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BACKGROUND: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). METHODS: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO3-) to nitrite (NO2-) with nitrate reductase, followed by quantitation of NO2- based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE. RESULTS: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively). CONCLUSION: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Quinolinas , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Óxido Nítrico , Dióxido de Nitrógeno/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Quinolinas/efectos adversosRESUMEN
BACKGROUND: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. OBJECTIVE: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. METHODS: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. RESULTS: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). CONCLUSION: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.
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Encefalopatía Hepática , Rifamicinas , Carnitina/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Hospitalización , Humanos , Cirrosis Hepática , Rifamicinas/uso terapéutico , Rifaximina/uso terapéuticoRESUMEN
BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC was composed of the presence and absence of complications, such as variceal bleeding, hepatic ascites, and hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort and (ii) the presence and absence of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD-related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD-related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol-related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD-related LC and its complications.
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Aciltransferasas/genética , Várices Esofágicas y Gástricas , Enfermedad del Hígado Graso no Alcohólico , Fosfolipasas A2 Calcio-Independiente/genética , Hemorragia Gastrointestinal , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lipasa/genética , Cirrosis Hepática/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: We aimed to evaluate the difference between computed tomography (CT)-based and bioelectrical impedance analysis (BIA)-based assessment of sarcopenia in patients with chronic liver disease (CLD). METHODS: We enrolled a total of 257 patients who were evaluated with or without sarcopenia. Sarcopenia was defined as a low skeletal muscle mass index (SMI) with low muscular strength by the Japan Society of Hepatology. To evaluate whether or not the different methods influence the diagnosis of sarcopenia for patients with CLD, we assessed the number and characteristics of mismatches between the low SMI using BIA and CT. We also compared the overall survival (OS) in patients with and without sarcopenia based on CT and BIA to evaluate the appropriate methods. RESULTS: The numbers of patients with low SMI using BIA or CT were 53 (20.6%) and 114 (44.3%) patients, respectively. Multivariate analysis revealed that hepatic ascites and body weight were independent factors of mismatch between SMI using BIA versus CT (hazard ratio [HR] 3.232, p < 0.001; HR 2.347, p = 0.005, respectively). The median OS in patients with sarcopenia based on CT was significantly lower than that in patients without sarcopenia (p = 0.006). In contrast, there was no difference between patients with sarcopenia based on BIA (p = 0.217). CONCLUSION: Muscle mass in patients with CLD may be overestimated by the BIA method compared to CT when assessing sarcopenia, especially in cases of fluid retention.
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Hepatopatías , Humanos , Japón , Hepatopatías/complicaciones , Hepatopatías/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Músculo Esquelético/diagnóstico por imagen , TomografíaRESUMEN
BACKGROUND: Bleeding can be a serious adverse event of endoscopic sphincterotomy (EST). However, the risk of EST bleeding between direct oral anticoagulant (DOAC) users and those who received no antithrombotic agents has not been clarified. This study analyzed the risk factors for bleeding after EST in patients on DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES) guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. METHODS: We retrospectively analyzed 524 patients treated with EST who received DOAC or no antithrombotic drug from May 2016 to August 2019. We investigated the risk factors for bleeding. DOAC was typically discontinued for ≤ 1-day based on the JGES guideline. Although DOAC therapy recommenced the next morning after EST in principle, the duration of DOAC cessation and heparin replacement were determined by the attending physician based on each patient's status. RESULTS: The number of patients on DOAC (DOAC group) and those not on antithrombotic drug (no-drug group) was 42 (8.0%) and 482 (92.0%), respectively. DOAC was discontinued for ≤ 1-day in 17 (40.0%) patients and for > 1-day in 25 (60.0%). Of the 524 patients, 21 (4.0%) had EST bleeding. The bleeding rate was higher in the DOAC group (14.0%) (p = 0.004). Multivariate analysis showed that bleeding occurred more frequently in patients on DOAC (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.37-11.4, p = 0.011), patients with low platelet counts (< 100,000/µl) (OR 6.74, 95% CI 2.1-21.6, p = 0.001), and elderly patients (> 80 years old) (OR 3.36, 95%CI 1.17-9.65, p = 0.024). CONCLUSIONS: DOAC treatment, low platelet count, and old age (> 80 years old) are risk factors for EST bleeding. Although the bleeding incidence increased in patients on DOAC who received antithrombotic therapy according to the JGES guidelines, successful hemostasis was achieved with endoscopy in all cases, and no thrombotic events occurred after cessation of DOAC. Thus, the JGES guidelines are acceptable.
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Anticoagulantes , Esfinterotomía Endoscópica , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrinolíticos/efectos adversos , Heparina , Humanos , Estudios Retrospectivos , Esfinterotomía Endoscópica/efectos adversosRESUMEN
BACKGROUND: Upper gastrointestinal (GI) bleeding is the most important presentation of an aorto-duodenal fistula (ADF). Early diagnosis is difficult, and the disease is associated with high mortality. The present study aimed to examine the clinical and the endoscopic characteristics of ADF in eight patients who presented to our hospital. We also sought to clarify the diagnostic approach towards the disease. METHODS: The present study examined the clinical and the endoscopic/computed tomography (CT) characteristics of ADF in eight patients who were definitively diagnosed with this condition in a 12-year period at our hospital. RESULTS: The patients comprised of five men and three women, with a mean age of 69.8 years. Upper gastrointestinal bleeding was the chief complaint for all the patients. Out of these, two patients presented with shock. The patients' mean haemoglobin at presentation was 7.09 g/dL, and the mean number of blood transfusions was 7.5. All patients had undergone intervention to manage an aortic pathology in the past. As the first investigation, an upper GI endoscopy in 5 and a CT scan in 3 patients were performed. In cases where CT scan was performed first, no definitive diagnosis was obtained, and the diagnosis was confirmed by performing an upper GI endoscopy. In cases where endoscopy was performed first, definitive diagnosis was made in only one case, and the other cases were confirmed by the CT scan. In some cases, tip attachments, converting to long endoscopes, and marking clips were found useful. CONCLUSIONS: In patients who have undergone intervention to manage an aortic pathology and have episodes of upper gastrointestinal bleeding, ADF cannot be definitively diagnosed with only one investigation. In addition, when performing upper GI endoscopy in cases where an ADF is suspected, tip attachment, converting to a long endoscope, and using marking clips can be helpful.
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Enfermedades de la Aorta , Enfermedades Duodenales , Fístula Intestinal , Anciano , Aorta , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades Duodenales/diagnóstico por imagen , Enfermedades Duodenales/etiología , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Fístula Intestinal/diagnóstico por imagen , Fístula Intestinal/etiología , Fístula Intestinal/cirugía , MasculinoRESUMEN
BACKGROUND: To make an accurate estimate of the response to thrombopoietin (TPO) receptor agonists for thrombocytopenia associated with chronic liver disease, we evaluated the influence of antiplatelet autoantibodies on the response to lusutrombopag in thrombocytopenic patients with liver disease. METHODS: A prospective study was conducted at 2 hospitals. Thrombocytopenic patients with liver disease received oral lusutrombopag 3.0 mg once daily for up to 7 days. We analyzed changes in platelet counts from baseline to the maximum platelet count on days 9-14. The definition of clinical response was a platelet count of ≥5 × 104/µL with an increased platelet count of ≥2 × 104/µL from baseline. We assessed the correlation between the response to treatment drug and antiplatelet autoantibodies measured by anti-GPIIb/IIIa antibody-producing B cells. RESULTS: Thirty patients received the trial drug. There were 25 responders and 5 nonresponders. The median change in platelet counts was 3.9 × 104/µL (95% CI 2.8-4.6, p < 0.0001). The correlation between change in platelet counts and the frequency of the anti-glycoprotein IIb/IIIa antibody-producing B cells was moderate (r = 0.414, 95% CI 0.064-0.674, p = 0.023). In multivariate analysis of factors affecting the change in platelet counts, the anti-GPIIb/IIIa antibody-producing B cells were identified as an independent factor (regression coefficient [B] = 0.089; CI 0.021-0.157, p = 0.013). CONCLUSION: Anti-GPIIb/IIIa antibody-producing B cells may be a predictor for TPO receptor agonists in patients with chronic liver disease.
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Autoanticuerpos/biosíntesis , Linfocitos B/inmunología , Cinamatos/uso terapéutico , Hepatopatías/complicaciones , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/inmunología , Tiazoles/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/inmunología , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Plaquetas/patología , Cinamatos/administración & dosificación , Femenino , Humanos , Hepatopatías/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tamaño de los Órganos , Recuento de Plaquetas , Estudios Prospectivos , Bazo/patología , Tiazoles/administración & dosificación , Trombocitopenia/sangre , Trombocitopenia/complicacionesRESUMEN
AIM: There are limited data from prospective studies showing the clinical usefulness of the new criteria for sarcopenia in liver disease produced by the Japan Society of Hepatology. Therefore, we aimed to evaluate the clinical usefulness of this new criteria for prognosis in cirrhotic patients. METHODS: This prospective study was performed at six centers. The 300 enrolled patients, aged more than 20 years with liver cirrhosis, were evaluated over a 3-year period for skeletal muscle mass index and grip strength. Sarcopenia was defined according to the Japan Society of Hepatology criteria by grip strength and computed tomography-based skeletal muscle mass index values. We investigated the correlation between sarcopenia and the survival rate of cirrhotic patients. RESULTS: Among the 300 assessed patients there were 99 (33%) patients with sarcopenia. The number of deaths in the sarcopenia and non-sarcopenia groups was 34 (34.3%) and 38 (18.9%), respectively (p = 0.002). Multivariate analysis confirmed that sarcopenia, decompensated phase, albumin-bilirubin grade, and hepatocellular carcinoma (HCC) stage 3/4 were independent factors correlated with death in patients with liver cirrhosis during the observation period. The interaction between sarcopenia and the presence of HCC was statistically significant (p < 0.001), and the presence of HCC had the highest hazard ratio of 6.665 for deaths in cirrhotic patients when non-sarcopenia and the absence of HCC were used as references. CONCLUSIONS: The new Japan Society of Hepatology criteria for sarcopenia are accurate predictors of poor prognosis in patients with liver cirrhosis.
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BACKGROUND: Few data have demonstrated that the combination therapy comprising a natriuretic drug and an aquaretic drug has improved renal function compared with the conventional diuretic therapy of only a natriuretic drug in patients with cirrhosis. OBJECTIVE: This study aimed to assess the influence to the renal function by furosemide dose reductions after administration of tolvaptan in cirrhotic ascites patients. METHODS: A 2-center, open-label, randomized study with a 24-week treatment period was conducted in Japan. Patients who met the study's criteria were randomized to a conventional therapy group or a combination therapy group in a 1:1 ratio. The combination therapy group received tolvaptan and reduced furosemide doses compared with those received before the study enrollment. The conventional therapy group continued with the original dosage regimens. We assessed the change in estimated glomerular filtration rate (eGFR) from baseline through the duration of the study in the 2 groups. RESULTS: Twenty-nine patients were randomized to receive either the combination therapy group (n = 14) or the conventional therapy group (n= 15). The change in the furosemide dose from baseline was -35.2 ± 10.1 mg in the combination therapy group. After 24 weeks of treatment, significantly greater improvement in eGFR was observed in the combination therapy group (2.4 ± 0.4 mL/min 1.73 m2) compared with those in the conventional therapy group (-5.1 ± 1.2 mL/min 1.73 m2; p = 0.013). CONCLUSION: A combination therapy of tolvaptan and furosemide enabled furosemide dose reductions. Systematic reductions of the furosemide doses can lead to the improvement of renal function.
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Furosemida/administración & dosificación , Furosemida/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Tolvaptán/uso terapéutico , Anciano , Anciano de 80 o más Años , Ascitis/complicaciones , Ascitis/tratamiento farmacológico , Ascitis/fisiopatología , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Furosemida/efectos adversos , Furosemida/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Japón , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Tolvaptán/efectos adversos , Tolvaptán/farmacologíaRESUMEN
AIM: The present study aimed to assess the correlation between loss of skeletal muscle mass (LSMM) and the clinical characteristics of patients with liver cirrhosis. METHODS: This multicenter, prospective study was undertaken at five locations in Japan and involved a 12-month observation period. After baseline assessment, the change in the skeletal muscle index per year (ΔSMI/y) was evaluated in the enrolled patients; LSMM was defined as ΔSMI/y < 0. We evaluated the relationships between LSMM and baseline clinical characteristics in patients with liver cirrhosis. RESULTS: A total of 166 patients with cirrhosis were enrolled and, of these, 123 patients (74.1%) showed LSMM. Multivariate analysis confirmed that hepatic encephalopathy, Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) (≥1.86), age (≥60 years), and grip strength (<18 kg for women and <26 kg for men) were independent predictors of skeletal muscle decline (P = 0.042, odds ratio [OR] 8.997, 95% confidence interval [CI] 1.083-74.71; P = 0.023, OR 3.970, 95% CI 1.468-6.177; P = 0.037, OR 2.526, 95% CI 1.056-6.045; and P = 0.002, OR 3.970, 95% CI 1.691-9.322, respectively). CONCLUSIONS: Advanced age, low grip strength, hepatic encephalopathy, and high WFA+ -M2BP might be risk factors for LSMM in liver cirrhosis patients.
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INTRODUCTION AND AIM: We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. MATERIAL AND METHODS: This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]). RESULTS: No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients. CONCLUSION: Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.
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Anilidas/administración & dosificación , Carbamatos/administración & dosificación , ADN Viral/genética , Tolerancia a Medicamentos , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Macrocíclicos/administración & dosificación , Ritonavir/administración & dosificación , Administración Oral , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Ciclopropanos , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Japón/epidemiología , Lactamas Macrocíclicas , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Prolina/análogos & derivados , Estudios Prospectivos , Factores de Riesgo , Sulfonamidas , ValinaRESUMEN
BACKGROUND AND AIM: An assay for Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+ -M2BP) has been reported as a useful non-invasive marker for the evaluation of the staging of fibrosis in several chronic liver diseases. However, available data on the effect of WFA+ -M2BP level in decompensated cirrhosis patients were limited. It is important that these investigations can validate the diagnostic utility of WFA+ -M2BP in the full range of patients with liver cirrhosis. METHODS: A multicenter study was conducted at five locations in Japan. A total of 207 patients with liver cirrhosis were enrolled in the present study. To determine whether or not the WFA+ -M2BP value was associated with a progression of fibrosis among cirrhosis, this study examined WFA+ -M2BP levels between patients with cirrhosis in the decompensated and compensated groups. RESULTS: The numbers and proportions of compensated and decompensated patients were 113 (54.6%) and 94 (45.4%), respectively. The average WFA+ -M2BP levels were 2.22 ± 1.61 in the compensated group and 6.91 ± 5.04 in the decompensated group. Significantly higher WFA+ -M2BP levels were observed in the decompensated group than those in the compensated group (P < 0.0001). The respective cut-off index values for decompensated cirrhosis were estimated using receiver-operating characteristic curves for WFA+ -M2BP levels. Using a cut-off index value of 3.37 for WFA+ -M2BP, predicting decompensated cirrhosis had a sensitivity of 77.8% and a specificity of 86.7%. CONCLUSIONS: WFA+ -M2BP values were higher in patients with decompensated liver cirrhosis.
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Antígenos de Neoplasias/sangre , Cirrosis Hepática/diagnóstico , Glicoproteínas de Membrana/sangre , Lectinas de Plantas/sangre , Receptores N-Acetilglucosamina/sangre , Anciano , Biomarcadores/sangre , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Fibrosis , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
AIM: To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients. METHODS: This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics. RESULTS: The mean body weight change from the baseline on the final dosing day was -2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768-0.9896) in the multivariate analyses. CONCLUSION: In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response.
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Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.
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Background and Aim: The appropriate duration of antimicrobial therapy for acute cholangitis (AC) arising from multiple hilar biliary obstructions as opposed to simple obstruction in the extrahepatic bile duct has not been established. This study assessed the efficacy of the duration of antimicrobial treatments in the Tokyo Guidelines 2018 for AC based on the cause and site of obstruction. Methods: This single-center retrospective study involved patients with AC who underwent successful biliary drainage and completed a 7-day or shorter antimicrobial treatment. Patients were categorized into three groups: Group 1, bile duct stone or benign obstruction; Group 2, simple biliary obstruction due to malignancy; and Group 3, multiple hilar biliary obstruction due to malignancy. The primary outcome was clinical cure rate, and the secondary outcomes were 3-month recurrence rate and length of hospital stay. Results: A total of 373 patients were selected. Patients in Group 3 were younger or had Charlson Comorbidity Index ≥4, and had fewer positive blood cultures. In Group 3, the clinical cure rate (87.1%) and 3-month recurrence rate (32.3%) were less favorable than those in the other groups. In Group 1, the clinical cure rate was significantly higher (98.1%, P = 0.02) with a much lower 3-month recurrence rate of only 3.4% (P < 0.001) than that in the other groups. The median hospital stay for all groups was 7 days. Conclusion: This study suggests that the outcomes in Group 3 may be worse than those in Groups 1 or 2, regardless of the duration of the antibiotic treatment.
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The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.
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Colangitis , Drenaje , Fiebre , Humanos , Colangitis/tratamiento farmacológico , Masculino , Femenino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Anciano , Estudios Retrospectivos , Enfermedad Aguda , Persona de Mediana Edad , Resultado del Tratamiento , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Antiinfecciosos/administración & dosificación , RecurrenciaRESUMEN
Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.
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We report two cases of ruptured pyogenic liver abscesses where one patient survived and the other died. We suspected that infection with gas-producing bacteria was the cause of the latter outcome, and we reviewed 47 case reports of ruptured pyogenic liver abscesses. Of the 47 cases, we determined that 77.6% included gas-producing pathogens. Moreover, the presence of gas-producing pathogens was associated with a mortality of 22.2%, whereas there were no deaths in cases with no gas-producing pathogens.
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Absceso Piógeno Hepático/microbiología , Anciano de 80 o más Años , Femenino , Gases/metabolismo , Humanos , Absceso Piógeno Hepático/mortalidad , Persona de Mediana Edad , Pronóstico , Rotura EspontáneaRESUMEN
Hepatic arteriovenous malformation occurs hyperpulsatile heart failure, hepatic encephalopathy, and ascites as clinical symptoms. Oral medication are effective, but hepatic angioembolization or heart surgery in case of its symptoms worsen.
RESUMEN
Most patients with hepatitis E virus (HEV) infection are asymptomatic and improve naturally without any treatment, but even non-immunocompromised individuals may develop persistent HEV infections and should be monitored regularly for the onset.