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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 [β = 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.

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.

Between early October and mid-December 2018, mortalities were detected in Iberian ibex (Capra pyrenaica) populations in southern Spain. In the same region and period, bluetongue virus (BTV) circulation was also reported in sentinel and clinically affected domestic ruminant herds. Molecular analyses confirmed BTV serotype 4 (BTV-4) infection in eight Iberian ibexes from six hunting areas, and in 46 domestic ruminants from seven herds in close proximity to affected hunting estates. Histopathological analyses revealed vascular changes in several organs, pneumonia, lymphoid depletion, inflammatory mononuclear cell infiltrate and fibrosis as the most frequently observed lesions in the affected Iberian ibexes. Epidemiological and laboratory results indicate that BTV-4 was the main aetiological agent involved in outbreaks detected in Iberian ibex populations during the study period. Sequence analyses indicated that the BTV-4 strain detected in Iberian ibex had high homology (99.4%-100%) with strains isolated in livestock during the same period, and with previous isolates (≥98.9%) from Spain and Mediterranean Basin countries. Further studies are warranted to determine the impact of BTV-4 on the health status of Iberian ibex populations after the outbreaks. The inclusion of this species in the surveillance programme may be useful for early detection of BTV, especially in epidemiological scenarios at the wildlife-livestock interface.

Microsporidia is a phylum of obligate emergent intracellular protist-like fungi pathogens that infect a broad range of hosts including vertebrates and invertebrates. Enterocytozoon bieneusi is the most common cause of microsporidiosis in humans, affecting primarily immunosuppressed patients but also reported in immunocompetent individuals. Epidemiological information on the presence and molecular diversity of E. bieneusi in livestock and wildlife in Spain is limited. Therefore, the occurrence of this microsporidia was investigated in sympatric extensively reared Iberian pigs (n = 186) and free ranging wild boars (n = 142) in the province of Cordoba, Southern Spain. Forty-two Iberian pigs (22.6%) and three wild boars (2.1%) were found E. bieneusi positive by PCR. In Iberian pigs, occurrence of E. bieneusi was significantly higher in sows than in fattening pigs (31.6% vs. 11.4%; p = .001). Five genotypes were identified in Iberian pigs, four previously reported (EbpA, PigEb4, O, Pig HN-II) and a novel genotype (named PigSpEb1), while only two genotypes were identified in wild boars, EbpA and novel genotype PigSpEb1. All five genotypes identified belong to Group 1 suggesting zoonotic potential. This study constitutes the first report on the occurrence and molecular characterization of E. bieneusi in Iberian pigs and wild boars. The identification of two genotypes with zoonotic potential in sympatric Iberian pigs and wild boars suggests that E. bieneusi can be potentially transmitted between those two hosts, but also implies that they may act as natural sources of microsporidia infection to other hosts including humans.

This review focuses on the milestones and challenges of precision medicine in the natural history of HCV infection.The manuscript summarizes the genetic and viral factors identified as predictive o...

Enteropathogenic parasites can infect a wide range of mammals, including humans, supposing an important zoonotic risk. Hepatitis E virus (HEV) is an emerging foodborne pathogen of increasing public health relevance, affecting both human and animal populations. Because both microorganisms share faecal-oral transmission route they may constitute an excellent model to evaluate the interplay between them. Thus, we aim to evaluate the viral-parasite interactions at the enteric interface in swine. We included pigs of two different breeds farming in South Spain under different production systems. We compared the HEV prevalence by the presence of Giardia duodenalis, Cryptosporidium spp., Balantioides coli, Blastocystis sp., and Enterocytozoon bieneusi in faecal samples. The HEV prevalence was 13.1 (62 out 475, 95% CI: 10.2-16.4). Those pigs infected with Cryptosporidium spp. showed a higher prevalence of HEV (30.8% vs. 12%; p = 0.012). In the same way, animals bearing E. bieneusi seem to have a higher rate of HEV infection (24.2% vs. 12.2%; p = 0.06). According to their location in the gut, animals bearing intracellular enteroparasites showed a higher HEV prevalence than those uninfected (29.6% vs. 12.7%; p = 0.038), meanwhile those carrying extracellular enteroparasites had a lower likelihood to be infected by HEV than those uninfected (12.1% vs. 23.1%; p = 0.071). Those animals bearing both type of enteroparasites showed a similar prevalence of HEV infection than those exhibiting negative for both (20.8% vs. 26.1%; p = 0.763). Our study provides evidence that intracellular and extracellular enteroparasites modulate the susceptibility to HEV infection in pigs. Meanwhile, the presence of extracellular enteroparasites shows a protective effect on the risk of HEV acquisition in swine, whereas intracellular enteroparasites seems to have the opposite effect, favouring the HEV infection. This article is protected by copyright. All rights reserved.

The objective was to evaluate the accuracy of a single determination of IgM antibodies for hepatitis E virus (HEV) diagnosis in patients with acute hepatitis. A prospective study included patients with suspicion of HEV infection, defined as individuals with acute hepatitis showing negative results for serological and molecular markers of other hepatitis viruses. All patients were evaluated for hepatitis E virus infection, including both IgM antibodies and viral RNA determinations. Hepatitis E virus infection was defined as positivity for any of these markers. A total of 182 patients were included in the study, of whom 68 (37.4%) were diagnosed with HEV infection. Of these, 29 (42.6%) were positive for both IgM and HEV RNA, 25 (36.8%) were positive only for IgM antibodies, and 14 (20.6%) were positive only for HEV RNA. Considering only those individuals who were positive for IgM antibodies, 54 of the 68 total cases (79.4%) could be identified, showing a percentage of false-negative individuals of 20.6%. The diagnostic algorithm of hepatitis E virus infection in patients with acute hepatitis should include the determination of both IgM antibodies and HEV RNA because single sampling for IgM antibody determination led to an important proportion of misdiagnosed cases., This work was supported by the Ministerio de Sanidad (RD12/0017/0012) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (research project grant number PI19/00864); and the Red de Investigación en SIDA de España ISCIII-RETIC (grant number RD16/0025/0034). A.R.-J. is the recipient of a Miguel Servet research contract by the Ministerio de Ciencia, Promoción, y Universidades of Spain (CP18/00111). M.F. is the recipient of a Sara Borrell research contract program by the Ministerio de Ciencia, Promoción, y Universidades of Spain (CD18/00091). A.R. is the beneficiary of Contratos para la Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud by the Ministerio de Ciencia, Promoción, y Universidades of Spain (INT20-00028).

GEHEP-004 Study Group: María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Óscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau., [Background & Aims] Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available., [Methods] GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded., [Results] A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin., [Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited., [Lay summary] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations., This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040), Fundación Progreso y Salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).

Background & Aims People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. Methods The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. Results Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%–96%) never injectors, 673 (92%, 95% CI 89%–93%) PWID not on OAT and 177 (89%, 95% CI 83%–92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p Conclusions HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. Lay summary Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

Hepatitis E virus (HEV) represents a major health problem worldwide. As the course of HEV cases is often subclinical, asymptomatic infections could represent an important source of viral spread and infection via routes such as blood donations. Before universal screening for HEV in blood donations can be implemented, studies evaluating the incidence of infection are needed to establish the potential risk of viral transmission. This is a prospective longitudinal study that included blood donors recruited at the Hospital de Ciudad Real Transfusion Service between October 2017 and January 2018. Pools of eight donations were tested for HEV viremia by PCR. Positive pools were individually evaluated following the same procedure. Positive samples were tested for anti-HEV IgG and IgM. Recipients of blood transfusions obtained from HEV-positive donors were retrospectively evaluated. The prevalence of HEV was calculated. A total of 11 313 healthy donors were analysed during the study period. Four blood donations from four different donors were HEV RNA-reactive. The prevalence of HEV infection was 0.035% (95% CI: 0.01%-0.09%), which meant a ratio of one positive donation per 2828 donations. All donors were negative for anti-HEV IgM at the time of the donation. Five patients received transfusions from HEV-positive blood donations, none of them showed an increase in alanine aminotransferase levels after transfusion. In conclusion, our study found a high prevalence of HEV infection in blood donors from south-central Spain. In view of the prevalence, Spanish blood banks should carefully consider including screening for HEV.

Background The dataset from genes used to predict hepatitis C virus outcome was evaluated in a previous study using a conventional statistical methodology. Objective The aim of this study was to reanalyze this same dataset using the data mining approach in order to find models that improve the classification accuracy of the genes studied. Methods We built predictive models using different subsets of factors, selected according to their importance in predicting patient classification. We then evaluated each independent model and also a combination of them, leading to a better predictive model. Results Our data mining approach identified genetic patterns that escaped detection using conventional statistics. More specifically, the partial decision trees and ensemble models increased the classification accuracy of hepatitis C virus outcome compared with conventional methods. Conclusions Data mining can be used more extensively in biomedicine, facilitating knowledge building and management of human diseases.

The objective of this study was to design a pangenotypic PCR-based assay for the detection and quantification of hepatitis E virus (HEV) RNA from across the entire spectrum of described genotypes belonging to the Orthohepevirus A genus. The optimal conditions and the performance of the assay were determined by testing the WHO standard strain (6219/10) and the WHO HEV panel (8578/13). Similarly, performance comparisons were made with two commercial assays (Real Star HEV RT-PCR 2.0 and ampliCube HEV 2.0 Quant) to detect HEV RNA at concentrations below 1,000 IU/mL with viral strains from the WHO and to test samples from 54 patients with acute hepatitis. The assay presented in this study was able to detect the entire spectrum of described genotypes belonging to the Orthohepevirus A genus, demonstrating a better performance than both commercial kits. This procedure may represent a significant improvement in the molecular diagnosis of HEV infection.

This article belongs to the Special Issue Wildlife Diseases., The hepatitis E virus (HEV) is an emerging zoonotic pathogen whose main reservoir is suids. Most of the ecological and epidemiological aspects of its sylvatic cycle remain unknown. Thus, in this work, we study the drivers of HEV exposure in the wild boar population of Doñana National Park (DNP, southwest Spain) operating in the medium and long-term (2005–2018). Anti-HEV antibodies are widely distributed throughout the wild boar (46.7 ± 3.8%, 327 out of 700 sampled), showing a statistically significant age-increasing pattern. The temporal pattern displayed important interannual fluctuations. This could be mediated by marked variations in the population control of the wild boar, and subsequent changes in abundance rates, and its interplay with climatic conditions; as wet years together with a low abundance of wild boar led to the lowest seroprevalence. The fact that seroprevalence is high during conditions of high abundance, and not affected by rainfall level, is probably due to the increased interactions among the animals, and possibly, the subsequent higher environmental contamination with HEV particles. The proximity to the marshland (the main water body of the study area) is associated with a higher risk of testing positive, which is probably mediated by the preferential use of this area during the dry season and the favourable environmental conditions for the survival of HEV particles. A deeper understanding of the epidemiology of HEV in host communities deserves future research concerning other susceptible species. Most importantly, wild boar population control remains a challenge at the international level, and an increase of shared pathogen-related conflicts associated with this species is expected, as exemplified by HEV. Therefore, surveillance of wild boar diseases, including integrated population monitoring and sustainable population control programmes, will be essential to control the associated risks., This research was funded by the Ministerio de Economía y Competitividad (MINECO; AEI/FEDER, UE; AGL2016-76358-R). S.J. is co-supported by the UCLM and the European Social Fund (2018/12504). J.C. received support from the Ministerio de Ciencia, Innovación y Universidades (FPU/17/01319). A.R.J. is the recipient of a Miguel Servet Research Contract by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00111).

[Background] Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015–2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling., [Methods] A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall., [Results] Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030., [Conclusion] Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk., This study was funded by Gilead Sciences. The funder had no role in the analysis or presentation of the results. NM and AB were additionally supported by the National Institute for Drug Abuse [grant number R01 DA037773]. NM and BS had partial support from the University of California San Diego Center for AIDS Research (CFAR), a National Institute of Health (NIH) funded program [grant number P30 AI036214] which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA NIGMS, and NIDDK. NM was supported by the National Institute of Allergy and Infectious Diseases and National Institue for Drug Abuse [grant number R01 AI147490], and BS was supported by the National Institute for Drug Abuse [grant number K01DA049665]. This work was also supported by the Ministerio de Sanidad (RD12/0017/0012) integrated in the Plan Nacional de I + D + I, and cofinanced by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI15/01017), and the Red de Investigación en SIDA de España ISCIII-RETIC (grant number: RD16/0025/0034).

BackgroundRibavirin (RBV) is been used for SARS-CoV-2 infection. This drug is associated with a wide range of side effects, mainly anemia, so its use in patients with potential respiratory affectation could not be appropriate. The evidences of adverse events associated with RBV-use has mainly been derived in the context of hepatitis C (HCV) treatment, however the possible use of RBV in CoVID-19 patients could be limited to 14 days.MethodsLongitudinal study including HIV/HCV coinfected patients. We evaluate the hemoglobin dynamics and reductions as well as evaluate the development rate of anemia during the first 2 weeks of therapy in HCV infected patients.Results189 patients were included in the study. The median hemoglobin levels were 14.6 g/dL (IQR: 13.2-15.6 g/dL) and 13.5 g/dL (IQR: 12.3-14.5 g/dL) at weeks 1 and 2 of therapy, respectively. A cumulative number of 27 (14.2%) patients developed anemia (23 grade 1 [12.1%] and 4 grade 2 [2.1%]). We identify a baseline hemoglobin levels of 14 g/dL as the better cut-off to identify those patients with a high chance to develop anemia. Of the 132 patients with baseline hemoglobin level >14 g/dL, 8 developed anemia (6.1%) compared with 19 of 57 (33.3%) with hemoglobin levels lower than 14 g/dL (p < 0.001).ConclusionsOur study shows valuable information about the early hemoglobin kinetic timing in patients on RBV-therapy, that could be useful to tailor CoVID-19 treatment if RBV use is considered.

Introduction The hepatitis E virus (HEV) is the leading cause of acute hepatitis around the world. In recent years, knowledge has increased concerning extrahepatic manifestations caused by HEV, including neurological manifestations such as Parsonage-Turner syndrome (PTS). PTS is characterized by severe shoulder or arm pain and patchy paresis with muscle weakness. The aim of the present study was to assess the association between HEV and PTS. Materials and Methods We reported two cases of PTS associated with HEV, which were diagnosed in a short period of time in the same village. PTS was diagnosed by physical examination and electrophysiological studies, and serology testing for IgM, low-avidity IgG, and RNA of HEV established the diagnosis of acute HEV infection. Results A 44-year-old man who presented cervicobrachial pain accompanied by paresthesia, dyspnea, and isolated derangement of liver enzymes and 57-year-old women with cervical pain radiated to upper limbs, paresthesia, and liver cytolysis, although, this patient was initially diagnosed as having drug-induced hepatitis. Finally, the diagnosis was Parsonage- Turner syndrome associated with hepatitis e virus. In both patients, symptoms were bilateral and they required hospital admission. Both consumed vegetables are grown in a local patch and the phylogenetic analysis showed genotype 3f. Then, we reviewed the literature on PTS and HEV and we found 62 previously described cases that were more likely to be men (86.20 %) with more frequent bilateral symptoms (85.71 %). Genotype 3 is the most commonly associated. Three of those cases were diagnosed in Spain. Conclusions According to our findings, HEV should be considered in patients with neuralgic amyotrophy, including those with the absence of liver cytolysis.

Background Several studies have independently evaluated the occurrence of hepatitis E virus (HEV) and enteroparasites in swine, but no surveys have been conducted to jointly assess the prevalence and genetic diversity of enteroparasites in pigs and wild boars, their sympatric transmission between hosts, and their potential interaction with HEV. Methods We prospectively collected serum and faecal samples from black Iberian domestic pigs and wild boars from southern Spain between 2015‒2016. We evaluated for HEV in serum and faeces, and for the presence of enteroparasites (Giardia duodenalis, Cryptosporidium spp., Blastocystis sp., Neobalantidium coli and Strongyloides spp.) in the same faecal samples. The prevalence of each intestinal parasite species was calculated. Results A total of 328 animals (56.7% black Iberian pigs and 43.3% wild boars) were included in the study. The overall global prevalence of HEV in serum was 16.8%. The overall global prevalence of each enteroparasite species was 19.5% for G. duodenalis, 8.2% for Cryptosporidium spp., 41.8% for Blastocystis sp., 31.4% for N. coli, and 8.8% for Strongyloides spp. HEV-infected animals showed a significantly lower prevalence of G. duodenalis (3.2 vs 20%; P = 0.002) and Blastocystis sp. (38.7 vs 80%; P G. duodenalis and Blastocystis sp. infections showed a significantly lower rate of HEV infection than those not harbouring these enteroparasites (P Conclusions Our study found a high prevalence of enteroparasites in black Iberian pigs and wild boars in southern Spain, suggesting a sympatric co-transmission of some of the species investigated. It is suggested that extracellular G. duodenalis and Blastocystis sp. might have a protective effect on HEV acquisition in swine.

Hepatitis E virus (HEV) is a major causative agent of acute viral hepatitis in many regions of the world including Africa. In Cameroon, there is no published molecular study on HEV in humans. However, based on serological assays, the first outbreak of HEV was detected in North-Cameroon. The objective of this study was to determine the molecular characterization of HEV that circulated during this period. A retrospective study design was used to select serum samples among those collected during the outbreak period. immunoglobulin M positive samples available in sufficient volumes to amplify HEV RNA were selected. RNA was extracted and then amplified by a real-time reverse transcription polymerase chain reaction (real time RT-PCR) assay, followed by a nested reverse transcription polymerase chain reaction (nested RT-PCR) assay for sequencing and phylogenetic analysis. Overall, 24 samples were selected and HEV RNA was amplified by real-time RT-PCR in 20 samples. Amongst these, 12 samples were positive for HEV RNA by nested RT-PCR and yielded good sequencing products. Phylogenetic analysis showed that 10 samples clustered with HEV genotype 1 (subtype 1e) and two samples clustered with HEV genotype 3 (subtype 3f). This study fills the gap of knowledge on the molecular epidemiology of HEV in Cameroon and confirms the first report of the hepatitis E outbreak in North-Cameroon.

[Background]: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself., [Aim]: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients., [Methods]: Multicenter cohort study (1999–2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed., [Results]: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1–Q3) follow-up of 11 (3–31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88–2.78; P = 0.12]., [Conclusion]: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage.

This review will summarize the role of pharmacogenetics in the natural history of hepatitis C, particularly in patients with HIV/HCV and will take the perspective of pharmacogenetics and its influence on the response to antiviral therapy and the susceptibility to develop adverse effects. This review will also devote a section to host genetics in other clinical situations, such as disease progression and acute HCV infection, which may determine whether treatment of HIV-/HCV-coinfected patients is implemented or deferred.

HEPAVIR-Cirrhosis Study Group., [Objectives] To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis., [Methods] This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence., [Results] The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27–84) months, 22 (4.4%; 95% CI 2.6–6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06–1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14–0.85) per 100 PY whereas it was 1.79 (1.11–2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12–0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070–0.991; P = 0.049)., [Conclusions] SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis., This study was supported by grants from the Consejería de Salud de la Junta de Andalucía (PI-0014/2014), the Servicio Andaluz de Salud (grant number SAS/111239) and the Fondo de Investigaciones Sanitarias ISCIII (grant number PI13/01621 and PI16/01443). J. A. P. is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS). In addition, this work has been partially funded by the Spanish AIDS Research Network RD16/0025/0010 as part of the Plan Nacional R + D+I and cofinanced by ISCIII Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).

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.

Background It has been shown that wildlife can serve as natural reservoirs of hepatitis E virus (HEV). The wild boar (Sus scrofa) is probably the main natural reservoir of HEV and could therefore represent an important route of transmission in Europe, especially in regions where game meat is widely consumed. We evaluated the prevalence of HEV infection in wild boar in the south of Spain, with the aim of identifying associated risk factors. A cross-sectional study that included hunted wild boar was carried out during the 2015/2016 hunting season (October 15 to February 15) in Andalusia (southern Spain). The outcome variable was HEV infection, defined as amplification of HEV RNA in serum by RT-PCR. Results A total of 142 animals, selected from 12 hunting areas, were included and formed the study population. Thirty-three wild boars (23.2%; 95% CI: 16.8%–30.7%) were positive for HEV infection. Prevalence peaked in October and November, then gradually declined until the end of December. After multivariate analysis, only hunting date was independently associated with HEV infection across sex and age. Conclusions Our study found a relatively high prevalence of HEV infection in wild boar in the south of Spain, suggesting that prevalence may depend on the season when the animal is hunted. In consequence, the potential risk of zoonotic transmission could fluctuate.

The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5, and 6. Following approval in 2016, new pharmacokinetic and pharmacodynamic data were reported, which led to important clinical applications. Areas covered: This review provides a summary of the pharmacokinetics, pharmacodynamics, efficacy and safety of SOF/VEL therapy for treatment of HCV infection. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion and antiviral activity strategies, such as clinical dose selection and treatment duration. Expert opinion: This novel combination therapy containing 400 mg of SOF plus 100 mg of VEL, taken orally, once daily, with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. SOF/VEL achieved very high rates of sustained virological response in treatment-naive and treatment-experienced patients with chronic HCV genotype 1-6 infection, including those with compensated cirrhosis or HIV-1 co-infection.

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 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.

Hepatitis E virus (HEV) infection is the most common cause of acute hepatitis in the world. It is not well established whether people infected with the human immunodeficiency virus (HIV) are more susceptible to infection with HEV than people not infected with HIV. Many studies have evaluated this relationship, although none are conclusive. The aim of this systematic review and meta-analysis was to assess whether patients with HIV infection constitute a risk group for HEV infection. A systematic review and meta-analysis was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), to find publications comparing HEV seroprevalences among HIV infected and uninfected populations. The analysis was matched by sex, age and geographical area, and compared patients who live with HIV and HIV-negative individuals. The odds ratio (OR) for patients with HIV was 0.87 (95% CI: 0.74–1.03) in the fixed effects meta-analysis and 0.88 (95% CI: 0.70–1.11) in random effects, with I2 = 47%. This study did not show that HIV infection was a risk factor for HEV infection when compared with those who are HIV-negative.

In recent decades, cases of autochthonous hepatitis E (HE) have sharply increased in European countries where foodborne transmission is considered the main route of HE virus (HEV) transmission. Although rabbits are considered the main reservoir of the zoonotic HEV‐3ra subtype, information on the role of wild lagomorphs in the epidemiology of HEV remains scarce. The aim of this study therefore was to assess the circulation of HEV in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis), the most important lagomorph species in Spanish Mediterranean ecosystems. Liver samples from 372 wild rabbits and 78 Iberian hares were analysed using a broad‐spectrum RT‐PCR that detects HEV genotypes 1–8. None of the 450 lagomorphs tested were positive for HEV infection. To the best of our knowledge, this is the first study to assess HEV circulation in wild rabbits in Spain and the first to evaluate HEV infection in Iberian hares. Our results indicate absence of HEV circulation in wild rabbits and Iberian hares in southern Spain during the study period, which suggests that the risk of transmission of HEV from wild lagomorphs to other species, including humans, is low., This work was supported by the Ministerio de Sanidad (RD12/0017/0012) integrated in the Plan Nacional de I+D+I and cofinanced by the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI16/01297) and Fundación Progreso y Salud de la Junta de Andalucía (PIN‐0477‐2017). J. Caballero‐Gómez is supported by an FPU grant from the Spanish Ministry of Education, Culture and Sport (FPU17/01319) and S. Jiménez‐Ruiz holds a PhD contract from the UCLM co‐supported by the European Social Fund (2018/12504). A. Rivero Juárez and M. Frías are the recipient of a Miguel Servet and Sara Borrell postdoctoral perfection grants by the Ministerio de Ciencia, Innovación y Universidades of Spain (CP18/00111) and (CD18/00091), respectively.

[Background] A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high‐penetrance common allele., [Objective] To explore whether low susceptibility to HCV infection is mainly driven by a high‐penetrance common allele., [Methods] In this genome‐wide association study (GWAS), a total of 804 HCV‐seropositive individuals and 27 high‐risk HCV‐seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)‐based and gene‐based association analyses respectively., [Results] No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925‐C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925‐C carriers in the HCV‐seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04‐11.58; and 24 out of 27 [88.9%] rs688‐T carriers in the HRSN group vs 556 of 804 [69.1%] rs688‐T carriers in the HCV‐seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65‐11.96)., [Conclusions] Low susceptibility to HCV infection does not seem to be mainly driven by a high‐penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved., This work was supported by grants from the Grupo de Estudio de Hepatitis Víricas from the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEHEP‐SEIMC) (GEHEP‐012), Consejería de Salud de la Junta de Andalucía (PI‐0001/2017), Plan Nacional de I+D+I cofinanced by ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) (www.red.es/redes/inicio) (RD16/0025/0040, RD12/0017/0012) and the Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de Hacer Europa”) (PI13/02434 and PI16/01861). LMR and JM are the recipients of grants from the Servicio Andaluz de Salud de la Junta de Andalucía (C‐0009‐2015 and B‐0037 respectively). ARJ and AGS are the recipient of Miguel Servet Research Contracts by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00111 and CP18/00146 respectively). JAP has received a research extension grant from the Programa de Intensificación de la Actividad de Investigación del Servicio Nacional de Salud Carlos III (I3SNS).

Background The hepatitis E virus (HEV) represents a major cause of acute hepatitis worldwide. The majority of HEV cases occur in low-income countries, mainly Asia and Africa, where HEV causes large outbreaks associated with the consumption of contaminated water and high mortality in specific populations. In high-income countries, HEV infection is considered a zoonotic disease that is linked to the consumption of contaminated food. Although a high proportion of cases have self-limiting asymptomatic or subclinical infections, immunosuppression may modify the pathogenesis and clinical impact of this emerging disease. Results and discussion Here, we review the current knowledge about the epidemiology, diagnosis, clinical manifestations, management and prevention of HEV infection in HIV-infected subjects. Conclusions Despite the increasing knowledge about the pathogenesis, epidemiology and clinical impact of HEV infection, several major factors are faced by HIV-infected patients, including treatment recommendations, immunization and risk practices.

GEHEP 012 study group., Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17–1.75] relative-units [ru] versus 1.71 [1.00–2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA., This work was supported by grants from the Consejería de Salud de la Junta de Andalucía (PI-0001/2017), the Grupo de Estudio de Hepatitis Víricas from the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEHEP-SEIMC) (GEHEP-012), the Plan Nacional de I + D + I cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) (www.red.es/redes/inicio) (RD16/0025/0040, RD12/0017/0012), the Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER- “Una manera de Hacer Europa”) (PI13/02434 and PI16/01861), the Ministerio de Economía Industria y Competitividad (SAF2016–8015-R), Fundación Bancaria “La Caixa” and Grifols SA (GR@ACE project). LMR and JM are the recipients of grants from the Servicio Andaluz de Salud de la Junta de Andalucía (C-0009-2015 and B-0037, respectively). JAP has received a research extension grant from the Programa de Intensificación de la Actividad de Investigación del Servicio Nacional de Salud Carlos III (I3SNS).

Background] Various recent outbreaks of hepatitis A virus (HAV) have been described in men who have sex with men despite the availability of an effective vaccine. This study aimed to determine the current rates of seroconversion after receiving HAV vaccine (HAV-V) in HIV-infected patients under real-life conditions. Setting: Patients were selected from a Southern Spanish multicentric cohort of HIV-infected subjects. Methods: Retrospective analysis of all patients who received 2 doses (standard scheme) from April 2008 to May 2016 or from June 2016 to February 2018 facing an HAV outbreak with shortage of HAV-V, 1 single dose of HAV-V. Response to HAV-V was defined as positive anti-HAV IgG between 1 and 12 months after the last vaccination dose. Results: A total of 522 patients were included, mainly men who have sex with men (86.2%). In the standard-dose group, 303/343 [88.3%; 95% confidence interval (CI): 84.5 to 91.5] patients showed seroconversion as compared with 149/179 (83.2%; 95% CI: 76.9 to 88.4) of the single-dose group (P = 0.107). Undetectable baseline HIV-RNA (adjusted odds ratio: 4.86; 95% CI: 1.86 to 12.75; P = 0.001) and a CD4+ T-cell count ≥350/μL (adjusted odds ratio, 3.96; 95% CI: 1.26 to 12.49; P = 0.019) were independently associated with response to both regimens. A higher CD4/CD8+ ratio was also associated with response after a single dose. Conclusions: HIV-infected patients should be encouraged to undergo HAV-V with 2 standard doses 6 months apart; a single dose achieves a high rate of seroconversion in those patients with favorable response factors and may be enough to limit future outbreaks in case of HAV-V shortage until supply is reestablished., [Setting] Patients were selected from a Southern Spanish multicentric cohort of HIV-infected subjects., [Methods] Retrospective analysis of all patients who received 2 doses (standard scheme) from April 2008 to May 2016 or from June 2016 to February 2018 facing an HAV outbreak with shortage of HAV-V, 1 single dose of HAV-V. Response to HAV-V was defined as positive anti-HAV IgG between 1 and 12 months after the last vaccination dose., [Results] A total of 522 patients were included, mainly men who have sex with men (86.2%). In the standard-dose group, 303/343 [88.3%; 95% confidence interval (CI): 84.5 to 91.5] patients showed seroconversion as compared with 149/179 (83.2%; 95% CI: 76.9 to 88.4) of the single-dose group (P = 0.107). Undetectable baseline HIV-RNA (adjusted odds ratio: 4.86; 95% CI: 1.86 to 12.75; P = 0.001) and a CD4+ T-cell count ≥350/μL (adjusted odds ratio, 3.96; 95% CI: 1.26 to 12.49; P = 0.019) were independently associated with response to both regimens. A higher CD4/CD8+ ratio was also associated with response after a single dose., [Conclusions] HIV-infected patients should be encouraged to undergo HAV-V with 2 standard doses 6 months apart; a single dose achieves a high rate of seroconversion in those patients with favorable response factors and may be enough to limit future outbreaks in case of HAV-V shortage until supply is reestablished.

[Background] Reducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a)., [Aim] Our aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to halt the HCV1a epidemic in Spain., [Methods] Epidemiological links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected between 2014 and 2016, and 1,317, 1,291 and 1,009 samples collected abroad between 1989 and 2016 were reconstructed using sequences covering the NS3, NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to a flexible Bayesian discrete phylogeographic inference method., [Results] The transmission network structure of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively from North America and European countries. The latter became increasingly relevant and have dominated in recent times. Export from Spain to other countries in Europe was also strongly supported, although Spain was a net sink for European HCV1a lineages. Spatial reconstructions showed that the epidemic in Spain is diffuse, without large, dominant within-country networks., [Conclusion] To boost the effectiveness of local intervention efforts, concerted supra-national strategies to control HCV1a transmission are needed, with a strong focus on the most important drivers of ongoing transmission, i.e. PWID and other high-risk populations., Bram Vrancken is a postdoctoral research fellow funded by the Research Foundation Flanders - Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO, Flanders, Belgium). Part of this research was sponsored by FWO grants G.0E84.16N, G.0B23.17N, G.0662.15N, G.0D51.17N and G.0B93.17N. Funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS) has been used for this study. A part of the computational resources and services used in this work were provided by the Hercules Foundation and the Flemish Government - department EWI-FWO Krediet aan Navorsers (Theys, KAN2012 1.2.249.12). This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.red.es/redes/inicio) (RD16/0025/0040), Fundación Progreso y salud, Junta de Andalucía (www.fps2.junta-andalucia.es/fundacionprogresoysalud/es/home) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004 and GEHEP-005).

An interferon λ4 gene (IFNL4) knockout allele (rs368234815; TT) is associated with spontaneous and IFN-α-dependent cure of hepatitis C virus infection. The role of this polymorphism in the susceptibility to human immunodeficiency virus type 1 (HIV-1) infection is controversial. This study aimed to assess the association of this knockout IFNL4 variant and sexually transmitted HIV-1 infection. A total of 228 HIV-1-positive individuals and 136 HIV-exposed seronegative individuals were investigated for their association with IFNL4 rs368234815 genotypes. The IFNL4 ΔG functional allele is associated with increased susceptibility to HIV-1 infection through the sexual route (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6; P = .004). A meta-analysis including a population of injection drug users suggests a codominant mode of inheritance of this risk factor (OR, 2.0; 95% CI, 1.3-3.2; P = .001).

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that has been detected in different animal species. A survey study was carried out to assess HEV infection in non‐human primates (NHPs) housed in zoos in Spain. Anti‐HEV antibodies were detected in eight of the 181 NHPs tested (4.4%; 95%CI: 1.4–7.4). At least one seropositive animal was detected in five of the 33 species sampled (15.2%). This is the first report of seropositivity in black‐and‐white ruffed lemurs (Varecia variegata ), common chimpanzees (Pan troglodytes ), and Barbary macaques (Macaca sylvanus ). Anti‐HEV antibodies were found in six of the eight zoos included in the study (75.0%). Seroconversion was detected in one chimpanzee, which confirms HEV circulation in one zoo between 2015 and 2016. Seropositivity was significantly higher in hominids than in other NHP families. HEV RNA was not detected in any of the serum samples tested. The results indicate susceptibility of NHPs to HEV infection. Further studies are required to elucidate the role of these species in the epidemiology of HEV., This work was partially supported by the Ministerio de Sanidad (RD12/0017/0012) included in the Plan Nacional de I+D+I and cofinanced by the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI16/01297) and the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). J. Caballero‐Gómez is supported by the FPU grant of the Spanish Ministry of Education, Culture and Sport (FPU17/01319). A. Rivero Juarez and M. Frias are the recipients of a Miguel Servet and Sara Borrell post‐doctoral perfection grants by the Ministerio de Ciencia, Innovación y Universidades of Spain (CP18/00111 and CD18/00091, respectively).

On behalf of the GEHEP-002 Study Group., [Objective]: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients., [Methods]: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of ‘ultrasound lack of detection’, defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of ‘surveillance failure’, defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used., [Results]: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038)., [Conclusion]: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis., The current study was supported by grants from the Consejería de Salud de la Junta de Andalucía (PI-0014/2014), the Servicio Andaluz de Salud (grant number SAS/111239) and the Fondo de Investigaciones Sanitarias ISCIII (grant number PI13/01621) and Project ‘PI16/01443’, funded by Instituto de Salud Carlos III, integrated in the national I+D+i 2013–2016 and co-funded by European Union (ERDF/ESF, ‘Investing in your future’). J.A.P. is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS). Besides, this work has been partially funded by the Grupo para el Estudio de las Hepatitis Víricas (GEHEP) de la SEIMC (2017 grant to project GEHEP-002 and 2018 grant to project GEHEP-002), the SPANISH AIDS Research Network RD16/0025/0010 as part of the Plan Nacional R+D+I and cofinanced by ISCIII Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).