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BACKGROUND: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher in men than in women. Hormonal and genetic causes may account for the sex differences in MASLD. Current human in vitro liver models do not sufficiently take the influence of biological sex and sex hormones into consideration. METHODS: Primary human hepatocytes (PHHs) were isolated from liver specimen of female and male donors and cultured with sex hormones (17ß-estradiol, testosterone and progesterone) for up to 72 h. mRNA expression levels of 8 hepatic lipid metabolism genes were analyzed by RT-qPCR. Sex hormones and their metabolites were determined in cell culture supernatants by LC-MS analyses. RESULTS: A sex-specific expression was observed for LDLR (low density lipoprotein receptor) with higher mRNA levels in male than female PHHs. All three sex hormones were metabolized by PHHs and the effects of hormones on gene expression levels varied depending on hepatocyte sex. Only in female PHHs, 17ß-estradiol treatment affected expression levels of PPARA (peroxisome proliferator-activated receptor alpha), LIPC (hepatic lipase) and APOL2 (apolipoprotein L2). Further changes in mRNA levels of female PHHs were observed for ABCA1 (ATP-binding cassette, sub-family A, member 1) after testosterone and for ABCA1, APOA5 (apolipoprotein A-V) and PPARA after progesterone treatment. Only the male PHHs showed changing mRNA levels for LDLR after 17ß-estradiol and for APOA5 after testosterone treatment. CONCLUSIONS: Male and female PHHs showed differences in their expression levels of hepatic lipid metabolism genes and their responsiveness towards sex hormones. Thus, cellular sex should be considered, especially when investigating the pathophysiological mechanisms of MASLD.
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Hormonas Esteroides Gonadales , Hepatocitos , Metabolismo de los Lípidos , Humanos , Masculino , Femenino , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/efectos de los fármacos , Hormonas Esteroides Gonadales/farmacología , Hormonas Esteroides Gonadales/metabolismo , Células Cultivadas , Persona de Mediana Edad , Testosterona/farmacología , Testosterona/metabolismo , Estradiol/farmacología , Adulto , Progesterona/farmacología , Progesterona/metabolismo , Factores SexualesRESUMEN
BACKGROUND AND AIMS: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles. METHODS: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration. RESULTS: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1-6% higher) when the first preferred TherapySelector option was given compared to the actual treatment. CONCLUSIONS: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics.
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Antivirales , Guías de Práctica Clínica como Asunto , Humanos , Antivirales/uso terapéutico , Guías de Práctica Clínica como Asunto/normas , Femenino , Persona de Mediana Edad , Masculino , Hepatitis C/tratamiento farmacológico , Toma de Decisiones Clínicas , Adulto , Anciano , Ribavirina/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológicoRESUMEN
Background & Aims: A goal of the World Health Organization's global hepatitis strategy is the elimination of chronic hepatitis C virus (HCV) infection by 2030. As part of its strategy, the Federal Joint Committee (Germany) decided to include hepatitis B and C screening in a preventive medical examination, which is performed at the primary care level in Germany. We investigated the results 1 year after implementation of screening between October 2021 and September 2022. Methods: HBsAg/HBV DNA and anti-HCV/HCV RNA screenings were identified by billing categories in 286,192 individuals of 11 ambulatory healthcare centers. Results: Compared to 30,106 HBsAg and 31,266 anti-HCV laboratory requisitions in the year 2018, the number of tests increased to 286,192 during the screening period. Compared to routine care, additional anti-HCV positive tests age dependently increased the tally by 98% (177 plus 170 positive cases in males) and 123% (96 plus 118 positive cases in females) in those aged 35-44 years up to 518% (17 plus 88 positive cases in males) and 514% (29 plus 149 positive cases in females) in those aged 75-84 years. Similar results were observed for HBsAg. Prevalences of HBsAg, anti-HCV and HCV RNA were 0.54%, 0.79% and 0.13%, respectively. Conclusions: A structured hepatitis screening program at the primary care level has been successfully established and leads to age- and-sex-dependent large additional effects compared to routine care. Impact and implications: Strategies to eliminate chronic hepatitis B and C virus infection are country specific and vary between clinical scenarios. Our analysis proves the efficacy of a screening program by primary care physicians compared to routine care in a low-prevalence country. This program should be accompanied by additional efforts in risk populations like people who inject drugs who are under-represented in the current screening approach.
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Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.
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Background and aims: Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA) and the related inflammatory response might add further information on the course of disease. The aim of the study was to evaluate the association between bactDNA, cytokine levels and clinical outcome. Methods: Ascites and serum samples of 98 patients with decompensated liver cirrhosis (42 with SBP and 56 without SBP) as well as serum samples of 21 healthy controls were collected. BactDNA in ascites and serum was detected and quantified by 16S rRNA PCR. Concentrations of IL-1ß, TNF-α, IL-6, IL-8 and IL-10 were measured by a LEGENDplexTM multi-analyte flow assay. Clinical data were collected and analyzed retrospectively. Results: BactDNA was detected more frequently in ascites of patients with SBP (n = 24/42; 57.1%) than in ascites of patients without SBP (n = 5/56; 8.9%; P < 0.001). Additionally, IL-6 levels in both ascites and serum were significantly higher in patients with SBP (ascites P < 0.001, serum P = 0.036). The quantity of bactDNA in ascites was strongly correlated with polymorphonuclear neutrophil count in ascites (r = 0.755; P < 0.001) as well as ascites IL-6 levels (r = 0.399; P < 0.001). Receiver operating characteristic (ROC) curve analysis to diagnose SBP provided an AUC of 0.764 (95% CI: 0.661-0.867) for serum IL-6 levels, an AUC of 0.810 (95% CI: 0.714-0.905) for ascites IL-6 levels, and an AUC of 0.755 (95% CI: 0.651-0.858) for bactDNA levels in ascites. Conclusions: The correlation between the amount of bactDNA and IL-6 confirms the pathophysiological relevance of bactDNA and IL-6 as potential biomarkers for the diagnosis of SBP.
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BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.
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Background/Aim: Transarterial radioembolization (TARE) is a treatment option for early or intermediate stage hepatocellular carcinoma (HCC). Sarcopenia is defined as loss of muscle strength and quality which can be estimated by imaging modalities and has been associated with prognosis and treatment response in HCC patients. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) can reflect the tissue composition and might be better to determine muscle changes of sarcopenia than the standard method of computed tomography (CT). The present study sought to elucidate ADC values of the abdominal wall muscles as a prognostic factor in patients undergoing TARE. Patients and Methods: A retrospective analysis was performed between 2016 and 2020. Overall, 52 patients, 9 women (17.3%) and 43 men (82.7%), with a mean age of 69±8.5 years were included into the analysis. In every case, the first pre-interventional magnetic resonance imaging (MRI) including DWI was used to measure the ADC values of paraspinal and psoas muscle. The 12-month survival after TARE was used as the primary study outcome. Results: Overall, 40 patients (76.9%) of the patient cohort died within the 12-month observation period. Mean overall survival was 10.9 months after TARE for all patients. Mean ADC values for all muscles were 1.31±0.13×10-3mm2/s. The ADC values of the paraspinal muscles were statistically significantly higher compared to the ADC values of the psoas muscles (p=0.0031). A positive correlation was identified between mean ADC and the thrombocyte count (r=0.37, p=0.005) and serum bilirubin (r=-0.30, p=0.03). In the multivariate Cox regression analysis, the mean ADC values of all muscles were associated with the survival after 12 months (HR=0.98, 95% CI=0.97-0.99, p=0.04). Conclusion: ADC values of the abdominal wall muscles could be used as a prognostic biomarker in patients with HCC undergoing TARE. These preliminary results should be confirmed by further studies using external validation cohorts and other treatment modalities.
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The inference of biogeographical ancestry (BGA) can assist in police investigations of serious crime cases and help to identify missing people and victims of mass disasters. In this study, we evaluated the typing performance of 56 ancestry-informative SNPs in 177 samples using the ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx system. Furthermore, we compared the prediction accuracy of the tools Universal Analysis Software v1.2 (UAS), the FROG-kb, and GenoGeographer when inferring the ancestry of 503 Europeans, 22 non-Europeans, and 5 individuals with co-ancestry. The kit was highly sensitive with complete aiSNP profiles in samples with as low as 250pg input DNA. However, in line with others, we observed low read depth and occasional drop-out in some SNPs. Therefore, we suggest not using less than the recommended 1ng of input DNA. FROG-kb and GenoGeographer accurately predicted both Europeans (99.6% and 91.8% correct, respectively) and non-Europeans (95.4% and 90.9% correct, respectively). The UAS was highly accurate when predicting Europeans (96.0% correct) but performed poorer when predicting non-Europeans (40.9% correct). None of the tools were able to correctly predict individuals with co-ancestry. Our study demonstrates that the use of multiple prediction tools will increase the prediction accuracy of BGA inference in forensic casework.
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Dermatoglifia del ADN , Polimorfismo de Nucleótido Simple , Humanos , ADN/genética , Dermatoglifia del ADN/métodos , Genética Forense/métodos , Genética de Población/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Población Blanca/genética , Europa (Continente)RESUMEN
Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
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The S2k guideline "Liver Transplantation", jointly developed by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society of General and Visceral Surgery (DGAV), represents the first German-language guideline for the care of adult patients before and after liver transplantation. This guideline has been crafted through a collaborative, consensus-based approach, involving experts from various disciplines. It integrates current scientific insights and clinical experience to ensure optimal care for patients undergoing liver transplantation. Targeting health care professionals in diagnostics and therapy, patient advocates, affected individuals, and their families, the guideline aims to establish a framework for common decisions in clinical practice.
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Gastroenterología , Trasplante de Hígado , Humanos , Consenso , AlemaniaRESUMEN
PURPOSE: The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC. METHODS: A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria. RESULTS: The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001). In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP. CONCLUSION: The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , alfa-Fetoproteínas , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico , SorafenibRESUMEN
Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, metabolic dysfunction-associated steatotic liver disease (MASLD) is gaining importance as the disease can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in MASLD development, but molecular mechanisms responsible for disease progression remained unresolved. Here, we uncover in primary hepatocytes from a preclinical model fed with a Western diet (WD) an increased basal MET phosphorylation and a strong downregulation of the PI3K-AKT pathway. Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveal patient-specific variability in basal MET phosphorylation, which correlates with patient outcome after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.
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Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Humanos , Fosforilación , Fosfatidilinositol 3-Quinasas/metabolismo , Hepatocitos/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Hígado Graso/metabolismo , Neoplasias Hepáticas/patologíaRESUMEN
PURPOSE: To objectively quantify glare of intraocular lenses (IOLs) using a diffractive principle to extend the visual range and to identify models with increased susceptibility to inducing glare. SETTING: David J Apple Laboratory, Heidelberg, Germany. DESIGN: Laboratory investigation. METHODS: Glare was assessed by means of a straylight parameter with a standard C-Quant intended for 7 degrees. In addition, 2 C-Quant modifications were used to test lower angles (ie, 2.5 degrees and 3.5 degrees). The following IOL models were assessed: PanOptix, AT Lisa Tri, Synergy, and Triumf, the latter 2 with chromatic aberration correction at distance. Straylight from trifocal IOLs was compared against a monofocal W-60R lens. The C-Quant test was performed through the studied IOLs by using additional optical components attached to their ocular. RESULTS: Straylight (deg 2 sr -1 ) of the control was <1 at all tested angles, with the trifocal models showing comparable straylight at 7 degrees. At 3.5 degrees, Triumf's straylight increased to 15.5 ± 0.6, followed by Synergy (6.2 ± 1.1), PanOptix (4.1 ± 0.3), and AT Lisa Tri (2.0 ± 0.8). The chromatic aberration-correcting models demonstrated correspondingly higher straylight (Synergy: 18.8 ± 1.3; Triumf: 17.3 ± 0.5) at 2.5 degrees compared with PanOptix (4.3 ± 0.4), AT Lisa Tri (2.1 ± 0.1), and monofocal IOLs yielding minimal or no increase. CONCLUSIONS: Trifocal IOLs induced increased straylight, but it was limited to lower angles, which may cause difficulties detecting these effects using a standard clinical approach. The latest IOL designs featuring chromatic aberration correction at far focus seem more susceptible than the established trifocal IOLs to inducing a glare phenomenon.
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Cristalino , Lentes Intraoculares , Presbiopía , Humanos , Deslumbramiento , Presbiopía/cirugía , Anteojos , Diseño de PrótesisRESUMEN
BACKGROUND & AIMS: Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up. METHODS: We studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy. RESULTS: We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR], 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg >100 IU/mL and HBV DNA >100 IU/mL (P < .001). CONCLUSIONS: Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.
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Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Humanos , Antígenos e de la Hepatitis B , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , ADN Viral , Antivirales/uso terapéutico , Estudios de Seguimiento , Virus de la Hepatitis B/genética , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Preescolar , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/inducido químicamente , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Antígenos e de la Hepatitis B , ADN Viral , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/inducido químicamente , Estudios de Cohortes , Infección Persistente , Antivirales/uso terapéutico , Factores de Riesgo , Virus de la Hepatitis B/genéticaRESUMEN
PURPOSE: To investigate straylight in the immediate postoperative period after cataract surgery. SETTING: Amphia Hospital, Breda, the Netherlands. DESIGN: Prospective, comparative, single-arm, single-center, single-surgeon study. METHODS: Patients underwent cataract surgery on both eyes. 1 eye was randomly selected for implantation with a Clareon CNA0T0 intraocular lens (IOL); the fellow eye received a Vivinex XY1 IOL. Straylight was measured with the C-Quant straylight meter. RESULTS: 25 patients were included. Preoperatively, 1 day, 1 week, 1 month, and 3 months postoperatively, eyes with a CNA0T0 IOL had straylight levels (mean ± SD) of 1.48 ± 0.23, 1.26 ± 0.20, 1.06 ± 0.19, 1.11 ± 0.25, and 1.09 ± 0.20 log(s), respectively. For eyes with an XY1 IOL, these values were 1.48 ± 0.21, 1.41 ± 0.41, 1.10 ± 0.20, 1.13 ± 0.20, and 1.16 ± 0.20 log(s), respectively. From 1 week postoperatively, straylight values did not change (1 week vs 3 months: P = .40 and P = .14 and 1 month vs 3 months: P = .74 and P = .50 for CNA0T0 and XY1, respectively). The Pearson correlation coefficient for straylight values between the 2 eyes of individual subjects was 0.80 at 3 months. CONCLUSIONS: Straylight levels can be considered stable 1 week after cataract surgery. We believe it is safe to use straylight measurements 1 month postoperatively for clinical trials. Straylight is highly correlated between the 2 eyes of an individual postoperatively.
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Extracción de Catarata , Catarata , Lentes Intraoculares , Humanos , Luz , Estudios Prospectivos , Dispersión de Radiación , Agudeza VisualRESUMEN
Chronic hepatitis B, a major cause of liver disease and cancer, affects >250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed.
Asunto(s)
Hepatitis B Crónica , Hepatitis B , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Virus de la Hepatitis B/genética , Resultado del Tratamiento , Biomarcadores , Antígenos de Superficie de la Hepatitis B , ADN Viral , Hepatitis B/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.