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The site of enterohepatic Helicobacter colonization/infection in humans is still unknown. We report microbiologically and histopathologically confirmed H. fennelliae localization in the large intestine in an immunocompromised patient in Japan. This case contributes to better understanding of the life cycle of enterohepatic Helicobacter species.
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Helicobacter , Intestinos , Humanos , Japón , Helicobacter/genética , Huésped InmunocomprometidoRESUMEN
No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing hepatitis B virus (HBV) reactivation has yet been reported. This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis.
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Hepatitis A , Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Antivirales/uso terapéutico , Alanina/uso terapéutico , Adenina/efectos adversos , Hepatitis B Crónica/tratamiento farmacológicoRESUMEN
Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (P = 0.011), chronic renal failure (P = 0.0087), septic shock (P < 0.0001), steroid administration (P = 0.0085), and liposomal amphotericin B breakthrough fungemia (P = 0.0011). An absolute neutrophil count of >500/µL was significantly more common in candidemia in the multivariate analysis (P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia (P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.
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Candidemia , Cryptococcus neoformans , Fungemia , Fusarium , Enfermedades Hematológicas , Trichosporon , Adulto , Antifúngicos/uso terapéutico , Candida , Candidemia/tratamiento farmacológico , Fungemia/tratamiento farmacológico , Fungemia/microbiología , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/tratamiento farmacológico , Humanos , Persona de Mediana EdadRESUMEN
AIM: A clinical trial (IMbrave150) indicated the efficacy and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma (HCC). In this study, we evaluated this therapeutic combination in a real-world setting, with a focus on patients who did not meet the IMbrave150 eligibility criteria. METHODS: In this multicenter study, patients with unresectable HCC treated with atezolizumab plus bevacizumab between October 2020 and May 2021 were screened. In patients who did not meet IMbrave150 eligibility criteria, treatment responses and safety at 6 and 12 weeks were evaluated. RESULTS: Atezolizumab plus bevacizumab was initiated in 64 patients, including 46 patients (71.9%) who did not meet IMbrave150 eligibility criteria. Most of these patients had a history of systemic therapy (44/46). The objective response rate and disease control rate observed using Response Evaluation Criteria in Solid Tumors 1.1 were 5.2% and 82.8% at 6 weeks and 10.0% and 84.0% at 12 weeks, respectively; these rates were similar between patients who met and did not meet the IMbrave150 criteria. Ten patients experienced progressive disease (PD) at 6 weeks. Portal vein tumor thrombosis was significantly associated with PD (p = 0.039); none of the 15 patients with hepatitis B virus-related HCC experienced PD (p = 0.050). The most common adverse events of grade 3 or higher were aspartate aminotransferase elevation (n = 8, 13.8%) and the safety profile was similar between patients who met and did not meet the IMbrave150 criteria. CONCLUSION: Most patients treated with atezolizumab plus bevacizumab did not meet the IMbrave150 criteria; however, the combination therapy showed good safety and efficacy at the early treatment phase.
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AIM: This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial). METHODS: In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression-free-survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial. RESULTS: Of the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child-Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child-Pugh-score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS. CONCLUSION: Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.
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AIM: Ultrasound technology can now be used for liver stiffness measurement (LSM) and for evaluating the amount of hepatic fat quantitatively known as the controlled attenuation parameter (CAP). This study aimed to determine the applicable cut-off values of LSM and the CAP for primary hepatocellular carcinoma (HCC), and to investigate their clinical usefulness for assessing HCC risk in patients with chronic liver disease. METHODS: A total of 1054 patients (88 with primary HCC and 966 without HCC) whose LSM and the CAP were measured by transient elastography with clinically evident hepatitis C virus (419 patients), hepatitis B virus (377 patients), and non-alcoholic fatty liver disease (258 patients) were enrolled in this study. Subsequently, a total of 966 patients who did not have HCC initially were followed, and the usefulness of the cut-off values of LSM and CAP for HCC development were evaluated. RESULTS: In hepatitis C virus patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥8.0 kPa and CAP ≤221 dB/m than among those with other values (log-rank test 0.0239, hazard ratio 2.66, 95%CI 1.07-6.47, P = 0.0362). In non-alcoholic fatty liver disease patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥5.4 kPa and CAP ≤265 dB/m than among others (log-rank test 0.0040, hazard ratio 8.91, 95% CI 1.47-67.97, P = 0.0192). CONCLUSION: In the hepatitis C virus and non-alcoholic fatty liver disease groups, a combination of LSM and the CAP cut-off values would be useful for screening to identify the high-risk group for primary HCC development.
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AIM: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first-line nucleos(t)ide analogues for hepatitis B virus (HBV)-infected patients. However, consecutive TDF treatment causes renal dysfunction, and the safety and efficacy of TAF have not been established in severe renal dysfunction patients, including hemodialysis patients. The efficacy and safety of ETV in these populations has not been clarified. The study aimed to clarify this. METHODS: In this retrospective multicenter study, between 2006 and 2018, a total of 567 HBV-infected patients treated with ETV monotherapy were screened. Patients were included if >20 years old, treated with ETV monotherapy for >1 year, and had proper clinical information. The efficacy of ETV and changes in renal function were evaluated according to renal function. RESULTS: A total of 273 patients were included: 9.2% (25/273), 1.8% (5/273), and 3.7% (10/273) had chronic kidney disease (CKD) stage G3, CKD stage G4/5, and were on hemodialysis, respectively. Overall, 84.2%, 94.0%, and 96.2% of patients experienced serum HBV-DNA disappearance at 1, 2, and 3 years, respectively, after treatment initiation. In patients with CKD stage G3-5, estimated glomerular filtration rate tended to restore with time, which was in contrast to patients without renal dysfunction. The rate of disappearance in serum HBV-DNA, alanine transaminase normalization, and virological breakthrough was similar between patients with or without renal dysfunction. ETV showed high efficacy for all 10 hemodialysis patients without virological breakthrough. CONCLUSIONS: Entecavir for HBV-infected patients with severe renal dysfunction, including hemodialysis patients, is highly effective and does not affect renal function.
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Background: Previous studies suggest that Helicobacter cinaedi can cause recurrent bacteremia. In this study, we elucidated the risk factors for recurrent H. cinaedi bacteremia and explored the efficacy of selective digestive decontamination (SDD) as a preventive measure. Methods: We retrospectively reviewed the medical records of patients with H. cinaedi bacteremia between March 2009 and December 2016 at 2 Japanese hospitals. Results: We identified 168 patients with H. cinaedi bacteremia. Bacteremia recurred in 34 patients. The 100-day cumulative incidence rate of recurrent bacteremia was 18.7%. In univariate analysis of factors associated with recurrent bacteremia, anticancer chemotherapy (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.86-7.58; P < .001), systemic steroids (HR, 3.79; 95% CI, 1.70-8.45; P = .0011), and hematological malignancy (HR, 3.18; 95% CI, 1.64-6.19; P < .001) were detected. Multivariate analysis indicated that anticancer chemotherapy (HR, 2.47; 95% CI, 1.19-5.12; P = .015) and systemic steroids (HR, 2.40; 95% CI, 1.03-5.61; P = .044) were the independent risk factors. Of the 168 patients, 47 received SDD. According to Gray's test, SDD might have reduced the rate of recurrence but this was not statistically significant (HR, 0.46; 95% CI, 0.18-1.18; P = .11). However, in a proportional hazard modeling analysis, SDD reduced the rate of recurrence (HR, 0.36; 95% CI, 0.13-1.00; P = .050). Conclusions: The 100-day cumulative incidence of recurrent H. cinaedi bacteremia was 18.7%. Anticancer chemotherapy and systemic steroids were independent risk factors for recurrent bacteremia. SDD is a potential strategy for reducing the recurrence.
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Antibacterianos/uso terapéutico , Bacteriemia/prevención & control , Infecciones por Helicobacter/prevención & control , Kanamicina/uso terapéutico , Prevención Secundaria/métodos , Adulto , Anciano , Anciano de 80 o más Años , Descontaminación , Femenino , Tracto Gastrointestinal/microbiología , Helicobacter/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Incidencia , Masculino , Registros Médicos , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The route of Helicobacter cinaedi bacteremia has not yet been clarified. Although bacterial translocation from the intestinal tract into the circulation has been suggested, it has not been demonstrated thus far. The objective of this study was to investigate the port of entry of this bacterium. MATERIAL AND METHODS: We conducted a retrospective study on patients with H. cinaedi bacteremia between March 2009 and May 2013. Records of patients in whom H. cinaedi was detected in both blood and stool cultures were extracted. H. cinaedi was identified using gyrB-targeted PCR. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes. RESULTS: Seventy-one patients were diagnosed with H. cinaedi bacteremia during the study period. H. cinaedi was detected in both blood and stool samples of 21 patients. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes in 18 evaluable strains (from 9 patients). The pulse-field gel electrophoresis patterns of the stool- and blood-derived strains of H. cinaedi were consistent among all 9 patients. Most of the 9 patients analyzed were immunocompromised and being treated with anticancer drugs or steroids, which suggests reduced intestinal immunity. CONCLUSIONS: This is the first study to demonstrate that bacterial translocation from the intestinal tract could represent one route of H. cinaedi bacteremia.
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Bacteriemia/microbiología , Traslocación Bacteriana/fisiología , Infecciones por Helicobacter/microbiología , Helicobacter/aislamiento & purificación , Intestinos/microbiología , Adulto , Anciano , Proteínas Bacterianas/genética , Girasa de ADN/genética , Heces/microbiología , Femenino , Helicobacter/genética , Infecciones por Helicobacter/sangre , Humanos , Huésped Inmunocomprometido , Japón , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios RetrospectivosRESUMEN
The aim of this study was to clarify the clinical characteristics of patients with Helicobacter cinaedi bacteremia and the time required for blood cultures to become positive. The medical records of all patients with H. cinaedi bacteremia at Toranomon Hospital and Toranomon Hospital Kajigaya between March 2009 and March 2013 were retrospectively reviewed. Sixty-three patients, 34 men and 29 women with a median age of 67 years (range, 37 to 88 years), were diagnosed with H. cinaedi bacteremia. A total of 51,272 sets of blood cultures were obtained during the study period, of which 5,769 sets of blood cultures were positive for some organism and 126 sets were H. cinaedi positive. The time required for blood cultures to become positive for H. cinaedi was ≤5 days in 69 sets (55%) and >5 days in 57 sets (45%). Most patients had an underlying disease, including chronic kidney disease (21 cases), solid tumor (19 cases), hematological malignancy (13 cases), diabetes mellitus (8 cases), chronic liver disease (6 cases), and postorthopedic surgery (3 cases). Only 1 patient had no apparent underlying disease. The clinical symptoms included cellulitis in 24 cases, colitis in 7 cases, and fever only in 27 cases, including 7 cases of febrile neutropenia. The 30-day mortality rate of H. cinaedi bacteremia was 6.3%. In conclusion, most cases of H. cinaedi bacteremia occurred in immunocompromised patients. We might have overlooked nearly half of the H. cinaedi bacteremia cases if the duration of monitored blood culture samples had been within 5 days. Therefore, when clinicians suspect H. cinaedi bacteremia, the observation period for blood cultures should be extended.
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Bacteriemia/sangre , Bacteriemia/diagnóstico , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/diagnóstico , Helicobacter/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Humanos , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/tratamiento farmacológico , Antivirales/uso terapéutico , Neoplasias Hepáticas/etiología , Estudios Retrospectivos , Angiopoyetina 2/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepacivirus/genética , Factores de Riesgo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicacionesRESUMEN
Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
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We report here two cases of neuroendocrine carcinoma which occurred in the biliary system. The prognosis of neuroendocrine carcinoma in the biliary system is generally poor. However, based on the preoperative pathological diagnosis of neuroendocrine carcinoma, multidisciplinary treatment consisting of preoperative chemotherapy, chemoradiation therapy, curative resection and adjuvant chemotherapy seemed to be very effective and long-term survival was obtained in our two cases. Therefore it is essential to diagnose preoperatively to improve prognosis.
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Neoplasias de los Conductos Biliares/mortalidad , Carcinoma Neuroendocrino/mortalidad , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Neoplasias de los Conductos Biliares/terapia , Carcinoma Neuroendocrino/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: In this study, we investigated diagnostic accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing and whether universal screening was effective to prevent a nosocomial outbreak of coronavirus disease 2019 (COVID-19). METHODS: All adult patients admitted to an acute-care hospital in Tokyo, Japan, after receiving LUMIPULSE SARS-CoV-2 Ag using a nasopharyngeal swab and a brief questionnaire to evaluate symptoms and exposures from December 3, 2020 to March 20, 2021 were included. RESULTS: Of the 5191 patients, 53 were antigen-positive, 19 were inconclusive and 5119 were negative. The sensitivity and specificity (positive or inconclusive results) of the quantitative antigen test for COVID-19 diagnosis at admission was 0.957 (95% confidence interval [CI]: 0.855-0.995) and 0.995 (95% CI: 0.992-0.997), respectively. Six asymptomatic patients were identified on admission. Two patients were antigen-negative and diagnosed with COVID-19 later; however, they had been isolated prior to diagnosis because both had symptoms of COVID-19 and exposure. No nosocomial infections occurred during the period. CONCLUSION: Quantitative SARS-CoV-2 antigen testing was found to be valid for the early detection of asymptomatic COVID-19 patients as a universal screening test on admission.
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COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Tamizaje Masivo , HospitalesRESUMEN
Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.
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Carcinoma Hepatocelular/epidemiología , Diagnóstico por Imagen de Elasticidad/estadística & datos numéricos , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Hígado/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Incidencia , Hígado/patología , Hígado/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Respuesta Virológica Sostenida , Adulto JovenRESUMEN
De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1ß levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94-333.3). HCV-infected patients with the IL-1ß gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1ß levels; no HCV-infected patient with the IL-1ß AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1ß levels. Low IL-1ß levels were not associated with HBV reactivation. IL-1ß levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.
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Antineoplásicos/uso terapéutico , Coinfección , Hepatitis B , Hepatitis C Crónica , Hepatitis C , Interleucina-1beta/sangre , Antivirales , Citocinas/farmacología , Hepacivirus/genética , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Terapia de Inmunosupresión , Interleucinas/farmacología , Activación ViralRESUMEN
The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.
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BACKGROUND: Factors associated with liver stiffness (LS) are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD) and non-alcoholic fatty (NAFLD) liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report. METHODS: We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI), liver function (LF), alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls. RESULTS: The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD) and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3%) of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results. CONCLUSIONS: Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso Alcohólico/diagnóstico , Hígado Graso/diagnóstico , Hígado/patología , Adulto , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Diagnóstico Diferencial , Hígado Graso/diagnóstico por imagen , Hígado Graso/patología , Hígado Graso Alcohólico/diagnóstico por imagen , Hígado Graso Alcohólico/patología , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Valores de Referencia , Factores de RiesgoRESUMEN
The liver-spleen contrast (LSC) using hepatobiliary-phase images could replace the receptor index (LHL15) in liver scintigraphy; however, few comparative studies exist. This study aimed to verify the convertibility from LSC into LHL15. In 136 patients, the LSC, not at 20 min, but at 60 min after injecting gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid was compared with the LHL15, albumin-bilirubin (ALBI) score, and the related laboratory parameters. The LHL15 was also compared with their biochemical tests. The correlation coefficients of LSC with LHL15, ALBI score, total bilirubin, and albumin were 0.740, -0.624, -0.606, and 0.523 (P < 0.00001), respectively. The correlation coefficients of LHL15 with ALBI score, total bilirubin, and albumin were -0.647, -0.553, and 0.569 (P < 0.00001), respectively. The linear regression equation on the estimated LHL15 (eLHL15) from LSC was eLHL15 = 0.460 · LSC + 0.727 (P < 0.00001) and the coefficient of determination was 0.548. Regarding a contingency table using imaging-based clinical stage classification, the degree of agreement between eLHL15 and LHL15 was 65.4%, and Cramer's V was 0.568 (P < 0.00001). Therefore, although the LSC may be influenced by high total bilirubin, the eLHL15 can replace the LSC as an index to evaluate liver function.
Asunto(s)
Gadolinio DTPA/química , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cintigrafía/métodos , Bazo/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Albúminas/análisis , Bilirrubina/análisis , Medios de Contraste , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos XRESUMEN
Studies describing reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay-based infection control strategies (LAMP-based ICSs) for coronavirus disease 2019 (COVID-19) are limited. We reviewed the medical records of cases in which RT-LAMP was performed. Standard ICSs and LAMP-based ICSs were implemented during the study period. The strategies were intended to impose longer periods of infection control precautions (ICPs) for specific patients, such as those with a history of exposure to COVID-19 patients and/or bilateral ground glass opacities (bGGO) on chest computed tomography (CT). Of 212 patients, which included 13 confirmed COVID-19 patients in the diagnostic cohort, exposure to COVID-19 patients (P <0.0001) and chest CT bGGO (P = 0.0022) were identified as significant predictors of COVID-19. In the 173 hospitalized patients in which the results of the first RT-LAMP were negative, the duration of ICPs was significantly longer in patients with exposure to COVID-19 and/or a high clinical index of suspicion and patients with bGGO than in the remaining patients (P = 0.00046 and P = 0.0067, respectively). Additionally, no confirmed COVID-19 cases indicating nosocomial spread occurred during the study period. Establishing a comprehensive system that combines rational LAMP-based ICSs with standard ICSs might be useful for preventing nosocomial spread.