Hepatitis E Research Articles

Seroprevalence and Associated Risk Factors of Hepatitis E Virus Infection Among Blood Donors in Tripoli, Libya

Hepatitis E (HE) is a transfusion-transmitted viral disease caused by the Hepatitis E virus (HEV). There are currently no national seroprevalence reports for Libyan blood donors. This study therefore aimed to evaluate HEV risk to blood safety by assessing the prevalence of anti-HEV IgG and anti-HEV IgM among Libyan healthy blood donors. A total of 267 serum samples were collected from blood donors. Using a questionnaire form, the risk factors for HEV infection of all blood donors were gathered. The sera of the blood donors were screened for anti-HEV IgM and anti-HEV IgG using ELISA kits (DIA. PRO Srl, Milan, Italy). The statistical significance of the association between dependent and independent variables was evaluated using the chi-square test. A P-value < 0.05 was considered an indicator of statistical significance. The overall seroprevalence of HEV infection was 5.24% (14/267). Of the 267 blood donors, 12 (4.49%) tested positive for anti-HEV IgG antibodies. In contrast, 2 (0.74%) tested positive for anti-HEV antibodies (IgM and IgG). Our seroprevalence of anti-HEV IgG was significantly associated with increased age, marital status, the technique of washing hands before eating, and smoking habit, and it was significantly low in blood donors who eat in cafes and restaurants. The overall seroprevalence of HEV infection was low in Libya. HEV is not currently prevalent among blood donors in Tripoli, Libya and poses little threat to the national blood supply. Therefore, current blood donor screening protocols are sufficient.

Active surveillance of hepatitis E: a 10-year epidemiological analysis in a city in eastern China

ABSTRACT Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50–69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.

Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report

BackgroundAlveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs.Case presentationWe present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries.ConclusionsThe multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Clinical characteristics and risk factors of Hepatitis E virus infection in Zhejiang Province: a multicenter case-control study.

Hepatitis E (HE), caused by the Hepatitis E virus (HEV), is a significant cause of acute viral hepatitis globally and a major public health concern, particularly in specific high-prevalence areas in China, which have diverse transmission routes and regional differences. Identifying the primary risk factors for HE transmission is essential to develop targeted interventions for vulnerable populations. This study employed a 1:1 matched case-control methodology, using a standardized questionnaire complemented by medical records for data validation. Among the 442 HE cases and 428 healthy controls, the case group had a higher prevalence of fatigue (46.21%) and loss of appetite (43.84%) compared to the control group. Furthermore, liver function indicators were significantly higher in the case group, with an average alanine aminotransferase (ALT) level of 621.94 U/L and aspartate aminotransferase (AST) level of 411.53 U/L. Severe HE patients were predominantly male, with significantly increased ALT and AST levels reaching 1443.81 U/L and 862.31 U/L respectively, along with a higher incidence of fatigue (90%) and loss of appetite (75%). Multifactorial analysis indicated that frequent dining out (OR = 2.553, 95%CI:1.686-3.868), poor hygiene conditions (OR = 3.889, 95%CI:1.399-10.807), and comorbid chronic illnesses (OR = 2.275, 95%CI:1.616-3.202) were risk factors for HE infection; conversely, good hygiene practices were protective factors against HE infection (OR = 0.698, 95%CI:0.521-0.934). In conclusion, HE infection in Zhejiang Province is closely associated with dietary habits and environmental hygiene, and individuals with chronic diseases or co-infections are at increased risk. This highlights the need for targeted health education to reduce the incidence of HE among these populations.

Omics-based investigation of pathological liver injury induced by Echinococcus multilocularis infection in mice

BackgroundAlveolar echinococcosis (AE) can cause severe liver injury and be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver injury. Therefore, by exploring the changes of gene proteins in mice with damaged liver, we attempted to identify the key molecules of liver damage, and provide data that will enable the development of drugs targeting hepatic AE. MethodsBALB/c mice were inoculated with protoscoleces via the hepatic portal vein. Three months later, B-ultrasound examination and Hematoxylin—eosin (H&E) staining were used to confirm liver damage in mice. RNA sequencing and Liquid chromatography–mass spectrometry (LC-MS) were used to screen differentially expressed molecules associated with liver damage through bioinformatics, and Quantitative Real-Time PCR (qRT-PCR) was used to verify their expression. ResultsB-ultrasound examination showed liver lesions in the infected group, and H&E staining showed liver inflammation, fibrosis and liver necrosis. RNA sequencing and LC-MS results showed changes in the levels of more than 1000 genes and proteins, with upregulation of immune and inflammation pathways. By contrast, the downregulated genes and proteins were mostly involved in various metabolic reactions. Correlation analysis was conducted between the transcriptome data and proteome data. The results revealed 240 differentially expressed genes, of which 192 were upregulated, and 48 were downregulated. Many of these genes were involved in metabolic reactions, such as Catalase (Cat), fatty acid synthase (Fasn), and IL-16 genes, which may have relevance to liver injury. The results of qRT-PCR were consistent with those of bioinformatics analysis. ConclusionsThe mechanisms of liver injury in mice infected with Echinococcus multilocularis are complex, involving abnormal metabolism, oxidative stress, inflammatory response, and many other factors. This study provides the data for preliminary exploration for the development of targeted therapies against AE.

Analysis of the spatial-temporal distribution characteristics of hepatitis E in Jiangsu province from 2005 to 2020.

This study attempts to analyze the spatial clustering and spatial-temporal distribution characteristics of hepatitis E (HE) at the county (city and district) level in Jiangsu province to provide a scientific basis for the prevention and control of HE. The information on HE cases reported in the Chinese Center for Disease Control and Prevention Information System from 2005 to 2020 was collected for spatial autocorrelation analysis and spatial-temporal clustering analysis. From 2005 to 2020, 48,456 HE cases were reported in Jiangsu province, with an average annual incidence rate of 3.87/100,000. Male cases outnumbered female cases (2.46:1), and the incidence was highest in the 30-70 years of age group (80.50%). Farmers accounted for more than half of all cases (59.86%), and in terms of the average annual incidence, the top three cities were all in Zhenjiang city. Spatial autocorrelation analysis showed that Global Moran's I of HE incidence varied from 0.232 to 0.513 for the years. From 2005 to 2020, 31 counties (cities and districts) had high and statistically significant HE incidence, and two clustering areas were detected by spatial-temporal scanning. HE incidence in Jiangsu province from 2005 to 2020 was stable, with age and gender differences, regional clustering, and spatial-temporal clustering. Further investigation of HE clustering areas is necessary to formulate corresponding targeted prevention and control measures.

Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition

BackgroundThis study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE).Patients and methodsA single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded.ResultsAcalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 ± 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 ± 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE.ConclusionAcalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.

Safety of hepatitis E vaccination for pregnancy: a post-hoc analysis of a randomized, double-blind, controlled phase 3 clinical trial

ABSTRACT Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18–45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38–1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74–8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

Molecular epidemiological study of clinical cases of acute hepatitis E in Belarus

Relevance. The frequency of occurrence of anamnestic antibodies to the hepatitis E virus (HEV) in the general population of the Republic of Belarus is 7.3%, which is clearly not consistent with the low incidence of hepatitis E (HE). Most of primary HEV infections remain undiagnosed. The intensive epidemic process of HEV in the Belarusian population is hidden. Conducting epidemiological studies, including genotyping of HEV sequences isolated on the territory of the republic, makes it possible to more accurately characterize the sources of HEV infection and the mechanisms of its transmission.&#x0D; Aim molecular epidemiological study of two cases of acute hepatitis E detected in patients from Belarus.&#x0D; Materials and methods. During 20212022, samples of biological material were obtained from two patients undergoing treatment with an established diagnosis of acute hepatitis E. Serum samples were tested to detect antibodies to HEV using enzyme immunoassay, HEV RNA was detected in fecal samples using nested RT-PCR. The nucleotide sequence was determined by an automatic sequencer using the Sanger method. Analysis of nucleotide sequences, their genotyping, and calculation of evolutionary distances were performed using MEGA X software.&#x0D; Results. The HEV sequence isolated from a pregnant woman who had an epidemiological episode of alimentary contact with raw pork meat is clustered into a common phylogenetic clade with HEV sequence obtained from the patient from Belarus with a history of kidney transplantation and HEV sequences isolated from a domestic pigs. The HEV sequence isolated from a patient with a history of travel to Pakistan belongs to the HEV genotype 1 and joins a clade of HEV sequences isolated in Pakistan, India, Nepal and Mongolia.

Application of a truncated ORF2 protein-based ELISA for diagnosis of hepatitis E in an endemic area.

Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis depends on detection of specific IgM antibodies in serum. Present study evaluated performances of two in-house and six commercial IgM detection enzyme-linked immunosorbent assays (ELISAs) using sera collected from volunteers/acute hepatitis patients (n = 716). The in-house ELISAs were based on complete and truncated open reading frame 2 (ORF2) proteins containing neutralizing epitope/s region of genotype 1 HEV (ORF2p, 1-660 amino acid (a.a.) and T1NEp, 458-607 a.a., respectively). The commercial ELISAs included Wantai (China), MP Diagnostics (MPD) (Singapore), DIA.PRO Diagnostics (Italy), MBS (Italy), abia (Germany), and ImmunoVision (USA). T1NE ELISA showed 97.0% positive percent agreement (PPA), 99.4% negative percent agreement (NPA), and 98.6% concordance (κ = 0.97, P = 0.0000) with ORF2 ELISA. ORF2, T1NE, Wantai, and MPD ELISAs agreed on results for 88% of sera tested. Two percent sera showed reactivity in each combination of three and two of aforementioned four ELISAs. Remaining 8% sera were single ELISA reactive. PPA and NPA value ranges were 76.3-99.0% and 84.8-99.5%, respectively. Pairwise concordances between all the eight ELISAs ranged from 88.0 to 100% (κ: 0.74-1.00). Both the in-house ELISAs agreed better with Wantai over MPD ELISA. In conclusion, both ORF2 and T1NE ELISAs were equally efficient in diagnosing HEV infections. T1NEp proved to be an excellent tool in HE sero-diagnosis and is worth exploring in development of simple rapid tests. KEY POINTS: • In-house ELISA based on bacterially expressed neutralizing epitope/s region protein • In-house ELISA based on complete ORF2 protein expressed in insect cells • Comparison of two in-house and six commercial anti-HEV IgM antibody detection ELISAs.

Laparoscopic resection of hepatic alveolar echinococcosis: A single-center experience.

IntroductionAlveolar echinococcosis (AE) remains a very rare disease requiring complete radical resection for curative treatment. While open approaches are common, safety and efficacy of laparoscopic resections remain unknown.MethodsThis is a single-center, retrospective cohort study with patients undergoing liver resection for hepatic AE at the Department of Visceral Surgery and Medicine, Bern University Hospital from December 2002 to December 2020. Postoperative outcomes of patients following laparoscopic hepatectomy (LH) for hepatic AE were compared with those of patients undergoing open hepatectomy (OH).ResultsA total of 93 patients underwent liver resection for hepatic AE. Laparoscopic hepatectomy was performed in 23 patients and open hepatectomy in 70 patients. While there were no significant differences in terms of gender, age and diagnostic tools, the majority of patients of the LH cohort were PNM stage 1 (78%) in contrast to only 39% in the OH cohort (p = 0.002). Patients undergoing laparoscopic hepatectomy were treated by minor liver resections in 91% and in 9% by major liver resections in comparison to the open hepatectomy cohort with 61% major liver resections and 39% minor resections. Laparoscopic hepatectomy was associated with shorter mean operation time (127 minutes vs. 242 minutes, p <0.001), lower major complication rate (0% vs. 11%, p = 0.322) and shorter mean length of hospital stay (4 days vs. 13 days, p <0.001). Patients with LH had a distinct, but not significant lower recurrence rate (0% vs. 4%, p = 0.210) during a mean follow-up of 55 months compared with a follow-up of 76 months in the OH cohort. After subgroup analysis of PNM stage 1 patients, similar results are seen with persistent shorter mean operation time (120 minutes vs. 223 minutes, p <0.001), lower major complication rate (0% vs. 8%, p = 0.759) and shorter length of hospital stay (4 days vs. 12 days, p <0.001).ConclusionLaparoscopy appears as a feasible and safe approach for patients with PNM stage 1 alveolar echinococcosis without impact on early disease recurrence.

Hepatitis E - epidemiology and clinical course in the largest cohort in the Czech Republic.

IntroductionThe majority of hepatitis E (HE) reports come from Western Europe. The aim of the study was to describe the typical epidemiological and clinical characteristics of HE in the Czech Republic.MethodsA retrospective analysis of 173 patients with HE.ResultsAt least 90% of cases were autochthonous (HEV-3 genotype). Seventeen patients were treated with ribavirin. Five underwent liver transplants because of fulminant HE. We noted neurological symptomatology in 9 cases. Six patients developed chronic HE.ConclusionsThere is a possibility of severe health complications caused by the hepatitis E virus in the Czech Republic.

Genetic characterization of hepatitis E virus from wild boar in China.

Hepatitis E virus (HEV), the causative agent of hepatitis E (HE), is classified into four major genotypes (1-4), with wild boar being the main natural reservoir for genotypes 3 and 4. However, little is known about the prevalence of HEV infection in wild boars in China. In this study, RT-nested PCR and RT-quantitative PCR were used to detect the HEV RNA in tissue samples taken from 331 free-ranging wild boars collected between 2018 and 2020 from 24 regions across China, and the partial ORF2 genes or complete genomes of the positive samples were sequenced. Furthermore, antibodies against HEV in 216 serum samples from wild boars were tested by ELISA. As a result, HEV RNA was detected in nine out of 331 liver samples of wild boars (2.72%), which were distributed in eight regions. Genetic and evolutionary analysis of partial ORF2 sequences indicated that the HEV strains identified in this study share 83.9%-100% nucleotide sequence identity and belong to subtypes 4d (n=6), 4g (n=2), and 4h (n=1), and similar phylogeny was obtained using the complete genome sequences of seven wild boar HEV strains. Additionally, the HEV viral loads were higher in the liver than in other tissues and blood. Moreover, 61 out of 216 sera (28.2%) from wild boars tested positive for anti-HEV antibodies. To our knowledge, this is the first study to report the epidemiological situations of HEV infections in free-ranging wild boars in China, and the obtained data are valuable for prevention and control of HE.

Low prevalence of hepatitis E virus in the liver of Corsican pigs slaughtered after 12 months despite high antibody seroprevalence.

Hepatitis E virus (HEV) infection can be acute and benign or evolve to chronic hepatitis with rapid progression toward cirrhosis or liver failure in humans. Hence, hepatitis E (HE) disease is a major public health concern. In countries where pig populations are highly contaminated with HEV, human cases of HE are mainly foodborne, occurring frequently after consumption of raw or undercooked pork products or liver. Among factors associated to the presence of HEV in pork livers from intensive rearing systems, early slaughter (≤6 months) seems to be major. In Corsica, local pigs are raised in extensive farming systems and slaughtered after 12 months. To evaluate if slaughter of pigs over 12 months reduces the risk of HEV presence in livers, 1197 liver samples were randomly collected in 2 Corsican slaughterhouses. Presence of HEV RNA was detected in liver and HEV seroprevalence was determined in paired serum. The sampling included 1083 livers from animals between 12 and 48 months and 114 livers from animals<12 months. The samples were predominantly from semi-extensive and extensive farms (n=1154). Estimated HEV seroprevalence was high, that is, >88%, and HEV RNA prevalence in adult pig livers (>12 months old) was low, that is, 0.18%. However, in livers from younger animals(<12 months), including piglets below 6 months old, 5.3% (6/114) of the samples were positive for HEV RNA. Sequences recovered from positive livers belonged to HEV genotype 3c and 3f. The presence of infectious HEV was confirmed in two livers by the detection of HEV replication in HepaRG cell cultures. Thus, this study demonstrates the low prevalence of HEV in livers of pigs over 12 months, even in farms with high HEV circulation. This observation may open new perspectives on the preferential use of livers from animals older than 12 months in raw pork liver products.

Prevalence of antibodies to the hepatitis E virus in the population of the Republic of Belarus

Rationale. Hepatitis E (HE) is a zooanthroponosis. Domestic pigs are the main reservoir for hepatitis E virus (HEV) in the Republic of Belarus (RB). Considering the well-developed pig farming, there is a high risk of infection spread among the population; however, the scale of virus circulation and patterns of HE epidemiology in the above region are still insufficiently explored.The aim of the study is to assess HEV seroprevalence specific for the HE epidemic process in RB.Materials and methods. Serum samples (n = 2,784) collected from patients of infectious disease departments at hospitals (n = 1,669) and relatively healthy people (n = 1,114) from different RB regions were used to measure the activity of alanine aminotransferase (ALT) by a kinetic rate method as well as IgG antibodies to HEV by the enzyme-linked immunosorbent assay (ELISA).Results. In the group of healthy people, anti-HEV IgG were detected in 7.3% (95% CI, 5.8–9.0). In the group of patients with liver disorders, the detection frequency was significantly higher, reaching 11.2% (95% CI, 9.6–12.9). In the groups of healthy people and patients with elevated ALT levels, the HEV seroprevalence did not depend on their gender or the region of residence. The anti-HEV IgG detection frequency gradually increased among olderage patients and reached the peak levels (15.9% on average) in the over-64 age group.Conclusions. RB is characterized by intensive HEV circulation, while the HE epidemic process is characterized by a latent nature. The actual prevalence of HЕ seromarkers among the RB population exceeds the frequency of diagnosed cases, suggesting insufficient vigilance of healthcare workers towards HE and subclinical forms of infection in most of the patients.

Epidemiological survey and risk factors associated with hepatitis E virus in small ruminants in southern Spain.

Autochthonous cases of hepatitis E (HE) associated with zoonotic genotypes HEV‐3 and HEV‐4 have significantly increased in industrialized countries over the last decade. Suidae are generally recognized as the main reservoirs of these genotypes. Susceptibility to HE virus (HEV) infection and zoonotic potential have also been confirmed in other species, including sheep and goat. However, the information about their role in the epidemiology of HEV remains very scarce. The objective of this study was to assess the prevalence, spatial distribution and risk factors associated with HEV exposure in sheep and goats in southern Spain, the country with the highest census of small domestic ruminants in the European Union. Blood samples from 240 sheep and 240 goats were collected between 2015 and 2017. Sera were analysed in parallel using a commercial double‐antigen ELISA and real‐time PCR. A total of 38 (7.9%; 95%CI: 5.5–10.3) out of 480 sampled animals showed anti‐HEV antibodies. By species, the seroprevalences found in sheep and goats were 2.1% (5/240; 95%CI: 0.3–3.9) and 13.8% (33/240; 95%CI: 9.4–18.1) respectively. Anti‐HEV antibodies were found on 19 (59.4%; 95%CI: 42.4–76.4) of the 32 sampled farms. The GEE model showed that species (goat) and number of small ruminants in the farm (≤348 animals and ≥538 animals) were risk factors potentially associated with HEV exposure in small ruminants in the study area. HEV RNA was not detected in any of the 480 (0.0%; 95%CI: 0.0–0.8) tested animals. Our results confirm that sheep and goats are naturally, but not equally exposed to HEV and indicate the widespread spatial distribution of HEV among small ruminant populations in southern Spain. Further studies are required to elucidate the role of sheep and goat in the epidemiology of HEV and their potential implications for public health.

Randomized phase II trial of neoadjuvant chemotherapy with modified FOLFIRINOX versus modified FOLFIRINOX and PD-1 antibody for borderline resectable and locally advanced pancreatic cancer (the CISPD-4 study).

562 Background: Neoadjuvant chemotherapy is recommended for BRPC and LAPC planned resection. PD-1 antibody alone was failed in advanced pancreatic cancer, but chemotherapy combined with PD-1 antibody are promising. Methods: This is a randomized, controlled, open-label phase II study including patients with BRPC or LAPC. Modified FOLFIRINOX (mFFX) is used as neoadjuvant chemotherapy. Patients will be randomly allocated into two groups: mFFX group and mFFX plus PD-1 antibody group (PD-1 group). Imaging evaluation will be discussed by the MDT. Surgical resection will be performed if the MDT confirms the resectability. (NCT03983057). Results: From March 4, 2019 to August 1, 2021, 146 patients (62 BRPCs and 84 LAPCs) were enrolled. 115 patients received at least four cycles of therapy. In PD-1 group, irAEs happened in seven patients (9.7%), including rash (3 patients, Grade 1), hepatic AE (2 patients Grade 3, 1 patient Grade 2), renal AE (2 patients, Grade 2), and hyperglycemia (2 patients). Radiological PR were noted in 13.3% patients in mFFX group, and 26.9% in PD-1 group. For BRPC patients, the radiological PR was 13.0% and 36.3%, respectively. The resection rate was similar in two groups (47.4% and 51.7%). R0 resections were performed in 70.3% and 86.6% patients, respectively. For LAPC patients, PD-1 group has a higher resection rate (37.1% vs. 48.0%). The survival data are not mature at present. Conclusions: Modified FOLFIRINOX plus PD-1 antibody is feasible and well-tolerated for BRPC and LAPC patients. The study will be continued and the detailed data will be reported. Clinical trial information: NCT03983057.

Stage-Oriented CT Classification and Intermodal Evolution Model inHepatic Alveolar Echinococcosis.

BackgroundAlveolar echinococcosis (AE) is one of the most dangerous human parasitoses. The main site of disease manifestation is the liver (about 98 %). The Echinococcus Multilocularis Ulm Classification for Computed Tomography (EMUC-CT), presented in 2016, was the first compilation of CT morphological criteria of hepatic AE. Studies based on EMUC-CT made it possible to draw conclusions about the development of the lesions in the course of disease beyond purely diagnostic typing. Among the most important findings of these precursor studies was that EMUC-CT type IV presented as an initial lesion, whereas EMUC-CT type III lesions were mostly associated with an advanced disease constellation. An intermodal view of image morphological criteria provides further multi-layered indications for lesion evolution.MethodWith the “Alveolar Echinococcosis Ulm Classification” (AEUC), a revision of the previous EMUC-CT was carried out with stage-oriented reorganization of the primary morphologies. Furthermore, an intermodal classification scheme for the evolution of hepatic AE lesions based on AEUC, MRI Kodama classification, and aspects of ultrasound could be outlined.ResultsThe first stage-oriented CT classification of hepatic AE “AEUC” is based with respect to its lesion characterization on the separate consideration of two classification pillars, the five “primary morphologies”, AEUC I–V (AEUC II–IV with subcriteria) and the five “patterns of calcification”. In addition, an intermodal classification scheme presents five stages of lesion evolution: “initial stage”, “progressive stage”, “advanced stage”, “transitional stage” and “regressive stage”.ConclusionThe imaging modalities differ with respect to their visualization of lesion criteria. This underlines the need for unimodal classification systems. Staging of an AE lesion can be done more accurately by evaluating different modalities.Key Points:The AEUC provides a stage-oriented CT classification for hepatic AE.Aspects of different modalities allow a more multi-layered view of lesion evolution.More accurate staging can be achieved by combining different modalities.Citation FormatGraeter T, Schmidberger J. Stage-Oriented CT Classification and Intermodal Evolution Model in Hepatic Alveolar Echinococcosis. Fortschr Röntgenstr 2022; 194: 532 – 544

Features of the Epidemic Process of Viral Hepatitis A and E in the Russian Federation

Relevance. In the Russian Federation, in recent decades, there has been a decrease in the incidence of hepatitis A (HA), at the same time, not only sporadic morbidity is registered, but also an outbreak. A decrease in the circulation of the HA virus affected the increase in the number of people without antibodies to the virus, which led to a shift in the incidence to older age groups and an increase in more severe forms of the disease. Hepatitis E (HE) is quite widespread in the world, and its specific weight in the structure of acute viral hepatitis in some countries reaches 50.0%. HE has been registered in the Russian Federation only since 2013. only in certain territories, and the incidence rates are very low. In all likelihood, this indicates a hidden circulation of the HE virus in the Russian Federation. To understand the current epidemiological situation in the incidence of HA and HE, it is necessary to understand the current trends in the epidemic process of these infections. The purpose of this work was to compile an epidemiological characteristic of the incidence of hepatitis A and E in the population of the Russian Federation at the present stage for the formation of proposals for improving the system of preventive and anti-epidemic measures.Materials and methods. To achieve this goal, a retrospective epidemiological analysis of the incidence of viral hepatitis A and E in the territory of the Russian Federation, including in federal districts, was carried out. The materials for the study were the forms of official statistical observation No. 2, 5, 6 and 23, as well as state reports «On the state of sanitary and epidemiological well-being» in the Russian Federation region for 2011–2020.Results. The conducted research allows us to compare the epidemic process of hepatitis A and E in the Russian Federation with other regions of the world. The intensity of the epidemic process of HA has significantly decreased, at the same time, there is an uneven distribution of morbidity in various federal districts. In the age structure of patients with HA, the highest incidence rates are observed among the child population and adolescents. The frequency of HA infection and a decrease in the specific weight in the structure of acute viral hepatitis were revealed. Although the territory of the Russian Federation is not endemic for hepatitis E, this disease has taken root completely. The incidence of hepatitis E in the Russian Federation is at a sporadic level. The highest incidence of HE in the Russian Federation was observed among the adult population aged 18 years and older. The issue of carrying out preventive measures, including vaccination, remains relevant.Conclusion. On the territory of the Russian Federation, there is currently a steady trend of reducing the incidence of hepatitis A. However, children under the age of 14, adolescents, as well as nonimmune adults, among whom cases of diseases are registered, are still at risk. This requires adjusting the methods of preventing this infection, which is possible not only by improving sanitary and communal improvements, but also by vaccination within the national vaccination calendar, and not only for epidemic indications. The true incidence of HE today is obviously much higher than that recorded in official statistical forms, and this requires the introduction into clinical practice (especially at the polyclinic level) of modern available tests for detecting markers of the hepatitis E virus when examining patients with symptoms of liver damage, as well as the development of effective prevention methods.

Historical Analysis of the Risk of Hepatitis E and Its Complications in Pregnant Women in Nepal, 1996-1998.

Hepatitis E (HE) during pregnancy can be fatal; there are no prospective risk estimates for HE and its complications during pregnancy. We followed 2,404 pregnant women for HE and pregnancy outcomes from 1996 to 1998. Subjects from Nepal were enrolled at an antenatal clinic with pregnancy of ≤ 24 weeks. Most women (65.1%) were anti-HE virus negative. There were 16 cases of HE (6.7 per 1,000); three mothers died (18.8%) having had intrauterine fetal death (IUFD). Thirteen mothers survived: five preterm and seven full-term deliveries, one IUFD. HE among seronegative women was the sole cause of maternal death and increased the risk of IUFD (relative risk [RR]: 10.6; 95% confidence interval [CI]: 4.29-26.3) and preterm delivery (RR: 17.1, 95% CI 7.56-38.5). HE vaccination of females in at-risk regions before or as they attain reproductive age would reduce their risk for preterm delivery, IUFD, and maternal death.