Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels.

Background and aims: Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Methods: Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. Results: One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045-1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138-2.014, P = 0.004) were independent factors associated with advanced inflammation. Conclusions: High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

A novel nomogram for predicting HBeAg seroclearance in HBeAg-positive chronic hepatitis B patients treated with nucleos(t)ide analogues.

INTRODUCTION AND OBJECTIVES: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). PATIENTS AND METHODS: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. RESULTS: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). CONCLUSIONS: The novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.

Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B.

Background: Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients. Methods: CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Results: A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727-0.803) and 0.766 (95% CI: 0.711-0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA. Conclusion: A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.

Baseline albumin-bilirubin score: a predictor for HBeAg clearance in patients with chronic hepatitis B after nucleos(t)ide analogue treatment.

BACKGROUND: Serum biomarkers for predicting HBeAg clearance in patients with chronic hepatitis B (CHB) virus infection during antiviral therapy remain lacking. This study aimed to investigate baseline albumin-bilirubin (ALBI) score for assessing HBeAg clearance in HBeAg-positive CHB patients treated with nucleos(t)ide analogues (NAs). METHODS: Six hundred and ninety-nine HBeAg-positive CHB patients treated with first-line NAs were retrospectively included. Kaplan-Meier curves were used to compare the possibility of HBeAg clearance and HBeAg seroconversion in different ALBI groups. Cox regression models were used to identify factors associated with HBeAg clearance and HBeAg seroconversion. RESULTS: Of the patients, 69.8% were male, with a median age of 36.0 years. 174 (24.9%) patients achieved HBeAg clearance after a median of 92.0 (interquartile range 48.0-134.0) weeks of antiviral treatment and 108 (15.5%) patients achieved HBeAg seroconversion. 74.0% and 26.0% of patients were classified as ALBI grade 1 and ALBI grade 2-3, respectively. ALBI grade 2-3 was identified as an independent predictor of HBeAg clearance (hazard ratio 1.570, 95% confidence interval 1.071-2.301, P  = 0.021). The cumulative incidence of HBeAg clearance and HBeAg seroconversion was significantly higher in ALBI grade 2-3 group than group of ALBI grade 1 ( P  < 0.001). Similar results were observed in different subgroups with different antiviral drugs, cirrhosis status, and ALT levels. CONCLUSION: Baseline ALBI score may be a valuable indicator for predicting antiviral response in HBeAg-positive CHB patients treated with NAs.

Interlayer structure and dynamic properties of CTMAB-montmorillonite: experiment and molecular dynamics.

The intercalation of cetyltrimethylammonium bromide (CTMAB) into montmorillonite will cause interlayer expansion and surface charge reversal. In this study, CTMAB-Mt is prepared by adding CTMAB with different multiples of montmorillonite cation exchange capacity (CEC), and the intercalated CTMAB structural arrangement, as well as the dynamics behavior, are investigated by combining molecular dynamics (MD) simulation with experimental characterization. According to RDF analysis of MD simulations, the interaction between CTMA+ and the surface of montmorillonite is mostly electrostatic interaction and hydrogen bond production. At low loading (≤1.00CEC), the XRD profile exhibits a peak value corresponding to one type of intercalation structure and interlayer spacing, but at high loading (>1.00CEC), two peaks are visible, each of which has a fixed value but a varied strength, corresponding to the existence of two types of expanded structures. The d-spacing (d 001) values obtained from MD simulations are quite close to XRD values when CTMAB loading is lower than 1.00CEC. Density distribution profiles obtained from MD analysis reveal that as loading increases, CTMA+ is arranged in the interlayer from a monolayer to a bilayer and then to a pseudo-trilayer. At high loadings (>1.00CEC), due to the fact that the excess loading leads to inhomogenous intercalation, XRD demonstrates the existence of two different arrangements: bilayer and pseudo-trilayer. The self-diffusion coefficients of MD simulations show that the dynamic behavior of CTMA+ is influenced by both the interlayer space and the electrostatic interaction of the montmorillonite clay. The abrupt rise in interlayer spacing increases mobility, whereas the increased interaction between alkyl chains decreases mobility.

Modified geosynthetic clay liners bentonite for barriers of Cr (VI) in contaminated soil.

Hydroxy-Fe-Al and cetyltrimethylammonium bromide (CTMAB) were chosen to modified Na-bentonite (Na-bent). The characteristics of Na-bent and modified bentonites were determined with scanning electron microscopy (SEM), energy disperse spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR) and zeta potential. It was found that CTMAB mainly entered the interlayer and hydroxy-Fe-Al groups were mostly loaded on the external surface of the Na-bent, respectively. The efficiency to remove Cr (VI) of Na-bent, organic modified bentonite (O-bent), inorganic modified bentonite (I-bent) and composite modified bentonite (Co-bent) followed the order: Co-bent > I-bent > O-bent > Na-bent. Adsorption experiments were carried out by the batch contact method. The highest removal rate of Cr (VI) by Co-bent was found to be 96.2% at optimal pH = 4. The Cr (VI) uptake on Co-bent from 50 mg/L solution rapidly attained equilibrium within 10 min, and the pesudo-second-order kinetic model could provide satisfactory fitting of the kinetic data (R2 = 0.999) compared to the intraparticle diffusion model (R2 = 0.585). The adsorption data were applied to the Langmuir, Freundlich, Temkin isotherm model. The Langmuir was found to be the most suitable equation to fit the experimental data (R2 = 0.956) with a high Cr (VI) adsorption capacity of 27.472 mg/g, and RL values (0.012-0.035) also indicated the adsorption could be accepted. The present study confirmed that Co-bent would be one of candidates for Cr (VI) adsorbent.