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Background Liver fibrosis is the result of diffuse excessive deposition of extracellular matrix (ECM) in liver. Collagen is the main component of extracellular matrix. Absent in melanoma 2 (AIM2) is involved in the formation of inflammsome and plays an important role in inflammatory response. However, it is unclear whether AIM2 is involved in the pathogenesis of liver fibrosis. In the present study, we explored the role of AIM2 in the expression of collagen I. Methods In this study, AIM2 was used to co-culture with HepG2 cells. Cell counting kit-8 (CCK-8) was used to measure cell viability. Real time-quantitative PCR (RT-qPCR) and Western blotting were used to detect collagen I expression at mRNA or protein level, respectively. Then HepG2 cells were treated with caspase activation recruitment domain (ASC), pcDNA(+)-AIM2, small interfering RNA (siRNA) and Z-YVAD-fluoromethylketone (Z-YVAD-FMK) to explore their roles in collagen I expression, respectively. Results The viability of HepG2 cells could be not affected with the increased concentrations of AIM2 and Z-YVAD-FMK. The filamentous prisms and vacuoles of HepG2 cells became more obvious when the concentrations of AIM2 increased to 80ng/ml. The expression level of collagen I increased with the increased concentrations of AIM2. The expression level of collagen I could be also induced by pcDNA(+)-AIM2 vector. The expression level of collagen I could be inhibited by ASC siRNA and Z-YVAD-FMK, respectively. Conclusion Collagen I expression could be induced by AIM2 through ASC/caspase-1 signaling pathway. AIM2 might be involved in the pathogenesis of liver fibrosis through inducing collagen I expression.

Background Severe COVID-19 caused by SARS-CoV-2 should closely be cared because of the relatively high mortality rate. If SARS-CoV-2 could be cleared as soon as possible, the mortality rate might lower. In the present study, we analyzed factors which might be related to the clearance of SARS-CoV-2. Methods One hundred and twenty-eight severe COVID-19 cases were enrolled. All of them had been isolated and treated at Shenzhen Third People’s Hospital because they were positive for nucleic acid of SARS-CoV-2 tested by qRT-PCR. Their baseline clinical characteristics and antiviral regimens were collected and analyzed, respectively. Results Of the 128 enrolled severe COVID-19 cases, unfortunately 3 died. The mean viral duration of all patients was 23.5 (range 17−32) days. All patients achieved viral clearance during 9 weeks. 13.4% of patients achieved viral clearance within 2 weeks, and 63.0% of patients achieved viral clearance within 4 weeks. The combined regimens of three or more antiviral drugs, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 2 weeks. The use of arbidol, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 4 weeks. Patients often had a prolonged course of COVID-19 and hospitalization, and were more likely transferred to intensive care unit (ICU) for treatment, if they could not clear SARS-CoV-2 during 23 days. Conclusion Severe COVID-19 cases should be admitted to hospital as soon as possible. The combined regimens of three or more antiviral drugs might not be useful for viral clearance, and should be performed carefully and cautiously.

Background: CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Methods: 6-8 weeks old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were anesthetized and sacrificed at 12 to 16 days after infection, and the livers were picked out. Sections of the livers were stained, and serum AST and ALT levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ T cell were analyzed by using flow cytometry, respectively. Results: Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. CD103 expression was increased on CD8+ T and γδ T cells. The decrease of CD103 expression was significantly on CD8+ T cells. Compared to that of CD103- CD8+ T cells, CD103+ CD8+ T cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. Conclusion:CD103+CD8+ T cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.

Interleukin-32 (IL-32), a multiple pro-inflammatory cytokine, played a vital role in immune-related diseases and infectious diseases. The promoter region of IL-32, which showed functional polymorphism, could regulate IL-32 expression. Although IL-32 rs28372698 polymorphism was related to a lot of inflammatory diseases, the association of IL-32 rs28372698 polymorphism with hepatic flare of chronic HBV infection was not been reported. In the present study, IL-32 rs28372698 polymorphism was genotyped in 104 chronic HBV carriers and 151 active chronic hepatitis B (CHB) patients. The frequency of IL-32 T/T genotype in patients with active CHB was significantly higher than that in chronic HBV carriers. Furthermore, the frequency of the T allele at IL-32 rs28372698 in active CHB patients was also higher than that in chronic HBV carriers. Serum level of IL-32 in active CHB patients was higher than that in chronic HBV carriers. Our results imply that IL-32 T/T polymorphism might be associated with hepatic flare of chronic HBV infection. This article is protected by copyright. All rights reserved.

Background: Liver fibrosis is a diffuse excessive deposition of extracellular matrix (especially collagen) in the liver. It is a repair response of the body to chronic liver injury. AIM2 regulates the activation of caspase-1 and thus promotes the maturation and secretion of the cytokine precursors of pro-IL-1β and pro-IL-18. It also regulates caspase-1-dependent pyroptosis. However, it is unclear whether AIM2 is involved in the pathogenesis of liver fibrosis. Methods: In the present study, CCK-8 was used to measure cell viability. Evaluation of functional AIM2-induced ECM and fibrosis using protein blotting and quantitative real-time polymerase chain reaction. Validation of the effect of the AIM2/ASC/caspase-1 signalling axis on liver fibrosis using ASC siRNA and caspase-1 inhibitors. Overexpression of AIM2 in cells using transient techniques to evaluate the extent of collagen and focal death. Cells with COL1A1 (pGL3-COL1A1) were constructed and characterised. Activation of its activity by AIM2 was measured in vitro. 2 Results: Absent in melanoma 2 (AIM2) is a pro-inflammatory cytokine that plays a key role in inflammation. However, the role of hepatocytes in AIM2 expression remains unclear. In the present study, we demonstrate that AIM2 increases COL1A1 expression via the COL1A1 promoter. AIM2 increases COL1A1 expression in a dose-dependent manner. Furthermore, we demonstrated that AIM2 failed to cause an increase in COL1A1 expression after inhibition of ASC and caspase-1 expression in HepG2 cells. These results suggest that the AIM2/ASC/caspase-1 signalling axis can induce liver fibrosis in HepG2 cells. Conclusion: Collagen I is expressed by hepatocytes through activation AIM2/ASC/caspase-1 pathway.

The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with

Background: The role of CD3+γδTCR+(γδT) cells during the Plasmodium yoelii nigeriensis infection has been reported in our previous studies. However, there is a paucity of studies on the characteristics of myeloid cells which expressed γδTCR. Therefore, the aim of this study was to observe the properties of γδTCR-expressing myeloid cells in the spleen of C57BL/6 mice infected by P. yoelii NSM. Methods: Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the spleens. The samples from the experimental group before and after infection underwent RNA sequencing (RNA-seq), and the differentially expressed genes (DEGs) were screened. Flow cytometry (FCM) was used to evaluate the frequency of γδTCR+ cells and the characteristics of γδTCR+ cells in Plasmodium yoelii-infected mice.Results: We observed obvious infiltration of inflammatory in infected C57BL/6 mouse spleens. The proportions of γδTCR+ cells and CD11b+ γδTCR+cells from infected group were higher than that from normal group. γδTCR+CD11b+ cells expressed high levels of activated-mediated genes and inflammatory-mediated genes. We characterized the heterogeneous pathway activities among γδTCR+CD11b+ cells from normal and infected group. The oxidative phosphorylation, respiratory electron transport chain and leukocyte activation involved in immune response pathways were up-regulated, while the alpha-beta T cell activation and myeloid leukocyte migration pathways were down-regulated. Importantly, we found that Ly6c2 was higher expressed in γδTCR+CD11b+ cells than Ly6g. Consistent with it, flow cytometry results revealed that a subset of Ly6C+Ly6G-CD11b+γδTCR+ cells was higher than Ly6G+Ly6C-CD11b+γδTCR+ cells in the spleen. Conclusions: Taken together, our data suggest the existence of a population of γδTCR-expressing myeloid cells and played potential role in the context of Plasmodium infection. The molecular markers and pathways screened warrant further study.

Few studies were conducted to assess safety and efficacy of continuous antiviral therapy administrated from preconception. In the present study, 136 eligible women with chronic HBV infection were recruited, and assigned to active chronic hepatitis B (CHB) (Group A, B or C) or chronic HBV carrier (Group D). Antiviral therapy was administrated in preconception (Group A), in early (Group B) or late pregnancy (Group C and Group D). Immunoprophylaxis was administrated to all infants. Mothers’ HBV status and ALT were assessed at delivery and 7 months postpartum. Offspring’s HBV status was examined at 7 months old. Group A women showed low HBV DNA level and normal ALT throughout pregnancy. All women at delivery had an HBV DNA level of less than 106 IU/ml, but the proportion of patients with lower HBV DNA level in Group A was higher than any of other three groups (P

BACKGROUND This single center study, which enrolled 108 patients with chronic hepatitis B virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha), aimed to follow up and monitor off-treatment responses, including virological relapse, and analyze predictors of long-term efficacy of the PEG-IFN-alpha regimen. MATERIAL AND METHODS In total, 108 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B who had completed the PEG-IFN-alpha regimen and achieved virological suppression were enrolled. The patients were followed up for 5 years to monitor off-treatment responses. Twenty-eight relevant factors, including the history of antiviral therapy and HBeAg seroconversion, were analyzed using the Cox proportional hazards regression model. RESULTS The cumulative rates of virological suppression were 75.70%, 68.68%, 65.25%, 63.91%, and 63.91% at 1, 2, 3, 4, and 5 years of the follow-up period, respectively. Compared with the rates of virological suppression, the cumulative rates of clinical suppression were 88.41%, 79.83%, 78.59%, 75.65%, and 75.65%, respectively, for the 5 years. Alanine aminotransferase (ALT) normalization at 24 weeks after off-therapy (relative risk [RR]=3.430, P=0.013) was a potential predictor for sustained virological suppression, and the history of anti-viral therapy (RR=0.164, P=0.004), quantitative value of hepatitis B virus surface antigen (HBsAg) at 48 weeks of anti-viral therapy (RR=2.697, P=0.039), and ALT normalization at 24 weeks after off-therapy (RR=5.467, P=0.004) were potential predictors for sustained clinical suppression. CONCLUSIONS Our results suggested that increased HBsAg levels at 48 weeks and normalization of ALT at 24 weeks after off-therapy might be predictive factors for long-term treatment efficacy.[color=red] [/color].

The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear.Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed.Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood.These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.

Recently, there is a paucity of studies focus on the characteristics of myeloid cells which expressed γδTCR. The aim of this study was to observe the properties of γδTCR-expressing myeloid cells in the spleen of C57BL/6 mice infected by P. yoelii nigeriensis NSM. Haematoxylin-eosin (HE) staining was used to observe pathological changes in the spleens from infected mice. The differentially expressed genes (DEGs) between the infection and control groups were analyzed by RNA sequencing (RNA -seq). Flow cytometry (FCM) was used to evaluate the frequency of γδTCR

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six patients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4

Background: A lot of recent researches have focused on the duration of the nature immunity elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. An improved understanding of the immunity offered by the antibodies developed against SARS-CoV-2 in recovered patients is critical for the development of diagnostic tests and vaccines. Methods: We enrolled 114 donors, which providing blood samples after discharge for half a year and one year. Neutralizing antibodies (NAbs) were tested using a micro-neutralization assay. Results: In two tests, 82 of 114 recovered patients completed the first test half a year after discharge and NAbs remained detectable in the vast majority of patients (75/82, 91.46%). In the comparison of the two intervals, 50% (27/54) of individuals had increased NAbs titers. when 31.48% (17/54) of patients remained unchanged. Conclusion: Our results suggest that immune ability is acquired in most individuals infected with SARS-CoV-2 and is sustained in a majority of patients for up to a year after recovery.

The pandemic of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 is ravaging the world. Diagnosis and isolation of persons who are infected with SARS-CoV-2 is very important medical emergency to contain the epidemic of COVID-19. To date, the diagnosis of COVID-19 is mainly depending on positive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) results for SARS-CoV-2. In the present study, we reported that two cases with uncommon symptoms from a family cluster were ultimately diagnosed as COVID-19 after more than twice of collecting samples and qRT-PCR tests were done. It is easily to miss diagnosis of COVID-19 especially for patients with uncommon symptoms. More attention should be paid to observe the clinical characteristics of it and invent more accurate and convenient methods to detect SARS-CoV-2 as soon as possible.

Background: The data of antiviral therapy throughout the entire pregnancy are relatively scarce. The aim of the present study was to evaluate the safety and efficacy of antiviral therapy for chronic HBV infection throughout the entire pregnancy. Methods: This was a single-center, prospectively study. Fifty-five women received antiviral therapy (TDF or LDT) from pre-conception to the entire pregnancy. Sixty-four women did not receive antiviral therapy during pre-conception and the entire pregnancy. All infants in the two groups had received immunoprophylaxis on schedule. Mother-infant pairs were followed up at least 7 months postpartum. The outcome was the safety and efficacy of antiviral therapy for mothers and offspring. Findings: All mothers tolerated antiviral therapy (TDF or LDT) well. The mean maternal HBV DNA level in the antiviral therapy group was less than that of the control group before delivery as well as in the three months postpartum (P 0.05). Furthermore, there was not a statistically significant difference in the birth weight, the birth length, and the congenital diseases of infants between the two groups, respectively (P>0.05). In 7 months postpartum, none of infants who tested HBV status in the two groups was positive for HBsAg. Interpretation: Antiviral therapy (TDF or LDT) from pre-conception to the entire pregnancy could be safe and effective for pregnant women with HBV infection and their fetuses/ infants. Trial Registration: The present study was registered in ClinicalTrials.gov (No. NCT03181607). Funding Statement: The present study was funded by the National Key Research and Development Program of China (2017YFC1001402, 2018YFC1002900), National Natural Science Foundation of China (81401306, 81830045), Clinical Research Project of Guangzhou Medical University (No. 2017[160]) and Sino-German Center for Research Promotion (SGC)'s Rapid Response Funding Call for Bilateral Collaborative Proposals between China and Germany in COVID-19 Related Research (No. C-0032). Declaration of Interests: All authors declare no financial, potential personal or commercial conflict of interest. Ethics Approval Statement: The present study was approved by the Institutional Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University, and was carried out in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent was obtained from each participant in the present study.

The main symptoms of coronavirus disease 2019 (COVID-19) are respiratory manifestations, while some confirmed patients developed gastrointestinal symptoms or even initially presented digestive symptoms. The link between pneumonia and gastrointestinal symptoms caused by severe acute respiratory symptoms coronavirus 2 focused our attention on the concept of 'gut-lung axis'. In this review, we discuss the inevitability and possible mechanisms of the occurrence of intestinal symptoms or intestinal dysfunction in COVID-19 from the perspective of the gut-lung axis, as well as the influence of the imbalance of intestinal homeostasis on the respiratory symptoms of COVID-19. The interaction between lung and intestine might lead to a vicious cycle of pulmonary and intestinal inflammation which may be a potential factor leading to the death of patients with COVID-19.

Background At present, novel coronavirus disease 2019 (COVID-19) has become a serious global public health problem. The current meta-analysis aimed to find risk factors for the COVID-19-related death, helping to enhance the efficacy and reduce the mortality of COVID-19. Methods We searched PubMed, Embase, medRxiv, and Cochrane Library for articles published between January 1, 2020, and April 13, 2020. We statistically analyzed the risk factors of the COVID-19 deceased with meta-analysis. Results A total of 2401 patients in 15 articles were included in this study. Meta-analysis showed that 66.6% of COVID-19 deceased were male, with a median age of 69.9 years. Common symptoms of deceased included fever (70.6–100%), dyspnea (38.89–85.7%), cough (22.4–78%), and fatigue (22–61.9%). The incidence of hypertension, chronic cardiovascular disease, diabetes, and chronic cerebrovascular disease among the COVID-19 deceased were 38.56% (95% confidence interval (CI) 25.84 ~ 52.12%), 17.54% (95% CI 13.38 ~ 21.69%), 22.2% (95% CI 19.30 ~ 25.10%), and 15.58% (95% CI 10.05 ~ 21.12%), respectively. Compared with the surviving COVID-19 patients, the deceased had lower platelet levels (mean difference (MD) = − 39.35, 95% CI − 55.78 ~ − 22.93) and higher C-reactive protein (CRP) (MD = 80.85, 95% CI 62.53 ~ 99.18) and lactate dehydrogenase (LDH) (MD = 246.65, 95% CI 157.43 ~ 335.88) at admission. The most common complications of the deceased were acute respiratory distress syndrome (ARDS) (OR = 100.36, 95% CI 64.44 ~ 156.32) and shock (OR = 96.60, 95% CI 23.80 ~ 392.14). Conclusion Most of the COVID-19 deceased were elderly males. Fever, dyspnea, dry cough, fatigue, hypertension, chronic cardiovascular and cerebrovascular disease, diabetes, and laboratory examinations showed low levels of platelet content, increased CRP and LDH were associated with the risk of dying. ARDS and shock were risk factors for death in COVID-19 patients.

Since December, 2019, coronavirus disease 2019 (COVID‐19), caused by SARS‐CoV‐2, has spread to a lot of countries worldwide1,2. On Jan 30, 2020, the World Health Organization (WHO) had declared that the outbreak of COVID‐19 is a Public Health Emergency of International Concern. On March 11, 2020, the spread of COVID‐19 was declared a pandemic by the WHO. This article is protected by copyright. All rights reserved.

Background and Aims: COVID-19, caused by SARS-CoV-2 is a newly emerged disease. Since December 2019, more and more confirmed COVID-19 cases and deaths are reported by almost all of countries in the world. In the present study, we report the various clinical features of 12 confirmed COVID-19 cases in our hospital, Guangzhou. Methods: Electronic medical records of 12 confirmed COVID-19 patients who had been referred to the Third Affiliated Hospital of Guangzhou Medical University were collected. The clinical manifestations, laboratory examinations and related imaging results were analyzed, respectively. Results: Twelve confirmed patients had different clinical manifestations, ranging from asymptomatic, mild to severe manifestations. Seven patients had a fever as the main symptom. Three patients showed nasal obstruction, or stuffy nose, or sore throat without fever. Nine patients did not show abnormal white blood cell and lymphocyte counts. Seven patients did not show radiological features of COVID-19. The first symptoms of Case 4 were vomiting, diarrhea, and Case 4 was wrong diagnosed as gastroenteritis when he saw a doctor firstly. Two patients had negative qRT-PCR results for SARS-CoV-2, but their serum IgM and IgG antibodies to SARS-CoV-2 were positive. Conclusion: The clinical characteristics of SARS-CoV-2 infection are very complex and diverse. More attention should be paid to observe the characteristics of COVID-19 in order to correctly recognize and diagnose cases with SARS-CoV-2 infection as soon as possible.

Aim: To investigate the effect of HBx on CTGF expression by hepatocytes. Materials & methods: HepG2 cells were transfected with the full-length gene of HBV, HBV protein-expressing plasmids, rhTGFβ1, LY2109761 or Smad2 siRNA, respectively, using Lipofectamine 3000. CTGF expression was detected by real-time PCR, ELISA, respectively. Then the effect of IL-32 on CTGF promoter was assayed by the Dual Luciferase® Reporter Assay System. Results: We found that HBx could induce CTGF expression by HepG2 cells in a concentration-dependent manner. CTGF expression induced by HBx employed the activation of TGFβ1-Smad2 signal pathway. Inhibition of TGFβ1 or Smad2 decreased CTGF expression induced by HBx. Conclusion: HBV might be involved in the pathogenesis of liver fibrosis through the HBx-induced CTGF expression.

Hepatic stellate cell (HSC) activation is important in the pathogenesis of liver fibrosis. However, the molecular mechanism of HSC activation is not completely understood. In the present study, it was demonstrated that interleukin-32γ (IL-32γ) is capable of enhancing intefgrin αvβ6 expression by inducing integrin αvβ6 promoter activity in a dose-dependent manner in HSCs. Furthermore, it was determined that nuclear factor κB (NF-κB) activation is required for IL-32γ-induced integrin αvβ6 expression. Increased integrin αvβ6 expression is then able to activate HSCs. These results indicate that NF-κB activation is required for IL-32γ to induce integrin αvβ6 expression and consequently promote HSC activation. Therefore, IL-32γ activates HSCs and therefore may be associated with hepatic fibrogenesis. These results may enable the development of novel effective strategies to treat hepatic fibrosis.

Absent in melanoma 2 (AIM2) is a recently recognized cytoplasmic receptor which could sense cytoplasmic double-stranded DNA (dsDNA). After AIM2 detects the presence of parasitic nucleic acids (dsDNA) derived from invasive bacteria or viral genomes (for example, vaccinia virus and cytomegalovirus) within infected cells, AIM2 inflammasome could be formed. The formed AIM2 inflammasome could induce innate immune response and increase expressions of IL-1β and IL-18. Hepatitis B virus (HBV) is a hepatotropic, non-cytopathic double-stranded DNA virus. The immune response to viral antigens or virus is thought to be responsible for both liver damage and viral clearance in patients with HBV infection. However, there are no reports about whether AIM2 inflammasome exists in hepatocytes. In the present study, we investigated the presence and activity of AIM2 inflammasome in human hepatocytes. We found that AIM2 was expressed in cytoplasm of hepatocytes, and IL-18 expression was increased after AIM2 sensed HBV in hepatocytes in vitro. These results showed that AIM2 inflammasome was active in hepatocytes. We also found that hepatic AIM2 expression of chronic hepatitis B (CHB) patients was higher than that of controls. Hepatic AIM2 expression levels were positively correlated to the severity of liver inflammation. IL-18 is already considered to be associated with hepatic injury during HBV infection. In conclusion, we, therefore, believe that AIM2 inflammasome in hepatocytes might play an important role in the development and maintenance of HBV-related hepatitis.

Hepatic fibrosis is a necessarily stage from the progression of chronic liver diseases to cirrhosis, even hepatocellular carcinoma (HCC). Hepatic fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM). The balance between ECM production and degradation is mediated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is an important regulator in the synthesis and degradation of ECM. IL-32, a multi-function cytokine, could induce IL-1β, IL-6, IL-8 and other cytokine expressions by activating AP-1, NF-κβ, p38MAPK signal pathways. IL-32 expression is increased in liver tissues of hepatic fibrosis. However, the role of IL-32 in the pathogenesis of liver fibrosis is not thoroughly clear. Recently, it is demonstrated that TIMP-1 expression is induced by the activation of AP-1 signal pathway. So we assayed the effect of IL-32 on TIMP-1 expression by LX-2 cells (one of HSCs cell lines) in the present study. We found that IL-32 could induce TIMP-1 expression by LX-2 cells at a dose-dependent manner. IL-32 could increase TIMP-1 promoter activity and induce TIMP-1 expression by activating AP-1 signal pathway. Moreover, the increase of TIMP-1 expression could promote the migration of LX-2 cells. In conclusion, we believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression.

Background and Aims Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF. Methods Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis. Results An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner. Conclusion Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up-regulation of IL-32 expression in HBV-ACLF.

AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E. METHODS: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the χ2 test or Fisher’s exact test for categorical variables and the Student’s t test for continuous variables. A P value < 0.05 was considered statistically significant. RESULTS: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure. CONCLUSION: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.