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INTRODUCTION: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis. METHODS: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients. RESULTS: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission. DISCUSSION: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course.
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Colite , Divertículo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Resultado do Tratamento , Colite/complicações , Colite/epidemiologia , Colite/diagnóstico , Divertículo/complicaçõesRESUMO
BACKGROUND: Whereas Artificial Intelligence (AI) based tools have recently been introduced in the field of gastroenterology, application in inflammatory bowel disease (IBD) is in its infancies. We established AI-based algorithms to distinguish IBD from infectious and ischemic colitis using endoscopic images and clinical data. METHODS: First, we trained and tested a Convolutional Neural Network (CNN) using 1796 real-world images from 494 patients, presenting with three diseases (IBD [n = 212], ischemic colitis [n = 157], and infectious colitis [n = 125]). Moreover, we evaluated a Gradient Boosted Decision Trees (GBDT) algorithm using five clinical parameters as well as a hybrid approach (CNN + GBDT). Patients and images were randomly split into two completely independent datasets. The proposed approaches were benchmarked against each other and three expert endoscopists on the test set. RESULTS: For the image-based CNN, the GBDT algorithm and the hybrid approach global accuracies were .709, .792, and .766, respectively. Positive predictive values were .602, .702, and .657. Global areas under the receiver operating characteristics (ROC) and precision recall (PR) curves were .727/.585, .888/.823, and .838/.733, respectively. Global accuracy did not differ between CNN and endoscopists (.721), but the clinical parameter-based GBDT algorithm outperformed CNN and expert image classification. CONCLUSIONS: Decision support systems exclusively based on endoscopic image analysis for the differential diagnosis of colitis, representing a complex clinical challenge, seem not yet to be ready for primetime and more diverse image datasets may be necessary to improve performance in future development. The clinical value of the proposed clinical parameters algorithm should be evaluated in prospective cohorts.
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Colite Isquêmica , Colite , Doenças Inflamatórias Intestinais , Humanos , Inteligência Artificial , Diagnóstico Diferencial , Estudos Prospectivos , Colite/diagnóstico por imagem , Doenças Inflamatórias Intestinais/diagnóstico , InteligênciaRESUMO
BACKGROUND: Nucleotide-binding oligomerization domain containing 2 (NOD2) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation. AIM: To evaluate the association between the presence of NOD2 risk variants, BT, inflammation, and hepatic encephalopathy (HE). PATIENTS AND METHODS: This prospective multicenter study included patients with cirrhosis and testing for NOD2 risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.-958T>C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL-6, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum. RESULTS: Overall, 172 patients (70% men; median age 60 [IQR 54-66] years; MELD 12 [IQR 9-16]; 72% ascites) were included, of whom 53 (31%) carried a NOD2 risk variant. In this cohort, 11% presented with OHE and 27% and CHE. Presence and severity of HE and surrogates of inflammation, BT, and immune activation did not differ between patients with and without a NOD2 risk variant, also not after adjustment for MELD. HE was associated with increased ammonia and systemic inflammation, as indicated by elevated CRP (w/o HE: 7.2 [2.7-16.7]; with HE 12.6 [4.5-29.7] mg/dL; p < 0.001) and elevated soluble CD14 (w/o HE 2592 [2275-3033]; with HE 2755 [2410-3456] ng/mL; p = 0.025). CONCLUSIONS: The presence of NOD2 risk variants in patients with cirrhosis is not associated with HE and has no marked impact on inflammation, BT, or immune activation. In contrast, the presence of HE was linked to ammonia, the acute phase response, and myeloid cell activation.
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Encefalopatia Hepática , Proteína Adaptadora de Sinalização NOD2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amônia , Translocação Bacteriana , Encefalopatia Hepática/complicações , Inflamação , Receptores de Lipopolissacarídeos , Cirrose Hepática/complicações , Proteína Adaptadora de Sinalização NOD2/genética , Estudos ProspectivosRESUMO
BACKGROUND: The implementation of an early detection program for liver cirrhosis in a general population has been discussed for some time. Recently, the effectiveness of a structured screening procedure, called SEAL (Structured Early detection of Asymptomatic Liver cirrhosis), using liver function tests (AST and ALT) and APRI to early detect advanced fibrosis and cirrhosis in participants of the German "Check-up 35" was investigated. METHODS: This study identifies the expected diagnostic costs of SEAL in routine care and their drivers and reports on prevailing CLD etiologies in this check-up population. The analysis is based on theoretical unit costs, as well as on the empirical billing and diagnostic data of SEAL participants. RESULTS: Screening costs are mainly driven by liver biopsies, which are performed in a final step in some patients. Depending on the assumed biopsy rates and the diagnostic procedure, the average diagnostic costs are between EUR 5.99 and 13.74 per Check-up 35 participant and between EUR 1,577.06 and 3,620.52 per patient diagnosed with fibrosis/cirrhosis (F3/F4). The prevailing underlying etiology in 60% of cases is non-alcoholic fatty liver disease. DISCUSSION: A liver screening following the SEAL algorithm could be performed at moderate costs. Screening costs in routine care depend on actual biopsy rates and procedures, attendance rates at liver specialists, and the prevalence of fibrosis in the Check-up 35 population. The test for viral hepatitis newly introduced to Check-up 35 as once-in-a-lifetime part of Check-up 35 is no alternative to SEAL.
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Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Técnicas de Imagem por Elasticidade/métodos , Biópsia , Biomarcadores , FibroseRESUMO
OBJECTIVE: To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA). DESIGN: A multicentre, prospective, international cohort study. SETTING: 43 gastroenterology and endoscopy centres located in Europe and South America. PARTICIPANTS: 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications. INTERVENTIONS: A 3-year follow-up was performed. MAIN OUTCOME MEASURES: To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score). RESULTS: The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981). CONCLUSIONS: DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score. TRIAL REGISTRATION NUMBER: NCT02758860.
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Doenças Diverticulares , Diverticulite , Diverticulose Cólica , Divertículo , Estudos de Coortes , Colonoscopia , Doenças Diverticulares/diagnóstico , Diverticulite/complicações , Diverticulite/diagnóstico , Diverticulose Cólica/diagnóstico , Divertículo/complicações , Humanos , Inflamação/complicações , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible. METHODS: SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care. RESULTS: A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83 vs. 3.36). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51, controls: 2.21). CONCLUSIONS: The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program. REGISTRATION: DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.
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Cirrose Hepática , Alanina Transaminase , Aspartato Aminotransferases , Biomarcadores , Fibrose , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Contagem de Plaquetas , Estudos ProspectivosRESUMO
BACKGROUND: Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional liver capacity, but has not been investigated in this setting. AIMS: The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in patients with cirrhosis and HCC undergoing repetitive TACE. METHODS: From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx measurements (n = 42) were conducted before and after each TACE. Laboratory parameters were correlated with the volume-function data. RESULTS: The median LiMAx levels before (276 ± 166 µg/kg/h) were slightly reduced after TACE (251 ± 122 µg/kg/h; p = 0.08). This corresponded to a median drop of 7.1%. Notably, there was a significant correlation between LiMAx levels before TACE and bilirubin (but not albumin nor albumin-bilirubin [ALBI] score) increase after TACE (p = 0.02, k = 0.56). Furthermore, a significantly higher increase in bilirubin in patients with LiMAx ≤ 150 µg/kg/h was observed (p = 0.011). LiMAx levels at different time points in single patients were similar (p = 0.2). CONCLUSION: In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers (bilirubin) of liver failure after TACE. Specific subgroups at high risk of PTHF should be investigated. This might facilitate the future development of strategies to prevent occurrence of PTHF.
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Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Transjugular intrahepatic shunt (TIPSS) is placed in patients with variceal bleeding, refractory ascites, and for other indications. Postprocedural liver function-associated complications (LFAC), including hepatic encephalopathy (HE) and liver failure, represent a major setback. Current methods to predict complications are insufficient. OBJECTIVES: We investigated in a pilot study of patients prior TIPSS placement whether the risk of LFAC correlates with the functional reserve of the liver, as assessed by liver maximum function capacity (LiMAx) test. METHODS: Prospectively we included patients prior TIPSS placement between June 2016 and November 2017 at Saarland University Medical Center. LiMAx was conducted before and after TIPSS placement. Patients with HE prior TIPSS, as well as other factors predisposing to HE, including concomitant sedative drugs, current bacterial infections and sepsis, were excluded. Overt HE (OHE), LiMAx, and laboratory values were assessed before and after TIPSS placement. Data were analyzed in multivariate regression and AUROC models. RESULTS: Mean age was 60 ± 8 years. Patients (n = 20) were mainly men (65%), and presented predominantly with Child-Pugh class B (90%). Indications for TIPSS were most commonly refractory ascites or recurrent variceal bleeding. In total, 40% of the patients developed LFAC after TIPSS placement. Expectedly, LiMAx decreased and serum bilirubin increased after TIPSS. LiMAx drop ≥20% was the only parameter predicting the development of LFAC after TIPSS in multivariate regression and AUROC analysis. CONCLUSIONS: In multivariate regression models and AUROC analysis, a drop in LiMAx predicted the development of LFAC after TIPSS placement. Additional larger studies assessing OHE and early liver failure separately are warranted.
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Fígado/fisiopatologia , Derivação Portossistêmica Transjugular Intra-Hepática , Área Sob a Curva , Pressão Sanguínea , Varizes Esofágicas e Gástricas/complicações , Feminino , Encefalopatia Hepática/fisiopatologia , Encefalopatia Hepática/cirurgia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Valor Preditivo dos Testes , Curva ROC , Análise de RegressãoRESUMO
ATP-binding cassette subfamily B member 4 (ABCB4) is a phospholipid translocator at the canalicular membrane of the hepatocyte, which "flops" phosphatidylcholine into bile. Dysfunction of this transporter due to ABCB4 gene variants can cause liver diseases and has been called ABCB4 deficiency. Several diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3), low phospholipid-associated cholelithiasis (LPAC), a subgroup of patients developing intrahepatic cholestasis of pregnancy (ICP), drug-induced liver injury and chronic cholangiopathy with biliary fibrosis and cirrhosis were attributed to ABCB4 deficiency and characterized in the past decade. LPAC and ICP are usually caused by monoallelic variants, whereas patients affected by PFIC3 are homozygous or compound heterozygous carriers of ABCB4 variants. Treatment with ursodeoxycholic acid is often effective, but as the more severe forms of ABCB4 deficiency progress, nevertheless, new diagnostic and therapeutic approaches are warranted. Current functional classifications for ABCB4 deficiency-associated mutations can guide the development of novel genotype-based targeted pharmacotherapies for these conditions. Recently, increasing evidence from genome-wide association studies is emerging on associations of ABCB4 variants with hepatobiliary malignancies.
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Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Colelitíase/genética , Colestase Intra-Hepática/genética , Colestase/genética , Complicações na Gravidez/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Bile , Colangiocarcinoma/genética , Colelitíase/tratamento farmacológico , Colestase Intra-Hepática/tratamento farmacológico , Feminino , Neoplasias da Vesícula Biliar/genética , Humanos , Neoplasias Hepáticas/genética , Masculino , Mutação de Sentido Incorreto , Gravidez , Complicações na Gravidez/tratamento farmacológicoRESUMO
BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.
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Colágeno Tipo III/genética , DNA/genética , Doença Diverticular do Colo/genética , Polimorfismo Genético , População Branca/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colágeno Tipo III/metabolismo , Colonoscopia , Doença Diverticular do Colo/etnologia , Doença Diverticular do Colo/metabolismo , Feminino , Seguimentos , Estudos de Associação Genética , Técnicas de Genotipagem , Alemanha/epidemiologia , Humanos , Incidência , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Bacterial infections (BI) negatively affect the natural course of cirrhosis. The most frequent BI are urinary tract infections (UTI), pneumonia, and spontaneous-bacterial peritonitis (SBP). AIM: To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables. METHODS: We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center. BIs were classified as typical and atypical, and clinical as well as laboratory parameters were compared between the two groups. RESULTS: In a cohort of 488 patients with cirrhosis, we identified 225 typical BI (95 UTI, 73 SBP, 72 pulmonary infections) and 74 atypical BIs, predominantly cholangitis and soft tissue infections (21 each), followed by intra-abdominal BIs (n = 9), cholecystitis (n = 6), head/throat BIs (n = 6), osteoarticular BIs (n = 5), and endocarditis (n = 3). We did not observe differences concerning age, sex, or etiology of cirrhosis in patients with typical vs atypical BI. Atypical BIs were more common in patients with more advanced cirrhosis, as evidenced by Model of End Stage Liver Disease (15.1 ± 7.4 vs 12.9 ± 5.1; P = 0.005) and Child-Pugh scores (8.6 ± 2.5 vs 8.0 ± 2; P = 0.05). CONCLUSION: Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease. Hence, the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.
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Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively). Conclusions: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.
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BACKGROUND: Patients with cirrhosis who carry NOD2 mutations are susceptible to bacterial infections. The aim was to evaluate the association of NOD2 mutations with hepatic and systemic hemodynamics in cirrhosis. PATIENTS AND METHODS: This is a secondary analysis of a prospectively collected database in the context of the screening for the INCA trial (EudraCT 2013-001626-26). This cross-sectional study compared hemodynamic findings according to NOD2 status in 215 patients. Patients were genotyped for NOD2 variants (p.N289S, p.R702W, p.G908R, c.3020insC, rs72796367). Hepatic hemodynamic study and right heart catheterization were performed. RESULTS: Patients had a median age of 59 (IQR 53-66) years, and 144 (67%) were men. Most patients (64%) were Child-Pugh stage B. Sixty-six patients (31%) carried a NOD2 mutation, which was slightly more common among Child-Pugh stage C (p = 0.05), without differences in MELD [wild-type: 13 (10-16); NOD2 variants 13 (10-18)]. No differences in hepatic and systemic hemodynamics were observed according to NOD2 status. If excluding patients on prophylactic or therapeutic antibiotics, again no association between hepatic or systemic hemodynamics and NOD2 status could be observed. CONCLUSION: NOD2 mutations are not associated with hepatic or systemic hemodynamic abnormalities in patients with decompensated cirrhosis, suggesting that other mechanisms leading to bacterial translocation predominate.
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Hemodinâmica , Cirrose Hepática , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Transversais , Cirrose Hepática/genética , Cirrose Hepática/complicações , Mutação , Proteína Adaptadora de Sinalização NOD2/genéticaRESUMO
Background and Aims: Hepatocellular carcinoma (HCC) surveillance in patients at risk is strongly recommended and usually performed by ultrasound (US) semiannually with or without alfa-fetoprotein (AFP) measurements. Quality parameters except for surveillance intervals have not been strictly defined. We aimed to evaluate surveillance success and risk factors for surveillance failure. Methods: Patients with ≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed. Surveillance success was defined as HCC detection within Milan criteria. Results: Only 47% of 156 patients, median age 63 (interquartile range: 57-70) years, 56% male, and 96% with cirrhosis, received recommended surveillance modality and interval. Surveillance failure occurred in 29% and was significantly associated with lower median model for end-stage liver disease (MELD) score odds ratio (OR) 1.154, 95% confidence interval (CI): 1.027-1.297, p=0.025) and HCC localization within right liver lobe (OR: 6.083, 95% CI: 1.303-28.407, p=0.022), but not with AFP ≥200 µg/L. Patients with surveillance failure had significantly more intermediate/advanced tumor stages (93% vs. 6%, p<0.001), fewer curative treatment options (15% vs. 75%, p<0.001) and lower survival at 1 year (54% vs. 75%, p=0.041), 2 years (32% vs. 57%, p=0.019) and 5 years (0% vs. 16%, p=0.009). Alcoholic and non-alcoholic fatty liver disease (OR: 6.1, 95% CI: 1.7-21.3, p=0.005) and ascites (OR: 3.9, 95% CI: 1.2-12.6, p=0.021) were independently associated with severe visual limitations on US. Conclusions: US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes. Lower MELD score and HCC localization within right liver lobe were significantly associated with surveillance failure.
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BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.
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Doenças Diverticulares , Diverticulose Cólica , Divertículo , Humanos , Diverticulose Cólica/diagnóstico , Diverticulose Cólica/terapia , Diverticulose Cólica/complicações , Colonoscopia , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Doenças Diverticulares/complicações , Doenças Diverticulares/diagnóstico , Doenças Diverticulares/terapia , Divertículo/complicações , Inflamação/diagnóstico , Inflamação/complicaçõesRESUMO
Intrahepatic cholestasis of pregnancy (ICP) is characterized by increased serum bile acid levels in the third trimester of pregnancy and resolves quickly after delivery. Here, we present the case of a 29-year-old woman who developed idiopathic liver damage during puberty, and subsequently ICP and severe pruritus during two pregnancies. DNA sequencing revealed a heterozygous deletion (c.393_delG) in the fibroblast growth factor receptor 4 (FGRF4) gene causing a premature stop codon. The resulting FGFR4 haploinsufficiency is likely to impede the enterohepatic feedback repression of hepatic bile acid synthesis via FXR and FGF19. It represents a new genetic etiology of ICP.
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Colestase Intra-Hepática , Complicações na Gravidez , Adulto , Ácidos e Sais Biliares , Colestase Intra-Hepática/genética , Feminino , Humanos , Gravidez , Complicações na Gravidez/genética , Receptor Tipo 4 de Fator de Crescimento de FibroblastosRESUMO
High-quality DNA extraction is a crucial step in metagenomic studies. Bias by different isolation kits impairs the comparison across datasets. A trending topic is, however, the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases. We thus collected bile, stool, saliva, plaque, sputum, and conjunctival swab samples and performed DNA extraction with three commercial kits. For each combination of the specimen type and DNA extraction kit, 20-gigabase (Gb) metagenomic data were generated using short-read sequencing. While profiles of the specimen types showed close proximity to each other, we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits. No kit outperformed all selected kits on every specimen. We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit. Depending on the specimen, our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution, but DNA-based identification is superior to identification by mass spectrometry. Finally, long-read nanopore sequencing confirmed the results (correlation coefficient > 0.98). Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.
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Metagenoma , Microbiota , Humanos , Metagenômica/métodos , Microbiota/genética , Fezes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , DNA/genética , DNA Bacteriano/genéticaRESUMO
BACKGROUND AND AIMS: Colonic diverticulosis (CD) is among the most common conditions of the large bowel. Several factors have been associated with an increased risk of CD and its complications, including advanced age, obesity, physical inactivity, and a low-fiber diet. Available data is conflicting and a comprehensive analysis of different bowel, dietary and environmental habits linked with CD is lacking. We aimed to investigate the relationship between potential risk factors and CD prevalence using full data from a colonoscopy-based cross-sectional study in Europe. METHODS: The study was conducted at three tertiary referral centers in Germany and Lithuania. It included consecutive adult patients referred for routine colonoscopy who completed a detailed questionnaire on our considered multiple risk factors for diverticulosis and diverticulitis, including dietary and environmental factors, and bowel habits. RESULTS: The study included 1,333 patients, 696 women and 635 men. Colonic diverticulosis was diagnosed in 858 (64%) of patients. Multivariate analysis revealed that age (OR: 1.08, 95%CI: 1.06-1.10, p<0.001) and obesity (OR: 1.05, 95%CI: 1.02-1.09, p=0.004) were associated with CD. We also revealed new risk factors for CD: increased frequency of bowel movements (OR: 0.10, 95%CI: 0.03-0.33, p<0.001) and feeling of incomplete bowel emptying (OR: 2.05, 95%CI: 1.47-2.87, p<0.001). Older participants had reduced odds (OR: 0.921, 95 CI: 0.89-0.95, p<0.05) of diverticulitis compared to younger subjects. Feeling of incomplete bowel emptying after defecation was associated with increased odds (OR: 2.769, 95% CI 1.35-5.7, p<0.006) for diverticulitis. Moreover, participants with a higher educational status had increased odds (OR: 2.453, 95%CI: 1.31-4.59, p=0.005) for diverticulitis compared to the lower education group. CONCLUSIONS: Study shows that older age, obesity, frequency of bowel movements, and feeling of incomplete bowel emptying are associated with the risk of CD. Furthermore, older age, feeling of incomplete bowel emptying, and higher education were associated with the risk of diverticulitis among CD patients.
Assuntos
Dieta , Diverticulite/epidemiologia , Diverticulose Cólica/epidemiologia , Meio Ambiente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Estudos Transversais , Defecação/fisiologia , Feminino , Alemanha/epidemiologia , Humanos , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Razão de Chances , Fatores de RiscoRESUMO
OBJECTIVES: Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage. METHODS: Consecutive patients with cirrhosis in 2 academic medical centers were included and genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. Electronic medical records were screened for BI (requiring antibiotic therapy) and past and present decompensation (as defined by variceal bleeding, encephalopathy, ascites, and/or jaundice). Clinically significant portal hypertension (CSPH) was assessed with liver stiffness and/or hepatic venous pressure gradient measurements. RESULTS: Overall, 735 patients were recruited (men 65%; interquartile age range 53-68 years). Alcoholic cirrhosis was the predominant etiology (n = 406, 55%), and most patients were in the decompensated stage (n = 531, 72%). In total, 158 patients (21%) carried at least one NOD2 variant. BIs were detected in 263 patients (36%), and NOD2 variants were associated with BI (odds ratio = 1.58; 95% confidence interval 1.11-2.27; P = 0.02). In compensated patients, the combination of NOD2 variants and presence of CSPH was the best independent predictors of BI, whereas other factors, such as spleen size and hemoglobin, and decompensations including hepatic encephalopathy or jaundice, gained relevance in decompensated patients. CONCLUSIONS: NOD2 risk variants are associated with BI in cirrhosis. The genetic effect on BI is strongest in compensated patients, whereas in decompensated patients their presence is less relevant. In this situation, CSPH becomes an independent factor associated with BI.