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Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with obesity. Sexual dimorphism is present in MASLD. A noninvasive test to diagnose the severity of the disease, in particular the presence of Metabolic dysfunction-associated steatohepatitis (MASH), is lacking. This European multicenter prospective study uses a blood test based on mid-infrared (MIR) metabolic fingerprinting of individuals with severe or morbid obesity to diagnose MASH. Three hundred eighty-two individuals with severe or morbid obesity undergoing bariatric surgery were enrolled prospectively. Liver biopsies were obtained during surgery and assessed centrally. An algorithm was defined to calculate a score from the recorded MIR spectrum and to establish a diagnostic threshold to classify patients with MASH. Among the women (n = 217), MASH was diagnosed in 14.3% of cases. For women, the performance in terms of AUC were 0.83 and 0.82 in the calibration and validation groups, respectively. For a threshold of 0.1817, sensitivities were 86% and 70%, specificities were 81% and 75%, PPV were 43% and 32%, NPV were 97% and 94% and ACC were 82% and 74% for the calibration and validation groups, respectively. For men (n = 78; MASH: 33.3%), the performance of the spectral model was poor. The metabolic fingerprint obtained by MIR spectroscopy can rule out MASH in women with severe or morbid obesity. Its value in men needs new studies.Trial registration: ClinicalTrials.gov identifier: ClinicalTrials.gov identifier: NCT03978247 (04/06/2019).
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Cirugía Bariátrica , Obesidad Mórbida , Humanos , Femenino , Cirugía Bariátrica/métodos , Masculino , Estudios Prospectivos , Adulto , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Obesidad Mórbida/sangre , Obesidad Mórbida/metabolismo , Espectrofotometría Infrarroja/métodos , Hígado Graso/diagnóstico , Hígado Graso/sangre , Europa (Continente)RESUMEN
Cytokines like interleukins (ILs) play important roles in inflammation and innate immune. Yang and Zhang carried out an interesting study related to ILs and hepatic diseases. They described the role of ILs in the pathogenesis and resolution of hepatic disorders. The authors summarized alcohol-related liver disease and virus-induced hepatitis, as far as clinical studies a fortiori carried out on IL-mediated treatments pertaining to these dysfunctions. This editorial contributes to the review by Yang and Zhang titled, "Interleukins in liver disease treatment", and focuses on therapies mediated by ILs in comorbid liver diseases. The documentary search was conducted on recent pertinent literature, primarily using the Google Scholar and PubMed databases.
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Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.
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Cirugía Bariátrica , Índice de Masa Corporal , Trasplante de Hígado , Pérdida de Peso , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Femenino , Bélgica/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/estadística & datos numéricos , Cirugía Bariátrica/métodos , Resultado del Tratamiento , Anciano , Aumento de Peso , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/diagnóstico , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Factores de Tiempo , Hígado Graso/etiología , Hígado Graso/epidemiología , Hígado Graso/diagnóstico , Hígado Graso/cirugía , Gastrectomía/efectos adversos , Gastrectomía/estadística & datos numéricos , Gastrectomía/métodosRESUMEN
Streptococcus pneumoniae infections cause community-acquired pneumonia and invasive pneumococcal disease such as sepsis and acute meningitis. In the adult population, the risk of severe infections, which can be lethal, is particularly high among people aged above 65 years and subgroups with comorbidities. Pneumococcal vaccines underwent progressive improvement and a new conjugated vaccine targeting 20 serotypes (PCV20) is now available. The Belgian Superior Health Council has recently reiterated the importance of vaccinating at-risk individuals against S. pneumoniae and now recommends vaccination with PCV20 (Apexxnar®) as the preferred primary vaccination regimen in all at-risk adults. The present article reminds the risk of severe pneumococcal infections among patients with comorbidities, by targeting five of them, chronic respiratory diseases, heart failure, chronic kidney disease, diabetes mellitus and cirrhosis. It emphasizes the too low rate of pneumococcal vaccination in these at-risk subgroups and summarizes the last guidelines of the Belgian Superior Health Council in favor of pneumococcal vaccination in at-risk patients with comorbidities. Finally, it describes the Belgian reimbursement criteria recently granted to people aged 65-85 years with comorbidities.
Les infections par le Streptococcus pneumoniae sont responsables de pneumonies communautaires et de maladies invasives à pneumocoques telles que sepsis et méningites aiguës. Dans la population adulte, le risque d'infections graves, potentiellement léthales, est particulièrement élevé chez les personnes âgées de plus de 65 ans et parmi des sous-groupes avec comorbidités. Les vaccins antipneumococciques ont été progressivement améliorés et un nouveau vaccin conjugué ciblant 20 sérotypes (PCV20) est désormais disponible. Le Conseil Supérieur de la Santé (CSS) belge a rappelé, en 2022, l'importance de vacciner contre S. pneumoniae les personnes à risque et privilégie le PCV20 (Apexxnar®) pour la primo-vaccination chez les personnes adultes dans tous les groupes à risque. Cet article rappelle le risque d'infections pneumococciques graves chez les patients avec comorbidités, en ciblant plus particulièrement quatre d'entre elles, les maladies respiratoires chroniques, l'insuffisance cardiaque, la maladie rénale chronique, le diabète sucré et la cirrhose. Il insiste sur le trop faible taux de vaccination antipneumococcique dans ces populations à risque et résume les dernières recommandations du CSS en faveur de la vaccination antipneumococcique des groupes à risque en fonction de la présence de comorbidités. Enfin, il fait état des conditions de remboursement récemment accordées à la vaccination antipneumococcique dans les groupes à risque chez les personnes âgées de 65 à 85 ans.
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Infecciones Neumocócicas , Adulto , Humanos , Bélgica/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae , Vacunación , Vacunas Neumococicas , Vacunas ConjugadasRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) found in a non cirrhotic liver represents a minority of HCC cases and remains poorly studied. Due to its specific characteristics and evolution, this tumour requires a different management compared to HCC in a cirrhotic liver. CASE REPORT: The authors describe the case of a 68-year-old man diagnosed with a large giant and only mildly symptomatic HCC in a non-cirrhotic liver. The 23 cm HCC was discovered when a thoracoabdominal computed tomography was performed following mild abdominal pain. After a multidisciplinary discussion the tumour was judged to be borderline, but potentially resectable after neoadjuvant therapy and preparation for surgery. The patient underwent selective internal radiation therapy radioembolization of the right hepatic artery lobe with 5,5 GBq of 90Y-labeled glass microspheres. It was followed by extended right hepatectomy after preparation by embolization of the right portal and the right hepatic veins. Thirty months after surgical resection the patient showed neither clinical, radiological nor biological signs of HCC recurrence. DISCUSSION: HCC in non-cirrhotic liver is less common than in cirrhotic liver but has a better prognosis, thanks to a greater opportunity for surgical resection. The symptoms often emerge late and are unspecific, thus delaying the HCC diagnosis. Advances in surgical resection by laparotomy or laparoscopy, and neoadjuvant therapy in preparation for surgery, have proven to be effective. However, high mortality persists due to late diagnosis linked to the inability of identifying groups at risk of HCC in the non-cirrhotic population and inadequate screening.
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BACKGROUND AND AIMS: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. METHODS: A five-year prospective multi-centric observational study in 21 hospitals in Belgium gathered a study population of 198 symptomatic PLD-patients of whom the disease-specific symptom questionnaire PLD-complaint-specific assessment (POLCA) scores were calculated. The thresholds of the POLCA score for the need for volume reduction therapy were analyzed. RESULTS: The study group consisted of mostly (82.8%) women with baseline mean age of 54.4 years ±11.2, median liver volume expressed as height-adjusted total liver volume(htLV) of 1994 mL (interquartile range [IQR] 1275; 3150) and median growth of the liver of +74 mL/year (IQR +3; +230). Volume reduction therapy was needed in 71 patients (35.9%). A POLCA severity score (SPI) ≥ 14 predicted the need for therapy both in the derivation (n = 63) and the validation cohort (n = 126). The thresholds to start somatostatin analogues (n = 55) or to consider liver transplantation (n = 18) were SPI scores of ≥14 and ≥ 18 and the corresponding mean htLVs were 2902 mL (IQR 1908; 3964) and 3607 mL (IQR 2901; 4337), respectively. Somatostatin analogues treatment resulted in a decrease in the SPI score -6.0 versus + 4.5 in patients without somatostatin analogues (p < 0.01). Changes in the SPI score were significantly different between the liver transplantation group and no liver transplantation group, +4.3 ± 7.1 versus -1.6 ± 4.9, respectively, (p < 0.01). CONCLUSION: A polycystic liver disease-specific questionnaire can be used as a guide on when to start a volume reduction therapy and to assess the effect of treatment.
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Hepatopatías , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Hepatopatías/diagnóstico , Hepatopatías/etiología , Hepatopatías/terapia , Somatostatina , Encuestas y CuestionariosRESUMEN
BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.
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Virus de la Hepatitis E , Hepatitis E , Adulto , Humanos , Bélgica/epidemiología , Bilirrubina , Genotipo , Hepatitis E/diagnóstico , Hepatitis E/epidemiología , Filogenia , ARN Viral/análisis , Protocolos de Ensayos Clínicos como AsuntoRESUMEN
An enhanced cascade of care should include a younger population, helping to achieve the goal of the World Health Organization with a focus on elimination in the pediatric population. Furthermore, enhanced screening and awareness efforts and continued education of health care providers will improve the outcomes of chronic hepatitis C virus (HCV) infection in the pediatric population. The present work discusses and comments on the topic "cascade of care in HCV chronic pediatric patients".
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Niño , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/terapia , Humanos , Tamizaje Masivo , Organización Mundial de la SaludRESUMEN
BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.
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Hepatitis Alcohólica , Trasplante de Hígado , Hepatitis Alcohólica/cirugía , Humanos , Cirrosis Hepática Alcohólica , Recurrencia Local de Neoplasia , Estudios ProspectivosRESUMEN
INTRODUCTION: Strong correlation has been demonstrated between tumor dose and response and between healthy liver dose and side effects. Individualized dosimetry is increasingly recommended in the current clinical routine. However, hepatic and tumor segmentations could be complex in some cases. The aim of this study is to assess the reproducibility of the tumoral and non-tumoral liver dosimetry in selective internal radiation therapy (SIRT). MATERIAL AND METHODS: Twenty-three patients with hepatocellular carcinoma (HCC) who underwent SIRT with glass microspheres were retrospectively included in the study. Tumor (TV) and total liver volumes (TLV), and mean absorbed doses in tumoral liver (TD) and non-tumoral liver (THLD) were determined on the 90Y PET/CT studies using Simplicit90YTM software, by three independent observers. Dosimetry datasets were obtained by a medical physicist helped by a nuclear medicine (NM) physician with 10 years of experience (A), by a NM physician with 4-year experience (B), and by a resident who first performed 10 dosimetry assessments as a training (C). Inter-observer agreement was evaluated using intra-class correlation coefficients (ICC), coefficients of variation (CV), Bland-Altman plots, and reproducibility coefficient (RDC). RESULTS: A strong agreement was observed between all three readers for estimating TLV (ICC 0.98) and THLD (ICC 0.97). Agreement was lower for TV delineation (ICC 0.94) and particularly for TD (ICC 0.73), especially for the highest values. Regarding TD, the CV (%) was 26.5, 26.9, and 20.2 between observers A and B, A and C, and B and C, respectively, and the RDC was 1.5. Regarding THLD, it was 8.5, 12.7, and 9.4, and the RDC was 1.3. CONCLUSION: Using a standardized methodology, and regardless of the different experiences of the observers, the estimation of THLD is highly reproducible. Although the reproducibility of the assessment of tumor irradiation is overall quite high, large variations may be observed in a limited number of patients.
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BACKGROUND: Recent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC. METHODS: 526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing. RESULTS: Overall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence. CONCLUSIONS: All validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.
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Carcinoma Hepatocelular/cirugía , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Selección de Paciente , Anciano , Bélgica , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/metabolismo , Hepatopatías Alcohólicas/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Retrospectivos , Tasa de Supervivencia , alfa-Fetoproteínas/metabolismoAsunto(s)
Síndrome Hepatopulmonar/cirugía , Trasplante de Hígado , Enfermedad Hepática en Estado Terminal/cirugía , Europa (Continente) , Humanos , Trasplante de Hígado/mortalidad , Oxígeno/metabolismo , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Riesgo , Resultado del TratamientoAsunto(s)
Albendazol/uso terapéutico , Equinococosis Hepática/diagnóstico por imagen , Equinococosis Hepática/cirugía , Anciano , Astenia/diagnóstico , Astenia/etiología , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Equinococosis Hepática/complicaciones , Equinococosis Hepática/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Náusea/diagnóstico , Náusea/etiología , Cuidados Preoperatorios/métodos , Medición de Riesgo , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Positron emission tomography computed tomography (PET-CT) using 18-Fluoro-deoxyglucose (18FDG) is an imaging modality that reflects cellular glucose metabolism. Most cancers show an uptake of 18FDG and benign tumors do not usually behave in such a way. The authors report herein the case of a 38-year-old female patient with a past medical history of cervical intraepithelial neoplasia and pheochromocytoma, in whom a liver lesion had been detected with PET-CT. The tumor was laparoscopically resected and the diagnosis of inflammatory hepatic adenoma was confirmed. This is the first description of an inflammatory hepatic adenoma with an 18FDG up-take.
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INTRODUCTION: Hepatitis C virus (HCV) is a major global health issue and successful treatment has been associated with a reduction of risk of all-cause mortality. Advancements have been made in HCV treatment through the use of interferon-free regimens. Most trials have been conducted in HCV genotype (GT) 1 and data for interferon-free regimens in GT4 patients are limited. The aim of this study was to evaluate the safety and efficacy of sofosbuvir plus simeprevir in a real-world cohort of HCV GT4 patients with advanced fibrosis. PATIENTS AND METHODS: Eighty-seven GT4 treatment-naïve or -Interferon (IFN) ribavirin (RBV) experienced patients treated with sofosbuvir and simeprevir +/- ribavirin (RBV) were enrolled in this cohort study (41% severe fibrosis, 59% cirrhosis). RESULTS: Patients were 51.7% male, 78.2% IFN/RBV treatment-experienced, and 37.9% received RBV treatment. The overall sustained virologic response at least 12 weeks after treatment (SVR12) rate was 87.4% while patients treated with and without RBV had rates of 87.9% and 87% (p = 0.593), respectively, and patients with advanced fibrosis (F3) and patients with cirrhosis had SVR12 rates of 94.4% and 82.4% (p = 0.087), respectively. SVR12 rates in treatment-naïve patients and in IFN/RBV -experienced patients were 78.9% and 89.7% (p = 0.191), respectively. Treatment failure occurred most commonly in patients with cirrhosis and severe disease. The treatment was well tolerated and no patient died or discontinued treatment due to adverse events. CONCLUSIONS: Sofosbuvir in combination with simeprevir +/- ribavirin in GT 4 HCV patients with advanced fibrosis achieved high SVR12 rates and was well tolerated. RBV did not appear to increase the rate of SVR12.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Bélgica , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Viral , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS: Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS: 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS: Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Consumo de Bebidas Alcohólicas , Etanol , Hepacivirus , Hepatitis B , Hepatitis C , Humanos , Cirrosis Hepática , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a life-threatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18-75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%-55.9%) and 52.1% of controls died (95% CI, 39.4%-63.4%) (P = .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8-78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%-43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment. ClinicalTrials.gov number: NCT01801332.
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Corticoesteroides/uso terapéutico , Nutrición Enteral , Hepatitis Alcohólica/terapia , Metilprednisolona/uso terapéutico , Adolescente , Corticoesteroides/efectos adversos , Adulto , Anciano , Bélgica , Biopsia , Terapia Combinada , Ingestión de Energía , Nutrición Enteral/efectos adversos , Nutrición Enteral/mortalidad , Femenino , Francia , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/mortalidad , Hepatitis Alcohólica/fisiopatología , Humanos , Análisis de Intención de Tratar , Masculino , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Evaluación Nutricional , Estado Nutricional , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Hepatitis C virus genotype 4 (HCV-4) is the most prevalent genotype in Central Africa. AIM: To compare epidemiology, clinical characteristics and any differences in access to HCV therapy in two populations of HCV-4 patients residing in Belgium. METHODS: This multicenter study selected 473 HCV-4 patients from seven hospital databases and compared them according to ethnic origin, i.e., Black African (n=331) or not (n=142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 Black African and 30 non-Black African patients. RESULTS: Compared to other patients, the Black African patients were more likely to be female and were older, commonly overweight, frequently had abnormal glucose metabolism and arterial hypertensionâ; they were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in Black African than in other patients. Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups. CONCLUSION: In this Belgian cohort, patients with HCV-4 infection were more frequently of Black African origin than of other origin. Infected Black African patients were more commonly -female, older at diagnosis, and had more co-morbidities than other patients; they also had less advanced liver fibrosis than infected non-Black African patients and fewer had a CC genotype.