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A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host’s defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC.

We analyzed long‐term incidence trends in liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma) with an aim to interpret the changes in terms of known risk factors and hypothesize that historical exposure to Thorotrast, a radiographic contrast medium emitting alpha particles, has changed population rates. The NORDCAN database was used to collect cancer registry data from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE), which we used from 1953 (DK, FI and NO) and 1960 (SE) through 2019. Thorotrast, which caused a 100‐fold risk of liver cancer was used in DK and SE, and probably also in FI between 1930 and 1950, but not in NO. The incidence trend for liver cancer showed a broad maximum at around 1980, most prominent and statistically significant in SE and DK men and women, and in all countries, a steadily increasing trend towards the end of follow‐up. Incidence for NO was lower than for the other countries and the rates showed no peaking at around 1980. Birth cohort analysis identified a transient risk which could be dated to a period between 1930 and 1950 in countries other than NO. Considering a lag time between Thorotrast use and liver cancer appearance, the large incidence peak around 1980 in DK and DE was probably contributed by Thorotrast but considering the ecological nature of the findings, the association should be considered cautiously as hypothesis generating. The late increase in liver cancer risk is most likely lifestyle related and largely preventable. [ABSTRACT FROM AUTHOR]

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare disease with low malignancy, and its aetiology is unclear. A 65-year-old man presented with abdominal pain. Hepatitis virus examination revealed a previous hepatitis B virus (HBV) infection, and a carbon-13 urea breath test result was positive for the patient. Abdominal contrast-enhanced computed tomography revealed a patch of abnormal density in the right posterior lobe of the liver. The patient underwent VI segment hepatectomy and was pathologically diagnosed with hepatic MALT lymphoma. After the operation, he received quadruple anti-Helicobacter pylori (HP) therapy and refused other treatments. He has been followed up by telephone for 20 months after discharge and is now in a stable condition. In this study, we counted 105 cases of hepatic MALT lymphomas reported in English or Chinese since 1995 and summarised the clinical characteristics and concomitant diseases in this condition. Based on the literature review, we speculated that chronic infectious diseases, especially viral infections (including hepatitis C virus (HCV) and HBV) and HP infection, are associated with the pathogenesis of primary hepatic MALT lymphoma. In addition, autoimmune diseases might also play a role in this condition. [ABSTRACT FROM AUTHOR]

Abstract Background Liver cancer has become one of the most common cancers and has a high mortality rate. Hepatocellular carcinoma is one of the most common liver cancers, and its occurrence and development process are associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Main body The serious consequences of chronic hepatitis virus infections are related to the viral invasion strategy. Furthermore, the viral escape mechanism has evolved during long-term struggles with the host. Studies have increasingly shown that suppressor of cytokine signaling (SOCS) proteins participate in the viral escape process. SOCS proteins play an important role in regulating cytokine signaling, particularly the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Cytokines stimulate the expression of SOCS proteins, in turn, SOCS proteins inhibit cytokine signaling by blocking the JAK-STAT signaling pathway, thereby achieving homeostasis. By utilizing SOCS proteins, chronic hepatitis virus infection may destroy the host’s antiviral responses to achieve persistent infection. Conclusions This review provides recent knowledge regarding the role of SOCS proteins during chronic hepatitis virus infection and provides some new ideas for the future treatment of chronic hepatitis.

We make a summary of the global and local cases, as well as the current etiological progress, constructive criticism is verified in order to improve the diagnostic process and limit the morbidity and mortality of patients, as well as the requirements of special therapies such as artificial liver support therapy or hepatic transplantation, not very affordable in our country. [ABSTRACT FROM AUTHOR]

Abstract 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.

Objective: To estimate the seroprevalence of enteric transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients presented with acute viral hepatitis in a tertiary care hospital, Delhi. Methods: It was a retrospective study from February 2019 to December 2020 conducted in a tertiary care hospital, Delhi. Serum samples from clinically suspected hepatitis patients sent for HAV and HEV testing were included in the study. The samples were tested for HAV and HEV Immunoglobulin (Ig)M antibody by enzyme-linked immunosorbent assay. Data collected in Excel sheet were analyzed using SPSS software version 21. Chi-square and Fischer exact test were used wherever necessary. Results: Viral etiology (HAV or HEV) was found in 122 (18%) patients. IgM HAV was detected in 75 (11%) patients whereas IgM HEV in 47 (7%) patients. The coinfection of HAV and HEV was not observed. HAV infection was significantly more common in pediatric age group 32.8% (59/180; P < 0.001) whereas HEV was significantly more common in adolescent and adult age group 8.6% (42/491; P < 0.001). Conclusions: Periodic surveillance of enteric transmitted viruses causing hepatitis needs to be conducted at hospital as well as community level to ascertain the true burden of the disease and changing epidemiology.

Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Much progress has been made regarding the understanding of hepatocarcinogenesis, yet the long-term survival rate of HCC patients remains poor. Recent efforts have shown parafibromin has a pathologic role in many human cancers, but little is known about the effects of parafibromin in HCC. This study aimed to investigate the pattern of parafibromin expression and its clinicopathologic significance in human HCC. Immunohistochemical analysis of HCC and matched non-tumor liver tissues from 50 HCC patients showed that the nuclear expression of parafibromin was higher in HCC tissues (50/50 cases) than in non-tumor liver tissues (17/50 cases). Moreover, elevated parafibromin expression was found to be significantly correlated with the presence of microvascular invasion (p = 0.017), hepatitis virus infection-induced occurrence (p = 0.005), and poorer tumor differentiation (Edmondson–Steiner grade; p = 0.000). Kaplan–Meier analysis showed that HCC patients with elevated parafibromin expression had poorer recurrence-free (p = 0.014, log-rank test = 6.079) and overall survival (p = 0.036, log-rank test = 4.414). These findings indicate parafibromin may be related to the pathogenesis of HCC and a potential prognostic marker for HCC patients after hepatectomy. [ABSTRACT FROM AUTHOR]

Infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) are among the primary causes of chronic liver disease across the world. Despite the fact that HBV and HCV both like to replicate in hepatocytes, their life cycles are very different. In the present work, we modeled the structure of HBV polymerase because we were interested in structurebased ligand identification for HBV and HCV infections. The model allowed us to identify a common ligand that targets both HBV and HCV as evidenced from docking score. The detailed protein-ligand interactions were presented in this paper. Dihydrochondrillasterol has better interaction characteristics, indicating that it might be employed as a lead molecule for HBV and HCV infections. Overall, the polymerase enzyme is a potential target for a range of liver disorders and therefore our findings open up new avenues for drug development and therapeutic intervention for HBV and HCV infections. [ABSTRACT FROM AUTHOR]

The 7th Asian Vaccine Conference (ASVAC 2019) was held in Yangon, Myanmar from 13 to 15, September 2019. It brought together stakeholders in the field of vaccination to address challenges and issues relevant to clinical practice and immunization programs in the region. The conference themed “Immunization: sustaining health security in Asia”, included pre-conference workshops, a Vaccinology Masterclass, plenary lectures, symposia, and poster presentations. There were over 700 participants ~ 400 local and 300 international from 31 countries ~ and 55 international and local speakers from 19 countries. An Asian EPI managers’ meeting was also held on 11–12 September in Naypyidaw, the new capital of Myanmar, and was hosted by the Ministry of Health and Sports, Myanmar with support from World Health Organization, UNICEF and other partners. This inter-regional meeting aimed to strengthen the cooperation and collaboration of EPI Managers and others involved in implementing immunization programs in the region. The conference was organized by the Immunization Partners in Asia Pacific (IPAP) and hosted by Myanmar Pediatric Society and the Ministry of Health and Sports, Myanmar. Other partners included the Confederation of Meningitis Organization, Philippine Foundation of Vaccination, Pediatric Infection Disease Society of the Philippines, Asia Pacific Alliance for the Control of Influenza, PATH, ROTA Council, International Society of Tropical Pediatrics, Asian Society for Pediatric Infection Diseases and other partners. Previous conferences have been held in Siem Reap (2009), Manila (2010), Jakarta (2011), Cebu (2013), Hanoi (2015) and Singapore (2017). The 8th Asian Vaccine Conference will be held in Penang, Malaysia in 2021 to further IPAP’s vision of a world where no one suffers from a vaccine-preventable disease.

Aim: This study aimed to evaluate if clinical or radiographic findings can be used for hepatocellular carcinoma (HCC) diagnosis particularly in high-risk patients. Methods: This was a prospective study and evaluated factors associated with HCC. Results: There were 260 patients met the study criteria: 219 patients (84.23%) were HCC. Two factors significantly associated with HCC: portal vein invasion and the largest mass size. The cutoff point for the largest mass size of 2 cm or over gave sensitivity and specificity for HCC of 83.56 and 87.80%, respectively. Conclusion: Portal vein invasion and the largest liver mass of 2 cm or over may be diagnostic factors for HCC in high-risk patients, while clinical factors were not suggestive for HCC.

Background: Background: Hepatitis virus infections are among the serious emerging health issues. They are the primary causes of cirrhosis and hepatocellular carcinoma. Growing evidence shows a link between certain genomic variations and inflammation including viral infection such as HBV and HCV. Therefore, this study aimed to comprehensively review studies that analyze the effect of host genomic variations on the risk of contracting viral hepatitis in Iranian population., Methods: The study was conducted according to the PRISMA Statement. All Persian and English case-control articles published until the beginning of June 2023 were included in the study. Two authors reviewed the articles independently. The third author reviewed the final results. Pathway analysis and protein interactions were also performed using GO and STRING databases., Results: Seventy relevant studies were retrieved. Fifty-three studies examined the association of SNPs with the risk of HBV infection. In terms of genetic variations, 25 genes and 44 SNPs were identified. Tumor necrosis factor alpha, Interleukin 28B, and Interleukin 10 were the most prevalent considered genes. The most common polymorphisms were in the interleukin family. Moreover, the top five identified molecular functions were cytokine activity, cytokine receptor binding, molecular function regulator, protein binding, and signaling receptor binding., Conclusion: The polymorphisms of genes involved in the production of immune factors, cytokines, interleukins, and their receptors are associated with the risk of HBV and HCV infections in the Iranian population. Moreover, the extracellular and intracellular signaling pathways and the regulating molecules of these processes can be considered as important factors in liability for these viral infections., (Copyright© 2024 Khorshid Shamshiri et al. Published by Tehran University of Medical Sciences.)

Hepatic stellate cells (HSC) are recruited to the site of injury in the liver tissue repair mechanism, and the changes HSC undergo reflect paracrine stimulation by all cell types (sinusoidal endothelial cells, Kupffer cells, hepatocytes, platelets, and leukocytes). This study aimed to analyse a possible correlation between the degree of liver fibrosis and thrombin generation in patients with chronic liver diseases. Background Coagulation disorders in patients with chronic liver disease continue to challenge clinicians. A more accurate assessment of the coagulation cascade is provided by investigating thrombin production in individuals with chronic liver disease with varying degrees of fibrosis. Methods This prospective observational pilot study was done on hospitalized patients with chronic liver diseases. Thrombin generation from their platelet-poor plasma was studied and the degree of liver fibrosis assessed by transient elastography versus that of control subjects. Results The peak thrombin is significantly higher in those with severe liver stiffness (F3) than in those with more advanced fibrosis/liver cirrhosis (F4). Also, the total concentration of thrombin formed in the time interval (area under the curve (AUC)) and velocity index (VI) is higher in those with F3 than those with F4. Conclusion Thrombin generation decreases with the progression of liver fibrosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethical Committee of the Emergency Hospital of Sibiu County issued approval No 22524 on October 3, 2016. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vecerzan et al.)

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Only a minority of the patients with acute febrile jaundice evaluated through the Yellow Fever surveillance program were found positive for antibodies against Yellow Fever Virus (YFV). In order to characterize patients with acute febrile jaundice negative for YFV, we collected 255 sera between January to December 2019. We screened for HBV antigens, and antibodies against HCV and HEV. The seroprevalences observed were 10.6% (27/255) for HBV, 2% (5/255) for HCV, 17.3% (44/255) for HEV IgG, 4.3% (11/255) for HEV IgM, and 12.5% (32/255) for both IgG and IgM HEV. Prevalence of HEV was significantly higher in females than males (p < 0.01). HEV IgG prevalence was highest in those 20–29 years old, but the highest incidence rate (IgM positive) was in children 0–9 years old. Exposure to HEV was higher in the Sahelian zone (55.8%, 95%CI: 40.97–70.66) than in the Sudanese zone (30.2%, 95% CI: 24.01–36.37, p = 0.003). The high prevalence rates and hepatitis virus diversity underline the challenge of routine clinical diagnosis in Chad's Yellow Fever surveillance program. [ABSTRACT FROM AUTHOR]

Viruses manipulate cellular machinery and functions to subvert intracellular environment conducive for viral proliferation. They strategically alter functions of the multitasking mitochondria to influence energy production, metabolism, survival, and immune signaling. Mitochondria either occur as heterogeneous population of individual organelles or large interconnected tubular network. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections, and is dynamically maintained by mitochondrial fission and fusion. Mitochondrial dynamics in tandem with mitochondria-selective autophagy 'mitophagy' coordinates mitochondrial quality control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis, metabolism, and innate-immune signaling, and thus can be major determinant of the outcome of viral infections. Herein, we review how mitochondrial dynamics is affected during viral infections and how this complex interplay benefits the viral infectious process and associated diseases.

Hepatitis viruses are primary causative agents of hepatitis and represent a major source of public health problems in the world. The host innate immune system forms the first line of defense against hepatitis viruses. Hepatitis viruses are sensed by specific pathogen recognition receptors (PRRs) that subsequently trigger the innate immune response and interferon (IFN) production. However, hepatitis viruses evade host immune surveillance via multiple strategies, which help compromise the innate immune response and create a favorable environment for viral replication. Therefore, this article reviews published findings regarding host innate immune sensing and response against hepatitis viruses. Furthermore, we also focus on how hepatitis viruses abrogate the antiviral effects of the host innate immune system.

Hepatitis viruses are primary causative agents of hepatitis and represent a major source of public health problems in the world. The host innate immune system forms the first line of defense against hepatitis viruses. Hepatitis viruses are sensed by specific pathogen recognition receptors (PRRs) that subsequently trigger the innate immune response and interferon (IFN) production. However, hepatitis viruses evade host immune surveillance via multiple strategies, which help compromise the innate immune response and create a favorable environment for viral replication. Therefore, this article reviews published findings regarding host innate immune sensing and response against hepatitis viruses. Furthermore, we also focus on how hepatitis viruses abrogate the antiviral effects of the host innate immune system. [ABSTRACT FROM AUTHOR]

The incidence of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) is increasing in our country. This study assesses the feasibility of employing an identical surgical treatment strategy for resectable NBNC-HCC as that for hepatitis virus-associated HCC (HV-HCC). A retrospective analysis (1993–2023) of 1321 curative liver resections for HCC at a single institution was performed. Propensity score matching ensured a balanced comparison of preoperative clinical factors, including tumor status and background liver condition. The proportion of NBNC-HCC cases has gradually increased, reaching up to 70 %. After matching, 294 of 473 NBNC-HCC patients and 294 of 848 HV-HCC patients were compared. Operative outcomes, including operation time, blood loss, type of surgical procedure, and morbidity, were comparable. Long-term outcome analysis showed similar recurrence-free survival (HR: 0.86, 95 % CI: 0.70–1.06, P = 0.167) and overall survival (HR: 0.98, 95 % CI: 0.79–1.23, P = 0.865) for NBNC-HCC. Multivariable analysis identified ICGR15 ≥ 15 %, ALBI grade 2 or 3, aspartate aminotransferase ≥40, tumor size > 5 cm, multiple tumors, macrovascular invasion, and microvascular invasion as independent prognostic factors for overall survival, while hepatitis B or C virus status lost significance. Despite the increasing incidence of NBNC-HCC, comparable outcomes were achieved between the two groups of matched cohort. [ABSTRACT FROM AUTHOR]

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2–specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2–positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.

Hepatitis B- and C-virus (HBV and HCV) infections contribute to hepatocellular carcinoma (HCC) development through several different mechanisms. In addition to a diverse molecular background, HCC subtypes also show differences in their metabolic profiles, suggesting that prevention and treatment might require the integration of multiple different approaches. We here analyzed the response of two HCC cell lines representative of different virus-related etiology, namely Hep3B (HBV+) and HUH7 (permissive to HCV replication) to sorafenib treatment. Our findings suggest that virus-related specificities influence treatment response in HCC, along with molecular, metabolic and microenvironmental factors. These differences have to be taken into account in the design of future clinical trial aimed to improve HCC patients' outcome. [ABSTRACT FROM AUTHOR]

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti‐hepatitis C virus antibody (anti‐HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at‐risk population, such as immunocompromised hosts and end‐stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at‐risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at‐risk patients who require monitoring of HCV infection and reinfection. Highlights: ‐ Anti HCV antibody is used as screening test/ ‐ Anti HCV antibody test is falsely negative in immunocompromised hosts. ‐ HCV antigen testing can be used as screening test in this group. [ABSTRACT FROM AUTHOR]

Hepatitis viruses are chief pathogens of hepatitis and end-stage liver diseases. Their replication and related pathogenic process highly rely on the host micro-environment and multiple cellular elements, including exosomes. Representing with a sort of cell-derived vesicle structure, exosomes were considered to be dispensable cellular components, even wastes. Along with advancing investigation, a specific profile of exosome in driving hepatitis viruses' infection and hepatic disease progression is revealed. Exosomes greatly affect the pathogenesis of hepatitis viruses by mediating their replication and modulating the host immune responses. The characteristics of host exosomes are markedly changed after infection with hepatitis viruses. Exosomes released from hepatitis virus-infected cells can carry viral nucleic or protein components, thereby acting as an effective subterfuge for hepatitis viruses by participating in viral transportation and immune escape. On the contrary, immune cell-derived exosomes contribute toward the innate antiviral immune defense and virus eradication. There is growing evidence supporting the application of exosomal biomarkers for predicting disease progress or therapeutic outcome, while exosomal nanoshuttles are regarded as promising therapeutic options based on their delivery properties and immune compatibility. In this review, we summarize the biogenesis and secretion mechanism of exosomes, review the recent findings pertaining to the role of exosomes in the interplay between hepatitis viruses and innate immune responses, and conclude their potential in further therapeutic application. [ABSTRACT FROM AUTHOR]

BackgroundDysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated.AIMTumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathwayMethodsAll consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221, and -16) change in circulation and AFP-ratio at 1-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 overexpressing Huh7 stable cell lines.ResultsPost-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA-21 and -221 expression was observed in PD (p = 0.040, 0.047) and PR patients (miR-21, p = 0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572–0.799) and CR from PD at AUROC 0.734 (95% CI, 0.595–0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR, and RPS6KB1 genes were found significant (P < 0.005) and anti-miR-21 specifically reduced mTOR gene (P = 0.02) expression.ConclusionsThe miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted.

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.

The animal health monitoring is required to issue health certificates. The viral hepatitis virus is one of the most important infectious agents in mice breeding colonies. This research used RT-PCR to identify contaminations to mouse hepatitis virus. 18 out of 29 specimens were found to be infected, a prevalence of 62%. PCR product was purified and sequenced. Phylogenetic analysis revealed that the identified strain in this study was closely related to a strain reported from France. In the conventional system, contamination with different infectious agents is inevitable, thus it is better to replace the contaminated colonies with clean animals.

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.

Introduction and aim. Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients.Material and methods. The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence.Results. NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. Conclusions. NEK2 plays a significant role in cell cycle progression in the inter- and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.

Abstract Objective The objective of this study was to see the aetiology and outcome of sporadic acute viral hepatitis (AVH) in Kathmandu, Nepal. Results Among 210 patients, 94 (45%) were male and 116 (55%) were female. Mean age was 30 years. 52 (24.7%) out of 210 were positive for either of the hepatitis virus infection. Major causative agent for AVH among hepatitis positive patients were hepatitis E virus (HEV) in 36 (69.2%), followed by hepatitis A virus (HAV) 8 (15.3%), hepatitis B virus (HBV) 7 (13.4%) and hepatitis C virus (HCV) 1 (1.9%). The 158 (75.3%) patient were negative for all hepatitis viral markers. Co-infections with more than one virus were found in 4 (7.6%) patients. All liver-specific enzymes including bilirubin increased in hepatitis-infected patients. We found large number circulation of HEV in Kathmandu, Nepal, indicating that this region is endemic for hepatitis virus infection.

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. [ABSTRACT FROM AUTHOR]

Background: Dysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated. AIM: Tumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathway Methods: All consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221, and -16) change in circulation and AFP-ratio at 1-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 overexpressing Huh7 stable cell lines. Results: Post-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA-21 and -221 expression was observed in PD (p = 0.040, 0.047) and PR patients (miR-21, p = 0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572–0.799) and CR from PD at AUROC 0.734 (95% CI, 0.595–0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR, and RPS6KB1 genes were found significant (P < 0.005) and anti-miR-21 specifically reduced mTOR gene (P = 0.02) expression. Conclusions: The miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted. [ABSTRACT FROM AUTHOR]

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is still poor, and the 5-year survival rate in patients undergoing radical surgery (R0) is less than one-third. Since the prognosis depends mainly on tumor factors, so early diagnosis is necessary. To extend the survival time of these patients with a poor prognosis, cases of long-term survival were examined based on the results of our experiences and the literature. It was found that the hepatitis virus was highly involved in the carcinogenesis of ICC, and patients who were infected with hepatitis virus had rather good survival. [ABSTRACT FROM AUTHOR]

Objective: To estimate the seroprevalence of enteric transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients presented with acute viral hepatitis in a tertiary care hospital, Delhi. Methods: It was a retrospective study from February 2019 to December 2020 conducted in a tertiary care hospital, Delhi. Serum samples from clinically suspected hepatitis patients sent for HAV and HEV testing were included in the study. The samples were tested for HAV and HEV Immunoglobulin (Ig)M antibody by enzyme-linked immunosorbent assay. Data collected in Excel sheet were analyzed using SPSS software version 21. Chi-square and Fischer exact test were used wherever necessary. Results: Viral etiology (HAV or HEV) was found in 122 (18%) patients. IgM HAV was detected in 75 (11%) patients whereas IgM HEV in 47 (7%) patients. The coinfection of HAV and HEV was not observed. HAV infection was significantly more common in pediatric age group 32.8% (59/180; P < 0.001) whereas HEV was significantly more common in adolescent and adult age group 8.6% (42/491; P < 0.001). Conclusions: Periodic surveillance of enteric transmitted viruses causing hepatitis needs to be conducted at hospital as well as community level to ascertain the true burden of the disease and changing epidemiology. [ABSTRACT FROM AUTHOR]

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology. Highlights: The development of liver pathology as a result of HCV infection is not straightforward to characterise.Serial biopsies from infected individuals are clinically impractical and unlikely to be available from early infection.We have characterised pathology in tamarins at various time‐points during infection with GBV‐B ‐ a surrogate model of HCV infection.We identified changes in the liver soon after infection; we also noted development of fibrosis which has not been reported previously in tamarins.This report highlights refinement of the tamarin model and its value in the pre‐clinical evaluation of antiviral treatments and vaccines. [ABSTRACT FROM AUTHOR]

Background: It has been widely known that viral hepatitis is a major cause of liver disease that can cause chronic inflammation and carcinoma. This study aimed to describe thefrequencies of CD4+ and CD8+ T cells, as well as regulatory T cells (CD25+ and Foxp3+ T cells) in the liver of patients with viral hepatitis in order to understand the comprehensive role of T lymphocytes in the progression of liver diseases attributed to viral hepatitis. Method: Liver biopsies were performed on adult patients presenting to a tertiary hospital in Surakarta, Indonesia with viral hepatitis from 2017 to 2018. Immunohistochemical staining was performed to identify cells expressing CD4+, CD8+, CD25+ and Foxp3+ which represent T helper, T cytotoxic, and T regulatory cells, respectively. Additional data were retrieved from the patients' medical records, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, 'viral load, and results ofultrasonography andfibroscan. Results: A total of 25 liver samples were collected from patients with chronic HBV infection (n = 21), chronic HCV infection (n = 2), acute HBV infection (n = 1), and from a with multiple liver nodules. The liver injury is minimum in all patients. The study found that CD8+ and CD4+ T cells were predominant whilst the frequency of T regulatory cells is generally low. Conclusions: Thefindings indicate the involvement ofintrahepatic T helper and T cytotoxic in the pathogenesis of viral hepatitis. These liver infiltrating T cell subsets may be readily differentiated into regulatory T cells expressing CD25+ and Foxp3+ in order toprevent severe inflammation and maintain disease chronicity. [ABSTRACT FROM AUTHOR]

Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, alcoholic- and non-alcoholic steatohepatitis, and autoimmune hepatitis, and highlight their driving mechanisms. These include external factors such as alcohol misuse, viral infection and supernutrition, as well as intrinsic parameters such as genetic disposition and failure, in immune tolerance. Additionally, we describe what is known about the translational machinery within all these diseases. Distinct eukaryotic translation initiation factors (eIFs) with specific functional roles and aberrant expression in HCC are reported. Many alterations to the translational machinery are already triggered in the precancerous lesions described in this review, highlighting mTOR pathway proteins and eIFs to emphasize their putative clinical relevance. Here, we identified a lack of knowledge regarding the roles of single eIF proteins. A closer investigation will help to understand and treat HCC as well as the antecedent diseases.

Comments on "Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C" Keywords: Anti-hepatitis C virus DAA (directly acting antivirals); Antiviral agents; Hepatitis C virus; Hepatitis virus; Virus classification EN Anti-hepatitis C virus DAA (directly acting antivirals) Antiviral agents Hepatitis C virus Hepatitis virus Virus classification 436 438 3 12/13/21 20220201 NES 220201 Elhence et al.1 assessed the retreatment outcomes of direct-acting antivirals (DAAs) therapy failure in a cohort of 40 patients with chronic hepatitis C (HCV) and previous virological failure (VF) to DAAs. Addressing hesitancy in HCV retreatment prescription and nonadherence to second-line DAAs with a tailored approach is crucial to scale up HCV treatment and eradicate HCV infection in people with previous VF to DAAs. [Extracted from the article]

Background and aims: The contribution of hepatitis B virus (HBV) infection to the aggressiveness of primary liver cancer (PLC) remains controversial. We aimed to characterize this in eastern China.Methods: We enrolled 8,515 PLC patients whose specimens were reserved at the BioBank of the hepatobiliary hospital (Shanghai, China) during 2007–2016. Of those, 3,124 who received primary radical resection were involved in survival analysis. A nomogram was constructed to predict the survivals using preoperative parameters.Results: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular cholangiocarcinoma (CHC) accounted for 94.6, 3.7, and 1.7%, respectively. The rates of HBV infection were 87.5, 49.2, and 80.6%, respectively. HBV infection was significantly associated with 10-year earlier onset, more cirrhosis, higher α-fetoprotein, higher carbohydrate antigen 19-9 (CA19-9), more microvascular invasion (MVI), lower neutrophil-to-lymphocyte ratio (NLR), and lower platelet-to-lymphocyte ratio (PLR) in HCC. HBV infection was also associated with 7-year earlier onset, more cirrhosis, higher α-fetoprotein, more MVI, and lower PLR in ICC. In the multivariate Cox analysis, high circulating HBV DNA, α-fetoprotein, CA19-9, NLR, tumor size, number, encapsulation, Barcelona Clinic Liver Cancer (BCLC) stage, and MVI predicted an unfavorable prognosis in HCC; only CA19-9 and BCLC stage, rather than HBV-related parameters, had prognostic values in ICC. A nomogram constructed with preoperative HBV-related parameters including HBV load, ultrasonic cirrhosis, and α-fetoprotein perform better than the current staging systems in predicting postoperative survival in HCC.Conclusion: HBV promotes the aggressiveness of HCC in Chinese population. The contributions of HBV to ICC and other etiological factors to HCC might be indirect via arousing non-resolving inflammation.

Chronic viral hepatitis is a risk factor for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are considered potential candidates for early phase clinical trials of anti-cancer agents. The impact of chronic viral hepatitis on the efficacy of anticancer agents for patients with HCC in phase I trials (P-Is) still remains unclear and has not been reported. We retrospectively analyzed the outcomes of consecutive HCC patients in P-Is conducted in a single institute, focusing on chronic viral hepatitis. Of 85 patients enrolled in P-Is, 46 (54%) patients positive and 39 (46%) patients negative for chronic viral hepatitis showed no significant difference in clinical and laboratory variables and on the point of the best response based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria; moreover, the frequency of Grade ≥3 adverse events (AE) was not significantly different. The median time to treatment failure (TTF) and overall survival (OS) from the P-I enrolment were 2.0 and 13.7 months, respectively. No patient experienced reactivation of hepatitis B virus (HBV) or treatment-related death. Chronic viral hepatitis does not independently affect the outcomes of anticancer drugs. Advanced HCC patients with chronic viral hepatitis could be feasible for P-Is.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental., Aim: To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019., Methods: In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019)., Results: Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis ( P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology ( P < 0.05) and alpha-fetoprotein (AFP) levels ( P < 0.01)., Conclusion: In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology ( P < 0.05) and AFP levels ( P < 0.01)., Competing Interests: Conflict-of-interest statement: None of the authors have any potential conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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 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.

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 <.01). Moreover, receiver operating characteristic analysis predicted >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. [ABSTRACT FROM AUTHOR]

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2-specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2-positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV. [ABSTRACT FROM AUTHOR]