Abstract:
BACKGROUND & AIMS:Affordable point-of-care tests for hepatitis C (HCV) viraemia are needed to improve access to treatment in low- and middle-income countries. Our aims were to determine the target limit of detection (LOD) necessary to diagnose the majority of people with HCV eligible for treatment, and identify characteristics associated with low-level viraemia (LLV) (defined as the lowest 3% of the distribution of HCV RNA) to understand those at risk of being misdiagnosed. METHODS:We established a multi-country cross-sectional dataset of first available quantitative HCV RNA measurements linked to demographic and clinical data. We excluded individuals on HCV treatment. We analysed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates. RESULTS:The dataset included 66,640 individuals with HCV viraemia from across the world. The LOD for the 95th and 99th percentiles were 3,311 IU/ml and 214 IU/ml. The LOD for the 97th percentile was 1,318 IU/ml (95% CI 1,298.4-1,322.3). Factors associated with LLV, defined as HCV RNA <1,318 IU/ml, were younger age 18-30 vs. 51-64 years (odds ratios [OR] 2.56; 95% CI 2.19-2.99), female vs. male sex (OR 1.32; 95% CI 1.18-1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44; 95% CI 1.21-1.69). Only the younger age group had a decreased relative sensitivity below 95%, at 93.3%. CONCLUSIONS:In this global dataset, a test with an LOD of 1,318 IU/ml would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable point-of-care diagnostics to expand HCV testing and linkage to care in low- and middle-income countries. LAY SUMMARY:We created and analysed a dataset from 12 countries with 66,640 participants with chronic hepatitis C virus infection. We determined that about 97% of those with viraemic infection had 1,300 IU/ml or more of circulating virus at the time of diagnosis. While current diagnostic tests can detect as little as 12 IU/ml of virus, our findings suggest that increasing the level of detection closer to 1,300 IU/ml would maintain good test accuracy and will likely enable development of more affordable portable tests for use in low- and middle-income countries.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Freiman JM,Wang J,Easterbrook PJ,Horsburgh CR,Marinucci F,White LF,Kamkamidze G,Krajden M,Loarec A,Njouom R,Nguyen KV,Shiha G,Soliman R,Solomon SS,Tsertsvadze T,Denkinger CM,Linas Bdoi
10.1016/j.jhep.2019.02.011subject
Has Abstractpub_date
2019-07-01 00:00:00pages
62-70issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(19)30125-4journal_volume
71pub_type
杂志文章abstract:BACKGROUND/AIMS:The aim of the study was to investigate the effect of a standard albumin load on blood volume distribution, arterial compliance, and the renin-angiotensin-aldosterone system in patients with different degrees of cirrhosis. METHODS:31 patients with cirrhosis (Child classes A/B/C=8/14/9) received an intr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00160-0
更新日期:2003-07-01 00:00:00
abstract::A joint EASL/AASLD Monothematic Conference on 'Nuclear Receptors and Liver Disease' was held from February 27th to March 1st, 2009, in Vienna, Austria, to discuss the latest advances at the forefront of basic and clinical nuclear receptor research and its potential implications for liver diseases. This article reports...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2009.12.002
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND/AIMS:Oxidative DNA damage, identifiable in the formation of 8-hydroxydeoxyguanosine (8-OHdG), is relevant in the mutagenesis/carcinogenesis process. The aim of this study was to assess 8-OHdG levels in patients with hepatitis C virus (HCV) infection in relation to extent of liver damage and HCV genotype. ME...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00098-2
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND & AIMS:Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.03.028
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. However, their origin is still unknown. We tested the hypothesis that bone marrow (BM) contributes to the population of HSCs. METHODS:Chimeric mice transplanted with donor BM from collagen alpha1(I)-GFP+ reporter mice were subjected...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.04.014
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND & AIMS:Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the lig...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.02.012
更新日期:2014-06-01 00:00:00
abstract::Maturity onset diabetes of the young type 3 (MODY3) and hepatocellular adenomas (HCAs) are associated with mutations in the HNF1A gene. HNF1A codes for the transcription factor HNF1α, which interacts with DNA as a homodimer or a heterodimer with HNF1β, to regulate multiple cellular functions including glucidic metabol...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.05.024
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND/AIMS:To compare carotid intima-media thickness (IMT) - an index of early atherosclerosis - among patients with non-alcoholic steatohepatitis (NASH), patients with chronic hepatitis B (HBV) or C (HCV) and control subjects. METHODS:We studied 60 consecutive patients with biopsy-proven NASH, 60 patients with H...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.021
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND & AIMS:Cholangiocarcinoma (CCA) carries a very poor prognosis due to a typically late clinical presentation and a poor response to current therapeutics. While these tumors commonly express PD-1 and PD-L1, the response to immune checkpoint inhibitors (ICI) is poor. Stimulating antigen-presenting cells includi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.11.037
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND/AIMS:After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS:In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80017-8
更新日期:1999-01-01 00:00:00
abstract::Symptomatic hepatic involvement is a rare complication of hereditary hemorrhagic telangiectasia and most commonly consists of fibrosis or cirrhosis. We describe a 33-year-old woman in whom multiple hepatic arteriovenous malformations led to high output cardiac failure and liver failure due to biliary necrosis with ref...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80455-2
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND/AIMS:To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-alpha therapy, 11 untreated anti-HCV positive individuals and 10 healthy control...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80146-3
更新日期:1998-10-01 00:00:00
abstract::Liver transplantation is performed successfully across major HLA differences between donor and recipient. This may be influenced by the organ specific expression of major histocompatibility complex (MHC) molecules which determine the local immune reactivity and rejection response. The tissue expression of MHC molecule...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/0168-8278(90)90264-r
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND/AIMS:The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypot...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.026
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND/AIMS:Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecul...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00052-1
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND & AIMS:Living donor liver transplantation (LDLT) provides a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatitis C virus-related (HCV-related) diseases in the circumstances of severe organ dearth. However, the patient and graft outcomes, and recurrence of HCV after LD...
journal_title:Journal of hepatology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jhep.2012.07.015
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND & AIMS:miR-224 is up-regulated in human HCCs as compared to both paired peri-tumoral cirrhotic tissues and cirrhotic livers without HCC. Here, we have cloned the miR-224 regulatory region and characterized its transcriptional regulation by the NFκB-dependent inflammatory pathways. METHODS:Mature miRNA expre...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.11.017
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND & AIMS:Disturbance in lipid metabolism is one of the features of chronic hepatitis C, being a crucial determinant of the progression of liver fibrosis. Experimental studies have revealed that the core protein of hepatitis C virus (HCV) induces steatosis. METHODS:The activities of fatty acid metabolizing enz...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.07.039
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND & AIMS:To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b (PEG-IFN) and ribavirin (RBV) in patients with chronic hepatitis C. METHODS:In a multi-center randomized clinical trial in Japan, on patients infected with HCV of genotype 1, 126 patients were assigned to telaprev...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2011.07.016
更新日期:2012-01-01 00:00:00
abstract::It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of high...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(88)80503-8
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND & AIMS:Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, co...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2010.07.011
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND/AIMS:The tropical parasite Schistosoma mansoni causes granulomatous inflammation following lodging of eggs in portal capillaries. In vitro studies indicated that the host reaction should involve reactive oxygen intermediates; however, it is not known what occurs in vivo at the site of the disease. Moreover, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80189-5
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND/AIMS:Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver bio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80391-8
更新日期:2000-03-01 00:00:00
abstract:AIMS/METHODS:During cholestasis, components normally excreted into bile, e.g. bilirubin, accumulate in liver cells and biliary passages. In order to assess the conjugation of bilirubin retained in the hepatocyte during cholestasis, we analyzed the pattern of bilirubin pigments in rat serum and bile, using reversed phas...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80330-3
更新日期:1997-11-01 00:00:00
abstract::Since the first tests for antibodies to components of the hepatitis C virus became widely available there has been considerable interest in evidence linking HCV infection with autoimmune liver diseases and other autoimmune conditions. With respect to autoimmune hepatitis, it is now clear that the early tests were quit...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:
更新日期:1996-01-01 00:00:00
abstract::Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Amo...
journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2008.10.009
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND/AIMS:In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS:We conducted an epidemiological investigat...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.06.012
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND/AIMS:This study evaluates the agreement between reported use of interventions for patients with liver diseases and research evidence in Cochrane systematic reviews. METHODS:In July 2002, the Cochrane Hepato-Biliary Group had completed 28 systematic reviews on 36 interventions that were available in Denmark....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.06.017
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND & AIMS:Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease usually requiring life-long immunosuppression. The mechanisms for disease initiation and chronicity are largely unknown. A contribution of deficient regulatory T cells (Tregs) in the blood was controversially discussed recently. So far i...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.05.034
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) has developed strategies to evade immune responses. However, the mechanisms involved remain unclear. The NLRP3 inflammasome plays crucial roles in antiviral host defense and its downstream factor IL-1β has been shown to inhibit HBV infection in vivo. This study aims to assess w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.12.018
更新日期:2017-04-01 00:00:00