RÉSUMÉ
Hepatitis E virus (HEV) genotype 3 is the most prevalent HEV genotype in Europe causing mostly asymptomatic infections in humans, but can also sporadically cause severe acute hepatitis, chronic liver disease, chronic hepatitis in immunocompromised patients and extra-hepatic manifestations. Although much is today known about the swine reservoir, no information is available on the occurrence of HEV from widely distributed deer species in Portugal. Here, we investigated the presence and characterized HEV in free-living deer in Portugal by screening stools from red deer (Cervus elaphus) (n = 95) and fallow deer (Dama dama) (n = 35) for HEV by a broad-spectrum nested RT-PCR, followed by sequencing and phylogenetic analysis. Two red deer females, sampled in central Portugal, showed to be shedding HEV (2.1%; 95% confidence interval: 0.58-7.35). Sequencing and genetic characterization showed that these two deer HEV sequences were 98.96% identical to each other, being both of HEV genotype 3 subgenotype 3e. The increasing numbers and distribution of deer in Portugal and the zoonotic features of the circulating HEV genotype 3 subgenotype 3e highlights the importance of continued surveillance directed to food-borne diseases, especially those involving wild animals and deer in particular.
Sujet(s)
Cervidae , Virus de l'hépatite E , Hépatite E , Maladies des porcs , Animaux , Femelle , Génotype , Hépatite E/épidémiologie , Hépatite E/médecine vétérinaire , Virus de l'hépatite E/génétique , Humains , Phylogenèse , Portugal/épidémiologie , SuidaeRÉSUMÉ
BACKGROUND: Liver stiffness (LS) at sustained viral response (SVR) is strongly associated with a lower incidence of subsequent hepatic events. HIV NNRTIs may have a beneficial impact on fibrogenesis. OBJECTIVES: Our aim was to analyse the influence of NNRTI-based therapy on the change in LS from starting direct-acting antiviral (DAA) therapy to achieving SVR in HIV/HCV-coinfected patients. METHODS: Three hundred and thirteen HIV/HCV-coinfected patients who fulfilled the following criteria were included: (i) had achieved SVR with an IFN-free, DAA-including regimen; (ii) LS ≥9.5 kPa before therapy; (iii) LS measurement available at SVR; (iv) seronegative for HBsAg; and (v) ART containing 2 NRTIs plus either 1 NNRTI or 1 integrase inhibitor (INI) or 1-2 NRTIs plus 1 PI. LS changes were assessed. RESULTS: Seventy-four patients received NNRTI-based combinations [53 (71.6%) rilpivirine and 16 (21.6%) efavirenz] and 239 patients received other regimens. At baseline, the median (IQR) LS was 16.7 kPa (11.8-25.6) in the NNRTI group and 17.3 kPa (11.9-27.4) in the non-NNRTI group (P = 0.278). The median (IQR) percentage of LS decrease from baseline to SVR was 35.2% (18.2%-52.3%) for NNRTI-based therapy and 29.5% (10%-45.9%) for PI- or INI-based therapy (P = 0.018). In multivariate analysis, adjusted for sex, age, HCV genotype, NRTI backbone and propensity score for HIV therapy, NNRTI-based regimen use was associated with a higher LS decrease [ß = 11.088 (95% CI = 1.67-20.51); P = 0.021]. CONCLUSIONS: Treatment with NNRTI plus 2 NRTI combinations is associated with a higher LS decline than other ART combinations in HIV/HCV-coinfected patients receiving DAA-based therapy.
Sujet(s)
Infections à VIH , Hépatite C chronique , Antiviraux/usage thérapeutique , Infections à VIH/complications , Infections à VIH/traitement médicamenteux , Hépatite C chronique/complications , Hépatite C chronique/traitement médicamenteux , Humains , Inhibiteurs de la transcriptase inverse/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.
Sujet(s)
Infections à VIH , Hépatite C , Minorités sexuelles , Infections à VIH/complications , Infections à VIH/épidémiologie , Hepacivirus , Hépatite C/complications , Hépatite C/épidémiologie , Homosexualité masculine , Humains , Incidence , Mâle , Espagne/épidémiologieRÉSUMÉ
BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.
Sujet(s)
Carcinome hépatocellulaire , Infections à VIH , Hépatite C chronique , Hépatite C , Tumeurs du foie , Antiviraux/usage thérapeutique , VIH (Virus de l'Immunodéficience Humaine) , Infections à VIH/complications , Infections à VIH/traitement médicamenteux , Hepacivirus , Hépatite C/traitement médicamenteux , Hépatite C chronique/complications , Hépatite C chronique/traitement médicamenteux , Humains , Cirrhose du foie/traitement médicamenteux , Études prospectives , Réponse virologique soutenueRÉSUMÉ
OBJECTIVES: Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV-coinfected patients. METHODS: A prospective longitudinal study was carried out. HIV-infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct-acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow-up and those who were not. RESULTS: Of the 15 556 HIV-infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow-up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment-naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST-PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST-PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409-0.746) and recent PWID (OR 0.019; 95% CI 0.004-0.087) were identified as independent factors associated with low odds of treatment implementation. CONCLUSIONS: We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years.
Sujet(s)
Antiviraux/usage thérapeutique , Co-infection/traitement médicamenteux , Utilisation médicament/statistiques et données numériques , Infections à VIH/complications , Hépatite C chronique/traitement médicamenteux , Toxicomanie intraveineuse/complications , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Études longitudinales , Mâle , Adulte d'âge moyen , Études prospectives , Jeune adulteSujet(s)
Virus de l'hépatite E/isolement et purification , Hépatite E/épidémiologie , Foie/virologie , Donneurs de tissus , Adulte , Sujet âgé , Études transversales , Femelle , Génotype , Hépatite E/transmission , Virus de l'hépatite E/génétique , Humains , Transplantation hépatique/statistiques et données numériques , Mâle , Adulte d'âge moyen , ARN viral/analyse , Études rétrospectives , Espagne/épidémiologie , Donneurs de tissus/statistiques et données numériques , Receveurs de transplantation , Transplantation homologueRÉSUMÉ
Diagnosis of acute hepatitis E virus (HEV) infection is established by detection of anti-HEV IgM antibodies by ELISA or by amplification of serum viral RNA. Here, we evaluate the diagnostic value of testing HEV RNA in saliva to identify patients with acute HEV infection. Prospective proof-of-concept study including patients with acute hepatitis. Whole blood and neat saliva samples were obtained from all patients. Saliva samples were processed and analysed for HEV RNA by RT-PCR within 2 hr after collection. A total of 34 patients with acute hepatitis and 12 healthy donors were included in the study. HEV RNA in serum was confirmed by RT-PCR in eight of these patients (23.5%; 95% CI: 12.2%-40.2%). HEV was isolated in the saliva of eight of 34 patients (23.5%; 95% CI: 12.2%-40.2%). All patients with HEV RNA amplified in saliva had detectable HEV RNA in serum. HEV was isolated neither in the saliva of any of the 26 patients without detectable HEV RNA in serum nor in healthy donors. Our study suggests that acute HEV infection could be diagnosed by assessing viral load in saliva.
Sujet(s)
Virus de l'hépatite E , Hépatite E/diagnostic , ARN viral/isolement et purification , Salive/virologie , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Études prospectives , ARN viral/sang , ARN viral/composition chimique , RT-PCR/méthodes , Tests sérologiques , Jeune adulteRÉSUMÉ
The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV-coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well-conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver-related death (LRD) and death of any cause. After a median (Q1-Q3) follow-up of 51 (27-72) months, 67 patients (24%; 95% CI: 19-29) developed their first LD or died during follow-up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83-196, 197-355, >355 [copies/µL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1-0.6, 0.6-1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis.
Sujet(s)
Translocation bactérienne , Marqueurs biologiques/sang , Co-infection/virologie , Infections à VIH/complications , Hépatite C/microbiologie , Cirrhose du foie/virologie , Adulte , Infections bactériennes/sang , Co-infection/microbiologie , Femelle , Hepacivirus , Hépatite C/complications , Hépatite C/mortalité , Humains , Antigènes CD14/sang , Lipopolysaccharides/sang , Cirrhose du foie/mortalité , Mâle , Adulte d'âge moyen , Péritonite/microbiologie , Études prospectives , ARN ribosomique 16S/sang , Études rétrospectivesRÉSUMÉ
Our objective was to determine the incidence and clinical manifestations of acute hepatitis E virus (HEV) in HIV-infected patients. A prospective longitudinal study including HIV-infected HEV-seronegative patients was conducted; HEV seroconversion (to IgG and/or IgM) was the main outcome variable. All patients were tested for HEV antibodies every 3-6 months. For patients who developed HEV seroconversion, a data collection protocol was followed to identify associated clinical manifestations and analytical alterations. A total of 627 patients (89.9%) were followed during a median of 11.96 months (IQR: 8.52-14.52 months) and formed the study population. Forty-one patients developed detectable anti-HEV antibodies (7.2 cases per 100 patients/year). Our study found a high incidence of HEV in HIV-infected patients in southern Spain strongly associated with a rural habitat.
Sujet(s)
Infections à VIH/complications , Virus de l'hépatite E/immunologie , Hépatite E/complications , Adulte , Co-infection , Femelle , Hépatite E/épidémiologie , Hépatite E/virologie , Humains , Incidence , Études longitudinales , Mâle , Adulte d'âge moyen , Facteurs de risque , Population rurale , Tests sérologiquesRÉSUMÉ
An HIV-infected patient was diagnosed with acute hepatitis E infection in our hospital. An epidemiological inquiry was performed to collect demographic, food and animal exposure variables in order to identify the potential route of transmission. The patient reported that his family traditionally hunted wild boar for food. All family members were analysed for hepatitis E virus infection. Additionally, route of transmission by wild boar meat consumption and prevalence of HEV infection among wild boar from the same hunting area were investigated. In all-family members (n = 8), HEV-RNA was amplified. Two wild boar meat slices consumed was analysed, showing the presence of HEV. The virus isolated was consistent with genotype 3, revealing 100% homology between family members and meat. Additionally, we tested nine wild boar hunted in the same hunting area. All of them were RNA-HEV positive, isolating the same HEV genotype 3 viral strain. We demonstrated by phylogenetic analysis zoonotic transmission of HEV by wild boar meat consumption. The prevalence of HEV infection among wild boar found in our study suggests that this species is an important route of transmission to human.
Sujet(s)
Épidémies de maladies , Microbiologie alimentaire , Hépatite E , , Animaux , Génotype , Hépatite E/étiologie , Hépatite E/transmission , Hépatite E/virologie , Virus de l'hépatite E/génétique , Virus de l'hépatite E/isolement et purification , Infections à VIH/complications , Phylogenèse , ARN viral/isolement et purification , Espagne , Sus scrofa , Zoonoses/transmission , Zoonoses/virologie , Humains , /virologieRÉSUMÉ
OBJECTIVES: Fatty liver disease (FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV-infected patients. METHODS: FLD was defined as a value of the controlled attenuation parameter (CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population. RESULTS: Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [P = 0.009; adjusted odds ratio 1.88; 95% confidence interval (CI) 1.17-3.01]. CONCLUSIONS: Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors.
Sujet(s)
Alpha-ketoglutarate-dependent dioxygenase FTO/génétique , Stéatose hépatique/génétique , Prédisposition génétique à une maladie , Infections à VIH/complications , Obésité/complications , Polymorphisme de nucléotide simple , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Études transversales , Imagerie d'élasticité tissulaire , Stéatose hépatique/anatomopathologie , Femelle , Techniques de génotypage , Humains , Mâle , Adulte d'âge moyen , Jeune adulteRÉSUMÉ
Our aim was to evaluate the killer cell immunoglobulin-like receptors (KIRs) as a marker for the development of thrombocytopenia secondary to Peg-interferon (IFN) therapy in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. Patients were naive to HCV treatment, receiving a first course of Peg-IFN/Ribavirin combination therapy. Total platelet count (cells ml-1) was determined at each visit, determining platelet decline from baseline to weeks 1, 2, 4, 8 and 12 after starting therapy. The end point of the study was development of thrombocytopenia, defined as a platelet count of <1 50 000 cells ml-1. Fifty-eight HIV/HCV co-infected patients were included in the study, of whom 20 (34.4%) developed thrombocytopenia. The absence of KIR2DS2 was associated with higher and faster rate of thrombocytopenia (54.2% vs 22.5%; P=0.012; 6.6 vs 10.3 weeks; P=0.008). The absence of KIR2DS2 was associated with a greater decline in platelet count and development of thrombocytopenia during Peg-IFN treatment in HIV/HCV co-infected patients.
Sujet(s)
Interféron alpha/usage thérapeutique , Récepteurs KIR/métabolisme , Thrombopénie/traitement médicamenteux , Thrombopénie/métabolisme , Adulte , Antiviraux/usage thérapeutique , Co-infection/traitement médicamenteux , Co-infection/métabolisme , Association de médicaments/méthodes , Femelle , Infections à VIH/traitement médicamenteux , Infections à VIH/métabolisme , Hepacivirus/effets des médicaments et des substances chimiques , Hépatite C chronique/traitement médicamenteux , Hépatite C chronique/métabolisme , Humains , Mâle , Numération des plaquettes/méthodes , Ribavirine/usage thérapeutiqueRÉSUMÉ
Our aim was to analyze the influence of HLA-B haplotypes on liver fibrosis progression in HIV/hepatitis C virus (HCV) co-infected patients. Retrospective longitudinal study including HIV/HCV, non-cirrhotic and HCV treatment-naïve patients. The main outcome variable was liver fibrosis progression of at least one stage. One hundred and four patients constituted the study population (F0-F1: 62 (59.6%); F2: 22 (21.2%); F3: 20 (19.2%)). During a median follow-up of 54.5 months (IQR: 26.2-77), 45 patients (43.3%) showed an increase in the stage of liver fibrosis (time to event: 29 (IQR: 14-49.5) months). HLA-B18pos patients more frequently had a higher and faster fibrosis progression rate (73.3%; 24 (IQR: 8-29) months) than HLA-B18neg patients (38.2%; 34.5 (IQR: 14.7-51.2) months). This association was also observed in the development of F3-F4 fibrosis among F0-F2 patients (HLA-B18pos: 69.2%; 18 (6.5-37) months vs HLA-B18neg: 28.2%; 37 (IQR: 19-52) months). These results could impact the timing of HCV therapy in F0-F2 patients.
Sujet(s)
Infections à VIH/traitement médicamenteux , Antigène HLA-B18/génétique , Hépatite C/traitement médicamenteux , Cirrhose du foie/immunologie , Adulte , Co-infection , Évolution de la maladie , Femelle , Génotype , Infections à VIH/complications , Infections à VIH/génétique , Infections à VIH/virologie , Hépatite C/complications , Hépatite C/génétique , Hépatite C/virologie , Humains , Cirrhose du foie/étiologie , Cirrhose du foie/génétique , Mâle , Adulte d'âge moyen , Études rétrospectives , Facteurs de risque , Indice de gravité de la maladie , Analyse de survie , Facteurs temps , Échec thérapeutique , Charge viraleSujet(s)
Infections à VIH/traitement médicamenteux , Antigène HLA-B18/génétique , Hépatite C/traitement médicamenteux , Cirrhose du foie/génétique , Co-infection , Évolution de la maladie , Génotype , Infections à VIH/complications , Infections à VIH/génétique , Hépatite C/complications , Hépatite C/génétique , Humains , Cirrhose du foie/étiologie , Cirrhose du foie/immunologie , Facteurs de risque , Analyse de survie , Échec thérapeutiqueRÉSUMÉ
In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.
Sujet(s)
Antiviraux/usage thérapeutique , Infections à VIH/complications , Accessibilité des services de santé , Hépatite C chronique/complications , Hépatite C chronique/traitement médicamenteux , Cirrhose du foie/épidémiologie , Défaillance hépatique/épidémiologie , Adulte , Sujet âgé , Femelle , Politique de santé , Hépatite C chronique/diagnostic , Hépatite C chronique/mortalité , Humains , Cirrhose du foie/anatomopathologie , Défaillance hépatique/anatomopathologie , Mâle , Adulte d'âge moyen , Études prospectives , Espagne , Analyse de survie , Résultat thérapeutiqueRÉSUMÉ
The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.
Sujet(s)
Antiviraux/usage thérapeutique , Techniques d'aide à la décision , Hépatite C chronique/traitement médicamenteux , Hépatite C chronique/anatomopathologie , Cirrhose du foie/anatomopathologie , Foie/anatomopathologie , Inhibiteurs de protéases/usage thérapeutique , Adulte , Sujet âgé , Femelle , Hépatite C chronique/complications , Humains , Mâle , Adulte d'âge moyen , Études prospectives , Récidive , Espagne , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVES: There are scant data on the progression of hepatic steatosis (HS) in HIV infection. We therefore evaluated changes in HS over time in HIV-infected patients using the controlled attenuation parameter (CAP). METHODS: A prospective cohort of 326 HIV-infected patients was included in this study. All patients underwent a CAP measurement. Changes in steatosis were evaluated by calculating the median (Q1-Q3) difference between baseline and 12-month CAP values. RESULTS: The median (Q1-Q3) CAP was 221 (196-252) dB/m at baseline and 224 (198-257) dB/m at the 12-month visit (P = 0.617). Significant steatosis, that is, CAP ≥ 238 dB/m, was observed in 76 individuals (37%) at baseline and in 80 (39%) at the 12-month visit (P = 0.683). The following variables were associated with ΔCAP: plasma HIV RNA [< 50 vs. ≥ 50 HIV-1 RNA copies/mL: median (Q1-Q3) ΔCAP, 4 (-21, 27) vs. -21 (-49, 4) dB/m, respectively; P = 0.024]; body mass index (BMI) [no increase vs. increase: -13 (-40, 4) vs. 14 (-6, 32) dB/m, respectively; P < 0.001]; triglycerides [no increase vs. increase: -1 (-30, 22) vs. 15 (-3, 40) dB/m, respectively; P = 0.001]; fasting plasma glucose [not impaired vs. impaired: -4 (-31, 16) vs. 30 (15, 49) dB/m, respectively; P < 0.001]; and raltegravir [no vs. yes: 5 (-20, 29) vs. -11 (-37.5, 15) dB/m, respectively; P = 0.018]. The only factor independently associated with ΔCAP was BMI [B (standard error): 9.03 (1.9); P < 0.001]. CONCLUSIONS: Increases in CAP values over a period of 12 months in HIV-infected patients were strongly associated with elevations in BMI. Other metabolic factors and antiretroviral drugs were not predictors of CAP changes independent of BMI.
Sujet(s)
Imagerie d'élasticité tissulaire , Stéatose hépatique/diagnostic , Stéatose hépatique/anatomopathologie , Infections à VIH/complications , Adulte , Indice de masse corporelle , Femelle , Humains , Études longitudinales , Mâle , Adulte d'âge moyen , Études prospectivesRÉSUMÉ
The implementation of hepatitis C (HCV) direct-acting antiviral drugs is prioritized in several populations in which its application provides the most immediate and impactful benefit. In this scenario, a precise knowledge of the situation of human immunodeficiency virus (HIV)/HCV chronic co-infection is required to adequately address this disease. This cross-sectional study was performed in 21 hospitals in Andalusia (Spain). The study population consisted of HIV-infected patients with an active HCV chronic infection who were not receiving HCV treatment at the time of inclusion. A total of 13,506 HIV-infected patients were included in the study. Of them, 2561 (18.9 %) presented chronic HCV infection. The majority of the patients included were on highly active antiretroviral therapy (HAART; 96.2 %), showed plasma levels with an undetectable HIV viral load (92.5 %), and had a good immunological status (median CD4+ cell count of 486 cells/mL). The HCV genotype distribution was as follows: 58.1 % were genotype 1, 1.1 % were genotype 2, 16.1 % were genotype 3, and 22.1 % were genotype 4 (2.6 % were missing data). In total, 24.8 % of the patients showed liver fibrosis stage F0-F1, 27.9 % showed stage F2, 16.7 % showed stage F3, and 21 % showed stage F4 (9.6 % were missing data). With regards to previous HCV treatment experiences, 68.05 % of the patients were naïve and 31.95 % had failed to respond to a previous treatment. The burden of HCV/HIV co-infected patients in our population was reported as one in five HIV-infected patients requiring HCV treatment. The implementation of extra resources to face this important health challenge is mandatory.
Sujet(s)
Co-infection/épidémiologie , Infections à VIH/complications , Hépatite C chronique/complications , Hépatite C chronique/épidémiologie , Cirrhose du foie/épidémiologie , Adulte , Co-infection/anatomopathologie , Études transversales , Femelle , Génotype , Hepacivirus/classification , Hepacivirus/génétique , Hepacivirus/isolement et purification , Humains , Cirrhose du foie/anatomopathologie , Mâle , Adulte d'âge moyen , Prévalence , Études prospectives , Espagne/épidémiologieRÉSUMÉ
Hepatitis C virus (HCV) viral persistence in patients with spontaneous viral clearance is controversial. Several studies have shown HCV-RNA in peripheral blood mononuclear cells (PBMCs) and/or liver tissue among patients who have cleared the virus spontaneously, suggesting that viral persistence is a common situation that could involve the entire population studied. Thus, our aim was to evaluate HCV-RNA persistence in PBMCs and hepatocytes in subjects infected with the human immunodeficiency virus (HIV). A total of 1508 patients were prospectively followed and tested for anti-HCV antibodies and HCV-RNA to identify the patients who achieved spontaneous viral clearance. In all of the patients, the persistence of HCV-RNA in PBMCs was evaluated longitudinally during 2 years of follow-up. Fifty-nine patients fulfilled the inclusion/exclusion criteria and were included in the study. HCV-RNA was not detected in the PBMCs at baseline [59 PBMCs samples tested; 0 %; 95 % confidence interval (CI): 0-3.3 %] or during the follow-up (147 PBMCs samples tested; 0 %; 95 % CI: 0-2.02 %). Our study shows that HCV viral persistence is not a frequent occurrence in HIV-infected patients who have spontaneously resolved an HCV infection. Thus, the lack of serum HCV-RNA should continue to be addressed as the standard of healing.
Sujet(s)
Infections à VIH/complications , Hépatite C/virologie , Hépatocytes/virologie , Agranulocytes/virologie , ARN viral/isolement et purification , Rémission spontanée , Sérum/virologie , Adulte , Femelle , Hépatite C/diagnostic , Anticorps de l'hépatite C/sang , Humains , Études longitudinales , Mâle , Adulte d'âge moyen , Études prospectivesRÉSUMÉ
It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.