RESUMO
OBJECTIVES: To identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function. METHODS: We selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS. RESULTS: Low value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence. CONCLUSIONS: Patients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS.
Assuntos
Varizes Esofágicas e Gástricas , Varizes , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Hemodinâmica , Humanos , Cirrose Hepática , Veia Porta/diagnóstico por imagem , Escleroterapia/métodosRESUMO
INTRODUCTION: This study aimed to identify factors affecting presepsin levels and to determine their diagnostic utility. METHODS: This cross-sectional study was conducted at an outpatient clinic and emergency department at an acute care hospital in Japan between January 2015 and December 2017. We enrolled 1,840 consecutive outpatients with at least one measurement of serum presepsin, who were suspected of having bacterial infection. The outcome variables were bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections diagnoses, based on the chart review. We collected blood analysis data on the patients' presepsin levels. RESULTS: There was a significant association between presepsin level and the diagnosis of bacterial infection even when adjusted for age, sex, renal function, and biliary enzyme levels. An increase of 1 unit in the log of presepsin values resulted in a relative risk ratio of 1.71 (1.09-2.66), 2.1 (1.58-2.79), 2.93 (2.05-4.19), 4.7(2.90-7.61), and 2.41(1.70-3.43), for bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections, respectively. CONCLUSIONS: Presepsin showed a statistically significant increase in the diagnosis of bacterial infections (lower respiratory tract infections, urinary tract infections, cholangitis, and non-severe patients) in a community hospital setting. However, in patients with renal dysfunction, presepsin levels should be interpreted with caution.
Assuntos
Receptores de Lipopolissacarídeos , Sepse , Biomarcadores , Proteína C-Reativa/análise , Calcitonina , Estudos Transversais , Humanos , Japão/epidemiologia , Fragmentos de PeptídeosRESUMO
BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. CASE PRESENTATION: A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed-Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. CONCLUSIONS: This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Obstrução Intestinal/virologia , Úlcera/complicações , Idoso de 80 Anos ou mais , Colo Transverso/cirurgia , Colo Transverso/virologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Mucosa Intestinal/cirurgia , Mucosa Intestinal/virologia , Obstrução Intestinal/cirurgia , Masculino , Úlcera/virologiaRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Aminoisobutíricos , Antivirais/farmacologia , Benzimidazóis/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Hepatite C/diagnóstico , Humanos , Japão , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas/uso terapêutico , Análise de Sequência de DNA , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Falha de Tratamento , Resultado do Tratamento , Adulto JovemAssuntos
Dermatomiosite , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/complicações , Dermatomiosite/imunologia , Dermatomiosite/diagnóstico , Dermatomiosite/sangue , Dermatomiosite/complicações , Fatores de Transcrição/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. METHODS: Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. RESULTS: For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. CONCLUSIONS: Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. TRIAL REGISTRATION: UMIN ID 000006147 , registration data: August 11, 2011.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/uso terapêutico , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Seguimentos , Artéria Hepática , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIM: The therapeutic benefit of adding ribavirin (RBV) to 12 weeks of ledipasvir/sofosbuvir (LDV/SOF) for patients who experienced failure of a previous nonstructural protein (NS) 5A inhibitor-containing regimen is unclear. METHODS: A total of 29 genotype 1b HCV patients who had failed prior daclatasvir (DCV) plus asunaprevir (ASV) treatment were retreated for 12 weeks of LDV/SOF, with or without RBV. Antiviral efficacy and predictive factors associating with a sustained virological response at 24 weeks (SVR24) were evaluated retrospectively. RESULTS: SVR24 was achieved in 67% (10/15) of patients who received LDV/SOF with, and 64% (9/14) without, RBV. The SVR24 rates were 80% in patients with, and 58% without, mild fibrosis (FIB-4 < 3.25). The SVR24 rate was lower with unfavorable IL28B rs8099917 SNP genotypes; specifically, the TT, TG and GG had SVR24 rates of 78%, 50% and 40%. The SVR24 rate was lower with a poor response to prior DCV plus ASV, where relapse, viral breakthrough and no response had SVR24 rates 71%, 58% and 0%. The SVR24 rate was lower with the number of NS5A resistance-associated substitutions (RAS), where 2, 3, 4 and 5 RAS had SVR24 rates of 78%, 67%, 50% and 0%. A patient with an NS5A-P32 deletion, which shows resistance to next-generation NS5A inhibitors, was retreated with LDV/SOF with RBV and achieved SVR24. CONCLUSIONS: The addition of RBV to 12 weeks of LDV/SOF has little therapeutic benefit when retreating patients in whom a prior NS5A inhibitor-containing regimen had failed.
RESUMO
The diagnosis of hepatocellular carcinoma (HCC) in the early stages is important for successful clinical management. Laminin (Ln)-γ2 expression has been reported in various types of malignant carcinomas. We recently developed a highly sensitive method to measure serum monomeric Ln-γ2 levels using a fully automated chemiluminescent immunoassay (CLIA). Using our CLIA, we evaluated its diagnostic value in sera from patients with chronic liver disease (CLD) and patients with hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were also examined in these subjects. Median levels of Ln-γ2 were significantly higher in patients with HCC (173.2 pg/mL; range: 39.5-986 pg/mL) compared with patients with CLD (76.7 pg/mL; range: 38.7-215.9 pg/mL) and with healthy volunteers (41.1 pg/mL; range: 10.9-79.0 pg/mL). The optimal cutoff value for Ln-γ2 that allowed us to distinguish between HCC and nonmalignant CLD was 116.6 pg/mL. Elevated Ln-γ2 levels were observed in 0% of healthy volunteers, 17% of patients with CLD, and 63% of patients with HCC. The positivity rate in patients with HCC for the combination of Ln-γ2 and DCP was 89.5%, which was better than that for either of the two markers alone (63% and 68%, respectively). Among patients with early-stage HCC (T1 or T2), the positivity rates for monomeric Ln-γ2, AFP and DCP were 61%, 39% and 57%, respectively. Serum Ln-γ2 may be a potential biomarker for HCC surveillance. The combination of Ln-γ2 and DCP may be more sensitive for laboratory diagnosis of HCC than the combination of AFP and DCP.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Laminina/sangue , Neoplasias Hepáticas/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/sangue , Protrombina , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre-existence of Y93 H resistance-associated variants (RAVs) in the non-structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post-treatment was possible. Pre-treatment RAVs in the non-structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)-Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR-Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1-25% in 5 patients, 26-75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of <1%, 1-25%, 26-75%, and ≥76% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (P < 0.0001). The dominancy of pre-treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct-acting antiviral agent treatments. J. Med. Virol. 89:99-105, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Mutação de Sentido Incorreto , Sulfonamidas/uso terapêutico , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbamatos , Farmacorresistência Viral , Feminino , Genótipo , Técnicas de Genotipagem , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Pirrolidinas , Resposta Viral Sustentada , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
AIM: We identified four cases of infection with hepatitis B virus genotype G and A2 recombinant (HBV/G/A2) strains, which were initially overlooked by enzyme immunoassay-based genotyping. The patients were all men who have sex with men (MSM) and inhabited several metropolitan areas of Japan, suggesting that the recombinant strains may be circulating among high-risk groups such as MSM. Here, we investigated the genomic structure and virological properties of the HBV/G/A2 strains. METHODS: Complete genome sequences of the isolates were determined and phylogenetically analyzed. Replication efficiency of HBV/G/A2 was investigated by transfecting plasmids containing 1.24-fold viral genome. The in vivo viral kinetics of HBV/G/A2 were investigated using chimeric mice with humanized livers. RESULTS: Phylogenetic analysis revealed that the four strains were almost identical (>99.7% homologous). The preS2/S region of these strains was highly homologous to that of genotype A2 and the remaining region was almost identical to that of genotype G, reflecting inter-genotypic recombination. Interestingly, in all four cases, genotype A was co-infected as a minor population. In vitro analysis revealed that HBV/G/A2 had a low replication rate. Although detectable viremia was not measurable following the inoculation of HBV/G/A2 into chimeric mice, subsequent superinfection of HBV genotype A greatly enhanced HBV/G/A2 replication and viral spread. CONCLUSION: We found that four cases of HBV/G/A2 recombinant among MSM patients in the metropolitan areas of Japan, and HBV/A co-infections are required for its efficient replication. High-risk groups such as MSM should be carefully tested for infection of genotype G-derived variants.
RESUMO
The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.
Assuntos
Hemodinâmica , Hepatite C Crônica/fisiopatologia , Cirrose Hepática/fisiopatologia , Fígado/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adulto , Idoso , Biomarcadores/análise , Progressão da Doença , Feminino , Hepacivirus/fisiologia , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/metabolismo , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/metabolismo , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/metabolismo , Curva ROC , Fluxo Sanguíneo Regional/fisiologia , Tomografia Computadorizada por Raios X/métodos , XenônioRESUMO
We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess.
Assuntos
Abscesso Hepático Piogênico/microbiologia , Neoplasias Gástricas/diagnóstico por imagem , Infecções Estreptocócicas/complicações , Streptococcus intermedius , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Humanos , Abscesso Hepático Piogênico/tratamento farmacológico , Imagem Multimodal , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologiaRESUMO
Cytopenia during interferon-based (IFN-based) therapy for chronic hepatitis C (CHC) often necessitates reduction of doses of drugs and premature withdrawal from therapy resulting in poor response to treatment. To identify genetic variants associated with IFN-induced neutropenia, we conducted a genome-wide association study (GWAS) in 416 Japanese CHC patients receiving IFN-based therapy. Based on the results, we selected 192 candidate single nucleotide polymorphisms (SNPs) to carry out a replication analysis in an independent set of 404 subjects. The SNP rs2305482, located in the intron region of the PSMD3 gene on chromosome 17, showed a strong association when the results of GWAS and the replication stage were combined (OR = 2.18, P = 3.05 × 10(-7) in the allele frequency model). Logistic regression analysis showed that rs2305482 CC and neutrophil count at baseline were independent predictive factors for IFN-induced neutropenia (OR = 2.497, P = 0.0072 and OR = 0.998, P < 0.0001, respectively). Furthermore, rs2305482 genotype was associated with the doses of pegylated interferon (PEG-IFN) that could be tolerated in hepatitis C virus genotype 1-infected patients treated with PEG-IFN plus ribavirin, but not with treatment efficacy. Our results suggest that genetic testing for this variant might be useful for establishing personalized drug dosing in order to minimize drug-induced adverse events.
Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Neutropenia/genética , Polietilenoglicóis/efeitos adversos , Complexo de Endopeptidases do Proteassoma/genética , Idoso , Antivirais/uso terapêutico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Interferon-alfa/uso terapêutico , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêuticoRESUMO
European studies have revealed that the ABCB11 c.1331T>C (V444A) polymorphism (rs2287622) C-allele frequency is higher among patients with drug-induced cholestasis. Given the low incidence of this disease, however, this association has not been sufficiently elucidated. We aimed to investigate the significance of this polymorphism in Japanese patients. We determined ABCB11 V444A polymorphism frequencies and HLA genotypes in two independent drug-induced cholestasis cohorts. Expression and taurocholate transport activity of proteins from 444A variants were analyzed using Madin-Darby canine kidney II cells. In cohort 1 (n = 40), the V444A polymorphism C-allele frequency (66%) was lower than that in controls (n = 190, 78%), but this difference was not significant (P = 0.09). In cohort 2 (n = 119), comprising patients with cholestatic (n = 19), hepatocellular (n = 74), and mixed (n = 26) liver injuries, the C-allele frequency was lower among patients with cholestatic liver injury (68%) than among those with hepatocellular (75%) or mixed liver injury (83%), although this difference was not significant. In cohort 1, HLA-A*0201 was observed more frequently in patients (22%) than in controls [11%; P = 0.003; odds ratio, 2.4 (95% confidence interval, 1.4-4.0)]. Taurocholate transport activity of 444A-encoded protein was significantly lower than that of 444V-encoded protein (81% of 444V, P < 0.05) because of the reduced protein stability. In conclusion, ABCB11 444A had slightly reduced transport activity, but it did not contribute to the occurrence of drug-induced cholestasis in Japanese patients. Therefore, genetic susceptibility to acquired cholestasis may differ considerably by ethnicity.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Povo Asiático/genética , Colestase/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular , Colestase/induzido quimicamente , Cães , Feminino , Frequência do Gene/genética , Genótipo , Antígeno HLA-A2/genética , Humanos , Células Madin Darby de Rim Canino , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full- to half-dose sorafenib. METHODS: We reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full-dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score-matching analysis was used to adjust for potential bias. RESULTS: Multivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half-dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05-1.15; P < 0.001). Fifty-eight patients each in the half-dose and full-dose groups were selected for propensity score matching. The incidence of grade 3-4 severe adverse effects was lower in the half-dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression-free survival (PFS) and overall survival (OS) rates were not significantly different (half-dose group, 3.8 and 10.2 months; full-dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively). CONCLUSION: Propensity score-matched analyses indicate that initial half-dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.
RESUMO
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is technically more challenging in patients who have undergone gastrointestinal (GI) reconstruction. AIMS: The aim of this study was to evaluate the utility of the anterior oblique-viewing endoscope (AOE) for ERCP in patients with a retained major duodenal papilla after GI reconstruction. METHODS: This was a retrospective study involving 40 patients (50 procedures) with a retained papilla after GI reconstruction who underwent ERCP using AOE. Reconstruction consisted of Billroth II gastrectomy (BII) in 25 patients (30 procedures) and Roux-en-Y anastomosis (RY) in 15 patients (20 procedures). In RY cases, the long single-balloon enteroscope (LSBE) was exchanged with AOE after reaching the papilla. RESULTS: The overall rate of reaching the papilla using AOE was 90.0 % (45/50) [BII; 86.7 % (26/30), RY; 95.0 % (19/20)]. The overall rate of biliary cannulation was 97.8 % (44/45) [BII; 100 % (26/26), RY; 94.7 % (18/19)], and the rate of biliary cannulation for intact papilla was 96.6 % (28/29) [BII; 100 % (14/14), RY; 93.3 % (14/15)]. Treatment success rate in cases of successful biliary cannulation was 97.7 % (43/44) [BII; 100 % (26/26), RY; 94.4 % (17/18)]. The rate of adverse events was 6.0 % (3/50) [BII; 3.3 % (1/30), RY; 10.0 % (2/20)], with mild pancreatitis occurring in 3 cases. CONCLUSIONS: High biliary cannulation and treatment rates can be achieved during ERCP using AOE in altered GI anatomy cases with a retained papilla, as long as the papilla can be reached. In RY cases, exchanging AOE with LSBE is useful after reaching the papilla.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/métodos , Gastrectomia , Idoso , Idoso de 80 Anos ou mais , Anastomose em-Y de Roux , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
AIM: Treatment with telaprevir (TVR) entails adverse side-effects including anaemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C. METHODS: Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (i) patients with an increase in SCr during the treatment (n = 8), and (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were evaluated. RESULTS: Although there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase-in-SCr group during the triple therapy. The SCr level returned to the pre-treatment level after cessation of TVR. There were no differences in urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre-treatment tended to be higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR. CONCLUSION: Elevation of SCr levels with TVR therapy may not suggest renal impairment.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Antivirais/uso terapêutico , Creatinina/sangue , Hepatite C Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Oligopeptídeos/uso terapêutico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Biomarcadores/urina , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Hepatite C Crônica/diagnóstico , Humanos , Interferon-alfa/uso terapêutico , Japão , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND/AIMS: Endoscopic papillary balloon dilation (EPBD) was reported to be superior for preserving the function of the sphincter of Oddi and to cause fewer late complications than endoscopic sphincterotomy. If the early complication of post-EPBD pancreatitis can be prevented, EPBD might be useful as long-term outcomes. This study assessed the feasibility of a novel EPBD for the purpose of reliable post-EPBD pancreatic stenting. METHODOLOGY: Among 1814 ER-CPs, in 17 patients undergoing biliary cannulation with pancreatic duct guidewire placement method, we performed EPBD with the guidewire left in the pancreatic duct by the two-devices-in-one-channel method. This approach employed in order to ensure pancreatic stenting. RESULTS: Procedures were successfully performed without the guidewire displacement, and pancreatic stents were easily placed in all patients. Post-EPBD pancreatitis occurred in only 1 patient (5.9%), and the severity was mild. Asymptomatic hyperamylasemia occurred in 3 patients (17.6%). There were no other early complications. The mean serum amylase levels (mean ± SD) before, 1 day, and 2 days after procedure were 81.4 ± 61.9, 301.2 ± 273.0, and 220.0 ± 177.6 IU/L. CONCLUSIONS: EPBD with a guidewire left in the pancreatic duct is useful method allowing reliable pancreatic stenting and may contribute to the prevention of pancreatitis.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/cirurgia , Ductos Pancreáticos , Esfíncter da Ampola Hepatopancreática/cirurgia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Coledocolitíase/diagnóstico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite , Complicações Pós-OperatóriasRESUMO
BACKGROUND: Although pancreatic stenting is recommended for the prevention of postprocedure pancreatitis during endoscopic papillectomy (EP), in some patients it is technically difficult to perform postprocedure insertion of a pancreatic stent after endoscopic resection. GOALS: This study assessed the feasibility of a novel EP for the purpose of reliable post-EP pancreatic stenting. STUDY: We conducted a prospective pilot study involving 10 consecutive patients with tumor of the major duodenal papilla. We developed a novel pancreatic stent, which is attached to a suture, and devised a method by which the stent is first placed at an upstream migration into the major pancreatic duct above the orifice before resection and then placed at an appropriate location after endoscopic resection by pulling the suture attached to the stent [inside pancreatic stenting papillectomy (IPSP)]. RESULTS: The pancreatic stent was successfully placed at an upstream migration into the pancreatic duct above the orifice in 9 of the 10 patients. For the 9 patients with successful pancreatic stent placement, IPSP was performed. Although the suture was cut in 1 patient, pancreatic stents could be placed appropriately across the orifice by pulling the suture in all patients. Although bleeding occurred in 3 patients, there was no pos-procedure pancreatitis. CONCLUSIONS: IPSP is a practicable method allowing reliable post-EP pancreatic stenting and can contribute to pancreatitis prevention. However, larger studies need to be performed before its use can be recommended.
Assuntos
Pólipos Adenomatosos/cirurgia , Neoplasias Duodenais/cirurgia , Pancreatite/prevenção & controle , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica/métodos , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/cirurgia , Projetos Piloto , Complicações Pós-Operatórias/prevenção & controle , Estudos ProspectivosRESUMO
AIM: Hepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis. METHODS: In our multicenter, randomized, double-blind, placebo-controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7-day administration of either tolvaptan at 7.5 mg/day or placebo as an add-on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline. RESULTS: Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was -0.44 kg (standard deviation [SD], 1.93) in the placebo group and -1.95 kg (SD, 1.77) in the tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites-related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline. CONCLUSION: Add-on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites-related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add-on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.