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1.
Hepatol Res ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799975

RESUMO

BACKGROUND/AIM: Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple. MATERIAL/METHODS: From September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST). RESULTS: Atez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%). CONCLUSION: Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition.

2.
Clin Endosc ; 54(6): 810-817, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34775697

RESUMO

Afferent loop syndrome (ALS) is a mechanical obstruction of the afferent limbs after gastrectomy with gastrojejunostomy reconstruction. Patients with cancer recurrence require immediate and less invasive treatment because of their poor condition. Percutaneous transhepatic/transluminal drainage (PTD) and endoscopic enteral stenting offer reasonable palliative treatment for malignant ALS but are not fully satisfactory in terms of patient quality of life (QoL) and stent patency. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using a lumen-apposing metal stent may address these shortcomings. Clinical data from 11 reports showed that all patients who had undergone EUS-GE had positive technical and clinical outcomes. The adverse event rate was 11.4%, including only mild or moderate abdominal pain, with no severe adverse events. Indirect comparative studies indicated that patients who had undergone EUS-GE had a significantly superior QoL, a higher clinical success rate, and a lower reintervention rate than those who had undergone PTD or endoscopic enteral stenting. Although the evidence is limited, EUS-GE may be considered as a first-line treatment for malignant ALS because it has better clinical outcomes than other less invasive treatments, such as PTD or endoscopic enteral stenting. Further prospective randomized control trials are necessary to establish EUS-GE as a standard treatment for ALS.

3.
Surg Today ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708306

RESUMO

PURPOSE: This study assessed the significance of measuring liver stiffness using virtual touch quantification before hepatectomy to predict posthepatectomy refractory ascites. METHODS: A total of 267 patients with hepatocellular carcinoma who underwent hepatectomy were prospectively analyzed. Liver stiffness was defined as the median value of the virtual touch quantification (Vs; m/s) by acoustic radio-force-impulse-based virtual touch. RESULTS: A multivariate analysis showed that Vs and the aspartate aminotransferase-to-platelet ratio index were independent risk factors for postoperative refractory ascites (odds ratio = 3.27 and 3.08, respectively). The cutoff value for Vs was 1.52 m/s (sensitivity: 59.5%, specificity: 88.6%) as determined by the analysis of the receiver-operating characteristic curve, and the area under the receiver-operating characteristic curve was 0.79. The cutoff value for the aspartate aminotransferase-to-platelet ratio was 0.952 (sensitivity: 65.5%, specificity: 82.9%), and the area under the receiver-operating characteristic curve was 0.75. CONCLUSIONS: Vs is an independent risk factor for refractory ascites after hepatectomy. The measurement of liver stiffness by virtual touch quantification before hepatectomy can help estimate the risk of postoperative refractory ascites. Nonsurgical treatments should be considered for the management of patients who are at high risk for refractory ascites.

4.
Diagnostics (Basel) ; 11(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34359344

RESUMO

We aimed to examine the association between sarcopenia-related factors and metabolic syndrome (Met-S) in patients with chronic liver diseases (CLDs, n = 582, average age = 59.5 years, 290 males, 168 liver cirrhosis cases). Met-S was determined based on the Japanese criteria. Sarcopenia was determined based on grip strength (GS) and skeletal muscle index (SMI) by bioelectrical impedance analysis. Our cohort was divided into the four groups: (A) sarcopenia (n = 44), (B) dynapenia (n = 45), (C) presarcopenia (n = 112), and (D) the control (n = 381). Impacts of GS and SMI on Met-S were investigated. In males, waist circumference (WC) ≥ 85 cm was observed in 199 patients (68.6%), while in females, WC ≥ 90 cm was observed in 94 patients (32.2%). Met-S was identified in 109 patients (18.7%). The proportion of Met-S in the group A, B, C and D were 18.2%, 48.9%, 8.0%, and 18.4% (A vs. B, p = 0.0033; B vs. C, p < 0.0001; C vs. D, p = 0.0081; A vs. C, p = 0.0867; A vs. D, p = 1.000, B vs. D, p < 0.0001; overall p value < 0.0001). Multivariate analysis revealed that age, gender, and group B (dynapenia) were significant factors linked to the presence of Met-S. In conclusion, dynapenia rather than sarcopenia is associated with Met-S in CLD patients.

5.
In Vivo ; 35(4): 2451-2456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182530

RESUMO

AIM: To examine the relationship between longitudinal quality of life (QOL) change, as assessed by the 36-Item Short Form Health Survey (SF-36), sarcopenia-related factors and body composition in patients with chronic liver diseases (CLDs). PATIENTS AND METHODS: Data from patients with CLDs (n=184) were retrospectively analyzed, focusing on factors associated with the difference of physical and mental component summary score (PCS and MCS) in SF-36 between the two visits (ΔPCS and ΔMCS). The difference of serum albumin level, body mass index (BMI), arm circumference, arm muscle circumference, grip strength (GS), skeletal muscle index, extracellular to total body water ratio between the two visits were included into the multiple regression analysis. RESULTS: Δalbumin (p=0.0325) and ΔGS (p<0.0001) were independent factors linked to ΔPCS Δalbumin (p=0.0005) and ΔBMI (p=0.0232) were independent factors linked to ΔMCS Conclusion: Significance of serum albumin level, muscle strength and body composition on health-related QOL in CLD patients should be emphasized.


Assuntos
Hepatopatias , Sarcopenia , Humanos , Força Muscular , Qualidade de Vida , Estudos Retrospectivos
6.
Cancer Rep (Hoboken) ; : e1464, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114752

RESUMO

BACKGROUND: Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported. AIM: This retrospective clinical study aimed to elucidate early responses to Atez/Bev. METHODS: From September 2020 to April 2021, 171 u-HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin-bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively. RESULTS: In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR-6W/DCR-6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR-6W/DCR-6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post-progression treatment following lenvatinib (ORR-6W/DCR-6W = 7.7%/79.5%), for which no known effective post-progression treatment has been established. In 111 patients who underwent a 6-week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (-2.525 ± 0.419 vs -2.323 ± 0.445, p < .001), but then recovered at 6-weeks (-2.403 ± 0.452) as compared to 3-weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%). CONCLUSION: Atez/Bev might have therapeutic potential not only as first but also later-line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.

7.
Hepatol Res ; 51(8): 860-869, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34046970

RESUMO

AIM: The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with chronic hepatitis C virus who receive direct-acting antiviral therapy and achieve sustained virological response. This study investigated two risk factors for HCC in these patients; specifically, hepatic fibrosis and steatosis. METHODS: A total of 355 patients in whom hepatitis C virus was eradicated by direct-acting antiviral were evaluated. Fibrosis and steatosis were assessed using transient elastography (TE) and the controlled attenuation parameter (CAP). Inverse probability weighting was applied to patient age, sex, albumin-bilirubin, α-fetoprotein, history of HCC, TE, or CAP. RESULTS: The 12-, 24-, and 36-month cumulative incidence rates of HCC were 0.9%, 2.4%, and 4.1%, respectively. Univariate analysis with the Cox proportional hazards model showed that whereas a high TE value (≥10 kPa) was significantly associated with HCC development (HR 7.861, 95% CI 2.126-29.070; p = 0.002), CAP was not. Additionally, univariate analysis with the Cox proportional hazards model adjusted by inverse probability weighting showed that a high TE value was significantly associated with HCC development (HR 3.980, 95% CI, 1.036-15.290; p = 0.044), whereas CAP was not. The cumulative inverse probability weighting-adjusted incidence of HCC rates at 12, 24, and 36 months were 0.0%, 0.5%, and 1.7%, respectively, in patients with a low TE value, and 2.5%, 5.1%, and 7.6%, respectively, in those with a high TE value. CONCLUSION: A high TE value was a risk factor for HCC in hepatitis C virus patients who received direct-acting antiviral therapy and achieved sustained virological response.

8.
Ann Transl Med ; 9(8): 624, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987322

RESUMO

Background: Sarcopenia and body composition can be associated with mortality in chronic liver diseases (CLDs). We sought to identify predictors in CLD patients (n=631, 309 males) and create a prognostic model using easily available indexes. Methods: Reference values for low-grip strength (GS) were 26 kg in men and 18 kg in women. Reference values for low-skeletal muscle index (SMI) were 7.0 kg/m2 in men and 5.7 kg/m2 in women using bioelectrical impedance analysis (BIA). Reference values for low-calf circumference (CC) were 34 cm in men and 33 cm in women. Reference values for high-waist circumference were 85 cm in men and 90 cm in women. Using significant factors in the multivariate analysis contributing to the overall survival (OS), we created a simple predictive model. Akaike information criterion (AIC) was compared. Results: Men (P<0.0001), presence of liver cirrhosis (LC) (P<0.0001), presence of hepatocellular carcinoma (HCC) (P<0.0001), low-GS (P<0.0001), low-CC (P<0.0001), serum albumin (P=0.0355), estimated glomerular filtration rate (P=0.0461), hepatitis B virus (P=0.0044) and hepatitis C virus (P<0.0001) were significant factors contributing to the OS by the multivariate analysis. The study subjects were classified into the 4 groups (combined GS-SMI system): (I) low-GS and low-SMI (sarcopenia, n=73); (II) low-GS and high-SMI (n=65); (III) high-GS and low-SMI (n=110); and (IV) high-GS and high-SMI (n=383). The cumulative OS rates were well stratified among 4 groups (overall P<0.0001, AIC =360.895). The study subjects were also classified into the 4 groups (combined GS-CC system): (I) low-GS and low-CC (n=60); (II) low-GS and high-CC (n=78); (III) high-GS and low-CC (n=70); and (IV) high-GS and high-CC (n=423). The cumulative OS rates were also well stratified among 4 groups (overall P<0.0001, AIC =349.521). In receiver operating characteristic (ROC) curve analysis for CC based on the OS, the optimal cutoff point in men was 34.6 cm [area under the ROC (AUC) =0.70, sensitivity =0.558, specificity =0.842], and that in women was 32.8 cm (AUC =0.72, sensitivity =0.619, specificity =0.787). Conclusions: CC can be an alternative marker for muscle mass in CLD patients. Our proposed combined GS-CC system can be helpful in the community settings without special equipment for muscle mass measurement.

9.
Ann Palliat Med ; 10(4): 3976-3987, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33832301

RESUMO

BACKGROUND: The causal relationship between sarcopenia and depression in chronic liver disease (CLD) patients is unclear. To elucidate these issues, we aimed to investigate the impacts of muscle strength as assessed by grip strength (GS) and muscle mass as assessed by bioelectrical impedance analysis (BIA) on the progression of depression in CLD patients (n=189, 49 cirrhotic cases, and 87 males). METHODS: The Beck Depression Inventory-2nd edition (BDI-II) was used for the evaluation of depression. Time interval from the date of baseline BDI-II and the first confirmed date of elevation of BDI-II score was calculated in each subject. We analyzed factors associated with the elevation of BDI-II score. RESULTS: The baseline mean BDI-II score was 8.4 (median value, 7). Depression (BDI-II score >11) was found in 63 patients (33.33%). GS decline at baseline was found in 13 male patients (14.9%) and 37 female patients (36.3%). Skeletal muscle index (SMI) by BIA decline at baseline was found in 25 male patients (28.7%) and 40 female patients (39.2%). During the follow-up period, 84 patients (44.4%) had the elevation of BDI-II score. For all cases, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 39.2%, 46.6% and 54.9%. In patients with GS decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 53.1%, 67.8% and 77.9%, while in patients with GS non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 34.4%, 39.8% and 47.4% (P=0.0006). In patients with SMI decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 43.5%, 50.8% and 62.1%, while in patients with SMI non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 36.9%, 44.5% and 51.0% (P=0.2487). As per the multivariate analyses, only lower GS at baseline (P=0.0022) was identified to be a significant factor associated with the elevation of BDI-II score. CONCLUSIONS: Reduced GS rather than loss of muscle mass can be independently associated with an elevated risk for the progression of depression.


Assuntos
Hepatopatias , Sarcopenia , Depressão , Feminino , Força da Mão , Humanos , Masculino , Músculo Esquelético
10.
Int J Mol Sci ; 22(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671926

RESUMO

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle-liver-adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.


Assuntos
Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Sarcopenia/etiologia , Sarcopenia/metabolismo , Tecido Adiposo/metabolismo , Citocinas/metabolismo , Disbiose/metabolismo , Terapia por Exercício/métodos , Jejum , Humanos , Resistência à Insulina , Cirrose Hepática/dietoterapia , Cirrose Hepática/tratamento farmacológico , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Desnutrição Proteico-Calórica/metabolismo , Sarcopenia/dietoterapia , Sarcopenia/tratamento farmacológico
11.
Metab Eng ; 65: 88-98, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33722652

RESUMO

Succinate, fumarate, and malate are valuable four-carbon (C4) dicarboxylic acids used for producing plastics and food additives. C4 dicarboxylic acid is biologically produced by heterotrophic organisms. However, current biological production requires organic carbon sources that compete with food uses. Herein, we report C4 dicarboxylic acid production from CO2 using metabolically engineered Synechocystis sp. PCC 6803. Overexpression of citH, encoding malate dehydrogenase (MDH), resulted in the enhanced production of succinate, fumarate, and malate. citH overexpression increased the reductive branch of the open cyanobacterial tricarboxylic acid (TCA) cycle flux. Furthermore, product stripping by medium exchanges increased the C4 dicarboxylic acid levels; product inhibition and acidification of the media were the limiting factors for succinate production. Our results demonstrate that MDH is a key regulator that activates the reductive branch of the open cyanobacterial TCA cycle. The study findings suggest that cyanobacteria can act as a biocatalyst for converting CO2 to carboxylic acids.


Assuntos
Synechocystis , Carbono , Ciclo do Ácido Cítrico/genética , Ácidos Dicarboxílicos , Ácido Succínico , Synechocystis/genética
12.
Hepatol Res ; 51(5): 603-613, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33772972

RESUMO

AIM: To elucidate the relationship between the finger-circle test (Yubi-wakka [in Japanese] test; three levels of bigger, just-fits, and smaller) and sarcopenia-related factors and anthropometric parameters in patients with chronic liver disease (n = 202, 99 men, mean age 61 years). METHODS: Patients with both grip strength decline (<26 kg for men and <18 kg for women) and skeletal muscle index (SMI) decline (<7.0 kg/m2 in men and <5.7 kg/m2 in female) were diagnosed as sarcopenia. RESULTS: Liver cirrhosis was found in 56 patients (27.7%). The proportions of bigger, just-fits, and smaller in liver cirrhosis versus non-liver cirrhosis patients were 51.8%, 21.4%, and 26.8% versus 77.4%, 11.4%, and 8.2% (p < 0.01). The proportions of grip strength decline in patients with bigger, just-fits, and smaller were 12.0% (77/142), 21.2% (7/33), and 40.7% (11/27; overall p < 0.01). The proportions of SMI decline in patients with bigger, just-fits, and smaller were 9.9% (14/142), 45.5% (15/33), and 77.8% (21/27; overall p < 0.01). The proportions of sarcopenia in patients with bigger, just-fits, and smaller were 3.5% (5/142), 18.2% (6/33), and 33.3% (9/27; overall p < 0.01). In both sexes, arm circumference, triceps skinfold thickness, calf circumference, and waist circumference were significantly stratified according to the finger-circle test. In the multivariate analysis, smaller was an independent predictor for SMI decline (p < 0.01, risk ratio 8.188, bigger as a reference), and body mass index was an independent predictor for both SMI decline and sarcopenia. CONCLUSION: The finger-circle test can be helpful for the screening of sarcopenia in chronic liver disease and is closely linked to body composition.

13.
In Vivo ; 35(2): 1163-1168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622916

RESUMO

BACKGROUND/AIM: This study aimed to assess the association of the modified albumin-bilirubin (mALBI) grade with the endoscopic findings of gastroesophageal varices (GEVs). PATIENTS AND METHODS: A total of 141 patients with histologically proven cirrhosis who underwent a liver biopsy and esophagogastroduodenoscopy were enrolled. The relationships between the mALBI grade and endoscopic findings were evaluated. RESULTS: The incidence of GEVs and high-risk GEVs differed among mALBI grades. Patients with mALBI grades of 2b-3 had higher rates of GEVs and high-risk GEVs in comparison to those with mALBI grades of 1-2a (p<0.0001). In addition, patients with mALBI grade 2b or grade 3, but not those with mALBI grade 2a, had significantly higher rates of complicated GEVs and high-risk GEVs in comparison to those with mALBI grade 1. CONCLUSION: The mALBI grade may be useful in predicting the presence of GEVs and for stratifying their bleeding risk.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Varizes , Bilirrubina , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Prognóstico , Estudos Retrospectivos
14.
Carcinogenesis ; 42(5): 672-684, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33617626

RESUMO

Hepatocellular carcinoma (HCC) developing after hepatitis C virus (HCV) eradication is a serious clinical concern. However, molecular basis for the hepatocarcinogenesis after sustained virologic response (SVR) remains unclear. In this study, we aimed to unveil the transcriptomic profile of post-SVR liver tissues and explore the molecules associated with post-SVR carcinogenesis. We analysed 90 RNA sequencing datasets, consisting of non-cancerous liver tissues including 20 post-SVR, 40 HCV-positive and 7 normal livers, along with Huh7 cell line specimens before and after HCV infection and eradication. Comparative analysis demonstrated that cell cycle- and mitochondrial function-associated pathways were altered only in HCV-positive non-cancerous liver tissues, whereas some cancer-related pathways were up-regulated in the non-cancerous liver tissues of both post-SVR and HCV-positive cases. The persistent up-regulation of carcinogenesis-associated gene clusters after viral clearance was reconfirmed through in vitro experiments, of which, CYR61, associated with liver fibrosis and carcinogenesis in several cancer types, was the top enriched gene and co-expressed with cell proliferation-associated gene modules. To evaluate whether this molecule could be a predictor of hepatocarcinogenesis after cure of HCV infection, we also examined 127 sera from independent HCV-positive cohorts treated with direct-acting antivirals (DAAs), including 60 post-SVR-HCC patients, and found that the elevated serum Cyr61 was significantly associated with early carcinogenesis after receiving DAA therapy. In conclusion, some oncogenic transcriptomic profiles are sustained in liver tissues after HCV eradication, which might be a molecular basis for the liver cancer development even after viral clearance. Among them, up-regulated CYR61 could be a possible biomarker for post-SVR-HCC.


Assuntos
Carcinoma Hepatocelular/genética , Proteína Rica em Cisteína 61/genética , Neoplasias Hepáticas/genética , Transcriptoma/genética , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Hepacivirus/patogenicidade , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , RNA-Seq , Resposta Viral Sustentada
15.
Hepatol Res ; 51(4): 436-444, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33462941

RESUMO

AIM: Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically. METHODS: A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically. RESULTS: The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p < 0.001). In patients with F0-1, F2, and F3, TE and VTQ values of A2 or A3 were significantly higher than those of A0 or A1 (p value, all <0.05), but not in patients with F4. The median alanine aminotransferase (ALT) values increased significantly with the progression of liver inflammation (p < 0.001). Moreover, TE and VTQ in patients with ALT ≥70 IU/L were significantly higher than those in patients with ALT <70 IU/L (p < 0.01), but not in patients with F4. CONCLUSION: Shear wave elastography can be affected by hepatic necroinflammation in F0-F3 fibrosis, but not in F4.

16.
Ultrasound Med Biol ; 47(4): 941-946, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33413966

RESUMO

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.


Assuntos
Hemangioma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia , Idoso , Meios de Contraste , Feminino , Hemangioma/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral
17.
In Vivo ; 35(1): 363-371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402485

RESUMO

BACKGROUND/AIM: To elucidate factors associated with secular changes of grip strength (GS) in patients with chronic liver diseases (CLDs) (n=241, 102 males, median age=63 years, 87 liver cirrhosis cases). MATERIALS AND METHODS: ΔGS (kg/year) was defined as [GS value (second time) - GS value (first time)]/[time interval between the first and second time]. GS loss (GSL) was defined as ΔGS <0 kg/year. RESULTS: The median ΔGS in patients with non-LC, Child-Pugh A (n=70) and Child-Pugh B (n=17) were 0.3, -0.2 and -1.6 kg/year (overall p<0.0001). In the multivariate analysis of factors linked to the GSL for all cases, extracellular water (ECW) to total body water (TBW) ratio was significant (p=0.0007). In the multivariate analysis in male, no significant factor was found, while in female, ECW to TBW ratio was significant (p=0.0024). CONCLUSION: Liver functional parameters can be closely linked to the GSL especially in female CLD patients.


Assuntos
Água Corporal , Cirrose Hepática , Espaço Extracelular , Feminino , Força da Mão , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Água
18.
Surg Today ; 51(5): 764-776, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32964250

RESUMO

PURPOSE: This study aimed to clarify what hepatocellular carcinoma (HCC) phenotype, as categorized by intraoperative contrast-enhanced ultrasonography (CEUS), showed a high risk of recurrence after hepatic resection. METHODS: Patients who underwent initial curative hepatectomy with intraoperative CEUS for a single HCC nodule were retrospectively assigned to three patterns of fine (FI), vascular (VA), and irregular (IR) according to the maximum intensity projection pattern based on intraoperative CEUS. Staining was performed for Ki-67, pyruvate kinase type M2 (PKM2), and vascular endothelial growth factor (VEGF) to assess the tumor proliferative activity, tumor glucose metabolism, and angiogenesis, respectively. RESULTS: Of 116 patients, 18, 50, and 48 were assigned to the FI, VA and IR patterns, respectively. IR patients demonstrated a significantly worse prognosis for both the recurrence-free survival (RFS) and overall survival (OS) (P = 0.0002, 0.0262, respectively) than did patients with other patterns. A multivariate analysis revealed an IR pattern in intraoperative CEUS to be an independent predictive factor for a poor RFS, and major hepatectomy and an IR pattern were independent predictive factors for a poor OS. An IR pattern was closely related to the tumor size (≥ 3.3 cm) and poor histological differentiation and showed a high Ki-67 index, low VEGF expression, and high PKM2 expression. CONCLUSION: IR-pattern HCCs as classified by intraoperative CEUS may be associated with a higher risk of recurrence and worse outcomes in HCC patients after hepatic resection than other patterns.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Ultrassonografia/métodos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Expressão Gênica/genética , Humanos , Período Intraoperatório , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Recidiva Local de Neoplasia , Estudos Retrospectivos , Risco , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
J Med Ultrason (2001) ; 47(4): 511-520, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33089412

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is entering a new era in terms of diagnosis and conceptualization. The term NAFLD is considered to not reflect current knowledge. Metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested as a more appropriate overarching term by experts in this field. Regarding NAFLD progression, most patients die from non-liver-related diseases, even patients with advanced fibrosis. Liver biopsy is essential for the diagnosis of nonalcoholic steatohepatitis (NASH); it is the only procedure that reliably differentiates NAFLD from NASH. Recently, various noninvasive methods for diagnosing steatosis and fibrosis have been developed. Ultrasound attenuation measurements and proton density fat fraction with magnetic resonance imaging (MRI) have been developed as imaging tools for predicting steatosis. Fibrosis-4 index and NAFLD fibrosis score are complex scores for predicting fibrosis in patients with NAFLD. In addition, elastography based on ultrasound and MRI has been developed as an imaging tool for predicting fibrosis. There is a strong correlation between values from various real-time shear wave elastography devices and transient elastography, which is the gold standard for ultrasound-based measurements of liver stiffness. In conclusion, NAFLD is at a turning point in terms of its conceptualization, terminology, and diagnostics. It is now time to reconfirm the role of ultrasonography for the assessment of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Ultrassonografia/métodos , Humanos , Fígado/diagnóstico por imagem , Masculino
20.
J Med Ultrasound ; 28(2): 59-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32874864

RESUMO

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.

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