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BACKGROUND AND AIMS: Chronic hepatitis D infection is the most severe form of viral hepatitis and can rapidly progress to cirrhosis or hepatocellular carcinoma. Despite recommendations for systematic screening of hepatitis B surface antigen (HBsAg)-positive individuals, data from real-world studies have reported a low frequency of hepatitis D (or delta) virus (HDV) screening. Our cross-sectional analysis evaluated the diagnostic cascade for hepatitis D infection in tertiary centres and described the characteristics of HDV-positive patients. METHODS: A total of 6772 individuals who tested HBsAg positive for the first time between 2018 and 2022 were retrospectively included. Demographic, clinical and laboratory data were analysed. RESULTS: A total of 5748 HBsAg-positive individuals (84.9%) were screened for HDV infection. The screening rate varied from 63% to 97% according to the screening strategy used in the centres including or not HDV reflex testing. The prevalence of HDV infection was 6.3%. HDV RNA levels were determined in 285 of the 364 (78.3%) HDV antibody screening-positive patients, and 167 (58.6%) had active HDV infection. 66.8% were males, with a mean age of 44.9 years. A total of 97.5% were born abroad, and 92.9% were HBeAg negative. At the time of diagnosis, HDV RNA levels were 6.0 Log UI/mL; 60.1% had alanine aminotransferase >40 U/L, and 56.3% had significant fibrosis (≥F2), including 41.6% with cirrhosis. The most common genotype was HDV-1 (75.4%). Coinfections were not uncommon: 7.4% were HIV positive, and 15.0% were HCV antibody positive. CONCLUSIONS: The present study highlights the need for increased screening and monitoring of HDV infection. Reflex testing helps to identify HDV-infected individuals.
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OBJECTIVES: Migrants from high HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) endemicity regions have a great burden of these infections and related diseases in the host countries. This study aimed to assess the predictive capacity of the Test Rapide d'Orientation Diagnostique (TROD) Screen questionnaire for HIV, HBV and HCV infections among migrants arriving in France. DESIGN: An observational and multicentre study was conducted among migrants. A self-questionnaire on demographic characteristics, personal medical history and sexual behaviours was completed. SETTING: The study was conducted in the centres of the French Office for Immigration and Integration (OFII). PARTICIPANTS: Convenience sampling was used to select and recruit adult migrants between January 2017 and March 2020. OUTCOME MEASURES: Participants were tested for HIV, HBV and HCV with rapid tests. For each infection, the test performance was assessed using receiver operating characteristics curves, using area under the curve (AUC) as a measure of accuracy. RESULTS: Among 21 133 regular migrants seen in OFII centres, 15 343 were included in the study. The participants' mean age was 35.6 years (SD±11.1). The prevalence (95% CI) of HBV, HCV and HIV was 2.0% (1.8% to 2.2%), 0.3% (0.2% to 0.4%) and 0.3% (0.2% to 0.4%), respectively. Based on the sensitivity-specificity curve analysis, the cut-off points (95% CI) chosen for the risk score were: 2.5 (2.5 to 7.5) for HBV infection in men; 6.5 (0.5 to 6.5) for HBV infection in women; 9.5 (9.5 to 12.5) for HCV infection; and 10.5 (10.0 to 18.5) for HIV infection. Test performance was highest for HIV (AUC=82.15% (95% CI 74.54% to 87.99%)), followed by that for HBV in men (AUC=79.22%, (95% CI 76.18% to 82.26%)), for HBV in women (AUC=78.83 (95% CI 74.54% to 82.10%)) and that for HCV (AUC=75.95% (95% CI 68.58% to 83.32%)). CONCLUSION: The TROD screen questionnaire showed good overall performance for predicting HIV, HBV and HCV infections among migrants in OFII centres. It could be used to optimise screening for these infections and to propose rapid screening tests to those who are at high risk. TRIAL REGISTRATION NUMBER: NCT02959684.
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Infecciones por VIH , Hepatitis B , Hepatitis C , Tamizaje Masivo , Migrantes , Humanos , Masculino , Femenino , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Francia/epidemiología , Hepatitis C/epidemiología , Hepatitis C/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/diagnóstico , Migrantes/estadística & datos numéricos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Medición de Riesgo/métodos , Curva ROC , Encuestas y Cuestionarios , PrevalenciaRESUMEN
BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.
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INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.
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Background & Aims: Among people living with HBV, only a subset of individuals with chronic hepatitis is in need of treatment, and this proportion varies according to the population, region, and setting. No estimates of the proportion of people who are infected with HBV and meet the treatment eligibility criteria in France are available. Methods: 552 treatment-naïve individuals with chronic HBV infection referred for the first time to a hepatology reference centre between 2008 and 2012 were prospectively included. Demographic, clinical, and laboratory data were analysed. Results: In total, 61.1% of patients were males, with a median age of 37.5 years. Moreover, 64% were born in an intermediate- or high-HBV endemicity country, and 90% were HBeAg-negative. At referral, median HBV DNA and HBsAg levels were 3.3 and 3.6 log IU/ml, respectively; 37.8% of patients had alanine aminotransferase >40 U/L, and 29.0% had moderate or severe fibrosis (≥F2), including 9.4% with cirrhosis. The most prevalent genotypes were D (34.7%), E (27.4%), and A (25.7%). Coinfections were rare: 2.4% were HIV-positive, 4.0% were HCV-positive, and 6.0% were HDV-positive. According to the 2017 EASL Clinical Practice Guidelines, using a single time point analysis, 2.7% of patients were classified as HBeAg-positive chronic infection, 6.1% as HBeAg-positive chronic hepatitis B, 26.5% as HBeAg-negative chronic hepatitis B, and 61.1% as HBeAg-negative chronic infection, whereas 3.6% patients could not be classified. The performance of HBsAg level quantification to identify individuals with HBeAg-negative chronic hepatitis B was poor. A total of 29.1% met the criteria for initiation of antiviral treatment, whereas 66.5% remained under routine clinical surveillance. Most eligible patients initiated recommended first-line therapies, including tenofovir (45.3%), entecavir (36.8%), or pegylated interferon alpha (11.6%). Conclusions: Of all cases, 9.4% had cirrhosis at presentation and 29.1% met the 2017 EASL Clinical Practice Guidelines treatment criteria. HBsAg levels failed to accurately identify individuals with HBeAg-negative chronic infection. Lay summary: Among French adults chronically infected with HBV referred for the first time to hepatology reference centres, about one-third had a significant liver disease. Approximately one-third of individuals met criteria for initiation of antiviral treatment based on entecavir or tenofovir or, occasionally, pegylated interferon alpha.
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INTRODUCTION AND OBJECTIVES: Liver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. RESULTS: A total of 84% of the patients were male, and the median age was 66 years old (IQR 58-74). Thirty-nine (33%) had Child-Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6-6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55-110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p<0.001), portal veinous invasion (p=0.003) and cirrhosis (p=0.020). Using these factors, we created a simple recurrence-risk scoring system that classified three groups with distinct disease-free survival medians (p<0.001): no risk factors (65 months), 1 risk factor (36 months), and ≥2 risk factors (8.9 months). CONCLUSION: Liver resection is the only curative option for large HCC, and we confirmed that survival could be acceptable in experienced centres. Recurrence is the primary issue of surgery, and we proposed a simple preoperative score to help identify patients with the most worrisome prognosis and possible candidates for combined therapy.
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Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Humanos , Masculino , Anciano , Femenino , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Pronóstico , Estudios Retrospectivos , Enfermedad Hepática en Estado Terminal/cirugía , Recurrencia Local de Neoplasia , Índice de Severidad de la Enfermedad , Cirrosis Hepática/complicacionesRESUMEN
BACKGROUND: Direct antiviral agents (DAAs) became available in France in 2014 for the treatment of chronic hepatitis C (CHC) in patients with severe fibrosis (prioritized access); in 2017, DAAs became available to all CHC patients (universal access). We evaluated the impact of extending DAA availability on CHC patient care, especially on screening and time to treatment. METHODS: Adult patients affiliated with the national health insurance system (SNDS) who were screened or treated for CHC between 2015 and 2019 were included. Algorithms were developed to identify at-risk subpopulations. FINDINGS: The proportion of screened patients increased by 1% between 2015 and 2019, from 4·6% to 5·6%. The main nonexclusive risk factors for CHC were psychiatric conditions (27%), drug use (21%) and HIV positivity (11%); more than 50% of psychiatric patients had additional risk factors, mainly drug use with a 38% to 52% overlap.The median interval between the last screening test and treatment initiation decreased from 64 days in 2015 to 37 days in 2019.During the study period, 71,466 patients began CHC treatment (median age 55 [48-62]; 59% male), including 46% of "at-risk" patients with an increase in treatment initiation by 44% between 2015 and 2017 and a decrease of 46% between 2017 and 2019. Only 2,212 (3%) patients were treated at least twice.Among treated patients, the proportion of HIV+ patients decreased from 19% to 8% (prioritization consequence), while the proportions increased in the other at-risk subpopulations. INTERPRETATION: we showed that policies extending DAA availability are associated with a screening increase and a decrease in the time to treatment initiation, while universal access led to a surge in treatment initiations in 2017. This study may also contribute to improving the cascade of care in the at-risk subpopulations. For instance, by pointing out their relative importance, especially for the psychiatric subpopulation, it highlights the importance to address them with tailored policies.
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Aim: HCV diagnosis will become the bottleneck in eliminating hepatitis C. Simple, accurate and cost-effective testing strategies are urgently needed to improve hepatitis C screening and diagnosis. Materials & methods: Performance of seven rapid diagnostic tests (RDT) have been assessed in a large series (n = 498) of serum or plasma specimens collected in France and in Cameroon. Results: Specificity varied from 96.1 to 100%. The clinical sensitivity, compared with immunoassays as the reference, was high for all seven RDT (97.2-100%). The Multisure HCV antibody assay and OraQuick HCV rapid antibody test reached sensitivity ≥99%. Conclusion: A number of RDT may be suitable for WHO prequalification and may be implemented in the framework of large-scale low-cost treatment programs to achieve the WHO viral hepatitis objectives by 2030.
Lay abstract Diagnosis of hepatitis C infection is crucial in order to envisage elimination of hepatitis C virus (HCV). Diagnosis is usually based on the detection of antibodies in blood after phlebotomy in a centralized laboratory approach. New simpler testing strategies are urgently needed. We assessed the performance of several rapid tests for the detection of HCV antibodies. Rapid tests offer many advantages over classical tests because they are simple, easy-to-use, rapid and can perform close to the site of patient care. Most of the rapid tests included in our study showed satisfactory performance. They can confidently use to detect hepatitis C antibodies in clinical practice.
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Pruebas Diagnósticas de Rutina , Hepatitis C , Camerún , Pruebas Diagnósticas de Rutina/métodos , Francia , Hepatitis C/diagnóstico , Humanos , Tamizaje Masivo/métodos , Sensibilidad y EspecificidadRESUMEN
Hepatitis B surface antigen (HBsAg) is a key marker for screening and laboratory diagnosis of HBV infection. Rapid diagnostic tests (RDTs) represent promising alternatives to immunoassay-based methods because they are simple, fast and cheap. These tests, therefore, represent a powerful tool for large-scale screening and diagnosis of HBV infection in the clinical setting. Performance of 6 RDTs have been assessed in a large series of serum or plasma samples (n = 501) collected in France and in Cameroon. Specificity varied from 98.0% to 99.5%, while clinical sensitivity, compared to immunoassays as the reference, was excellent for all six RDTs (98.3%-99.3%). The VIKIA HBsAg and First Responseࣨ HBsAg Card Test reached sensitivity ≥99%. False-negative results were rare and mostly encompassed inactive HBsAg carriers or patients treated with nucleoside/nucleotide analogues. A number of RDTs may widely use to increase access to testing to all levels of the health care system.
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Pruebas Diagnósticas de Rutina/métodos , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/sangre , Hepatitis B/diagnóstico , Pruebas Serológicas/métodos , Camerún/epidemiología , Estudios de Casos y Controles , Francia/epidemiología , Hepatitis B/epidemiología , Humanos , Técnicas para Inmunoenzimas , Sensibilidad y EspecificidadRESUMEN
Hepatitis C is a global health problem, with an estimated 71·1 million individuals chronically infected worldwide, accounting for 1% (95% uncertainty interval: 0.8-1.1) of the population. HCV transmission is most commonly associated with direct exposure to blood, via blood transfusions, unsafe health-care-related injections and intravenous drug use. The global incidence of HCV was 23·7 cases per 100 000 population (95% uncertainty interval 21·3-28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. An estimated 2.3 millions of people living with HIV have serological markers of past or current HCV infection. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). Approximately 10-20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, end stage liver disease, and hepatocellular carcinoma over a period of 20-30 years. Direct-acting antiviral therapy is curative, dramatically reducing the mortality related to HCV and the need for liver transplantation, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.
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Antivirales , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.
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BACKGROUND: Injecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide, and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care (POC) hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different nonclinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV ribonucleic acid (RNA) POC and fingerstick DBS testing in social-medical risk-reduction centers and to describe the cascade of care among PWID in France. METHODS: Between June 2018 and February 2019, 89 consecutive HCV-seropositive PWID attending 2 drug treatment services and 1 supervised consumption room in inner Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick DBS sampling. RESULTS: Of the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pan-genotypic antiviral treatment. The proportion of PWID with sustained virologic response at 12 weeks was 81.2%, with data for 3 patients still pending. CONCLUSIONS: One-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.
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BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.
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Carcinoma Hepatocelular , Hepatitis D Crónica , Virus de la Hepatitis Delta , Cirrosis Hepática , Neoplasias Hepáticas , Viremia , Adulto , Carcinoma Hepatocelular/etnología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Femenino , Francia/epidemiología , Hepatitis D Crónica/complicaciones , Hepatitis D Crónica/diagnóstico , Hepatitis D Crónica/epidemiología , Hepatitis D Crónica/terapia , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/aislamiento & purificación , Virus de la Hepatitis Delta/patogenicidad , Humanos , Interferones/uso terapéutico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etnología , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etnología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Características de la Residencia/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Carga Viral/métodos , Carga Viral/estadística & datos numéricos , Viremia/diagnóstico , Viremia/etnologíaRESUMEN
BACKGROUND AND AIMS: Markers predicting complications of post-hepatitis C cirrhosis are needed. We asked whether changes in noninvasive markers of fibrosis can predict liver-related complications. METHODS: This was a case-controlled study using a prospective national cohort (ANRS-CO12-CIRVIR) of 1323 HCV-infected patients with compensated cirrhosis: 97 patients who developed liver-related complications such as hepatocellular carcinoma or hepatic decompensation (cases) matched in age, sex and follow-up duration were compared with 257 patients without complications (controls). Actitest/Fibrotest™, Inflameter/Fibrometer™, ELF™ and Fibroscan™ were performed at baseline and yearly. Samples based on Propensity score matching were built and mixed linear models performed. Outcomes in a sustained virological response (SVR) negative population and a SVR-positive population were also described. RESULTS: At baseline, all characteristics of patients were similar between the groups. All fibrosis tests were statistically higher for cases compared to controls, Fibroscan™ excepted: Fibrotest™: 0.83±0.13 vs. 0.77±0.16; Fibrometer™: 0.93±0.07 vs. 0.90±0.11; ELF™: 11.4±1.0 vs. 11.0±1.2 (P<0.02). The mean follow-up was 5.7±1.9 years. Over a 3-year period, the significant difference in fibrosis marker values between cases and controls remained constant; with a trend toward a decrease in inflammation markers in controls, independent of SVR status. CONCLUSIONS: Baseline noninvasive serum fibrosis and inflammation markers were significantly higher in patients developing a complication than in controls. During the follow-up only inflammatory markers decreased in controls, but not in cases, and thus could potentially be used to predict the occurrence of complications in cirrhotic patients.
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Hepatitis C/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Hepatopatías/etiología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
Migration of people from HCV endemic countries is a public health issue for the French healthcare system. The PRECAVIR study focused on migrant patients and provides a multidisciplinary, patient-centred approach to treat chronic HCV-infected migrants through a systematic screening programme. Between 2007 and 2017, 101 (2.98%) out of 3386 consecutive adult migrants attending two primary healthcare settings in Créteil, France, tested positive for HCV. The median age was 44.5 years old, and 55% were women. Patients were mainly from sub-Saharan Africa, Eastern Europe and Asia. Seventy-four patients were undocumented migrants, and 25 were asylum seekers. Eighty-four (83%) patients were unaware of their serological status. All patients were offered referral to a specialist in the same setting. HCV RNA testing was performed in 88 (87%) of the patients who tested anti-HCV positive. Forty-nine (57%) were chronically infected, while 39 (43%) had an undetectable viral load. All patients were treatment-naïve. More than half of patients had access to treatment. Before 2014, thirteen patients were treated with pegylated interferon and ribavirin, and an SVR was achieved in 8 (61.5%) of them. By 2017, 17 patients had begun oral, direct-acting antiviral treatment. An SVR was achieved in 16 of 17 patients (93%). However, all patients not initially eligible for treatment were lost to follow-up. This study showed the effectiveness of a coordinated care network when anti-HCV testing, linkage to care and treatment are organized for a migrant population in the same setting as long as universal treatment makes a test and treat policy possible.
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Atención a la Salud , Hepacivirus , Hepatitis C/epidemiología , Migrantes , Adulto , Femenino , Francia/epidemiología , Hepacivirus/inmunología , Hepatitis C/inmunología , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Anticuerpos contra la Hepatitis C/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Vigilancia en Salud Pública , Carga ViralRESUMEN
BACKGROUND: Sensitive and accurate hepatitis C virus (HCV) RNA detection and quantification are essential to diagnose and monitor the virological response to antiviral treatment and the emergence of resistance. OBJECTIVE AND STUDY DESIGN: The aim of this study was to assess the ability of the new Xpert HCV Viral Load assay to accurately detect and quantify HCV RNA in serum and in whole blood collected on dried blood spot (DBS). Serum and whole blood from a large series of patients chronically infected with different HCV genotypes were tested in parallel for HCV RNA detection and quantification. RESULTS: A significant relationship between HCV RNA levels measured with the Xpert HCV Viral Load assay and the two commercial real-time PCR comparators (Abbott RealTime HCV test and Cobas AmpliPrep/Cobas Taqman HCV 2.0 test) was found in serum as well as in whole blood specimens. CONCLUSIONS: The Xpert HCV Viral Load assay accurately quantifies HCV RNA regardless of the HCV genotype and can thus confidently be used to detect active HCV infection in serum and in whole blood specimens.
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Hepacivirus/fisiología , Hepatitis C/diagnóstico , ARN Viral/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/sangre , Humanos , Masculino , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Suero/virología , Carga ViralRESUMEN
BACKGROUND & AIMS: Management of patients with cirrhosis includes endoscopic screening and surveillance to detect esophageal varices (EV) and prevent bleeding. However, the Baveno VI guidelines recommend avoiding endoscopies for patients with liver stiffness measurements below 20 kPa and platelet counts above 150,000 (favorable Baveno VI status) and endoscopic assessment of patients with higher levels of liver stiffness and platelet counts (unfavorable Baveno VI status). We aimed to validate the Baveno VI guidelines, evaluating outcomes of patients in the ANRS-CO12 CirVir cohort with compensated cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, with or without a sustained response to antiviral therapy. METHODS: We performed an ancillary study using data from 891 patients in the ANRS CO12 CirVir cohort, treated at 35 centers in France, with HCV or HBV infection and biopsy-proven cirrhosis, Child-Pugh A scores, no previous complications, and no hepatocellular carcinoma who underwent an endoscopic procedure and had interpretable liver stiffness measurements and platelet counts. Progression of portal hypertension (PHT) was defined as the onset of varices needing treatment (VNT) or PHT-related bleeding. An sustained response to antiviral therapy was defined as undetectable level of HCV RNA by polymerase chain reaction assay (<50 IU/mL) 12 weeks after the end of treatment (SVR) or an undetectable level of HBV DNA. The primary aims were to validate the Baveno VI guidelines for screening and surveillance of EV in patients with compensated cirrhosis and to study the effects of an SVR on the progression of PHT. RESULTS: A total of 200 patients achieved an SVR (22.4%) (94 patients with HCV infection, 98 patients with HBV infection, and 8 patients with both); 80 of these patients had favorable Baveno VI status and none had VNT. Progression of PHT was studied in 548 patients; during a follow-up period of 61.2 months (interquartile range, 39.5-80.6 months), 105 of these patients (19.1%) had progression of PHT. Lack of an SVR and grade 1 EV were independently associated with progression of PHT. At the time of PHT progression, all patients had unfavorable Baveno VI status. Achieving favorable Baveno VI status after an SVR was associated with the absence of PHT progression. Favorable Baveno VI status and SVR were independently associated with survival. CONCLUSIONS: In an analysis of data from a large cohort of patients with HBV- or HCV-associated cirrhosis in France, we validated the Baveno VI guidelines on screening and surveillance of PHT, even for patients who achieved a sustained response to antiviral therapy.
Asunto(s)
Várices Esofágicas y Gástricas/diagnóstico por imagen , Cirrosis Hepática/fisiopatología , Tamizaje Masivo/normas , Vigilancia de la Población , Guías de Práctica Clínica como Asunto , Antivirales/uso terapéutico , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/etiología , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Tasa de Supervivencia , Respuesta Virológica SostenidaRESUMEN
It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.
Asunto(s)
Carcinoma Hepatocelular/virología , Enfermedad Hepática en Estado Terminal/epidemiología , Infecciones por VIH/epidemiología , Hepatitis C Crónica/epidemiología , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Adulto , Antirretrovirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/patología , Coinfección/virología , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/patología , Enfermedad Hepática en Estado Terminal/virología , Femenino , Francia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Hepacivirus/patogenicidad , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Carga ViralRESUMEN
BACKGROUND & AIMS: HIV/HCV co-infected patients with hepatocellular carcinoma (HCC) have poorer survival than HCV mono-infected patients. We aimed to evaluate the prognostic factors for survival. METHODS: From 2006 to 2013, 55 incident HCCs among HIV+/HCV+ patients, from three ANRS cohorts, were compared with 181 HCCs in HIV-/HCV+ patients from the ANRS Cirvir cohort. RESULTS: HIV+/HCV+ patients were younger (50 years [IQR: 47-53] vs 62 [54-70], P < 0.001), male (89% vs 63%, P < 0.001) than HIV-/HCV+ patients. At HCC diagnosis, both groups had a majority of non-responders to anti-HCV-therapy, and HIV+/HCV+ patients had more frequently known a previous cirrhosis decompensation (31% vs 14%, P = 0.005). At diagnostic imaging, there were more infiltrative forms of HCC in HIV+/HCV+ group (24% vs 14%, P < 0.001), associated with tumour portal thrombosis in 29%. During a median follow-up period of 11.96 [5.51-27] months since HCC diagnosis, a majority of palliative treatments were decided in HIV+/HCV+ patients (51% vs 19%, P < 0.001). The 1 and 2-year crude survival rates were 61% versus 78% and 47% versus 63%, P = 0.003 respectively. In a Cox model multivariate analysis adjusted for the cohort, age and sex, the most important prognostic factor for survival was the infiltrative form of the tumour (aRR: 8.10 [4.17-15.75], P < 0.001). CONCLUSIONS: The radiological aggressiveness of the tumour is the best prognostic factor associated with poorer survival of HCC in HIV+/HCV+ patients. High α-foetoprotein level and decompensated cirrhosis are other ones. This justifies a particular attention to the detection and the management of small nodules in this high-risk population.