Versatile Pickering emulsion gel lubricants stabilized by cooperative interfacial graphene oxide-polymer assemblies.

Although a large number of water- and oil-based gel lubricants have found extensive potential applications in industrial and biomedical fields, developing new-type emulsion-based gel lubricants that may effectively integrate their characteristics and preponderances remains a significant challenge. Here a water-in-oil Pickering emulsion gel lubricant that is able to combine the high colloidal stability of traditional Pickering emulsions, the good swelling and corrosion resistance of oil-based gel lubricants, and the high cooling capacity of water-based gel lubricants prepared from a binary mixture of aqueous graphene oxide (GO) dispersion and diamino-functionalized polydimethylsiloxane oil solution in a broad concentration, pH, and water volume fraction range is reported. It can provide favourable lubrication for the Si3N4/steel and Si3N4/silicone tribopairs either in air or under water owing to the formation of a sturdy adsorbed oil film and ball-bearing actions of the GO particles. It can also be printed into various colourful 2D and 3D geometries upon direct extrusion into water, thanks to its water-in-oil nature and inherent shear-thinning and thixotropic properties, which further shows good prospects in underwater operations and artificial biomimetic organs. Our study may provide new insights into the design and preparation of novel semi-solid materials for diverse industrial, engineering, and biomedical applications.

IRGM/Irgm1 increases autophagy to inhibit activation of NLRP3 inflammasome in inflammatory injury induced acute liver failure.

Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1ß, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that the expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P < 0.05). Rapamycin-induced autophagy ameliorated intrahepatic NLRP3 inflammasome activation and decreased inflammation and necrosis in the ALF mice. Irgm1 knockdown decreased autophagy and significantly upregulated NLRP3 inflammasome activation in AML12 cells (all P < 0.05). Rapamycin-induced autophagy also protected against hepatocyte injury following LPS stimulation in vitro by inhibiting NLRP3 inflammasome activation. Thus, IRGM/Irgm1 alleviates inflammation-mediated hepatocyte injury by regulating autophagy. This study provides new insight into potential molecular targets to treat liver failure.

Risk factors for short-term prognosis of end-stage liver disease complicated by invasive pulmonary aspergillosis.

BACKGROUND AND AIM: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. METHODS: This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. RESULTS: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). CONCLUSIONS: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.

Versatile MXene Gels Assisted by Brief and Low-Strength Centrifugation.

Due to the mutual repulsion between their hydrophilic surface terminations and the high surface energy facilitating their random restacking, 2D MXene nanosheets usually cannot self-assemble into 3D macroscopic gels with various applications in the absence of proper linking agents. In this work, a rapid spontaneous gelation of Ti3C2Tx MXene with a very low dispersion concentration of 0.5 mg mL-1 into multifunctional architectures under moderate centrifugation is illustrated. The as-prepared MXene gels exhibit reconfigurable internal structures and tunable rheological, tribological, electrochemical, infrared-emissive and photothermal-conversion properties based on the pH-induced changes in the surface chemistry of Ti3C2Tx nanosheets. By adopting a gel with optimized pH value, high lubrication, exceptional specific capacitances (~ 635 and ~ 408 F g-1 at 5 and 100 mV s-1, respectively), long-term capacitance retention (~ 96.7% after 10,000 cycles) and high-precision screen- or extrusion-printing into different high-resolution anticounterfeiting patterns can be achieved, thus displaying extensive potential applications in the fields of semi-solid lubrication, controllable devices, supercapacitors, information encryption and infrared camouflaging.

Factors affecting the transmission of dengue fever in Haikou city in 2019.

In this study, due to multiple cases of dengue fever in two locations in Haikou, Hainan, several factors affecting the transmission of dengue fever in Haikou in 2019 were analyzed. It was found that dengue fever spread from two sites: a construction site, which was an epidemic site in Haikou, and the university, where only four confirmed cases were reported. Comparative analysis revealed that the important factors affecting the spread of dengue fever in Haikou were environmental hygiene status, knowledge popularization of dengue fever, educational background, medical insurance coverage and free treatment policy knowledge and active response by the government.

Evaluation and Mechanistic Investigation of Human Milk Oligosaccharide against SARS-CoV-2.

Four human milk oligosaccharides (HMOs), 3'-sialyllactose (3'-SL), 6'-sialyllactose (6'-SL), 2'-fucosyllactose (2'-FL), and 3-fucosyllactose (3-FL), were assessed for their possible antiviral activity against the SARS-CoV-2 spike receptor binding domain (RBD) in vitro. Among them, only 2'-FL/3-FL exhibited obvious antibinding activity against direct binding and trans-binding in competitive immunocytochemistry and enzyme-linked immunosorbent assays. The antiviral effects of 2'-FL/3-FL were further confirmed by pseudoviral assays with three SARS-Cov-2 mutants, with a stronger inhibition effect of 2'-FL than 3-FL. Then, 2'-FL/3-FL were studied with molecular docking and microscale thermophoresis analysis, showing that the binding sites of 2'-FL on RBD were involved in receptor binding, in addition to a tighter bond between them, thus enabling 2'-FL to be more effective than 3-FL. Moreover, the immunomodulation effect of 2'-FL was preliminary evaluated and confirmed in a human alveolus chip. These results would open up possible applications of 2'-FL for the prevention of SARS-CoV-2 infections by competitive binding inhibition.

Biochemical and Structural Insights into a Thiamine Diphosphate-Dependent α-Ketoglutarate Decarboxylase from Cyanobacterium Microcystis aeruginosa NIES-843.

α-Ketoglutarate decarboxylase is a crucial enzyme in the tricarboxylic acid cycle of cyanobacteria, catalyzing the non-oxidative decarboxylation of α-ketoglutarate to produce succinate semialdehyde and CO2. The decarboxylation process is reliant on the cofactor of thiamine diphosphate. However, this enzyme's biochemical and structural properties have not been well characterized. In this work, two α-ketoglutarate decarboxylases encoded by MAE_06010 and MiAbw_01735 genes from Microcystis aeruginosa NIES-843 (MaKGD) and NIES-4325 (MiKGD), respectively, were overexpressed and purified by using an Escherichia coli expression system. It was found that MaKGD exhibited 9.2-fold higher catalytic efficiency than MiKGD, which may be attributed to the absence of glutamate decarboxylase in Microcystis aeruginosa NIES-843. Further biochemical investigation of MaKGD demonstrated that it displayed optimum activity at pH 6.5-7.0 and was most activated by Mg2+. Additionally, MaKGD showed substrate specificity towards α-ketoglutarate. Structural modeling and autodocking results revealed that the active site of MaKGD contained a distinct binding pocket where α-ketoglutarate and thiamine diphosphate interacted with specific amino acid residues via hydrophobic interactions, hydrogen bonds and salt bridges. Furthermore, the mutagenesis study provided strong evidence supporting the importance of certain residues in the catalysis of MaKGD. These findings provide new insights into the structure-function relationships of α-ketoglutarate decarboxylases from cyanobacteria.

[Glycosylation, glycan receptors recognition of SARS-CoV-2 and discoveries of glycan inhibitors against SARS-CoV-2].

COVID-19 represents the most serious public health event in the past few decades of the 21st century. The development of vaccines, neutralizing antibodies, and small molecule chemical agents have effectively prevented the rapid spread of COVID-19. However, the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies, which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods. In the process of SARS-CoV-2 infection, the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract, then specifically binds to hACE2. The S protein of SARS-CoV-2 is a highly glycosylated protein, and glycosylation is also important for the binding of hACE2 to S protein. Furthermore, the S protein is recognized by a series of lectin receptors in host cells. These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2. Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2, it is possible to develop glycan inhibitors against COVID-19. Recent studies have shown that sulfated polysaccharides originated from marine sources, heparin and some other glycans display anti-SARS-CoV-2 activity. This review summarized the function of glycosylation of SARS-CoV-2, discoveries of glycan inhibitors and the underpinning molecular mechanisms, which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.

Solvothermal synthesis of carbonate-type layered double hydroxide monolayer nanosheets: Solvent selection based on characteristic parameter matching criterion.

Monolayer nanosheets of CO32--type layered double hydroxides (LDHs) have many special applications, but their fabrication is challenging. Herein, Co2Al-CO3 and Co2Fe-CO3 LDH nanosheets were synthesized via a solvothermal method. 31 solvents with different characteristic parameters, including the surface free energy (γ) and solubility (δ) parameters were chosen, to explore the correlation between the formation of monolayer LDHs (ML-LDHs) and the characteristic parameters of solvents. The results reveal that when the solvents used have the characteristic parameters matching to those of the LDHs, CO32--type ML-LDHs with a thickness of ca. 1 nm can be obtained. The mixed-solvent strategy can provide the effective solvents for the synthesis of ML-LDHs. The dispersions of CO32--type ML-LDHs can be stable for at least six months without obvious precipitation. In addition, it is demonstrated that the δ parameters of LDHs can be calculated from the γ parameters via the molar volume-free γ-δ equations developed previously. Furthermore, a new parameter called "surface free energy distance" is introduced, which can be used for screening effective solvents for the synthesis of ML-LDHs. To the best of our knowledge, this is the first time to investigate the applicable of the characteristic parameter matching principle for the bottom-up synthesis of ML-LDHs. This work deepens the understanding on the feature of CO32--type LDHs and provides a solvent selection strategy for the synthesis of CO32--type ML-LDHs.

Specific Ion Effects on the Colloidal Stability of Layered Double Hydroxide Single-layer Nanosheets.

The surface charge properties and aggregation behavior of positively charged Mg-Al-NO3 layered double hydroxide (LDH) single-layer nanosheets dispersed in water were investigated in the presence of K+ salts with different mono-, di-, and trivalent anions, using electrophoresis and dynamic light scattering techniques. An increase in the salt concentration can significantly decrease the effective surface charge density (σeff) of LDHs, leading to the aggregation of nanosheets. The critical coagulation concentration (CCC) or ionic strength (CCIS) of salts for nanosheets significantly decreases with an increase in the valence of anions. Specific ion effects, with a partially reverse Hofmeister series, are observed. On the basis of the Stern model and the DLVO theory, the relationship of CCC with σeff and the ionic valences of salts (zi) is theoretically analyzed, which can accurately describe the dependence of CCC on the σeff and zi but cannot explain the origin of specific ion effects. To explore the origin of specific ion effects, a correlation between CCIS and the specific adsorption energy (Esc) of anions within the Stern layer is developed. Especially, an empirical relationship of Esc with the characteristic physical parameters of anions is proposed. Our model can accurately predict the CCISs of at least monovalent anions and divalent anions (CO32- and SO42-), demonstrating that the specific ion effects observed can be attributed to the differences in ionic size, polarizability, and hydration free energy (or the formation capacity of anion-cation pairs) of different anions. This work not only deepens the understanding of specific ion effects on the colloidal stability but also provides useful information for the potential applications of LDH single-layer nanosheets.

Estimation of surface free energy and solubility parameters of MgAl layered double hydroxides.

The characteristic parameters, surface free energy (γ) and solubility parameters (δ), of Mg2AlNO3, Mg3AlNO3, Mg4AlNO3, Mg3AlCl, and Mg3AlCO3 layered double hydroxides (LDHs) were estimated using contact angle and liquid phase exfoliation (LPE) methods. The γ parameters include total (γst), dispersive (γsd), and polar (γsp) ones. The δ parameters include the Hildebrand parameter (δt,s) and the Hansen dispersive (δd,s), polar (δp,s), and hydrogen-bonding (δh,s) ones. Results show that the γst, γsd, and γsp of the five LDHs are ∼50.9-56.9, 35.2-39.4, and 15.6-18.8 mJ/m2, respectively, and the δt,s, δd,s, δp,s and δh,s of the LDHs except for the Mg3AlCO3 LDH are ∼31.4-32.9, 17.2, 9.5-10.0, and 24.5-26.1 MPa1/2, respectively. The compositions of LDHs have no obvious impact on all the characteristic parameters. In comparison with van de Waals attraction-bonded materials, the electrostatic attraction-bonded LDHs exhibit higher γst and δt,s values and, especially, much larger δh,s values. The characteristic parameter matching principle and the mixed-solvent strategy are suitable for the LPE of LDHs. Non-toxic glycol/PEG200 mixed liquids are found to be a good medium for the direct LPE of LDHs, producing monolayer nanosheets. To the best of our knowledge, this is the first report on the γ and δ parameters of LDHs. This work not only deepens the understanding of the feature of LDHs, but also provides effective liquid media for the direct LPE of LDHs.

Correlations of surface free energy and solubility parameters for solid substances.

HYPOTHESIS: Both the surface free energy (γ) and solubility (δ) parameters of substances are related to their cohesive energies which are decided by intermolecular interactions, and there should be some intrinsic relationships between the two parameters. Understanding of the γ-δ correlations is of great fundamental and practical importance. Several empirical γ-δ equations have been proposed so far, but their application to solids is limited. This is because the molar volume (V~) as a parameter exists in these equations while the V~ of solids is commonly hard to be obtained. Hence, the development of γ-δ equations without the parameter V~ is essential for solids. METHOD: The γ and δ data of 21 solids including polymers and layered solid materials were chosen, and possible γ-δ relationships were systematically explored using the parameter data of solids by a trial and error fitting method. FINDING: Six γ-δ equations without the parameter V~ are proposed. The γ parameters include total (γt), dispersive (γd), and polar (γp) ones, and the δ parameters include the Hildebrand parameter (δt) and the Hansen dispersive (δd), polar (δp), and hydrogen-bonding (δh) ones. Interestingly, the so-obtained V~-free γ-δ equations are also valid for most liquids including nonpolar and polar ones. These γ-δ equations can provide a way to estimate non-measurable parameters from measurable parameters for solid materials, which is beneficial to the application of the characteristic parameters (γ and δ) for solid material engineering.

Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting

ABSTRACT Aims: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p < 0.001, Hazard Ratio (HR) = 2.203), elevated alanine aminotransferase (ALT) levels (p < 0.001, HR = 2.049), and non-vertical transmission (p = 0.006, HR = 1.656) were predictors of HBeAg seroconversion. Conclusion: Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

NKG2D modulates aggravation of liver inflammation by activating NK cells in HBV infection.

Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D+ and IFN-γ+ NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed. Serum and supernatant IFN-γ, TNF-α, perforin and granzyme B were measured. In results, peripheral NKG2D+ and IFN-γ+ NK cells frequencies, intrahepatic NKG2D and IFN-γ mRNA and protein levels, and serum IFN-γ, TNF-α, perforin and granzyme B levels were all highest in HBV-related acute-on-chronic liver failure group, followed by chronic hepatitis B and chronic HBV carrier groups. In vitro, NKG2D and IFN-γ mRNA and protein levels were higher in NK cells with IFN-α stimulation than without stimulation. Supernatant IFN-γ, TNF-α, perforin and granzyme B levels were increased under co-culture or IFN-α stimulating conditions, but were partially blocked by NKG2DmAb. In conclusion, NKG2D regulates immune inflammation and anti-viral response partly through activation of NK cells during HBV infection.

Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting.

AIMS: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). METHODS: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100mg daily), adefovir (ADV, 10mg daily), telbivudine (LDT, 600mg daily), entecavir (ETV, 0.5mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. RESULTS: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p<0.001, Hazard Ratio (HR)=2.203), elevated alanine aminotransferase (ALT) levels (p<0.001, HR=2.049), and non-vertical transmission (p=0.006, HR=1.656) were predictors of HBeAg seroconversion. CONCLUSION: Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

Predictive Value of Serum IFN-γ inducible Protein-10 and IFN-γ/IL-4 Ratio for Liver Fibrosis Progression in CHB Patients.

Noninvasive serum markers for assessment of liver fibrosis in chronic hepatitis B (CHB) patients have not been well-studied. The present study was to evaluate the predictive value of serum interferon gamma-inducible protein-10 (IP-10/CXCL10) and the interferon (IFN)-γ/interleukin (IL)-4 ratio for liver fibrosis progression in CHB patients. A total of 180 CHB patients were categorized into four groups: no fibrosis, mild fibrosis, moderate fibrosis, and severe fibrosis. Serum and intrahepatic levels of IP-10, IFN-γ, and IL-4 were examined, from which the IFN-γ/IL-4 ratio was calculated. We found that the serum IP-10 levels were positively correlated with the severity of liver fibrosis, whereas the IFN-γ/IL-4 ratio was negatively associated with the progression of hepatic fibrosis. Multivariate logistic regression analysis revealed that the serum IP-10 was an independent predictor for significant fibrosis. For predicting significant fibrosis, the IP-10 cut-off value of 300 ng/mL had a sensitivity of 92.7% and a specificity of 68.6%. When the IP-10 level was combined with the IFN-γ/IL-4 ratio, the specificity and positive predictive value were 93.8% and 94.6%, respectively; thus, the discriminatory ability was much improved. In conclusion, the serum IP-10 level and the IFN-γ/IL-4 ratio have great potential to predict significant fibrosis among CHB patients.

The relationship between hepatic resistin overexpression and inflammation in patients with nonalcoholic steatohepatitis.

BACKGROUND: The relationship between resistin and non-alcoholic steatohepatitis (NASH) is not clear, some studies claimed that serum resistin levels were associated with neither the presence of NASH nor its severity, others declared that serum resistin was related with inflammation and fibrosis in NASH. Our animal study verified that the distribution of resistin in the liver is correlated with inflammation in NASH. However, there is no pertinent study in humans. METHODS: Thirty patients with NASH, 28 simple steatosis, and 43 controls were recruited. Blood was collected for resistin, liver chemistries, fasting insulin and some metabolic parameters. Liver histology was scored according to NAFLD activity scoring system. Hepatic resistin expression was examined by real-time polymerase chain reaction, immunohistochemistry. Resistin protein expression was confirmed by western blotting in 13 patients with concomitant NAFLD and gallstone. RESULTS: Serum resistin was significantly elevated in both NASH and simple steatotic subjects compared with controls (all P < 0.05). Hepatic resistin was significantly increased in NASH patients in both mRNA and protein levels than those in simple steatosis and control subjects (all P < 0.05). Both serum and hepatic resistin had a correlation with obesity, but not with insulin resistance. The distribution of resistin positive cells was predominantly in perisinusoidal cells (such as Kupffer cells and hepatic stellate cells) in human NASH. Multivariate analysis revealed that waist-hip ratio, higher serum triglyceride, and hyperresistinemia were independent factors related to higher grade of steatosis; whereas hepatic resistin and serum cytokeratin predict NASH and severity of liver fibrosis. CONCLUSIONS: Hepatic resistin overexpression in NASH patients is associated with the severity of liver inflammation and fibrosis. Liver-derived resistin may be involved in the pathogenesis of human NASH.

Predictive value of interferon-gamma inducible protein 10 kD for hepatitis B e antigen clearance and hepatitis B surface antigen decline during pegylated interferon alpha therapy in chronic hepatitis B patients.

Chronic hepatitis B (CHB) is an immune-mediated infectious disease caused by the hepatitis B virus (HBV). No ideal immunological markers are available at present. In this study, the expression level of interferon-gamma inducible protein 10 kD (IP-10) in chronic asymptomatic HBV carriers (AsC), patients with CHB, and patients with HBV-related acute-on-chronic liver failure (ACLF) was detected. Serum IP-10 level changes were evaluated during the pre-, on- and post-treatment periods for CHB patients receiving Peg IFN-α therapy. The correlation between the IP-10 level and the inflammation activity (IA) score, alanine aminotransferase (ALT) level, HBV DNA load, and hepatitis B surface antigen (HBsAg) quantification were also evaluated. The IP-10 expression gradually increased from AsC to patients with CHB and was highest in patients with ACLF. Serum IP-10 levels were positively correlated with the hepatic IA score and ALT level, but negatively with the HBV DNA load and HBsAg quantification. The CHB patients achieved hepatitis B e antigen (HBeAg) clearance or HBsAg decline >1 log10 IU/ml had higher pre-treatment IP-10 levels and more obvious on-treatment reduction of the IP-10 level than did patients with HBeAg persistent-positive or HBsAg decline <1 log10 IU/ml. Multivariate logistic-regression analysis revealed that the serum IP-10 level was an independent predictor of HBeAg clearance and HBsAg decline. In conclusion, IP-10 expression distinctly varies at different clinical stages of HBV infection. Higher pre-treatment serum IP-10 expression and dynamic down-regulation might be associated with an increased probability of HBeAg clearance and HBsAg decline in CHB patients during Peg IFN-α therapy.

The efficacy and safety of Nucleos(t)ide analogues in patients with spontaneous acute exacerbation of chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Spontaneous acute exacerbation (AE) of chronic hepatitis B (CHB) is often detrimental but sometimes leads to sustained immune control and disease remission. The efficacy and safety of nucleos(t)ide analogues (NAs) in patients with spontaneous AE of CHB remains unclear. METHODS: We performed a systematic review and meta-analysis of NAs in patients with spontaneous AE of CHB. We calculated pooled effects of NAs in these patients of each study and conducted quantitative meta-analysis, displaying results using Forest plots. RESULTS: 15 studies were included and substantial heterogeneity was noted in the inclusion/exclusion criteria and controls. Pooled data showed no benefit of lamivudine (LAM) vs. untreated controls for transplant-free survival in patients with spontaneous AE of CHB (OR = 0.98 (95% CI, 0.50-1.92; P = 0.956)), hepatic decompensation (OR = 0.94 (95% CI, 0.47-1.88; P = 0.862)) and liver failure owing to AE (OR = 2.30 (95% CI, 0.35-15.37; P = 0.387)) at 3 months. Entecavir achieved even higher short-term mortality than LAM. NAs led to rates of ALT normalization, undetectable HBV DNA, HBeAg loss, HBeAg seroconversion and drug resistance at 1 year in 88%, 61%, 46%, 35% and 5%. Pooled data also showed benefit favoring LAM vs. untreated controls for ALT normalization (OR = 1.98 (95% CI, 1.03-3.80; P = 0.039)) and undetectable HBV DNA (OR = 38.50 (95% CI, 7.68-192.99; P<0.001)) at 3 months. All NAs were relatively safe and well tolerated. CONCLUSION: NAs had no obvious impact on short-term survival in patients with AE of CHB, despite of possible better antiviral responses. We suggest additional studies to evaluate the efficacy of other NAs and early introduction of immunosuppressant in combination with NAs. We highlight developing prognostic models to identify predictors of mortality and disease progression for AE of CHB.