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1.
Artigo em Inglês | MEDLINE | ID: mdl-32003276

RESUMO

Background: Endoscopic submucosal tunnel dissection (ESTD) has recently been an effective procedure for resecting large early esophageal neoplasm. However, excessive dissection beyond the distal limit may occur because the prepared distal end often cannot be distinguished through the tunnel. This study aimed to assess the efficacy and safety of a novel crystal violet navigation (CVN) for identifying the distal end.Material and methods: In the observational case series study, all 22 patients who underwent esophageal ESTD using the CVN were included. When setting the distal end, the distal incision line was dyed purple using a crystal violet solution. The rates of purple color identified via the tunnel, successful tunnel penetration without extra dissection, en bloc and curative resection, procedure time for ESTD and CVN, and procedure-associated complications were evaluated.Results: The rates of purple color and successful tunnel penetration were both 100%. En bloc and curative resection were 100%, and 86%, respectively. The mean total procedure time was 103.9 ± 46.2 (mean ± SD) minutes, while the mean time for the CVN was 14.1 ± 3.44 s. No complications were observed.Conclusions: The simple CVN method can be a navigation tool for identifying the distal end during the ESTD procedure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31905024

RESUMO

Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared to nontumor tissue. We thus examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-related deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002-2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: (1) HBV-related HCC and adjacent nontumor tissue, (2) HCV-related HCC and adjacent nontumor tissue, and (3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR-210-3p expression was significantly increased only in the HBV-related HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes including HBx in the HBV-positive HCC cells. MiR-210-3p might thus be a new biomarker for the risk of HBV-related HCC.

3.
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.

4.
J Gastrointestin Liver Dis ; 28(4): 397-404, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31826062

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric neoplasia. However, as the upper and middle body of the greater curvature has a rich vasculature and submucosal fibrosis, ESD of neoplasia in these locations requires a specific strategy. We aimed to investigate the efficacy and safety of the J-shaped superficial cutting and splashed submucosal dissection (JSCS) technique for neoplasia of the greater curvature by comparing ESD using JSCS with conventional ESD. METHODS: Twenty-two patients who underwent ESD for gastric neoplasia affecting the upper and middle body of the greater curvature were divided into two groups for retrospective analysis. Nine patients underwent conventional ESD (c-Group), while 13 underwent ESD with JSCS (j-Group). Primary outcome was the en bloc resection rate. Secondary outcomes included complete resection (R0) rate, procedure time, perforation rate, total bleeding time, and the total number of massive bleeding events and of hemostatic forceps times applied during ESD. RESULTS: There were no significant differences between both groups (c-Group vs j-Group) in en bloc resection rate, or R0 resection rate. Compared with the c-Group, the j-Group tended to have a decreased mean procedure time (mean 133 minutes vs 74 minutes, p=0.11) and perforation rate (11% vs 0%, p=0.41). Compared with the c-Group, the j-Group had significantly fewer bleeding incidents (13.4 times vs 6.6 times, p=0.0095), shorter total bleeding time (17.6 min vs 7.4 min, p=0.036), and fewer usages of hemostatic forceps (6.3 times vs 2.4 times, p=0.026) during ESD. CONCLUSION: Endoscopic submucosal dissection with JSCS is superior to conventional ESD, as it reduces intraprocedural bleeding. This technique has the potential to become the standard strategy for neoplasia affecting the upper and middle body of the greater curvature.

5.
Hepatol Res ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31883211

RESUMO

AIM: The incidence of hepatitis C virus (HCV) infection is much higher in hemodialysis patients than that in healthy individuals. The prognosis of hemodialysis patients with HCV infection is poorer than that without HCV infection. Therefore, antiviral intervention is pivotal for HCV infection in hemodialysis patients. Recent evaluations of the pangenotypic regimen of glecaprevir/pibrentasvir show that it is highly effective and safe for HCV-infected hemodialysis patients. However, a few reports showed that the effect of HCV elimination by glecaprevir/pibrentasvir improved liver dysfunction or anemia. The aim of the present study was to determine clinical outcomes after HCV elimination using the glecaprevir/pibrentasvir regimen in HCV-infected hemodialysis patients. METHODS: This study was a retrospective, six-center study conducted in Japan, in which 24 hemodialysis patients with HCV genotype 1-2 treated with glecaprevir/pibrentasvir were recruited. Blood examinations were performed at end of treatment (EOT), and at 3, 6, and 12 months post-treatment during the 12-month follow-up period. RESULTS: The overall sustained virologic response rate was 100% (24/24). During the DAA treatment period, adverse events were observed in 20.8% of patients (5/24), and pruritus was the most frequently observed in 12.5% (3/24). Interestingly, we observed an improved control of anemia after EOT with a significant increase in hemoglobin levels. In addition, total bilirubin was diminished, and platelet counts and albumin, total cholesterol, and alpha-fetoprotein levels remained unchanged after EOT in hemodialysis patients. Furthermore, erythropoietin concentration was not increased after EOT. CONCLUSIONS: HCV elimination using glecaprevir/pibrentasvir treatment might be a major breakthrough for the control of anemia in hemodialysis patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31881554

RESUMO

BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.

7.
Mol Clin Oncol ; 11(5): 447-454, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602300

RESUMO

The prognosis of hepatocellular carcinoma (HCC) patients exhibiting macroscopic vascular invasion (MVI) is poor, and the most appropriate treatment approach remains unclear. The current study aimed to investigate the efficacy and safety of sorafenib treatment following chemoradiotherapy for advanced HCC exhibiting MVI. A newly reported regimen, including 5-fluorouracil and cisplatin therapy (NewFP), plus three-dimensional conformal radiotherapy (3D-CRT) for MVI was used as the initial treatment. Additionally, sorafenib, as a secondary treatment, was administered after NewFP plus 3D-CRT for MVI. The present retrospective study enrolled patients with unresectable advanced HCC that was treated with NewFP plus 3D-CRT for MVI between January 2009 and December 2017. In total, 32 HCC patients with MVI were registered. Of these 32 patients, 18 were treated with NewFP plus 3D-CRT for MVI (NewFP + 3D-CRT group) and 14 were treated with sorafenib following NewFP plus 3D-CRT for MVI (sorafenib after NewFP + 3D-CRT group). The study endpoints were overall survival, overall response rate and disease control rate. Clinical factors influencing overall survival were identified using univariate and multivariate analyses. The median survival time in the NewFP + 3D-CRT group and sorafenib following NewFP + 3D-CRT group was 6.7 and 49.2 months, respectively (P=0.0003). For patients with advanced HCC exhibiting MVI, the initial treatment with NewFP plus 3D-CRT for MVI was well tolerated. The administration of sorafenib as the secondary treatment following NewFP plus 3D-CRT for MVI was associated with a significantly higher overall response rate, disease control rate and increased overall survival as compared with the NewFP plus 3D-CRT treatment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31609495

RESUMO

BACKGROUND: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan. METHODS: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen. RESULTS: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period. CONCLUSION: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen.

9.
J Clin Med ; 8(8)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430975

RESUMO

Albumin-bilirubin (ALBI) grade is defined using the ALBI score, which is calculated based on total serum bilirubin and albumin. This study aimed to evaluate the diagnostic ability of the ALBI score for determining hepatic fibrosis stage and transplant-free survival in primary biliary cholangitis (PBC) patients. A total of 181 Japanese patients with biopsy-proven or serologically diagnosed PBC were enrolled. The pathological stage was assessed using the Scheuer classification. The ALBI score differentiated fibrosis in stage 4 from that of 3 in the biopsy-proven cohort (p < 0.05). With an ALBI score cut-off value of -1.679, the sensitivity and specificity were 100% and 91.1%, respectively, with a likelihood ratio of 12.3 to differentiate stage 4 from stages 1-3. The ALBI score at the beginning of ursodeoxycholic acid (UDCA) prescription correlated with the two prognostic scores calculated after 1-year UDCA treatment. Kaplan-Meier analysis showed that the baseline ALBI score differentiated liver transplant-free survival (p < 0.05). The ALBI score presented a greater hazard ratio for transplant-free survival than aspartate aminotransferase-to-platelet ratio index (APRI) in Cox proportional hazard model. In conclusion, ALBI score indicates pathological stage in Japanese PBC patients and scores before UDCA prescription predict better liver transplant-free survival, which correlated well with the two major prognostic scores. The prognosis-predicting ability of the ALBI score might surpass that of APRI.

10.
J Viral Hepat ; 26(11): 1266-1275, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31278795

RESUMO

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

11.
Oncol Lett ; 18(1): 882-890, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289566

RESUMO

During diagnosis of early stage hepatocellular carcinoma (HCC), single or small lesions are difficult to identify using screening ultrasonography, and conventional tumor markers are frequently negative. MicroRNAs (miRNAs) are small non-coding RNAs that suppress the translation of target mRNAs and exert significance as biomarkers. The aim of the present study was to use samples of patients with HCC and those with other liver diseases caused by hepatitis C virus (HCV) infection to investigate the expression profile of serum miRNAs, and identify a miRNA that can serve as a HCC biomarker. Initially, changes in 2,555 miRNAs between pre- and post-curative treatment serum from 12 patients with early stage HCC were examined using microarray analysis. The serum levels of miR-125a-5p in 40 individuals with HCV-associated chronic hepatitis (CH), liver cirrhosis (LC) or HCC were measured using reverse transcription-quantitative polymerase chain reaction, and 5 miRNAs, including miR-125a-5p, miR-423-5p, miR-1247, miR-1304 and miR-3648, were identified to be downregulated following curative treatment in patients with HCC. Among these, miR-125a-5p was identified to be similarly decreased following treatment in all patients. Additionally, the expression levels of miR-125a-5p were significantly upregulated in patients with HCC in the early and advanced stages of disease, compared with patients with CH or LC (P<0.05). Serum miR-125a-5p fluctuates depending on the presence of HCC, and may serve as a noninvasive biomarker to aid in diagnosing early carcinogenesis in HCV-associated chronic liver diseases.

12.
Exp Ther Med ; 16(2): 1026-1028, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30116355

RESUMO

The treatment of chronic hepatitis C has radically changed due to the development of direct-acting antiviral agents (DAAs). Twelve-week treatment with ledipasvir and sofosbuvir (LDV/SOF), a combination of DAAs, is highly effective in patients with hepatitis C virus (HCV) genotype 1 infection. However, the overall sustained virological response rate 12 weeks after the end of treatment (SVR12) is not 100%. Elbasvir (EBR) combined with grazoprevir (GZR) is the latest approved therapy for patients with genotype 1 or 4 chronic hepatitis C. However, to the best of our knowledge no case reports have described retreatment with GZR/EBR in patients with a history of failed LDV/SOF treatment. The present case report indicated a case in which GZR/EBR was effective for the retreatment of a patient with a history of failed LDV/SOF treatment and chronic hepatitis C. The present study indicated a 55-year-old Japanese male with a history of chronic hepatitis C and compensated liver cirrhosis. The patient exhibited the amino acid mutation Y93H in NS5A. Therefore, treatment with LDV/SOF was initiated, which was effective and suppressed the virus during oral administration. However, 4 weeks after treatment, the patient's viral load relapsed and returned to its original level. After the patient provided informed consent, treatment with GZR/EBR was initiated. No problems related to GZR/EBR were observed during treatment and the patient's SVR12 was evaluated at 12 weeks posttreatment. In conclusion, GZR/EBR treatment was useful for treating a relapse of HCV genotype 1b infection in the present case after LDV/SOF treatment, despite liver fibrosis, in the presence of the high-frequency amino acid mutation Y93H in NS5A. Although it will be necessary to examine a large number of cases, the present findings suggest that GZR/EBR may be a potential treatment option for relapse of HCV genotype 1b infection after LDV/SOF treatment.

13.
Int J Mol Sci ; 19(7)2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-30004437

RESUMO

The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecutive chronic HBV infection patients negative for HBe antigen (HBeAg) with HBV-DNA levels <5 log copies/mL, alanine aminotransferase (ALT) <100 U/L, and compensated liver functions, were enrolled. The patients were subcutaneously injected with Peg-IFNα-2a weekly for 48 weeks (treatment period), followed by the 48-week observation period. HBsAg 1-log drop relative to baseline levels recorded at the end of the observation period was considered effective. Sera were obtained at weeks 0 and 24 during the treatment period analyzed for microRNAs. The microRNA (miRNA) antiviral activity was evaluated in vitro using Huh7/sodium taurocholate cotransporting polypeptide (NTCP) cells. As a result, six patients achieved the HBsAg 1-log drop after the observation periods. Comparison of serum microRNA levels demonstrated that high miR-6126 levels at week 24 predicted HBsAg 1-log drop. Furthermore, miR-6126 reduced HBsAg in culture medium supernatants and intracellular HBV-DNA quantities in Huh7/NTCP cells. In conclusion, high serum miR-6126 levels during Peg-IFN therapy predicted the HBsAg 1-log drop 48 weeks after the completion of therapy. In vitro assays revealed that miR-6126 was able to suppress HBsAg production and HBV replication.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , MicroRNAs/sangue , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo
14.
J Gastroenterol ; 53(12): 1276-1284, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29740665

RESUMO

BACKGROUND: The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics. RESULTS: Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment. CONCLUSIONS: The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.


Assuntos
Antivirais/administração & dosagem , Benzofuranos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Quinoxalinas/efeitos adversos , Estudos Retrospectivos , Resposta Viral Sustentada
15.
Oncol Lett ; 15(1): 528-532, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29391887

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Although the clinical success rate for the treatment of early-stage HCC has improved, the prognosis of advanced HCC remains poor owing to the high recurrence rate and the refractory nature of HCC for various anticancer drugs. A better understanding of the pathogenesis of HCC is therefore critically needed in order to treat HCC, including its genetic alterations. Next-generation sequencing (NGS) has provided an unbiased platform to systematically identify gene mutations and reveal the pathogenesis of various cancers. In the present study, a total of 118 samples (59 liver tissues including cancer and adjacent normal tissues) were sequenced using the AmpliSeq Hotspot Cancer Panel (version 2). The most common somatic mutations identified were tumor protein 53 (TP53; 35.6%) and ß-catenin 1 (CTNNB1; 30.5%), and the most frequent variants of those genes were missense variants. In addition, somatic mutations including those in genes encoding colony-stimulating factor 1 receptor (5.1%), epidermal growth factor receptor (6.8%), RET proto-oncogene (3.4%), Erb-B2 receptor tyrosine kinase 4 (ERBB4; 1.7%) and serine/threonine kinase 11 (STK11, also known as liver kinase B1; 6.8%) were also identified at a low frequency in patients with HCC. A frameshift variant in STK11, a splice acceptor variant in TP53, a splice region variant in ERBB4 and a stop-gained variant in TP53 were also specifically determined. The most abundant alteration was a C:G>T:A transition (50%) and other transversions, i.e., C:G>G:C (19.6%), T:A>C:G (19.6%), C:G>A:T (12.5%), T:A>G:C (12.5%) and T:A>A:T (5.4%). This spectrum pattern differs from that in other solid tumors. TP53 mutations in the tumors at advanced stages were significantly more frequent compared with those in early-stage tumors. Additionally, age (<70 vs. ≥70 years) was significantly associated with CTNNB1 mutations. Using NGS, a number of novel gene mutations were identified in HCC, including established mutations and disproved mutations. The results of the present study offer new insight and improved understanding of the etiology and the development of HCC.

16.
Intern Med ; 57(8): 1101-1104, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29279506

RESUMO

Combination therapy with ledipasvir and sofosbuvir (LDV/SOF), direct-acting antiviral agents, is highly effective against hepatitis C virus genotype 1 infection. Although LDV/SOF is safer than conventional treatment, reports have indicated that LDV/SOF was discontinued in certain cases due to severe skin disorders. A 68-year-old woman presented with a rash after starting LDV/SOF treatment. We interrupted LDV/SOF and began the oral administration of prednisolone (PSL). After the rash improved, we re-started LDV/SOF with PSL. After treatment, the rash clearly improved; we checked for a sustained virologic response 12 weeks after treatment. Steroids may therefore be an effective treatment option for controlling the side effects of LDV/SOF.


Assuntos
Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Fluorenos/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Dermatopatias/induzido quimicamente , Uridina Monofosfato/análogos & derivados , Idoso , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Feminino , Fluorenos/uso terapêutico , Humanos , Dermatopatias/tratamento farmacológico , Esteroides/uso terapêutico , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico
17.
J Gastroenterol Hepatol ; 33(2): 492-499, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28618039

RESUMO

BACKGROUND AND AIM: Chronic liver diseases progress from chronic inflammation to fibrosis to tumorigenesis. Galectin-9, a ß-galactoside-specific animal lectin, is indicated to contribute to all three steps of progression. The aim of this study was to determine which of the three steps was most dominant in elevating the serum galectin-9 concentration and to test the possibility of galectin-9 as a serum biomarker. METHODS: Japanese patients with chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), non-alcoholic fatty liver disease, or alcoholic liver disease who provided informed consent were enrolled in this study. Serum galectin-9 levels were measured using a sandwich ELISA. Multiple regression analyses were performed using ezr to identify factors that determined serum galectin-9 concentration. RESULTS: One hundred one patients with 50 of chronic hepatitis and 51 of liver cirrhosis were enrolled; the cohort included 45 cases of hepatitis C virus infection, 13 cases of hepatitis B virus infection, and 46 cases with HCC-related complications. The median serum galectin-9 concentration was 77.54 pg/mL (interquartile range: 18.89-241.9 pg/mL). Multiple linear regression analyses proved Fibrosis-4 index and aspartate aminotransferase to platelet ratio index, indexes of liver fibrosis, were able to predict the serum galectin-9 levels with statistical significance. A multiple logistic regression analysis determined 10 pg/mL increase in the serum galectin-9 concentration presented an odds ratio of 3.90 for liver fibrosis progression. CONCLUSIONS: The serum galectin-9 concentration represents a potential biomarker of liver fibrosis in patients with chronic liver diseases, regardless of chronic inflammation or the presence of HCC complications. Furthermore, higher serum galectin-9 levels are a predictor for liver fibrosis progression.


Assuntos
Galectinas/sangue , Cirrose Hepática/diagnóstico , Idoso , Biomarcadores/sangue , Doença Crônica , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Humanos , Cirrose Hepática/etiologia , Hepatopatias/complicações , Pessoa de Meia-Idade , Análise de Regressão
18.
Oncology ; 93 Suppl 1: 113-119, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29258090

RESUMO

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.


Assuntos
Síndrome Mão-Pé/etiologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Prognóstico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe , Taxa de Sobrevida , Resultado do Tratamento
19.
Ther Apher Dial ; 21(5): 465-472, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28880488

RESUMO

Patients with end-stage renal disease who are undergoing dialysis may be at high risk of developing hepatocellular carcinoma (HCC). We investigated the characteristics and prognosis of HCC in patients undergoing dialysis in Japan. Patients characteristics, progression of HCC at diagnosis, and survival rates after diagnosis were compared between 108 HCC patients undergoing dialysis and 526 non-dialysis patients followed up at liver center. The comparisons were also performed after adjusting for patient age, gender, platelet count, and etiology using propensity-score matching. HCC was more advanced in patients undergoing dialysis than in non-dialysis controls. The 3- and 5-year survival rates of patients undergoing dialysis were 56.3% and 38.3%, respectively, which were lower than those of non-dialysis controls (66.5% and 52.7%, respectively, P = 0.0026). The results were the same after propensity score matching (P = 0.0014). In Japan, HCC was more advanced at diagnosis in patients undergoing dialysis in comparison to HCC in patients at liver centers, resulting in a lower survival rate after diagnosis.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Falência Renal Crônica/terapia , Neoplasias Hepáticas/epidemiologia , Diálise Renal/métodos , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Japão , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Diálise Renal/efeitos adversos , Fatores de Risco , Taxa de Sobrevida
20.
Int J Oncol ; 51(2): 607-614, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28656219

RESUMO

Liver metastasis from gastrointestinal cancer defines a patient's prognosis. Despite medical developments, pancreatic cancer with liver metastasis confers a very poor prognosis. Galectin-9 (Gal­9) is a tandem-repeat-type galectin that has recently been demonstrated to exert antitumor effects on various types of cancer cells by inducing apoptosis. However, the apoptotic pathway of Gal­9 in solid tumors is unclear. The aim of the present study was to evaluate the effects of Gal­9 on human liver metastasis from pancreatic cancer. Gal­9 suppressed cell proliferation in metastatic liver cancer cell lines derived from pancreatic cancer (KMP2, KMP7, and KMP8) and increased the levels of caspase-cleaved keratin 18 and fluorescein isothiocyanate (FITC)-conjugated Annexin V. Furthermore, expression of apoptosis-related molecules such as caspase-7, cleaved caspase-3, cleaved PARP, cytochrome c, Smac/Diablo and HtrA2/Omi was enhanced. However, Gal­9 did not affect expression of various cell cycle-related proteins. The microRNA (miRNA) expression profile was markedly altered by Gal­9, and various miRNAs might contribute to tumor growth suppression. Our data reveal that Gal­9 suppresses the growth of liver metastasis, possibly by inducing apoptosis through a mechanism involving mitochondria and changes in miRNA expression. Thus, Gal­9 might serve as a therapeutic agent for the treatment of liver metastasis from pancreatic cancer.


Assuntos
Galectinas/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Galectinas/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , MicroRNAs/genética , Mitocôndrias/genética , Mitocôndrias/patologia , Metástase Neoplásica , Neoplasias Pancreáticas/patologia
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