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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.

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...

The hepatitis E virus (HEV) is the main cause of viral acute hepatitis in the world, affecting more than 20 million people annually. During the acute phase of infection, HEV can be detected in various body fluids, which has a significant impact in terms of transmission, diagnosis or extrahepatic manifestations. Several studies have isolated HEV in the genitourinary tract of humans and animals, which could have important clinical and epidemiological implications. So, our main objective was to evaluate the presence of HEV in testis of naturally infected wild boars (Sus scrofa). For it, blood, liver, hepatic lymph node and testicle samples were collected from 191 male wild boars. The presence of HEV was evaluated in serum by PCR, as well as in tissues by PCR and immunohistochemistry. Four animals (2.09%; 95%CI: 0.82–5.26) showed detectable HEV RNA in serum, being confirmed the presence of HEV-3f genotype in three of them by phylogenetic analysis. HEV was also detected in liver and/or hepatic lymph nodes of the four animals by RT-PCR, as well as by immunohistochemistry analysis. Only one of these wild boars also showed detectable viral load in testis, observing HEV-specific labelling in a small number of fibroblasts and some Sertoli cells. Our results confirm the presence of HEV genotype 3 in naturally infected wild boar testis, although no associated tissue damage was evidenced. This study does not allow us to discard semen as a possible source of HEV transmission in suids. Future experimental studies are necessary to evaluate the impact of HEV genotype 3 on fertility and the possibility of transmission through sexual contact in this specie., 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 (PI19/00864 and PI21/00793), and Fundación Progreso y Salud de la Junta de Andalucía (PI-0287-2019). ARJ is the recipient of a Miguel Servet Research Contract by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00111). MF is the recipient of a Sara Borrell contract by the Ministerio de Ciencia, Promoción y Universidades of Spain (CD18/00091). JCG and IAR are supported by a FPU grant from the Spanish Ministry of Education, Culture and Sport (FPU17/01319 and FPU19/03969, respectively). SJR holds a PhD contract from the UCLM co-supported by the European Social Fund (2018/12504). DJM holds a I+D+I contract from the UCO co-supported by the European Social Fund.

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.

Numerous protist species are shared between humans and pigs. Among those, Giardia duodenalis, Cryptosporidium spp. and Balantioides coli have a clear public and animal health significance. For others such as Enterocytozoon bieneusi and Blastocystis sp., their impact on animal health has not been fully established. Little information is currently available on the molecular diversity of these protists in swine populations. To fill this gap, we molecularly assessed G. duodenalis, Cryptosporidium spp., B. coli, Blastocystis sp. and E. bieneusi in faecal samples from Iberian and Large White pigs raised under different (intensive and/or extensive) management systems in southern Spain. A total of 151 extensively raised Iberian pigs, 140 intensively raised Iberian pigs, and 184 intensively raised Large White pigs were investigated. Blastocystis sp. was the agent most prevalently found (47.8%), followed by B. coli (45.5%), G. duodenalis (10.7%), E. bieneusi (6.9%), and Cryptosporidium spp. (5.5%). Blastocystis sp. was significantly less prevalent in intensively raised Iberian pigs (22.9%) than in their extensively raised counterparts (51.0%) or in intensively raised Large White pigs (64.1%). A significantly higher prevalence was found for G. duodenalis, Cryptosporidium spp., and E. bieneusi in Large White pigs than Iberian pigs. Balantioides coli was similarly distributed (40.0-51.1%) in all three investigated swine populations. Sequence analyses revealed the presence of G. duodenalis assemblage E, two Cryptosporidium species (Cryptosporidium scrofarum and Cryptosporidium suis), B. coli (genotypes A and B), Blastocystis sp. (ST1, ST3, and ST5), and E. bieneusi (EbpA, EbpC, EbpD, O, and a novel genotype named PigSpEb2). Novel genotype PigSpEb2 was found alone or in combination with EbpA. Data suggest a widespread exposure to protist enteroparasites in domestic pig populations irrespectively of breed and raising management system. Many of the species/genotypes identified have a zoonotic potential and might represent a public health concern.

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).

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.

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.

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 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.

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.

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.

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).

Wild boar (Sus scrofa ) is considered as the main wildlife reservoir of zoonotic hepatitis E virus (HEV) genotypes. The aim of this study was to evaluate the circulation of HEV in free‐ranging wild boar in the Doñana National Park (DNP), Spain. Blood samples were collected from 99 wild boar in the DNP during 2015. Sera were analysed in parallel using indirect ELISA and real‐time RT‐PCR. A total of 57 of the 99 tested animals (57.6%; 95%CI: 47.8%–67.3%) had anti‐HEV antibodies, indicating that this virus is widespread in wild boar in the DNP. HEV RNA was detected in one animal and phylogenetic analysis showed that the sequence isolated belonged to subtype 3r. The results suggest a potential risk of zoonotic transmission of this novel HEV‐3 subtype, which could be of public health concern. Further studies are required to assess the role of wild boar in the epidemiology of HEV‐3r and to determine the infectivity of this emergent HEV subtype in other species, including humans., This work was partially supported by the Ministerio de Sanidad (RD12/0017/0012) included in the Plan Nacional de I+D+I and co‐financed by the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI16/01297), the ISCIII‐Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and the Spanish Ministry of Economy and Competitiveness (MINECO) (AGL2016‐76358‐R). J. Caballero‐Gómez is supported by the FPU grant of the Spanish Ministry of Education, Culture and Sport (FPU17/01319). J.A. Barasona is supported by MINECO‐UCM through a “Juan de la Cierva” contract (FJCI‐2015‐23643). A. Rivero‐Juarez is the recipient of a Miguel Servet Research Contract by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00111).

Several studies have reported the persistence of HCV RNA in liver and/or peripheral blood mononuclear cells (PBMCs) in spite of undetectable viremia in patients who have achieved sustained virological response (SVR). This event, defined as occult HCV infection, remains controversial and low titers of persistent virus may be underestimated because it has not yet been analyzed by a highly sensitive test such as droplet digital PCR (ddPCR). This method provides an alternate ultra-sensitive detection technique for very low numbers of copies of viral RNA or DNA. The aim of this study was to evaluate the persistence of HCV in HIV-coinfected patients with long-term SVR using ddPCR. For each patient, the presence of HCV RNA in serum and PBMCs at baseline was determined by nested RT-ddPCR. Patients with HCV RNA in PBMCs at baseline were followed until the end of the study. One hundred and twenty-three patients were analyzed for persistence of HCV RNA in serum and PBMCs. Persistence of HCV was not found in serum in any patient. HCV RNA was detected in PBMCs in one patient (0.81%; 95% CI: 0.04–3.94) and resolved spontaneously during follow-up. Persistence of HCV RNA in PBMCs is not a common event in HIV/HCV co-infected patients with long-term SVR evaluated by RT-ddPCR., This work was supported by the Fundación Progreso y Salud, Consejería de Salud de la Junta de Andalucía (grants for health research projects: refs. PI0036/2010; PI0187/2013), 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). 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.

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-naive 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.

Background Identifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems. Methods Forty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm. Results Twenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (K=1; P Conclusion This non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.

The combination of daclatasvir (DCV), sofosbuvir (SOF), and ribavirin (RBV) is a direct-acting antiviral (DAA) regimen for the treatment of hepatitis C virus (HCV) infection. The inclusion of newer effective DAAs such as SOF and DCV with high efficacy and excellent tolerance introduced a new scenario in HCV infection therapy: high rates of sustained virological response (SVR), shorter therapies, less toxicity, and interferon-free treatments. This combination was approved for the treatment of HCV in treatment-naive or treatment-experienced patients with chronic HCV genotype 1 or 3 infection. Areas covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of DCV plus SOF and RBV therapy in the treatment of HCV infection. The topics include data regarding drug absorption, distribution, metabolism, excretion, and antiviral activity strategies, such as clinical dose selection and treatment duration. Expert opinion: This combination, taken orally with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. DAC/SOF/RBV achieves very high rates of SVR in treatment-naive and treatment-experienced patients with chronic HCV infection, including difficult-to-treat patients such as those with compensated cirrhosis, post-transplant recurrence, or HIV-1 co-infection.

Pigs are considered important reservoirs of HEV and so constitute a major risk of transmission to humans, either via direct contact or by consuming raw or undercooked contaminated pork products. Once the scale of this disease on European pig farms has been estimated, the identification of risk factors associated with HEV infection in these species could help determine contingency strategies to minimize the risk of transmission to humans. Our objective was to evaluate risk factors associated with HEV in pigs under different production systems. We included 1040 pigs from 26 farms. The prevalence of HEV infection in the study population, evaluated by RT-qPCR, was calculated, then studied according to animal and farm characteristics. Factors associated with HEV infection were analyzed by multivariate analysis. One hundred and seventy-two pigs were infected by HEV, which gave an individual prevalence of 16.5% (95% CI: 14.4%–18.9%). Factors associated with higher prevalence of HEV infection were: extensive farming [23.9%; OR = 2.239 (1.036–4.837)], absence of sanitary ford [33.8%; OR = 3.597 (1.649–7.850)], no quarantine period [20.8%; OR = 2.723 (1.450–5.112)], and contact with domestic species [24.5%; OR = 3.893 (1.453–10.431)]. Our evidence showed that pigs reared on extensive farms are at a higher risk of HEV infection than those reared intensively. The use of control measures could reduce the risk of HEV infection in pigs and minimize the risk of zoonotic transmission.

Objective To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy. Design Prospective longitudinal study. Methods HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24. Results The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol. Conclusions Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.

Hepatitis E (HE) is an important emerging disease in European countries. To analyse the role of equids as potential reservoirs for HE virus (HEV), we determined the prevalence of HEV infection in 861 equines from 464 herds in Spain. HEV RNA in serum was detected in 0.4% (3/692) of horses, 1.2% (1/86) of donkeys and 3.6% (3/83) of mules. Phylogenetic analysis identified the zoonotic genotype 3 as being closely related to viral human and swine strains. In this first report on HEV in equids in Europe, we confirm the susceptibility of horses, donkeys and mules to HEV infection. The low prevalence detected indicates that equids may be considered spillover hosts rather than true reservoirs.

Chronic liver disease (CLD) with a variety of causes is currently reported to be one of the main causes of death worldwide. Patients with CLD experience deteriorating liver function and fibrosis, progressing to cirrhosis, chronic hepatic decompensation (CHD), end-stage liver disease (ESLD), and death. Patients may develop acute-on-chronic liver failure (ACLF), typically related to a precipitating event and associated with increased mortality. The objective of this review was to analyze the role of acute hepatitis E virus (HEV) infection in patients with CLD, focusing on the impact of this infection on patient survival and prognosis in several world regions.

Objective Fatty liver disease (FLD) is frequently observed in HIV-infected patients and a cause of advanced liver disease. Genetic factors could play a role in determining risk for FLD development in those patients. The aim of this study was to evaluate the association of those single nucleotide polymorphisms (SNPs) previously found to be related to nonalcoholic FLD by genome-wide association analyses in the general population with the presence of FLD, including steatohepatitis, in HIV-infected individuals. Design This is a transversal study. Methods A total of 431 HIV-infected patients were included in this study. All of them underwent a transient elastography with the controlled attenuation parameter examination and were genotyped for 19 selected SNPs. A controlled attenuation parameter value higher than 238 dB/m was selected to define the presence of FLD. Elevated alanine aminotransferase levels and presence of FLD was considered as a surrogate marker of steatohepatitis. Results A total of 179 (41.5%) individuals showed FLD, including 122 (28.3%) with steatohepatitis. The rs12743824 and rs738491 SNPs were independently associated with FLD and steatohepatitis, respectively. For rs12743824, among 252 individuals without FLD, 182 (72.2%) were A-allele carriers vs. 111 (62%) of 179 patients with this disease (multivariate P = 0.006; adjusted odds ratio = 0.51; 95% confidence interval = 0.33-0.83). For rs738491, 20 (16.4%) of 122 patients with steatohepatitis were TT carriers vs. 18 (5.8%) of 309 patients without this condition (multivariate P = 0.005; adjusted odds ratio = 2.94; 95% confidence interval = 1.39-6.20). Conclusion LPPR4 and SAMM50 allelic variants are independent risk factors for FLD and steatohepatitis development, respectively, in HIV-infected individuals.

Summary Background & aims The seroprevalence of the hepatitis E virus (HEV) and its chronicity rate in the HIV-infected population has not been well established. As a result, the magnitude of this emerging disease in this population cannot be established. Methods Prospective study that included HIV-infected patients followed up between September 2012 and May 2013. All included patients were tested for anti-HEV IgG/IgM. In patients with confirmed anti-HEV IgG/IgM positivity, RT-PCR was performed. In patients where HEV RNA was amplified, a second RT-PCR assay was performed 6 months later to identify transient or chronic HEV infections. Results Eight hundred and ninety-four HIV-infected patients were enrolled in the study. Of these patients, 399 (44.6%) were monoinfected with HIV; 462 (51.6%) were co-infected with HIV/HCV; 12 (1.3%) were co-infected with HIV/HBV; and 21 (2.3%) were co-infected with HIV/HCV/HBV. In 88 patients, anti-HEV IgG/IgM was detected (seroprevalence: 9.8% [95% CI: 8.02%–11.9%]). In five patients (0.5%; 95% CI: 0.2%–1.2%), HEV RNA was detected; 5.7% (95% CI: 2.1%–12.1%) of the patients were anti-HEV IgG/IgM positive. None of these patients showed detectable HEV RNA six months later. Conclusion HEV infection is frequent in HIV-infected patients but developing a chronic HEV infection may be considered an uncommon liver disease in this population.