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The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

Glypican‐3 (GPC3) is a cancer antigen expressed in approximately 80% of hepatocellular carcinomas (HCC) and is secreted into the blood. To confirm the effectiveness of GPC3 as a biomarker in HCC, we analyzed the relationship between GPC3 expression levels in cancer cells and in blood in 56 patients with HCC. Preoperative plasma GPC3 levels were determined with an immunoassay, and expression of GPC3 in resected tumors was analyzed by immunohistochemical staining. Median plasma GPC3 level in all HCC cases was 4.6 pg/mL, and tended to be higher in patients with hepatitis C virus (HCV)‐related HCC (HCV group) (9.9 pg/mL) than in patients with hepatitis B virus (HBV)‐related HCC (HBV group) (2.6 pg/mL) or in those without virus infection (None group) (3.0 pg/mL), suggesting that the virus type most likely influences GPC3 secretion. Median percentage of GPC3+ cells in tumors was also higher in the HCV (26.2%) and HBV (11.1%) groups than in the None group (4.2%). In the HCV group, there was a positive correlation between the two parameters (r = 0.66, P 10% GPC3+ cells in a tumor if the cut‐off value was 6.8 pg/mL (sensitivity 80%, specificity 100%; area under the curve 0.875, 95% confidence interval 0.726‐1) in the HCV group. Plasma concentration of GPC3 could be a predictive marker of tumoral GPC3 expression in patients with HCV‐related HCC, suggesting a useful biomarker for immunotherapies targeting GPC3, although larger‐scale validations are needed., Glypican‐3 (GPC3) is a cancer antigen expressed in approximately 80% of hepatocellular carcinomas (HCC) and is secreted into the blood. We analyzed the relationship between GPC3 expression levels in cancer cells and in blood in 56 patients with HCC. In conclusion, plasma concentration of GPC3 could be a predictive marker of tumoral GPC3 expression in patients with HCV‐related HCC, suggesting a useful biomarker for immunotherapies targeting GPC3.

Hepatitis is inflammation of liver cells. There are two contributing factors: infectious factors and non-infectious factors. Factors causing infection include hepatitis viruses and bacteria. Non-infectious factors for example of drugs usage. The purpose of this study was to determine the effectiveness of boiled cherry leaves (muntingia calabura L) and Figs leaves (Ficus Carica) to reduce SGOT SGPT levels. The objects in this study were 30 male Wistar strain rats aged 2-3 months with a weight of 180-200 grams. Rats were divided into 3 groups randomly: negative control group, positive control group and treatment group. The positive treatment and control group was induced paracetamol 120 mg / day orally for 7 days. 0.4 grams of Figs leaves (Ficus Carica) and 5 grams of Cherry leaves (muntingia calabura L) is boiled in 200 cc of water to 100 cc of water given as much as 3.6cc orally for 7 days in the treatment group. Data were analyzed with SPSS version 24, ANOVA test was performed to compare SGOT SGPT levels. The results showed there were significant differences in SGPT SGPT levels between the treatment and positive control groups (p

Objective To discuss the risks related to the possibilities of accidents and contamination in autopsy rooms, especially the biological risk. Methods This is an exploratory study. The databases Lilacs, MEDLINE and SciELO virtual library were searched; from 2000 until 2017; from the following inclusion criteria: articles available in full, in Portuguese, English and Spanish languages; and those that portrayed the central theme of the article. Results 53 articles were analyzed, to following the sub-themes: chemical, ergonomic, biological and accident agents; exposure to radioactive materials; electrical and electronic equipment. Conclusions The death cause is essential for epidemiological surveillance. The prevalence of diseases in the population poses risk to autopsy room professionals. Often these diseases are not detected before death; can coexist with other conditions and be ignored; or don't have morphological evidence at autopsy. M.tuberculosis, hepatitis virus, HIV and prions were the main pathogens identified. They can be transmitted by blood and aerosols; but there are other risks such as sharps, chemicals and radioactive materials. RESUMEN Objetivo Discutir los riesgos relacionados con las posibilidades de accidentes y contaminación en las salas de autopsias, especialmente el riesgo biológico. Método Este es un estudio exploratorio. Se realizaron búsquedas en las bases de datos Lilacs, MEDLINE y la biblioteca virtual SciELO, desde 2000 hasta 2017, de los siguientes criterios de inclusión: artículos disponibles en su totalidad en portugués, inglés y español, y aquellos que retrataron el tema central del artículo. Resultados Se analizaron 53 artículos, siguiendo los subtemas agentes químicos, ergonómicos, biológicos y de accidentes; exposición a materiales radiactivos; equipos eléctricos y electrónicos. Conclusiones La causa de muerte es esencial para la vigilancia epidemiológica. La prevalencia de enfermedades en la población representa un riesgo para los profesionales de la sala de autopsias. A menudo, estas enfermedades no se detectan antes de la muerte; pueden coexistir con otras condiciones y ser ignoradas, o no se tiene evidencia morfológica en la autopsia. M. tuberculosis, virus de la hepatitis, VIH y priones fueron los principales patógenos identificados. Se pueden transmitir por sangre y aerosoles; pero existen otros riesgos como objetos punzantes, productos químicos y materiales radiactivos.

Background/Aims: We aimed to investigate incidence, characteristics, and possible risk factors of pancreatic cancer in patients under observation for hepatocellular carcinoma (HCC) because the association of hepatitis virus B infection and pancreatic cancer has been reported. Patients and Methods: We performed a retrospective cohort study in the Gastroenterology Department of a University Hospital in Japan between 2004 and 2012. A total of 1848 patients who underwent treatment for HCC were included at the initiation of treatment for HCC (mean follow-up period, 33.6 months). The patients received trimonthly radiological follow-ups. Newly developed cases of pancreatic cancer during follow-up for HCC were compared with that of an age- and sex-matched theoretical cohort from national statistics. Possible predisposing factors for pancreatic cancer related to HCC were assessed. Cumulative probabilities of developing a pancreatic cancer were compared using log-rank test. Results: About 13 of 1848 patients developed pancreatic cancer (mean follow-up period, 45.2 months). The risk ratio for all patients was 3.02 (log-rank test: P =0.01). Statistical analyses showed no effects of the following factors on the development of pancreatic cancer: age, sex, follow-up period, alcohol intake, laboratory data, presence of hepatitis virus, characteristics of HCC, type of treatment, number of radiological examinations, and cumulative effective dose. Conclusions: Increased incidence of pancreatic cancer was found in patients under observation for HCC in a relatively small cohort. HCC or other common underlying conditions might be a risk factor for development of pancreatic cancer.

BACKGROUND Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain. AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction. METHODS The expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes. RESULTS A total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank P = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways. CONCLUSION An eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC.

A point-of-care apparatus for hepatitis virus detection requires simple and easy-to-use processing steps and should have the same diagnostic capability as that in the central laboratory. However, no automated and efficient methods for hepatitis B virus (HBV) sample-to-answer detection include serum separation, and complete prestorage of reagents has been developed. We developed an automated sample-to-answer disc for rapid HBV detection from whole blood based on a double rotation axes centrifugal microfluidic platform. The disc with complete prestorage of reagents features fully automated and integrated serum separation from whole blood, magnetic bead-based DNA extraction, aliquoting of the nucleic acid, and real-time polymerase chain reaction. A laser diode for sequential release of prestored liquid reagents was used. Processing merely requires manual loading of the sample into the disc. We demonstrate successful sample-to-answer detection of HBV in a 500 μL whole blood sample with sample concentrations down to 10

AIM We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically-transmitted viral hepatitis worldwide. Increasing numbers of HEV infections, together with no available specific anti-HEV treatment, contributes to the pathogen's major health burden. A robust cell culture system is required for virologic studies and the development of new antiviral drugs. Unfortunately, like other hepatitis viruses, HEV is difficult to propagate in conventional cell lines. Many different cell culture systems have been tested using various HEV strains, but viral replication usually progresses very slowly, and infection with low virion counts results in non-productive HEV replication. However, recent progress involving generation of cDNA clones and passaging primary patient isolates in distinct cell lines has improved in vitro HEV propagation. This review describes various approaches to cultivate HEV in cellular and animal models and how these systems are used to study HEV infections and evaluate anti-HEV drug candidates.

目的 探讨Ⅱ型冷球蛋白血症患者的临床特征及预后。 方法 回顾性分析2015年5月至2020年1月北京协和医院确诊的61例Ⅱ型冷球蛋白血症患者的临床资料。 结果 61例患者中，男性26例（42.6％），中位诊断年龄为53（28～79）岁。继发病因包括丙型肝炎病毒（HCV）感染（21.3％）、乙型肝炎病毒（HBV）感染（21.3％）、自身免疫性疾病（14.8％）和血液系统肿瘤（11.5％）。31.1％患者为特发性。常见首诊症状包括皮肤紫癜、蛋白尿、血尿、肾功能不全、发热及关节痛。实验室检查显示，中位冷球蛋白水平为215.9（22.0～17 075.8）g/L，54例（88.5％）为IgM单克隆。类风湿因子（RF）升高患者占93.2％，C3下降患者占57.6％，C4下降患者占61.0％。共49例（80.3％）患者接受治疗，总体临床缓解率为75.5％，预计3年总生存率为89.3％。 结论 Ⅱ型冷球蛋白血症是一种多系统受累的全身性疾病，病因以肝炎病毒感染多见。早期诊断和干预对于改善预后有重要意义。

Waterborne epidemics of human hepatitis virus A and E (HAV and HEV) have been reported worldwide. Molecular biology techniques, such as reverse transcription polymerase chain reaction (RT-PCR), have been widely used to detect the two hepatitis viruses. However, comparative studies of various types of samples are needed, and different environmental factors, including the low copy pathogens, presence of PCR inhibitors in the sample, unknown non-specific reaction with template, and sequence diversity leading to new variants in viruses, should be considered. In addition, standard positive material is required to determine the accuracy of the PCR and should be able to distinguish between false and real positives. In this study, we developed RT-PCR primer sets and optimised standard templates for HAV and HEV detection to address the above concerns associated with test sensitivity and possible PCR inhibition. Finally, previously reported diagnostic methods of HAV and HEV were compared and an applicability test using groundwater was performed. The nested RT-PCR developed in this study is expected to contribute to assess water safety by monitoring HAV and HEV in non-disinfected water, like groundwater.

Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.

The humanized mouse is a widely used in vivo model for the investigation of pathogenesis and drug development. In this study, we generated new immunodeficiency cDNA-urokinase-type plasminogen activator (uPA)/SCID/Rag2-/-/Jak3-/- mice and established the mouse model with a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)-A24 resulted in establishment of a highly replaced liver in this mouse model. These mice were successfully infected with hepatitis B virus and hepatis C virus (HCV) for a prolonged period and are available for the analysis of the effect of anti-HCV drugs. Administration of peripheral blood mononuclear cells (PBMCs) obtained from a donor with HLA-A24 resulted in the establishment of 22.6–81.3% of human CD45-positive mononuclear cell chimerism in liver infiltrating cells without causing graft versus host disease. When mice were transplanted with human hepatocytes and then administered PBMCs, an alloimmune response between transplanted human hepatocytes and PBMCs occurred, with production of transplanted hepatocyte-specific anti-HLA antibody. The alloimmunity was never inhibited by methylprednisolone nor cyclosporine A. In conclusion, we succeeded in establishing a humanized liver and immune system using a novel cDNA-uPA/SCID/Rag2-/-/Jak3-/- mouse. This model is not only useful to study hepatitis virus virology but also to study alloimmunity.

The lack of an appropriate platform for a better understanding of the molecular basis of hepatitis viruses and the absence of reliable models to identify novel therapeutic agents for a targeted treatment are the two major obstacles for launching efficient clinical protocols in different types of viral hepatitis. Viruses are obligate intracellular parasites, and the development of model systems for efficient viral replication is necessary for basic and applied studies. Viral hepatitis is a major health issue and a leading cause of morbidity and mortality. Despite the extensive efforts that have been made on fundamental and translational research, traditional models are not effective in representing this viral infection in a laboratory. In this review, we discuss in vitro cell-based models and in vivo animal models, with their strengths and weaknesses. In addition, the most important findings that have been retrieved from each model are described.

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

The liver is a target organ of life-threatening pathogens and prominently contributes to the variation in drug responses and drug-induced liver injury among patients. Currently available drugs significantly decrease the morbidity and mortality of liver-dwelling pathogens worldwide; however, emerging clinical evidence reveals the importance of host factors in the design of safe and effective therapies for individuals, known as personalized medicine. Given the primary adherence of cells in conventional two-dimensional culture, the use of these one-size-fit-to-all models in preclinical drug development can lead to substantial failures in assessing therapeutic safety and efficacy. Advances in stem cell biology, bioengineering and material sciences allow us to develop a more physiologically relevant model that is capable of recapitulating the human liver. This report reviews the current use of liver-on-a-chip models of hepatotropic infectious diseases in the context of precision medicine including hepatitis virus and malaria parasites, assesses patient-specific responses to antiviral drugs, and designs personalized therapeutic treatments to address the need for a personalized liver-like model. Second, most organs-on-chips lack a monitoring system for cell functions in real time; thus, the review discusses recent advances and challenges in combining liver-on-a-chip technology with biosensors for assessing hepatocyte viability and functions. Prospectively, the biosensor-integrated liver-on-a-chip device would provide novel biological insights that could accelerate the development of novel therapeutic compounds.

BACKGROUND & AIM: Coexisting alcoholic liver disease and virus-induced liver cirrhosis (ALD+HBV and ALD+HCV) has not been thoroughly studied. This cross-sectional study aims to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis.METHOD: Patients diagnosed with liver cirrhosis (n=22287) from January 2010 to December 2019 were collected from our hospital electronic database, and divided into five groups according to the etiology: ALD (1652 cases, 7.4%), HBV (18079 cases, 81.1%), HCV (682 cases, 3.1%), ALD+HBV (1594 cases, 7.2%) and ALD+HCV (280 cases, 1.3%). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups.RESULTS: ALD+HBV and ALD+HCV presented with higher proportions of poor prognosis patients and cirrhosis complications compared to HBV and HCV respectively. Multivariate logistic regression revealed that the risk of HCC and that of EGVB in the ALD+HBV group was respectively 2.14-fold and 1.47-fold that in the HBV group (HCC: OR=2.14, 95%CI: [1.71-2.69]; EGVB: OR=1.47, 95%CI: [1.17-1.84]) after adjusting for potential confounders. Furthermore, a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence was observed. Similar pattern was noticed while comparing ALD+HCV group to HCV group.CONCLUSION: Alcohol significantly increased the severity of liver function impairment and the prevalence of liver cirrhosis complications such as HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long period of alcohol abstinence significantly decreased the prevalence of HCC and EGVB in these populations.

Humans are subjected to various diseases; hence, proper diagnosis helps avoid further disease consequences. One such severe issue that could cause significant damage to the human liver is the hepatitis C virus (HCV). Several techniques are available to detect HCV under various categories, such as detection through antibodies, antigens, and RNA. Although immunoassays play a significant role in discovering hepatitis viruses, there is a need for point-of-care tests (POCT). Some developing strategies are required to ensure the appropriate selection of POCT for HCV detection, initiate appropriate antiviral therapy, and define associated risks, which will be critical in achieving optimal outcomes. Though molecular assays are precise, reproducible, sensitive, and specific, alternative strategies are required to enhance HCV diagnosis among the infected population. Herein, we described and assessed the potential of various microfluidic detection techniques and confirmatory approaches used in present communities. In addition, current key market players in HCV chip-based diagnosis and the future perspectives on the basis of which the diagnosis can be made easier are presented in the present review.

In 2020, the Noble Prize for Medicine jointly went to three scientists for hepatitis C virus-related discoveries. Earlier in 1976, an American scientist won this award for the discovery of hepatitis B virus. The Noble Prize, constituted as per the will of Alfred Noble, is awarded every year for achievements that benefit human beings in the best possible way. Although humans have known hepatitis as a deadly disease for hundreds of years, it was the discovery of hepatitis B and C viruses that changed the way we knew the hepatitis viruses forever and paved the way for saving millions of lives all over the world, the reason why the Noble Committee has on two different occasions picked up the great minds behind the discovery of these two hepatitis viruses and recognized them by conferring them with the highest recognition that one dreams of. How to cite this article: Al-Mahtab M, Roy PP, Khan MSI, et al. Nobel Prize for the Discovery of Hepatitis B and C: A Brief History in Time. Euroasian J Hepatogastroenterol 2020;10(2):98–100.

BackgroundAnesthesia practitioners are at inherent risk for percutaneous injuries by blood-contaminated needles and sharp objects. These exposures may result in transmission of HIV and hepatitis viruses. Data about this occupational hazard from contaminated needles and sharp devices is limited and decades old. We conducted a web-based survey to assess the occurrence, reporting, characteristics, and outcome of contaminated percutaneous injuries (CPI) in anesthesia residents, fellows, and attendings.MethodsAfter institutional research board approval, an email was sent to 217 anesthesia practitioners requesting their participation in an online survey about contaminated percutaneous injuries. Responses were collected from February through March 2020. Results are reported as absolute numbers and proportions with 95% confidence interval (CI).ResultsThe overall survey response rate was 51% (110/217). 59% (65/110) (95% CI, 50–68) of participants reported having one or more contaminated percutaneous injury during their years of anesthesia practice (42% (21/50) of residents, 50% (4/8) of fellows, 77% (40/52) of anesthesia attendings). Prevalence of injuries related to attendings’ years of anesthesia practice was 69% (95% CI, 44–94) for 5-10 years, 62.5% (95% CI, 29–96) for 10-15 years, and 79% (95% CI, 63– 95) for greater than 15 years of practice.35% (95% CI, 26–44) of participants reported having one or more CPI within the last 5 years (40% of residents, 50% of fellows, 29% of attendings). Occurrence of CPI within the last 5 years based on attending anesthesiologist years of practice was 57% for less than 5 years, 37.5% for 10-15 years, and 20% for 15-20 years of practice. 75% (95% CI, 65–85) reported the incident at the time of injury. 59% (95% CI, 48–70) of injuries were due to hollow bore needles. 50% (95% CI, 39–61) of total injuries were high risk. 26% of injured anesthesia practitioners received post-exposure prophylaxis and there were zero seroconversions.ConclusionMost anesthesiologists will sustain a contaminated percutaneous injury during their careers. Incidence of these injuries decreases with years of practice. Occurrence of these injuries is high among anesthesia residents, with the majority reporting their injuries. Half of the injuries are high risk with a quarter requiring postexposure prophylaxis. More education and interventions are needed to reduce percutaneous injuries and improve reporting.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p &lt, 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.

International audience; Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies.

Purpose: Gender inequality is a barrier to education toward women and accessibility to health facilities, which are important for preventing vertical transmission. This study was conducted to analyze the impact of gender equity on vertically transmitted infections (hepatitis viruses, human immunodeficiency virus [HIV], and syphilis) using country-level indicators. Methods: The relationship between the Global Gender Gap Index (GGGI), which is indicator of gender equity, and vertical transmission was analyzed. GGGI scores were collected from 153 countries in 2020. Vertical transmission included 10 outcomes for hepatitis viruses, HIV, and syphilis. Generalized linear model (GLM) was used for analyzing the relationship. Other predictors included skilled birth attendant and country income. Results: The median GGGI score was 0.706 (interquartile range, 0.664–0.736). GLM showed that the GGGI score was significantly associated with the incidence of both chronic hepatitis B and C in under 5 years (both p

Background Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies. Methods This cross-sectional study enrolled 365 treatment-naïve patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C > T) and PNPLA3 (rs738409 c.444C > G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome. Results In HCV subjects, the frequencies of TM6SF2 CC and CT + TT were 89% and 11%, while PNPLA3 frequencies of CC and CG + GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT + TT genotype in HCV was associated with significant liver fibrosis (p = 0.047; OR 1.953; 95% CI 1.009–3.788). In comparison to the CT + TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p = 0.002), higher frequency of arterial hypertension (p = 0.032), obesity (p = 0.030), metabolic syndrome (p = 0.014) and lower total cholesterol levels (p = 0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p = 0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis. Conclusion In this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.

The authors have requested that this preprint be removed from Research Square.

Hepatitis B virus (HBV) infection is a major public health priority. In the present study, a lateral flow strip combined with the recombinase polymerase amplification (LF-RPA) assay was developed and evaluated for rapid HBV detection. A primer/probe pair targeting the conserved region of the HBV genome was designed and applied to the LF-RPA. TheRPA was achieved at the isothermal temperature of 39℃ for 30 min, and the RPA products were detected using the LF test. DNA extraction, RPA reaction and endpoint detection will take about 70 min. The LF-RPA assay could detect HBV at as low as 10 copies/reaction, with no cross-reactions with other common pathogens. The LF-RPA assay was performed on 85 samples. Of these, 36 samples tested HBV positive, whereas 49 were negative. Similar results were obtained using the conventional polymerase chain reaction method. Thus, the newly developed LF-RPA assay can be an improved diagnostic tool for rapid and simple HBV detection.

Hepatitis infection in HIV positive individuals with liver diseases causes high mortality worldwide. HIV worsens the pathological effect of hepatitis viruses and potentiates reactivation of latent hepatitis infections due to reduced immunity. This research therefore aimed to study the occurrence of HIV and hepatitis viruses among liver diseases patients (LVDP) attending tertiary hospitals in Osun State, southwestern Nigeria. A total of 121 LVDP blood samples collected were tested for HIV and Hepatitis B, C, and E using and enzyme linked Immunossorbent assay (ELISA). Data were analyzed using packages within SPSS and

Exosomes are small discoid extracellular vesicles (EVs) originating from endosomes that are 30-150 nm in diameter and have a double lipid layer. They participate in the immune response, cell migration, cell differentiation, and tumor invasion and mediate intercellular communication, regulating the biological activity of receptor cells through the proteins, nucleic acids, and lipids that they carry. Exosomes also play vital roles in the diagnosis and treatment of liver diseases. Macrophages, which show unique phenotypes and functions in complex microenvironments, can be divided into M1 and M2 subtypes. M1 macrophages function in immune surveillance, and M2 macrophages downregulate the immune response. Recent studies have shown that macrophages are involved in non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Moreover, several studies have demonstrated that liver diseases are associated with exosomes derived from or transferred to macrophages. This review focuses on the participation of macrophages and exosomes in liver diseases.