Hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) remain leading drivers of chronic viral hepatitis, cirrhosis, hepatocellular carcinoma, and liver-related mortality. This ESCMID Study Group for Viral Hepatitis (ESGVH) narrative review summarizes recent advances and expert perspectives in the field. For HBV, emerging biomarkers such as quantitative HBs antigen, HBV RNA, and hepatitis B core-related antigen offer opportunities to refine monitoring and to individualize treatment. HDV epidemiology is evolving, and is being increasingly studied; in parallel, the approval of bulevirtide represents a major breakthrough in therapy, with further agents in the HDV pipeline. For HCV, direct-acting antivirals provide curative therapy and have made elimination a realistic goal, while identifying remaining gaps in diagnosis, linkage-to-care, and equitable access offers clear opportunities to accelerate progress. Together, these advances bring the goal of a hepatitis-free future closer than ever.

Viral hepatitis remains a global health concern, with growing recognition of the impact of hepatitis A virus (HAV), hepatitis E virus (HEV), and herpesvirus-associated hepatitis, particularly in vulnerable groups. This narrative review from the ESCMID Study Group for Viral Hepatitis (ESGVH) summarizes recent advances and expert perspectives. For HAV, insights into viral evolution, epidemiology, and risk groups underline the preventable nature of severe disease. HEV is increasingly recognized as both a hepatotropic and a systemic pathogen, with expanding knowledge on natural and vaccine-induced immunity. Herpesvirus-associated hepatitis, while rare, poses significant challenges, especially in patients with immunosuppression or during pregnancy, where early suspicion and empirical antiviral therapy can be lifesaving. Collectively, these evolving insights highlight the importance of strengthened diagnostics, targeted prevention, and tailored management strategies to mitigate the burden of these underappreciated but clinically significant causes of viral hepatitis.

Abstract Background Transmission of coronavirus disease 2019 (COVID-19) can occur through inhalation of fine droplets or aerosols containing infectious virus. The objective of this study was to identify situations, patient characteristics, environmental parameters, and aerosol-generating procedures (AGPs) associated with airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Methods Air samples were collected near hospitalized COVID-19 patients and analyzed by RT-qPCR. Results were related to distance to the patient, most recent patient diagnostic PCR cycle threshold (Ct) value, room ventilation, and ongoing potential AGPs. Results In total, 310 air samples were collected; of these, 26 (8%) were positive for SARS-CoV-2. Of the 231 samples from patient rooms, 22 (10%) were positive for SARS-CoV-2. Positive air samples were associated with a low patient Ct value (OR, 5.0 for Ct <25 vs >25; P = .01; 95% CI: 1.18–29.5) and a shorter physical distance to the patient (OR, 2.0 for every meter closer to the patient; P = .05; 95% CI: 1.0–3.8). A mobile HEPA-filtration unit in the room decreased the proportion of positive samples (OR, .3; P = .02; 95% CI: .12–.98). No association was observed between SARS-CoV-2–positive air samples and mechanical ventilation, high-flow nasal cannula, nebulizer treatment, or noninvasive ventilation. An association was found with positive expiratory pressure training (P < .01) and a trend towards an association for airway manipulation, including bronchoscopies and in- and extubations. Conclusions Our results show that major risk factors for airborne SARS-CoV-2 include short physical distance, high patient viral load, and poor room ventilation. AGPs, as traditionally defined, seem to be of secondary importance.

Abstract Objectives Absence of a functional interferon-λ 4 (IFN-λ4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.

Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of aerosolized murine norovirus (MNV), a model for the human norovirus. Two aerosol generation principles were evaluated: bubble bursting, a common natural aerosolization mechanism, and nebulization, a common aerosolization technique in laboratory studies. The aerosolization setup was characterized by physical and viral dilution factors, generated aerosol particle size distributions, and the viral infectivity after aerosolization. We found a lower physical dilution factor when using the nebulization generator than with the bubble bursting generator. The viral dilution factor of the system was higher than the physical dilution; however, when comparing the physical and viral dilution factors, bubble bursting generation was more efficient. The infectivity per virus was similar using either generation principle, suggesting that the generation itself had a minor impact on MNV infectivity and that instead, the effect of drying in air could be a major reason for infectivity losses.

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.

Background: Hydrogen peroxide vapour is used as a room disinfectant. Its activity against murine norovirus, a surrogate viability marker for human norovirus, indicates that it is also active against human norovirus. Aim: The aim of this study is to assess how this effect on viability is reflected in measurements of RNA by quantitative PCR (qPCR). Methods: Faeces suspensions of two human norovirus field strains, genogroup I and II and one cultured murine norovirus strain, (genogroup V) were dried on plastic plates, and underwent hydrogen peroxide vapour treatment or were mock treated. The influence of hydrogen peroxide on RNA was measured on genogroups I, II and V by qPCRs and for the cultivable murine norovirus also for viability by cell culture. Virucidal activity on murine norovirus was measured by endpoint titrations as the 50% tissue culture infectious dose, based both on cytopathic effect and on presence of replicating intracellular minus strand RNA. Results: The mean impact on the human norovirus qPCRs was 0.4 log(10). The murine norovirus qPCR changed by 1.7 log(10) but by an alternative qPCR only by 0.4 log(10). These minor changes contrasted the 4.5-5.0 log(10) murine norovirus viability reduction after treatment measured by cytopathic effect or intracellular negative-strand RNA. Conclusion: Inactivation of murine norovirus viability by hydrogen peroxide vapour was not reflected in qPCR levels. This finding might be extrapolated to the related human norovirus genogroups. We further found that cellular minus strand murine norovirus PCR was an observer-independent marker to study reduction of murine norovirus viability.

Abstract Background Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in health-care facilities commonly occur. Contact with infected persons and contaminated environments are believed to be the main routes of transmission. However, noroviruses have recently been found in aerosols and airborne transmission has been suggested. The aim of our study was to investigate associations between symptoms of gastroenteritis and the presence of airborne norovirus, and to investigate the size of norovirus-carrying particles. Methods Air sampling was repeatedly performed close to 26 patients with norovirus infections. Samples were analyzed for norovirus RNA by reverse transcription quantitative polymerase chain reaction. The times since each patient’s last episodes of vomiting and diarrhea were recorded. Size-separating aerosol particle collection was performed. Results Norovirus RNA was found in 21 (24%) of 86 air samples from 10 different patients. Only air samples during outbreaks, or before a succeeding outbreak, tested positive for norovirus RNA. Airborne norovirus RNA was also strongly associated with a shorter time period since the last vomiting episode (odds ratio 8.1; P = .04 within 3 hours since the last vomiting episode). The concentrations of airborne norovirus ranged from 5–215 copies/m3, and detectable amounts of norovirus RNA were found in particles <0.95 µm and >4.51 µm. Conclusions The results suggest that recent vomiting is the major source of airborne norovirus and imply a connection between airborne norovirus and outbreaks. The presence of norovirus RNA in submicrometre particles indicates that airborne transmission can be an important transmission route.

Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches. Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996-2012, p=0.003). Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy. Abbreviations: ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers' exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann-Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol: polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance.

BACKGROUND:The HIV-1 spread in the Middle East and North Africa (MENA) has not been previously characterised using the phylogenetic approach. The aim of the current study was to investigate the genetic diversity and domestic transmission of HIV-1 in the MENA.METHODS:A total of 2036 HIV-1 sequences available in Genbank and collected in the MENA during 1988-2016 were used together with 715 HIV-1 reference sequences that were retrieved from Genbank based on genetic similarity with the MENA sequences. The REGA and COMET tools were used to determine HIV-1 subtypes and circulating recombinant forms. Maximum Likelihood and Bayesian phylogenetic analyses were used to identify and date HIV-1 transmission clusters.RESULTS:At least 21 HIV-1 subtypes and recombinant forms were prevalent in the MENA. Subtype B was the most common variant (39%), followed by CRF35_AD (19%) and CRF02_AG (14%). The most common genetic region was pol, and 675 partial pol sequences (average of 1005 bp) were eligible for detailed phylogenetic analysis. Fifty-four percent of the MENA sequences formed HIV-1 transmission clusters. Whereas numerous clusters were country-specific, some clusters indicated transmission links between countries for subtypes B, C and CRF02_AG. This was more common in North Africa compared with the Middle East (p < 0.001). Recombinant forms had a larger proportion of clustering compared to pure subtypes (p < 0.001). The largest MENA clusters dated back to 1991 (an Algerian CRF06_cpx cluster of 43 sequences) and 2002 (a Tunisian CRF02_AG cluster of 48 sequences).CONCLUSIONS:We found an extensive HIV-1 diversity in the MENA and a high proportion of sequences in transmission clusters. This study highlights the need for preventive measures in the MENA to limit HIV-1 spread in this region.

The molecular epidemiology of HIV-1 in Iceland has not been described so far. Detailed analyses of the dynamics of HIV-1 can give insights for prevention of virus spread. The objective of the current study was to characterize the genetic diversity and transmission dynamics of HIV-1 in Iceland. Partial HIV-1 pol (1020bp) sequences were generated from 230 Icelandic samples, representing 77% of all HIV-1 infected individuals reported in the country 1985-2012. Maximum likelihood phylogenies were reconstructed for subtype/CRF assignment and determination of transmission clusters. Timing and demographic growth patterns were determined in BEAST. HIV-1 infection in Iceland was dominated by subtype B (63%, n=145) followed by subtype C (10%, n=23), CRF01_AE (10%, n=22), sub-subtype A1 (7%, n=15) and CRF02_AG (7%, n=15). Trend analysis showed an increase in non-B subtypes/CRFs in Iceland over the study period (p=0.003). The highest proportion of phylogenetic clustering was found among injection drug users (IDUs; 89%), followed by heterosexuals (70%) and men who have sex with men (35%). The time to the most recent common ancestor of the oldest subtype B cluster dated back to 1978 (median estimate, 95% highest posterior density interval: 1974-1981) suggesting an early introduction of HIV-1 into Iceland. A previously reported increase in HIV-1 incidence among IDUs 2009-2011 was revealed to be due to two separate outbreaks. Our study showed that a variety of HIV-1 subtypes and CRFs were prevalent in Iceland 1985-2012, with subtype B being the dominant form both in terms of prevalence and domestic spread. The rapid increase of HIV-1 infections among IDUs following a major economic crisis in Iceland raises questions about casual associations between economic factors, drug use and public health.

BACKGROUND:People who inject drugs (PWID) are at particular risk of hepatitis B virus (HBV) acquisition, but often have poor access or adherence to HBV vaccination. Vaccination against HBV has been offered at a major Swedish needle exchange program (NEP) since 1994. The aim of this study was to evaluate vaccine completion and response rates, and the effect of sequential booster doses to non-responders to the standard vaccination schedule. METHODS:PWID enrolled in the NEP 1994-2013, without serological markers for HBV at baseline (negative for HBsAg/anti-HBc/anti-HBs), were offered a three-dose standard intramuscular vaccination schedule (Engerix®-B, GSK, 20μg/mL, intended to be received at months 0, 1 and 6). Vaccination response was defined as protective levels of anti-HBs (⩾10mIU/mL). Up to three booster doses were then offered for non-responders, each followed by anti-HBs testing. RESULTS:HBV data was available for 2352 identifiable individuals at NEP enrolment, of whom 1516 (64.5%) had no markers for previous HBV exposure or vaccination. Vaccination was initiated for 1142 (75.3%) individuals and 898 (59.2%) completed the standard vaccination schedule. Post-vaccination anti-HBs levels were available from 800 individuals, with 598 (74.8%) responding to the basic vaccination schedule. After up to three booster doses a total of 676 (84.5%) individuals achieved protective anti-HBs levels. Non-response to vaccination was associated with higher age and anti-HCV positivity (p<0.001). Eighteen incident cases of HBV infection were observed among vaccine non-responders, as well as 30 cases among those who had not completed vaccination. CONCLUSION:We demonstrate the feasibility of including HBV vaccination in the services offered by a NEP, with completion of vaccination in a majority of HBV-susceptible PWID. The response to HBV vaccination among PWID was relatively low; however, the addition of up to three booster doses improved the response rate from 74.8 to 84.5%.

OBJECTIVE To determine whether hydrogen peroxide vapor (HPV) could be used to decontaminate caliciviruses from surfaces in a patient room. DESIGN Feline calicivirus (FCV) and murine norovirus (MNV) were used as surrogate viability markers to mimic the noncultivable human norovirus. Cell culture supernatants of FCV and MNV were dried in triplicate 35-mm wells of 6-well plastic plates. These plates were placed in various positions in a nonoccupied patient room that was subsequently exposed to HPV. Control plates were positioned in a similar room but were never exposed to HPV. METHODS Virucidal activity was measured in cell culture by reduction in 50% tissue culture infective dose titer for FCV and by both 50% tissue culture infective dose titer and plaque reduction for MNV. RESULTS Neither viable FCV nor viable MNV could be detected in the test room after HPV treatment. At least 3.65 log reduction for FCV and at least 3.67 log reduction for MNV were found by 50% tissue culture infective dose. With plaque assay, measurable reduction for MNV was at least 2.85 log units. CONCLUSIONS The successful inactivation of both surrogate viruses indicates that HPV could be a useful tool for surface decontamination of a patient room contaminated by norovirus. Hence nosocomial spread to subsequent patients can be avoided. Infect Control Hosp Epidemiol 2016;37:561–566

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Fifty adult emergency room patients with symptoms of respiratory tract infections or acute onset of extreme fatigue were sampled by both nasopharyngeal aspirate (NPA) and flocked nasal swab (fNS). Respiratory agents were detected by a qualitative influenza PCR and an 18-valent multiplex PCR in 20 of 29 patients with a clinical diagnosis of respiratory tract infection, and in 3 of 21 without such a diagnosis. PCR detected influenza A and B in NPA samples from 11 patients and in fNS samples from 10 patients. Little or no discomfort was perceived by 60% of the patients when sampled by NPA and by 66% when sampled by fNS. We conclude that NPA and fNS were equally sensitive for detection of respiratory agents by multiplex PCR, and the two sampling methods did not differ significantly regarding discomfort perceived by patients (p = 0.171, Wilcoxon signed rank test). Hence less invasive sampling by fNS might be preferable in certain settings and situations.

Abstract Background: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. Methods: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Results: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3–F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Conclusions: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs.

To determine the prevalence of various types of viruses in infants hospitalised due to respiratory distress, compare molecular diagnostic tests and evaluate symptom severity. All 136 nasopharyngeal aspirates from infants hospitalised for respiratory distress over a 9-month period were analysed for virus type by in-house respiratory syncytial virus (RSV) polymerase chain reaction (PCR) microarray-based and/or Luminex-based multiplex molecular tests. Medical records were reviewed retrospectively for clinical data. Viral aetiology was confirmed in 126 subjects (92.6%) with 26 infected by more than one virus. RSVA/B was the most common (50.9%), followed by entero/rhinovirus (21.6%), human metapneumovirus (10.5%), parainfluenza virus (5.9%) and influenza (3.3%). RSV-infected infants had significantly lower saturation levels (89% versus 92%, p < 0.001), higher demand for oxygen (42.7% versus 21.6%, p = 0.021) and fluids (28% versus 9.8%; p = 0.014) and longer hospital stays (4 versus 3 days, <0.001) than other viruses. Luminex assays gave repeatable, slightly less sensitive results than in-house RSV PCR. Microarray-based assays were more sensitive, however, producing some unrepeatable results. Respiratory syncytial virus dominates as the viral cause in hospitalised infants with respiratory distress in Sweden during the winter season, resulting in a clinical course that is significantly more severe. The multiplex assays produced reasonably concordant results.

OBJECTIVES: To assess HCV viremia levels just before, during and one year after anti-HCV seroconversion in people who inject drugs (PWID). METHODS: PWID enrolling into a needle exchange program in Malmö, Sweden, 1997-2005 constituted the source population. Sera were obtained at enrolment and at approximately 3-4 monthly intervals afterwards, and were initially tested for anti-HIV, HBsAg/anti-HBc and anti-HCV and thereafter for markers previously negative. Seroconversion to anti-HCV had occurred during the study period in 186 out of 332 seronegative subjects. In these anti-HCV seroconverters, quantitative HCV RNA PCR was retrospectively performed on frozen sera to determine viremia levels in the last anti-HCV negative, the first anti-HCV positive and in one year follow-up samples. RESULTS: Among 150 subjects seroconverting to anti-HCV with samples available from all three defined time-points, eight different patterns of viremia were observed. Spontaneous clearance at one year was noted in 48 cases (32%) and was associated with female gender (p = 0.03, CI 0.17-1.00). In 13 cases HCV-RNA was not detected in any study sample. Among 61 subjects with pre-seroconversion viremia, viral load was significantly higher in the pre-seroconversion samples compared to subsequent samples. For the whole group, viral load declined to undetectable levels at seroconversion in 28% of cases (but with recurrent viremia in 15%). CONCLUSIONS: Different patterns of HCV RNA kinetics were observed among PWID with documented seroconversion to anti-HCV. The frequently observed absence of detectable HCV RNA in the first anti-HCV positive sample (irrespective of subsequent viremia) demonstrates the importance of repeated sampling and RNA testing for determination of the outcome of acute infection.