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We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient's blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients.

On March 31, 2022, severe acute hepatitis of unknown origin was first reported from the Royal Glasgow Children's Hospital in Scotland. According to the criteria by WHO-ECDC, a probable case of unknown acute hepatitis in children is defined as a subject under 16 years of age, who tested negative for viral hepatitis and transaminases >500 U/L, starting from the 1st of October 2021. WHO invites Member States to participate in the global effort to collect anonymized clinical data on probable cases of severe acute hepatitis of unknown aetiology. As of May 26, 2021, 650 cases were already registered on the platform worldwide, of whom at least 38 cases have required liver transplants. Several hypotheses such as previous SARS-CoV-2 infection or coinfection or infection with another virus were examined and a strong association was found between adenovirus (41F) and acute hepatitis of unknown aetiology cases. This review article summarizes the global epidemiological evidences on acute hepatitis of unknown origin in children, analysing their incidence and characteristics., (© 2024 John Wiley & Sons Ltd.)

Recent studies have identified a correlation between chronic viral hepatitis and cognitive impairment, yet the underlying mechanisms remain unclear. This study investigated the influence of TGFB1 genetic polymorphisms on cognitive function in individuals with and without hepatitis infections, hypothesizing that these polymorphisms and the viral hepatitis-induced inflammatory environment interact to affect cognitive abilities. Participants (173 with viral hepatitis and 258 healthy controls) were recruited. Genotyping of TGFB1 SNPs was performed using the C2-58 Axiom Genome-Wide TWB 2.0 Array Plate. Cognitive function was assessed using the MMSE and MoCA tests. Our results showed that healthy individuals carrying the C allele of rs2241715 displayed better performance in sentence writing (p = 0.020) and language tasks (p = 0.022). Notably, viral hepatitis was found to moderate the impact of the rs2241715 genotype on language function (p = 0.002). Similarly, those carrying the T allele of rs10417924 demonstrated superior orientation to time (p = 0.002), with viral hepatitis modifying the influence of the SNP on this particular cognitive function (p = 0.010). Our findings underscore the significant role of TGFβ1 in cognitive function and the moderating impact of viral hepatitis on TGFB1 SNP effects. These findings illuminate the potential of TGFB1 as a therapeutic target for cognitive impairment induced by viral hepatitis, thus broadening our understanding of TGFβ1 functionality in the pathogenesis of neurodegeneration., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 ( P =0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 ( P <0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8 + T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process., Competing Interests: Conflicts of Interest and Source of Funding: K.K. is an employee at Coppe Healthcare Solutions Inc. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The Central African Republic (CAR) is one of the countries with the highest prevalence of viral hepatitis infection in the world. Coinfection with HIV increases the morbidity and mortality beyond that of mono-infection with either hepatitis or HIV. The present study describes the geographic distribution of viral hepatitis infections and molecular characterization of these viruses in the CAR., Methodology: Out of 12,599 persons enrolled during the fourth Multiple Indicator Cluster Survey of 2010 in the CAR, 10,621 Dried Blood Spot (DBS) samples were obtained and stored at -20°C. Of these DBS, 4,317 samples were randomly selected to represent all regions of the CAR. Serological tests for hepatitis B, D, and C viruses were performed using the ELISA technique. Molecular characterization was performed to identify strains., Results: Of the 4,317 samples included, 53.2% were from men and 46.8% from women. The HBsAg prevalence among participants was 12.9% and that HBc-Ab was 19.7%. The overall prevalence of HCV was 0.6%. Co-infection of HIV/HBV was 1.1% and that of HBV/HDV was 16.6%. A total of 77 HBV, 6 HIV, and 6 HDV strains were successfully sequenced, with 72 HBV (93.5%) strains belonging to genotype E and 5 (6.5%) strains belonging to genotype D. The 6 HDV strains all belonged to clade 1, while 4 recombinants subtype were identified among the 6 strains of HIV., Conclusion: Our study found a high prevalence of HBV, HBV/HDV and HBV/HIV co-infection, but a low prevalence of HCV. CAR remains an area of high HBV endemicity. This study's data and analyses would be useful for establishing an integrated viral hepatitis and HIV surveillance program in the CAR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Basimane-Bisimwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa., Methods: Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses., Results: A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7-105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2-15.6]) and DNA (OR = 8.9; 95% CI = [5.9-13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3-14.0]) and RNA (OR = 16.5; 95% CI = [7.8-34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9-112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3-387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0-13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6-10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4-13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results., Conclusions: In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Chronic infections with either hepatitis B or C virus (HBV or HCV) are among the most common risk factors for developing hepatocellular carcinoma (HCC). The hepatocarcinogenic potential of these viruses is mediated through a wide range of mechanisms, including the induction of chronic inflammation and oxidative stress and the deregulation of cellular pathways by viral proteins. Over the last decade, effective anti-viral agents have made sustained viral suppression or cure a feasible treatment objective for most chronic HBV/HCV patients. Given the tumorigenic potential of HBV/HCV, it is no surprise that obtaining sustained viral suppression or eradication proves to be effective in preventing HCC. This review summarizes the mechanisms by which HCV and HBV exert their hepatocarcinogenic activity and describes in detail the efficacy of anti-HBV and anti-HCV therapies in terms of HCC prevention. Although these treatments significantly reduce the risk for HCC in patients with chronic viral hepatitis, this risk is not eliminated. Therefore, we evaluate potential strategies to improve these outcomes further and address some of the remaining controversies.

In the framework of a viral discovery research program using metagenomics, Human Pegivirus-1 reads (HPgV-1, formerly known as GBV-C) were detected in plasma pools of healthy blood donors from seven sub-Saharan African countries. For five of these countries, Mauritania, Mali, Niger, Burundi and Madagascar, no data about HPgV-1 genotypes was reported to date. To confirm our metagenomic findings and further investigate the genotype diversity and distribution of HPgV-1 in Africa, 400 blood donations from these five localities as well as from Cameroon, the Democratic Republic of Congo (DRC) and the Burkina Faso were screened with a RT-nested PCR targeting the viral 5'NCR region. Amplified products were sequenced, and the virus was genotyped by phylogenetic analysis. Out of the 400 plasma samples tested, 65 were positive for HPgV-1 RNA and 61 were successfully genotyped. Among these, 54 strains (88.5%) clustered with genotype 1, six (9.8%) with genotype 2 and one (1.6%) with genotype 5. Genotype 1 was observed in all countries studied, except in Madagascar, genotype 2 was detected in Mauritania and Madagascar, and genotype 5 in DRC. Overall, our results extend the geographic distribution of HPgV-1 in Africa and provide six additional nearly complete genomes. Considering that some HPgV-1 genotypes have been reported as potential predictive indicators of lower disease progression in HIV-1 infected subjects, further investigations should be conducted to better understand the positive impact, if any, of this virus., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: given the lack of studies on acute hepatitis (AH) in Tunisia, we carried out this study to find the etiological spectrum and clinical profile of AH and to investigate the impact of viral etiology on the outcomes of AH., Methods: retrospective descriptive study collecting all patients with AH from 2010 to 2017. The data were compared between two groups (viral AH and non-viral AH)., Results: one hundred and three patient´s files were included. The average age of our patients was 30.15 years. An etiology was found in 92 patients (89.3%). The viral etiology was found in 70 patients (76.1%). Hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV) and cytomegalovirus (CMV) were in the cause in 52, 16, 1 and 1 patient respectively. Elsewhere, it was toxic hepatitis in 10 patients (10.9%) including 7 of drug-related AH. Budd-Chiari syndrome and autoimmune hepatitis with acute onset were reported in 3 (3.3%) and 7 (7.6%) patients, respectively. Patients with viral AH were younger than those with non-viral AH (p = 10- 3 ). There was more recourse to hospitalization for non-viral AH. Patients with viral AH had a higher mean aminotransferase (ALT) level than those with non-viral AH. The liver damage was more severe in the non-viral AH group with lower PT. There was more severe form, more transition to chronicity and more deaths in the non-viral AH group. Conclusion: the results found in our study concerning the distribution of the etiologies of AH as well as their evolutionary aspects are consistent with the data in the literature., Competing Interests: The authors declare no competing interests., (Copyright: Nour Elleuch et al.)

Background: Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2'-5'-oligoadenylate synthase-3, oas-3)., Case Presentation: We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein-Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out., Conclusion: To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications., (© 2021. The Author(s).)

In this special issue, we present collected updated data on the hepatitis viruses [...].

Human pegivirus 1 (HPgV-1) belongs to the genus Pegivirus, family Flaviviridae, and until now has been considered a non-pathogenic agent, despite being considered a risk factor for non-Hodgkin lymphoma. However, a beneficial impact of HPgV-1 on HIV disease progression has been extensively reported. Given the high prevalence of HIV in sub-Saharan Africa and the scarcity of epidemiological data for many countries of West Africa, we conducted the first study of HPgV-1 in HIV-infected individuals from Cabo Verde. To obtain new data regarding prevalence and genetic diversity of HPgV-1 in Africa, serum samples from 102 HIV-infected Cabo Verdeans were tested for the presence of viral RNA, and the circulating genotypes were identified by sequencing of the 5' untranslated region. HPgV-1 RNA was detected in 19.6% (20/102) of the samples. In 72.2% (13/18) of the samples, the virus was identified as genotype 2 (11/13 subtype 2a and 2/13 subtype 2b), and in 27.8% (5/18), it was identified as genotype 1. The estimated substitution rate of HPgV-1 genotype 2 was 5.76 × 10 -4 , and Bayesian analysis indicated the existence of inner clusters within subtypes 2a and 2b. The prevalence of HPgV-1 viremia in Cabo Verde agrees with that reported previously in Africa. Genotypes 1 and 2 cocirculate, with genotype 2 being more common, and HIV/HPgV-1 coinfection was not associated with higher CD4 T cell counts in the studied population. This finding contributes for the expansion of the pegivirus research agenda in African countries.

More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction. ICIs appear to be relatively safe in HBV/HCV-infected patients, and hepatitis related to viral reactivation is rare. In some patients, viral load regressed during ICI treatment, so immune checkpoints may play a role in viral clearance. HBV/HCV do not appear to be a contraindication to ICIs, although careful clinical and biochemical follow-up is recommended and, whenever necessary, antiviral therapy commenced.

Viral hepatitis is a deadly disease which can manifest as acute, chronic, hepatocellular carcinoma, and liver failure. Information about hepatitis is scarce among animal handlers. Due to Federal Government of Nigeria diversification programmes, many people are now involved in animal farming which can make them susceptible to viral hepatitis. This study aimed at determining the prevalence of Hepatitis B, C, and E viruses among animal handlers in Abeokuta, southwestern Nigerian. A total of 156 subjects were recruited for the study. Sociodemographic and risks factors data were fetched from subjects using interviewer-administered questionnaire. Blood samples were collected via venepuncture and tested for HCV, HBV, and HEV using ELISA technique. Results were analyzed using SPSS software version 21.0 and P value ≤ 0.05 was considered significant. The prevalence of HCV, HBV, and HEV were 46 (29.5%), 20 (12.8%), and 4 (2.6%) respectively while 6 (3.8%), 1 (0.6%), and 1 (0.6%) had co-infection of HBV-HCV, HBV-HEV, and HCV- HEV respectively. This study concludes that there is high prevalence of hepatitis C and B viruses among animal handlers in Abeokuta, Ogun state which is of significant public health problem, warranting further attention and research.

Background and Goals: The aims of the present study were to investigate the natural history of cirrhosis and to determine trends in the etiology of cirrhosis., Methods: Between January 2001 and January 2018, a total of 1,341 patients had been diagnosed with cirrhosis and were included., Results: A total of 898 cirrhotic patients, who were followed up for at least 6 months were included into the analysis. The median age was 54 years. The median Child-Pugh and MELD scores were 7.5 and 11, respectively. Ascites (51%) was the most common causes of decompensation. Chronic viral hepatitis was the most frequent cause of cirrhosis (58%). Hepatitis B virus (HBV) infection was the main etiology (34%), followed by hepatitis C virus (HCV) infection (18%). Among 129 patients with cryptogenic cirrhosis (CC), 60 had metabolic abnormalities. If these 60 patients with CC were considered to have nonalcoholic fatty liver disease (NAFLD)-related cirrhosis, the proportion of NAFLD-related cirrhosis increased from 1.8 to 8.0%. At admission, 74 patients (8%) had been diagnosed with hepatocellular carcinoma (HCC). A new HCC developed in 80 patients during the follow-up period. The probability of developing HCC was 3.9% at 12 months. Logistic regression analysis showed that the development of HCC was significantly associated with older age (p < 0.001), male gender (p < 0.001), viral etiology (p = 0.026), and baseline high aspartate aminotransferase level (p = 0.01). Overall, 104 cirrhotic patients died., Conclusion: HBV and HCV remain the leading causes of etiology in cirrhosis and HCC. However, NAFLD-related cirrhosis is recognized as a growing burden., (© 2020 S. Karger AG, Basel.)

Viral hepatitis is the primary cause of liver diseases, among which liver cancer is the leading cause of death from cancer. However, this cancer is often diagnosed in the later stages, which makes treatment difficult or even impossible. This study applied deep learning (DL) models for the early prediction of liver cancer in a hepatitis cohort. In this study, we surveyed 1 million random samples from the National Health Insurance Research Database (NHIRD) to analyze viral hepatitis patients from 2002 to 2010. Then, we used DL models to predict liver cancer cases based on the history of diseases of the hepatitis cohort. Our results revealed the annual prevalence of hepatitis in Taiwan increased from 2002 to 2010, with an average annual percentage change (AAPC) of 5.8% (95% CI: 4.2-7.4). However, young people (aged 16-30 years) exhibited a decreasing trend, with an AAPC of -5.6 (95% CI: -8.1 to -2.9). The results of applying DL models showed that the convolution neural network (CNN) model yielded the best performance in terms of predicting liver cancer cases, with an accuracy of 0.980 (AUC: 0.886). In conclusion, this study showed an increasing trend in the annual prevalence of hepatitis, but a decreasing trend in young people from 2002 to 2010 in Taiwan. The CNN model may be applied to predict liver cancer in a hepatitis cohort with high accuracy., (© 2020 UICC.)

Human polyomaviruses (PyVs) and hepatitis viruses are often more prevalent or persistent in human immunodeficiency virus (HIV)-infected persons and the associated diseases are more abundant than in immunocompetent individuals. Here, we evaluated seroreactivities and viral loads of human PyVs and hepatitis viruses in HIV/AIDS patients and the general population in China in the combination antiretroviral therapy (cART) era. A total of 810 HIV-1-infected patients and age- and sex-matched HIV-negative individuals were enrolled to assess seroprevalence of PyVs BKPyV, JCPyV, MCPyV, TSPyV, and NJPyV and hepatitis viruses HBV, HCV, and HEV. 583 (72%) patients received cART, and among them, 31.2% had undetectable HIV RNA. While no significant difference was observed in prevalence of anti-PyV antibodies between HIV-positive and -negative groups, serum DNA positivity and DNA copy level of MCPyV were higher in the HIV-positive group. Among HIV-infected patients, BKPyV DNA positivity was significantly higher in patients with CD4 + cell counts < 200 cells/mm 3 compared to those with CD4 + cell counts > 500 cells/mm 3 , suggesting possible reactivation caused by HIV-induced immune suppression. Higher HBV and HCV seropositivities but not HEV seropositivity were also observed in the HIV-positive group. Further correlation analyses demonstrated that HBV and HEV are potential risk factors for increased prevalence of PyV infection.

Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Hepatitis E Virus (HEV) are highly endemic in several African countries including Nigeria with adverse effects on pregnancy outcomes resulting in fatality. This study aimed to determine the viral hepatitis in pregnant women attending antenatal clinic, AMTHI. Informed consent questionnaire was administered before blood collection via venipuncture. a total of 904 pregnant women plasma samples were tested for HBV, HCV, and HEV using ELISA kit. Data was analyzed using packages within SPSS software and P ≤ 0.05 was considered significant. Out of 904 samples analyzed, the overall prevalence of hepatitis infections among pregnant women attending antenatal clinic in AMTHI was 66(7.3%). High prevalence of the hepatitis infections was found among young women within the age group 21-30 which might be associated with active sex, intravenous drug use, sharing of sharp objects and alcoholism. Blood group O Positive had the highest prevalence of hepatitis. There was statistical significance between blood group and HBsAg infection ( P < .05). Genotype AA women had highest prevalence of hepatitis. This study showed significant association between HBsAg, HCV, and HEV positive status with blood group O positive and Genotype AA pregnant women.

In China, the prevalence of Clonorchis sinensis (C. sinensis) infections is only evaluated at the provincial level by national sampling surveys, and data from villages and counties are still lacking. In this study, we conducted a cross-sectional survey in 10 villages located along the Lalin River in northeast China. Clonorchiasis was diagnosed using a modified Kato-Katz method that detects the C. sinensis egg in stools. A total of 3,068 persons were screened and 2,911 were recruited for the study. Overall, the prevalence of C. sinensis infection was 29.3%. Among 175 participants who were cured after antiparasitic treatment, 54 (30.86%) were re-infected in this survey. After calibration of potential confounders, male gender, occupation as a farmer, smoking, and occasionally or frequently eating raw fish were independent risk factors for C. sinensis infection. The results of laboratory examinations in the C. sinensis/hepatitis B or C virus co-infection group were similar to those in the hepatitis B or C virus mono-infection groups. In conclusion, C. sinensis is highly endemic in villages along the Lalin River, and the primary route of infection is the consumption of raw freshwater fish. Co-infection with C. sinensis did't aggravate the clinical manifestations of viral hepatitis in this cross-sectional study.

BACKGROUND Cytomegalovirus (CMV) is a member of Herpesviridae family with its name derived from the fact that it causes enlargement of the infected cell resulting in the characteristic inclusion bodies seen on microscopy. CMV virus has an incubation period of about 4 to 6 weeks. Symptoms of CMV infection vary and depend on factors including the age and immune status of the patient. It usually presents as asymptomatic infection in immunocompetent individuals whereas severe disease is usually seen in immunocompromised patients. Here we present a case of an immunocompetent patient who presented with acute CMV hepatitis. CASE REPORT A 35-year-old male with no significant prior medical history who presented to the Emergency Department with a 2-week history of low-grade fever. Acute CMV infection was diagnosed by positive CMV antibody and polymerase chain reaction (PCR) testing. The patient was treated with valganciclovir that resulted in rapid improvement in clinical status as well as normalization of the liver enzymes. CONCLUSIONS This article presents a rare case of immunocompetent young male with acute CMV hepatitis who responded favorably to antiviral therapy.

Background: The capacity to integrate platforms across vendors and disciplines has become an essential feature in the design of total laboratory automation (TLA) due space and test menu constraints. However, data on its performance are lacking. We aim to evaluate an integrated third-party immunoassay platform to the TLA system for the performance of hepatitis testing using turnaround time (TAT)., Methods: We use the Beckman Power Express (PE) system with linked 2 Beckman AU5800, 2 Beckman DxI 800, 2 Abbott Architect i2000, and other accessory components. The PE system is managed and interfaced to the laboratory information system (LIS) through Beckman Remisol (middleware) and Cennexus (track software). The hepatitis tests are performed on the Abbott Architect i2000 using Abbott Instrument Manager (middleware) for test results and this is interfaced with LIS and Cennexus. Using Viewics and Microsoft Excel, the test volumes and TAT of hepatitis results were analyzed before (February 2017 to January 2018) and after (February 2018 to January 2019) integration., Results: The TAT for each hepatitis test has decreased significantly, ranging from 13 to 81-minute reductions (P value <0.0001 for all tests) after instrument integration. The standard deviations of the TAT also decreased for each test. In addition, savings in labor expenditure of around 2 hours per day were observed. There were no laboratory space savings identified. Instead, 47.6 square foot more of space was utilized by the track connection lines., Conclusions: Our findings show significant improvement of TAT of hepatitis testing with the integration of the third-party Abbott Architect i2000 to Beckman PE system. In addition, the synchronization of multiple middleware for specimen management and result reporting allow the laboratory to achieve new efficiencies handling reflex tests and managing human resources., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized., Methods: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared., Results: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups., Discussion: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

The SEN virus (SENV) has been linked to transfusion-associated non-A-E hepatitis; however, information regarding SENV infections in patients with thalassemia, particularly in those with hepatitis virus co-infections, remains limited. This study investigated the frequency of SENV (genotypes D and H) infections in Iraqi patients with thalassemic patients infected and not infected with hepatitis C virus. The study involved 150 β-thalassemia patients (75 with HCV infections and 75 without) and 75 healthy blood donors. Patient levels of vitamins C and E, liver function markers, and glutathione peroxidase (GPX) were determined. Recovered viral nucleic acids were amplified using the conventional polymerase chain reaction (SENV DNA) or the real-time polymerase chain reaction (HCV RNA) techniques. Only 10% of healthy donors had evidence of SENV infection. Among patients with thalassemia, 80% and 77% of patients with and without concurrent HCV infections, respectively, had SENV infections. DNA sequencing analyses were performed on blood samples obtained from 29 patients. Patients with thalassemia, particularly those with SENV infections, had higher levels of several enzymatic liver function markers and total serum bilirubin (P < 0.05) than did healthy blood donors. Among the examined liver function markers, only gamma-glutamyl transferase demonstrated significantly higher levels in HCV-negative patients infected with SENV-H than in those infected with SENV-D (P = 0.01). There were significantly lower vitamin C, vitamin E, and glutathione peroxidase levels in patients than in healthy donors (P < 0.05), but only glutathione peroxidase levels were significantly lower in HCV-negative thalassemia patients infected with SENV than in those without SENV infections (P = 0.04). The SENV-H genotype sequences were similar to the global standard genes in GenBank. These results broaden our understanding the nature of the SENV-H genotype and the differential role of SENV-H infections, compared to SENV-D infections, in patients with thalassemia, in Iraq., Competing Interests: No competing interests exist.

Background: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown., Methods: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined., Results: 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P <  0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge., Conclusions: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

In rare cases, hepatitis A virus (HAV) and hepatitis B virus (HBV) can cause fulminant viral hepatitis (FVH), characterized by massive hepatocyte necrosis and an inflammatory infiltrate. Other viral etiologies of FVH are rarer. FVH is life-threatening, but the patients are typically otherwise healthy, and normally resistant to other microbes. Only a small minority of infected individuals develop FVH, and this is the key issue to be addressed for this disease. In mice, mouse hepatitis virus 3 (MHV3) infection is the main model for dissecting FVH pathogenesis. Susceptibility to MHV3 differs between genetic backgrounds, with high and low mortality in C57BL6 and A/J mice, respectively. FVH pathogenesis in mice is related to uncontrolled inflammation and fibrinogen deposition. In humans, FVH is typically sporadic, but rare familial forms also exist, suggesting that there may be causal monogenic inborn errors. A recent study reported a single-gene inborn error of human immunity underlying FVH. A patient with autosomal recessive complete IL-18BP deficiency was shown to have FVH following HAV infection. The mechanism probably involves enhanced IL-18- and IFN-γ-dependent killing of hepatocytes by NK and CD8 T cytotoxic cells. Proof-of-principle that FVH can be genetic is important clinically, for the affected patients and their families, and immunologically, for the study of immunity to viruses in the liver. Moreover, the FVH-causing IL18BP genotype suggests that excessive IL-18 immunity may be a general mechanism underlying FVH, perhaps through the enhancement of IFN-γ immunity.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in immunocompetent hosts, commonly manifest as acute hepatitis, with severity varying from asymptomatic, self-limited icteric hepatitis to acute liver failure. Atypical manifestations, such as cholestasis, chronic hepatitis, precipitation of acute-on-chronic liver failure, and autoimmune hepatitis, are reported with EBV infection, whereas cholestasis, portal vein thrombosis, and Budd-Chiari syndrome are reported with CMV infection. In the setting of liver transplantation, CMV is the most common infectious complication and carries significant morbidity; EBV is the major cause of post-transplant lymphoproliferative disorders., Competing Interests: Conflict of Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

The review presents the data accumulated for more than 20 years of research of torque teno virus (TTV). Its molecular genetic structure, immunobiology, epidemiology, diagnostic methods, possible replication sites, and pathogenicity factors are described. TTV is a virus that is frequently detectable in patients with different viral hepatitides, in cases of hepatitis without an obvious viral agent, as well as in a healthy population. There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection. There are sufficient histological signs of liver damage, which confirm that the virus can undergo a replicative cycle in hepatocytes. Along with this, cytological hybridization in TTV-infected cells has shown no substantial cytopathic (cell-damaging) effects that are characteristic of pathogenic hepatotropic viruses. Studying TTV has led to the evolution of views on its role in the development of human pathology. The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses, including the viruses of the known types of hepatitides. The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a non-pathogenic virus. It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body's immune status. The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses. Fortunately, the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties. The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Disseminated herpes simplex virus (HSV) is mainly seen in immunocompromised individuals. Atypical lesions can be present in both primary infection and reactivation disease. Compared with the general population, inmunocompromised hosts are at greater risk of increased persistency and severity of clinical manifestations, including severe systemic involvement such as esophagitis, meningitis, and hepatitis. Herein, we report the case of a liver transplant recipient with atypical disseminated herpes simplex virus-1 complicated by HSV-related hepatitis. Dermatological consultation and histological assessment were crucial for a correct diagnosis and treatment.

Backgrounds: Neural growth factor (NGF) is a neurotrophin that can interact with the p75 NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75 NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon., Methods: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires., Results: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75 NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects., Conclusion: Mutations in the NGF (-198C > T, Ala35Val) and p75 NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Viral hepatitis is a major global public health problem affecting hundreds of millions of people and is associated with significant morbidity and mortality. Five major biologically unrelated hepatotropic viruses cause most of the global burden of viral hepatitis. Hepatitis B and hepatitis C are associated with a significant number of chronic infections. Most deaths from viral hepatitis are due to hepatitis B and hepatitis C. An estimated 257 million people were living with HBV and 71 million people were living with HCV. Most people are asymptomatic. New diagnostics and highly effective, pangenotypic direct-acting antivirals provide opportunities to cure and eradicate chronic hepatitis C virus infection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Neonatal herpes simplex viral infections are rare in the setting of appropriate prenatal care; however, under circumstances where prenatal care is not delivered, these infections can lead to significant disease. We report a fatal case of herpes simplex virus with severe herpes hepatitis in a 14-day old male neonate. The clinical history was limited and nonspecific, however there was no prenatal care and a known history of drug abuse in the family. Autopsy revealed extensive necrosis and hemorrhage of the liver and cerebellum. Histologically, the liver revealed viral intranuclear ground glass inclusions, characteristic of herpes virus. Immunohistochemistry for herpes simplex virus performed on the both the liver and cerebellum showed strong diffuse staining in the liver and negative staining in the cerebellum. Neonatal herpes simplex virus infection is a disease of low prevalence with significant morbidity and mortality, and an exceptionally high rate of fatality in those with disseminated disease with associated fulminant hepatic failure.

Objectives: The objectives of this study were to evaluate the prevalence of Human Pegivirus-1 (HPgV-1) viremia and genotype diversity among healthy blood donors from the Eastern Brazilian Amazon (city of Macapá, State of Amapá). There is little information for prevalence and circulation of HPgV-1 in this remote Brazilian region., Materials and Methods: We conducted a study evaluating the HPgV-1 RNA prevalence and circulating genotypes in 431 volunteer blood donors originating from the Eastern Brazilian Amazon. The obtained HPgV-1 positive samples were submitted to sequencing and genotyping analysis in order to examine the genotype diversity of this virus in the Brazilian Amazon., Results: Our results demonstrated a prevalence of HPgV-1 RNA in 9.5% of the tested blood donors. The phylogenetic analyses of the detected positive samples showed the presence of HPgV-1 genotypes 1, 2 and 3. The most frequently detected genotype was 2 (78.0% of the cases) represented by sub-genotypes 2A (39.0%) and 2B (39.0%). At lower rates, genotypes 1 (14.6%) and 3 (7.4%) were also detected., Conclusion: Our results revealed the presence of genotypes with European, Asiatic and African endemicity in Amazonian blood donors, probably due to the complex miscegenation processes that took place in this Brazilian region. More investigations, including information for the prevalence of HPgV-1 RNA in blood donors from other Latin American countries are needed to estimate the viremic rates and genotype distribution of this virus in a highly diverse continent like South America., (Copyright © 2019 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Hepatitis virus infections affect a large proportion of the global population. The host responds rapidly to viral infection by orchestrating a variety of cellular machineries, in particular, the mitochondrial compartment. Mitochondria actively regulate viral infections through modulation of the cellular innate immunity and reprogramming of metabolism. In turn, hepatitis viruses are able to modulate the morphodynamics and functions of mitochondria, but the mode of actions are distinct with respect to different types of hepatitis viruses. The resulting mutual interactions between viruses and mitochondria partially explain the clinical presentation of viral hepatitis, influence the response to antiviral treatment, and offer rational avenues for novel therapy. In this review, we aim to consider in depth the multifaceted interactions of mitochondria with hepatitis virus infections and emphasize the implications for understanding pathogenesis and advancing therapeutic development., (© 2019 The Authors Reviews in Medical Virology Published by John Wiley & Sons Ltd.)

The syndrome of infectious mononucleosis is commonly seen with Epstein-Barr virus (EBV) infection. It may cause acute hepatitis, which is usually self-limiting and characterised by mildly elevated liver enzymes, but rarely jaundice. The patient being reported showcases EBV infection with jaundice, which is an uncommon scenario., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of this study was to estimate the prevalence of different serological markers of hepatitis A, B and C viruses and Treponema pallidum among the adult population of Argentina. To achieve this, adults who attended health services for premarital exams (which are mandatory and includes screening for syphilis) were recruited. A cross-sectional study was designed with a cluster sampling strategy. Couples who attended selected health services for premarital screening between 2013 and 2014 in Buenos Aires, Cordoba, Mendoza and Santa Fe provinces were included. A total of 3833 individuals were recruited. Anti-HAV prevalence was 63.9%, anti-HCV 0.3%, anti-HBc (without HBsAg) 1.9%, HBsAg 0.3%, and T pallidum 0.8%. Anti-HAV was higher among older participants, foreigners and those from the lower strata. HBV increased with age and was higher among foreigners and those with lower formal educational level. Anti-HCV frequency increased with age. Premarital screening of viral hepatitis could constitute an instance of diagnosis, vaccination and inclusion in care of those in need. Results from this study will allow the national hepatitis programs to design public policies in order to diminish the impact of these infections on the population.

Background: Prison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population., Methods: A prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution., Results: In 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (p<0.0001) and was higher among Eastern Europe born inmates (p<0.0001). Between 2014 and 2017, HIV seroprevalence remained steady, while a decrease in HBV and HCV seroprevalence was observed., Conclusions: Compared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population., Competing Interests: The authors have declared that no competing interests exist.

Background: An escalation, as three times more, had been recognized in cases of hepatitis A (HAV) from 2009 to 2014 among Iraqi people. Regarding hepatitis B and C, Iraq is considered as a low endemic country comparing to neighbors., Study Design: A retrospective cohort study., Methods: Data incorporated from 2007 to 2016 were collected through a federal survey conducted by the Health Directorate of Karbala, who administrates all hospitals (three public hospitals and five private hospitals) and 40 health centers in Karbala City, Iraq. The four types of hepatitis and demographic information of all cases were included., Results: A vivid shifting in the prevalence of HAV showed a decreasing pattern, that is, from 632 cases (PR=61) in 2007 to 314 cases (PR=33) in 2008. In 2012, its prevalence was twice greater (695 cases, PR=63.2). The PR of HBV also changed from 52 cases (PR=5.8) in 2007 to 26 cases (PR=2.8) in 2008. Regarding HCV, a decreasing pattern with 13 cases (PR=1.4) in 2007 and 12 cases (PR=1.2) in 2009 was seen. This number increased to 60 cases (PR=3.9) in 2016. For HEV, more cases were reported (47 cases, PR=4.7) in 2010., Conclusion: The four types of hepatitis have been highly prevalent since 2010. The high number of migrants to Karbala Governorate and unavailability of immunization might be reasons behind the high prevalence of the four-types of hepatitis.