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1.
Z Gastroenterol ; 59(9): 954-960, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507374

RESUMO

BACKGROUND: The COVID-19 pandemic has caused a significant impact on the medical care of many diseases and has led to reduced presentations to the emergency department. Reduced presentations may be due to overwhelmed capacities of hospitals or collateral damage from fear of infection, lockdown regulations, or other reasons. The effect on patients with liver cirrhosis is not established. OBJECTIVE: We aim to assess the impact on the care of patients with liver cirrhosis in a tertiary center in Northern Germany. METHODS: All patients presenting to the emergency department with a diagnosis of cirrhosis between March 1 and May 31 from 2015-2020 were included. Reasons for presentation, duration of symptoms, the severity of liver disease, and 30-day mortality were assessed and compared between patients presenting during the COVID-19 pandemic and pre-COVID-19. RESULTS: Overall, 235 patients were included. Despite an overall decline in presentations to the emergency department by 11.7%, the frequency of patients presenting with liver cirrhosis has remained stable (non-significant increase by 19.5%). No significant difference could be detected for the MELD score, the CLIF-organ failure subscores, and the 30-day mortality before and during the COVID-19 pandemic. Up to 75% of patients with liver cirrhosis had symptoms >24 h before presenting to the emergency department. CONCLUSION: Despite the overall trend of reduced emergency presentations during the COVID-19 pandemic, the frequency of presentations of patients with liver cirrhosis did not decline. Morbidity and mortality were not affected in a setting of disposable healthcare resources. The late presentation to the emergency department in many cirrhotic patients may open opportunities for interventions (i.e., with early telemedicine intervention).


Assuntos
COVID-19 , Pandemias , Controle de Doenças Transmissíveis , Serviço Hospitalar de Emergência , Alemanha/epidemiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , SARS-CoV-2
2.
Hepatol Commun ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561972

RESUMO

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated-interferon alfa (peg-IFNα) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core-related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN-based treatment of hepatitis B virus (HBV) mono-infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co-infection undergoing peg-IFNα treatment. The Hep-Net-International-Delta-Hepatitis-Intervention Trial-2 study included 120 patients co-infected with HBV/HDV. Patients were treated for 96 weeks with peg-IFNα and either tenofovir or placebo. Ninety-nine patients with HDV-RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg-IFNα in patients with HBV/HDV co-infection and could be a promising marker to determine treatment futility.

3.
Hepatol Commun ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34585537

RESUMO

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension-related complications. However, careful selection of patients is crucial. The aim of this study was to evaluate the prognostic value of serum cholinesterase (CHE) for outcomes and mortality after TIPS insertion. In this multicenter study, 389 consecutive patients with cirrhosis receiving a TIPS at Hannover Medical School, University Hospital Essen, or Medical University of Vienna were included. The Hannover cohort (n = 200) was used to initially explore the role of CHE, whereas patients from Essen and Vienna served as a validation cohort (n = 189). Median age of the patients was 58 years and median Model for End-Stage Liver Disease (MELD) score was 12. Multivariable analysis identified MELD score (hazard ratio [HR]: 1.16; P < 0.001) and CHE (HR: 0.61; P = 0.008) as independent predictors for 1-year survival. Using the Youden Index, a CHE of 2.5 kU/L was identified as optimal threshold to predict post-TIPS survival in the Hannover cohort (P < 0.001), which was confirmed in the validation cohort (P = 0.010). CHE < 2.5 kU/L was significantly associated with development of acute-on-chronic liver failure (P < 0.001) and hepatic encephalopathy (P = 0.006). Of note, CHE was also significantly linked to mortality in the subgroup of patients with refractory ascites (P = 0.001) as well as in patients with high MELD scores (P = 0.012) and with high-risk FIPS scores (P = 0.004). After propensity score matching, mortality was similar in patients with ascites and CHE < 2.5 kU/L if treated by TIPS or by paracentesis. Contrarily, in patients with CHE ≥ 2.5 kU/L survival was significantly improved by TIPS as compared to treatment with paracentesis (P < 0.001). Conclusion: CHE is significantly associated with mortality and complications after TIPS insertion. Therefore, we suggest that CHE should be evaluated as an additional parameter for selecting patients for TIPS implantation.

4.
Hepatology ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473365

RESUMO

BACKGROUND & AIMS: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for workup of AIH lack either sensitivity or specificity leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macro-array. APPROACH & RESULTS: During the search for more precise autoantibodies to distinguish AIH from non-AIH liver diseases, IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macro-array and confirmed with solid phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) were exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). Diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation and a prospective validation cohort, in cryo-conserved samples from 1568 adults from ten centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional anti-nuclear and anti-smooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and anti-soluble liver antigen/liver pancreas antigen and a 12-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88 % of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy pIgG returns to background levels of non-AIH liver diseases. CONCLUSIONS: pIgG could be used as a new promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.

5.
J Clin Virol ; 142: 104932, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333392

RESUMO

OBJECTIVES: Quantification of plasma hepatitis D virus (HDV) RNA is the essential tool for patient management under antiviral therapy. The aim of this European multicenter study was to improve the comparability of quantitative results reported by different laboratories using the CE/IVD-labeled RoboGene HDV RNA Quantification Kit 2.0 (Roboscreen GmbH) with different manual or automated nucleic acid extraction protocols/platforms and amplification/detection devices. METHODS: For harmonization of HDV RNA concentrations obtained by different protocols, correction factors (CF) were determined using the 1st WHO International Standard for HDV RNA. The limit of detection (LOD) and accuracy were determined for each protocol by using reference material. Furthermore, clinical samples were analyzed and results compared. RESULTS: The CF ranged from 20 to 1,870 depending on the protocol used. The LOD was found between 4 and 450 IU/ml. When accuracy was tested, external quality control (EQC) samples containing low HDV RNA concentrations were not detected by those protocols with higher LODs. For EQC samples, the maximum standard deviation of HDV RNA concentrations was found to be 0.53 log10 IU/ml, for clinical samples 0.87 log10 IU/mL. CONCLUSION: To ensure reliability in quantification of HDV RNA, any modification of the extraction and amplification/detection protocol validated by the manufacturer requires revalidation. With the 1st WHO International Standard for HDV RNA, the CF could easily be calculated leading to harmonization of quantitative results. This warrants both accurate monitoring of response to existing anti-HDV treatment and comparability of study results investigating novel anti-HDV drugs.

7.
BMC Gastroenterol ; 21(1): 296, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284732

RESUMO

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.


Assuntos
Antibacterianos , Infecções Bacterianas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana , Alemanha/epidemiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico
8.
Blood ; 138(4): 350-353, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323939

RESUMO

We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Púrpura Trombocitopênica Idiopática/etiologia , Trombose/etiologia , Adulto , Idoso , Autoanticorpos/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , SARS-CoV-2/imunologia , Trombose/imunologia
9.
Cells ; 10(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209751

RESUMO

The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very­low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR­B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid­lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.

10.
J Viral Hepat ; 28(8): 1206-1218, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34003549

RESUMO

Improvement of health-related quality of life (HRQoL) is frequently reported as a benefit when treating hepatitis C virus infection (HCV) with direct acting antivirals (DAA). As most of the available data were obtained from clinical trials, limited generalizability to the real-world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real-world setting. HRQoL of 1180 participants of the German Hepatitis C-Registry was assessed by Short-Form 36 (SF-36) questionnaires. Scores at post-treatment weeks 12-24 (FU12/24) were compared to baseline (BL). Changes of ≥2.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS (p < .001, OR = 0.925) and PCS (p < .001, OR = 0.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue (p = .023, OR = 1.518), increased GPT levels (p = .005, OR = 0.626) and RBV containing therapy regimens (p = .001, OR = 1.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV-infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Qualidade de Vida , Sistema de Registros , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-33798713
12.
Liver Int ; 41(8): 1815-1823, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683813

RESUMO

BACKGROUND: RNA detection in plasma/stool is the gold-standard for diagnosis of hepatitis E virus (HEV) infection. The impact of viral extraction methods on HEV RNA detection is poorly investigated. METHODS: We determined the limit of detection of the RealStar HEV RT-PCR V2.0 Kit (altona Diagnostics, RS) utilizing 3 RNA extraction methods (COBAS® AmpliPrep Total Nucleic Acid Isolation Kit, TNAi Roche; MagNA Pure 96 DNA, Viral NA SV Kit, MgP; QIAamp Viral RNA mini Kit Qiagen; VRK) in plasma and stool. The most sensitive method was evaluated in a total of 307 longitudinal samples of patients with HEV infection (acute = 18/chronic = 36) and compared to results with the former diagnostic standard of our centre (TNAi/FastTrack Diagnostic; FTD). RESULTS: The plasma-LOD was 49, 94 and 329 IU/mL for extraction with MgP, VRK and TNAi respectively. In stool, the LOD was 21 IU/mL, 528 IU/mL and indefinable for extraction with TNAi, VRK and MgP respectively. Utilizing longitudinal patient plasma samples, MgP/RS revealed 56 HEV RNA-positive samples in 158 negative samples as determined by TNAi/FTD. In stool, from 37 HEV negative samples (TNAi/FTD), 15 were positive with TNAi/RS. At end of treatment, 8 out of 27 chronically infected patients were RNA positive with MgP/RS, while classified negative with TNAi/FTD. A relapse occurred in 3 of these patients. CONCLUSION: Different methods for RNA extraction and quantification have a significant, compartment-specific impact on the sensitivity of HEV detection. Knowledge about the favourable combinations of extraction and quantification has important implications for diagnosis and patients receiving antiviral therapy.


Assuntos
Vírus da Hepatite E , Hepatite E , Fezes , Hepatite E/diagnóstico , Vírus da Hepatite E/genética , Humanos , Reação em Cadeia da Polimerase , RNA Viral , Sensibilidade e Especificidade
15.
Aliment Pharmacol Ther ; 53(6): 733-744, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33465257

RESUMO

BACKGROUND: An accurate, single-point differential diagnosis between HBeAg-negative infection (ENI) and chronic hepatitis B (CHB) is an unmet need. AIMS: To assess the diagnostic value of the new hepatitis B core-related antigen (HBcrAg) assay. METHODS: A retrospective anonymised data analysis was performed in a multicentre European (nine centres and six countries) cohort of 1582 consecutive HBsAg-positive/HBeAg-negative subjects classified according to EASL guidelines as: 550-CHB, 710-ENI and 322-GZ (grey-zone, HBV-DNA <20 000 IU/mL). RESULTS: Mean age was 44 (±13.2 y), 59% were men; HBV genotypes were 15% A, 2% B, 2% C, 45% D, 9% E, 1% F and 26% unknown. Median HBV-DNA serum levels were 2.2 (1.5-2.7), 3.5 (3.2-3.8) and 5.6 (4.8-6.6) logIU/mL in ENI, GZ and CHB, P < 0.0001. HBsAg serum levels (HBsAgsl) were comparable in CHB and GZ, but lower in ENI (2.9 [2.1-3.6] logIU/mL), P < 0.0001. HBcrAg serum levels (HBcrAgsl) were <3 logU/mL in 90.7% (644/710) ENI, 75.2% (242/322) GZ and 4.7% (26/550) CHB (P < 0.0001). Median HBcrAgsl were 4.8 (3.9-5.7), 2.5 (2.0-2.9) and 2.0 (2.0-2.5) logU/mL in CHB, GZ and ENI, (P < 0.0001). ROC-AUCs for HBcrAg and HBsAg were 0.968 (95% CI, 0.958-0.977) and 0.732 (95% CI, 0.704-0.760) respectively. The optimal HBcrAgsl cut-off to distinguish CHB from ENI was 3.14 logU/mL (95% CI, 3.02-3.25, 91% SE, 93% SP and 92.4% DA). HBcrAgsl were associated with HBV genotypes (P < 0.001, one-way ANOVA) but using genotype-specific cut-offs, HBcrAg DA remained unchanged with overlapping 95% CI. CONCLUSION: The HBcrAg assay showed high diagnostic performance in the accurate single-point identification of patients with HBeAg-negative CHB, independently of HBV genotype. This should prompt future prospective studies to confirm its diagnostic role in clinical practice.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Adulto , DNA Viral/genética , Feminino , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos
16.
Artigo em Inglês | MEDLINE | ID: mdl-33465479
17.
Hepatol Commun ; 5(1): 97-111, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33437904

RESUMO

Treatment with nucleos(t)ide analogues (NAs) may be stopped after 1-3 years of hepatitis B virus DNA suppression in hepatitis B e antigen (HBeAg)-negative patients according to Asian Pacific Association for the Study of Liver and European Association for the Study of Liver guidelines. However, virological relapse (VR) occurs in most patients. We aimed to analyze soluble immune markers (SIMs) and use machine learning to identify SIM combinations as predictor for early VR after NA discontinuation. A validation cohort was used to verify the predictive power of the SIM combination. In a post hoc analysis of a prospective, multicenter therapeutic vaccination trial (ABX-203, NCT02249988), hepatitis B surface antigen, hepatitis B core antigen, and 47 SIMs were repeatedly determined before NA was stopped. Forty-three HBeAg-negative patients were included. To detect the highest predictive constellation of host and viral markers, a supervised machine learning approach was used. Data were validated in a different cohort of 49 patients treated with entecavir. VR (hepatitis B virus DNA ≥ 2,000 IU/mL) occurred in 27 patients. The predictive value for VR of single SIMs at the time of NA stop was best for interleukin (IL)-2, IL-17, and regulated on activation, normal T cell expressed and secreted (RANTES/CCL5) with a maximum area under the curve of 0.65. Hepatitis B core antigen had a higher predictive power than hepatitis B surface antigen but lower than the SIMs. A supervised machine-learning algorithm allowed a remarkable improvement of early relapse prediction in patients treated with entecavir. The combination of IL-2, monokine induced by interferon γ (MIG)/chemokine (C-C motif) ligand 9 (CCL9), RANTES/CCL5, stem cell factor (SCF), and TNF-related apoptosis-inducing ligand (TRAIL) was reliable in predicting VR (0.89; 95% confidence interval: 0.5-1.0) and showed viable results in the validation cohort (0.63; 0.1-0.99). Host immune markers such as SIMs appear to be underestimated in guiding treatment cessation in HBeAg-negative patients. Machine learning can help find predictive SIM patterns that allow a precise identification of patients particularly suitable for NA cessation.

19.
Clin Gastroenterol Hepatol ; 19(1): 46-60.e8, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360825

RESUMO

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

20.
J Viral Hepat ; 28(2): 410-419, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33185325

RESUMO

HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n = 59) or placebo (PEG-IFNα/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFNα/TDF-treated and 12 PEG-IFNα/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.

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