure in patients with unresectable hepatocellular carcinoma (u-HCC) is important to prolong post-progression survival (PPS), which has a good correlation with overall survival (OS). This study aimed to elucidate the clinical features of progressive disease (PD) in patients treated with lenvatinib (LEN). Materials/Methods: From March 2018 to June 2019, 156 u-HCC patients with Child-Pugh A were enrolled (median age: 71 years, Child-Pugh score 5:6 = 105:51, BCLC A:B:C = 8:56:92, modified albumin-bilirubin grade (mALBI) 1:2a:2b = 59:42:55, past history of sorafenib:regorafenib = 57:17). Clinical features were retrospectively evaluated. Results: The median observation period was 8.5 months. Median OS was not obtained, while median time to decline to Child-Pugh B (CPB) was 11.4 months, median time to progression (TTP) was 8.4 months, and the period of LEN administration was 7.3 months. When we compared predictive values for time to decline to CPB based on Child-Pugh score and mALBI, values for Akaike information criterion (AIC) score and c-index of mALBI were superior as compared to Child-Pugh score (AIC: 592.3 vs. 599.7) (c-index: 0.655 vs. 0.597). Of the 73 patients with PD, 32 (43.8%) showed no decline to CPB or death. After excluding 3 without alpha-fetoprotein data at PD determination, only 14 (20.0%) of 70 showed REACH-2 eligibility. Non-mALBI 1/2a at the start of LEN was a significant risk factor for decline to CPB during LEN treatment (HR 2.552, 95% CI: 1.577-4.129; p < 0.001). Conclusion: Introduction of TKI therapy including LEN for u-HCC patients with better hepatic function (mALBI 1/2a: ALBI score ≤-2.27), when possible, increases the chance of undergoing post-progression treatment, which can improve PPS.

18.
Oncology ; 98(5): 295-302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097925

RESUMO

BACKGROUND/AIM: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera's prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. METHODS: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36). RESULTS: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were "not reached" (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = -0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. CONCLUSIONS: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Bilirrubina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Testes de Função Hepática/métodos , Neoplasias Hepáticas/metabolismo , Masculino , Avaliação Nutricional , Prognóstico , Albumina Sérica Humana/metabolismo
19.
Liver Int ; 40(4): 968-976, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32064740

RESUMO

BACKGROUND AND AIMS: Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. METHODS: A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves. RESULTS: Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival. CONCLUSIONS: NLR can be associated with outcomes in patients with HCC treated with lenvatinib.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos , Neutrófilos , Compostos de Fenilureia , Prognóstico , Quinolinas
20.
J Gastroenterol Hepatol ; 35(8): 1420-1425, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31950525

RESUMO

BACKGROUND AND AIM: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent. METHODS: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen. RESULTS: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching. CONCLUSION: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/diagnóstico , Idoso , Ácidos Aminoisobutíricos , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Estudos de Coortes , Ciclopropanos , Humanos , Japão , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prolina/análogos & derivados , Pontuação de Propensão , Pirrolidinas , Quinoxalinas/administração & dosagem , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Fatores de Tempo
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