Recent advances of microneedles biosensors for plants.

As the lack of plants can affect the energy operation of the entire ecosystem, monitoring and improving the health status of plants is crucial. However, ordinary biosensing platforms lack accuracy and timeliness in monitoring plant growth status. In addition, the prevention and control of plant diseases often involve spraying and administering drugs, which is inefficient and prone to pollution. Microneedles have unique dimensions and shapes, and they have significant advantages as biosensors in the fields of sensing, detection, and drug delivery. Recent evidence suggests that microneedle biosensors can become effective tools for plant diagnosis and treatment. In this review, the comprehensive development of the application of microneedle biosensors in the field of plants is introduced, as well as their manufacturing processes and sensing and detection functions. Furthermore, the application of microneedle biosensors in this field is discussed, and future development directions are proposed.

Maternal and neonatal safety of COVID-19 vaccination during the peri-pregnancy period: A prospective study.

BACKGROUND: To investigate the safety of inactivated COVID-19 vaccine in Chinese pregnant women and their fetuses when inoculated during the peri-pregnancy period. METHODS: Eligible pregnant women were prospectively collected and divided into a vaccine group (n = 93) and control group (n = 160) according to whether they had been vaccinated against COVID-19 within 3 months before their last menstruation period (LMP) and after pregnancy. Demographic data of couples, complications during pregnancy and delivery of pregnant women, and data of newborns at birth were collected. RESULTS: Sixty-six women were vaccinated with a median time of 35.5 (range = 0-91) days before LMP, and 27 women were vaccinated with a median time of 17 (range = 1-72) days after LMP. The incidence of premature rupture of membrane (PROM) in the vaccine group was significantly higher than that in the control group (16.13% vs. 6.88%, p = 0.019). Multivariate logistic regression analysis revealed that maternal peri-pregnancy COVID-19 vaccination was not an independent risk factor for PROM (odds ratio: 2.407, 95% confidence interval: 0.932-6.216, p = 0.069). There was no difference in the incidence of other complications during pregnancy and delivery between the two groups. A total of 253 neonates were delivered, including two cases with congenital abnormalities in each group. The incidence of congenital abnormalities between the two groups was similar (2.15% vs. 1.25%, p = 0.626). There was no difference in neonatal length, weight, head circumference, and Apgar score between the two groups (p > 0.05), but the incidence of neonatal jaundice in the vaccine group was significantly higher than that in the control group (20.43% vs. 7.5%, p = 0.002). Multivariate logistic regression analysis revealed that maternal peri-pregnancy vaccination, postpartum blood loss, cesarean section, 1-min Apgar score, and paternal smoking were independent risk factors for neonatal jaundice. CONCLUSIONS: It is safe for pregnant women and their fetuses to be inoculated the inactivated COVID-19 vaccine during the peri-pregnancy period, but attention should be paid to neonatal jaundice.

Mobile multi-configuration clinical translational Raman system for oral cancer application.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

TE/TM mode electro-optic conversion based on a titanium diffusion lithium niobate waveguide with a polarization-maintained fiber structure.

For the development of photonic integrated circuits and lithium niobate (L i N b O 3, LN) optical waveguide technology, the implementation and application of polarization devices based on LN are also becoming more widespread, where titanium (Ti)-diffused LN waveguides form the basis of many important electro-optic (EO) integrated optical devices. Moreover, utilizing polarization conversion has the potential to enhance both the effectiveness and capacity of optical transmission. Thus, we have presented an EO polarization mode converter packaging with PANDA polarization-maintaining optical fibers (PMFs) in the broadband wavelength range (1440-1620 nm) to obtain the multiwavelength modulation, featuring the wavelength tunability. Additionally, the fabricated device is able to achieve transverse electric (TE) to transverse magnetic (TM) mode conversion efficiently with the applied voltage of  ±, which provides high conversion efficiency. Importantly, our device also features a high-frequency response of about 600 MHz with overall insertion loss below 5 dB. The rapid development of LN-based polarization devices holds great promise for chip-integrated systems in the field of polarization telecommunication.

Analysis of risk factors for impaired wound healing after kidney transplantation.

To analyse risk factors for impaired wound healing after kidney transplantation to guide clinical decision-making. A retrospective analysis was performed on patients who received kidney transplantation from January 1, 2019, to May 1, 2021, at Kidney Transplantation Center in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. A case-control study was used to identify a cohort of patients with similar baseline characteristics according to 1:4 ratio. Patients were divided into two groups according to whether there was impaired wound healing after surgery. The basic data and clinical examinations between the two groups were compared, and the risk factors for impaired wound healing after kidney transplantation were analysed using univariate and multivariate analyses. According to the data type, independent samples t-test or Chi-squared test was used for comparison between groups. Furthermore, multivariate logistic regression analysis was used to analyse different risk factors and calculate the odds ratio (OR) and 95% confidence interval (CI) of each factor. A total of 18 patients showed impaired wound healing after kidney transplantation. And we conducted 72 statically matched controls. Age, diabetes, transplant types, body mass index (BMI), albumin, haemoglobin, and wound infection were statistically different between the two groups. The factors with statistically significant differences in univariate analysis were included in multivariate logistic regression analysis. The results showed that BMI > 25, fasting blood glucose level, albumin level, and prealbumin level were independent risk factors for impaired wound healing after kidney transplantation. Risk factors for impaired wound healing after kidney transplantation can be detected after surgery. Strengthening postoperative monitoring and early intervention of recipients with such factors may effectively prevent impaired wound healing after kidney transplantation.

Electro-optic high-speed optical beam shifting based on a lithium niobate tapered waveguide.

We propose an electro-optic on-chip beam shifting device based on gradient microstructured electrodes and an optical tapered waveguide fabricated using lithium niobate (LN). The distribution of refractive index variations of the optical waveguide can be electro-optically defined and tailored by the designed gradient microstructured electrodes, which directs the beam propagation and shifting. The length of the beam shifting device is 18 mm and the width of the waveguide is gradually increased from 8 µm to 80 µm. The functionality of the beam shifting device is experimentally demonstrated, and it is observed that it has an electro-optic tunability of 0.41 µm/V, and a high-speed response time of 19 ns (λ=1310 nm). This study can provide potential applications in optical switching and modulation, beam scanning and ranging, optical spatial communications, etc.

Wavefront shaping for reconfigurable beam steering in lithium niobate multimode waveguide.

Reconfigurable photonic devices are important constituents for future optical integrated circuits, where electro-optic manipulation of the light field in a lithium niobate (LN) waveguide is one of the promising solutions. Herein, we demonstrate a paradigm shift of the beam steering mechanism where reconfigurable beam steering is enabled by the wavefront shaping technology. Furthermore, this strategy is fully compatible with the electro-optic tuning mechanism of the LN multimode waveguide, where microstructured serrated array electrodes are employed to fine tune the output beam upon its reconfigurable output position. Our results provide new, to the best of our knowledge, insight for molding the flow of light in multimode waveguides and shed new light on beam steering photonic devices.

Impact of in vitro fertilization-embryo transfer on mother-to-infant transmission in women with chronic HBV infection.

BACKGROUND AND AIMS: In vitro fertilization-embryo transfer (IVF-ET) may increase the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF-ET on MTCT in women with chronic HBV infection (CHB). METHODS: The data of 298 women who got pregnant by IVF-ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n = 224) and the control group (HBsAg negative, n = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant. RESULTS: There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P = .083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P = .167), 5-min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P = .212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P = .064) and neonatal malformation rate (0.71% vs. 0, P = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups. CONCLUSION: IVF-ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.

Plasmonic Helical Nanoantenna As a Converter between Longitudinal Fields and Circularly Polarized Waves.

A wide variety of optical applications and techniques require control of light polarization. So far, the manipulation of light polarization relies on components capable of interchanging two polarization states of the transverse field of a propagating wave (e.g., linear to circular polarizations, and vice versa). Here, we demonstrate that an individual helical nanoantenna is capable of locally converting longitudinally oriented confined near-fields into a circularly polarized freely propagating wave, and vice versa. To this end, the nanoantenna is coupled to cylindrical surface plasmons bound to the top interface of a thin gold layer. Helices of constant and varying pitch lengths are experimentally investigated. The reciprocal conversion of an incoming circularly wave into diverging cylindrical surface plasmons is demonstrated as well. Interconnecting circularly polarized optical waves (carrying spin angular momentum) and longitudinal near-fields provides a new degree of freedom in light polarization control.

Broadband mode-selective couplers based on tapered side-polished fibers.

We propose the broadband mode-selective coupler (MSC) formed with a side-polished six mode fiber (6MF) and a tapered side-polished small core single-mode fiber (SC-SMF) or an SMF. The MSCs are designed to allow the LP01 mode in the SC-SMF and SMF to completely couple to the LP01, LP11, LP21, LP02, LP31, LP12 modes in the 6MF over a broadband wavelength range. The phase-matching conditions of the MSCs are satisfied by tapering the SC-SMF and SMF to specific diameters. The tapered fibers are side-polished to designed residual fiber thickness using the wheel polishing technique. The effective indices of the side-polished fibers are measured with the prism coupling method. The MSCs provide high coupling ratio and high mode purity. High coupling efficiencies in excess of 81% for all the higher-order modes are obtained in the wavelength range 1530-1600 nm. For the LP01, LP11, LP21, LP02, LP31, LP12 MSCs at 1550 nm, the coupling ratios are 96.2%, 99.8%, 89.5%, 85.0%, 90.9%, 96.1%, respectively, and the mode purity of the MSCs is higher than 88.0%. The loss of the MSCs is lower than 1.8 dB in the wavelength range 1530-1600 nm. This device can be applied in broadband mode-division multiplexing transmission systems.

Ultrasensitive temperature sensor and mode converter based on a modal interferometer in a two-mode fiber.

This paper presents an ultrasensitive temperature sensor and tunable mode converter based on an isopropanol-sealed modal interferometer in a two-mode fiber. The modal interferometer consists of a tapered two-mode fiber (TTMF) sandwiched between two single-mode fibers. The sensor provides high-sensitivity temperature sensing by taking advantages of TTMF, isopropanol and the Vernier-like effect. The TTMF provides a uniform modal interferometer with LP01 and LP11 modes as well as strong evanescent field on its surface. The temperature sensitivity of the sensor can be improved due to the high thermo-optic coefficient of isopropanol. The Vernier-like effect based on the overlap of two interference spectra is applied to magnify the sensing capabilities with a sensitivity magnification factor of 58.5. The temperature sensor is implemented by inserting the modal interferometer into an isopropanol-sealed capillary. The experimental and calculated results show the transmission spectrum exhibit blue shift with increasing ambient temperature. Experimental results show that the isopropanol-sealed modal interferometer provides a temperature sensitivity up to -140.5 nm/°C. The interference spectrum has multiple dips at which the input LP01 mode is converted to the LP11 mode. This modal interferometer acts as a tunable multi-channel mode converter. The mode converter that can be tuned by varying temperature and mode switch is realized.

Transforming growth factor ß as a possible independent factor in chronic hepatitis B.

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-ß1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-ß1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-ß3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-ß3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-ß 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-ß2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-ß level might be an independent factor related to the occurrence of CHB.

Highly efficient second harmonic generation of thin film lithium niobate nanograting near bound states in the continuum.

Bound states in the continuum (BICs) are ubiquitous physical phenomena where such states occur due to strong coupling between leaky modes in side lossy systems. BICs in meta-optics and nanophotonics enable optical mode confinement to strengthen local field enhancement in nonlinear optics. In this study, we numerically investigate second-harmonic generation (SHG) in the vicinity of BICs with a photonic structure comprising one-dimensional nanogratings and a slab waveguide made of lithium niobate (LiNbO3, LN). By breaking the symmetry of LN nanogratings, BICs transition to quasi-BICs, which enable strong local field confinement inside LN slab waveguide to be supported, thereby resulting in improving SHG conversion with lower pump power of fundamental frequency (FW). With a peak intensity of 1.33 GW cm-2at the FW, our structure features a second-harmonic conversion efficiency up to 8.13 × 10-5at quasi-BICs. We believe that our results will facilitate the application of LN in integrated nonlinear nanophotonic.

Enhanced Peltier Effect in Wrinkled Graphene Constriction by Nano-Bubble Engineering.

Inspired by the promising applications in thermopower generation from waste heat and active on-chip cooling, the thermoelectric and electrothermal properties of graphene have been extensively pursued by seeking ingeniously designed structures with thermoelectric conversion capability. The graphene wrinkle is a ubiquitous structure formed inevitably during the synthesis of large-scale graphene films but the corresponding properties for thermoelectric and electrothermal applications are rarely investigated. Here, the electrothermal Peltier effect from the graphene wrinkle fabricated on a germanium substrate is reported. Peltier cooling and heating across the wrinkle are visualized unambiguously with polarities consistent with p-type doping and in accordance with the wrinkle spatial distribution. By direct patterning of the nano-bubble structure, the current density across the wrinkle can be boosted by current crowding to enhance the Peltier effect. The observed Peltier effect can be attributed to the nonequilibrium charge transport by interlayer tunneling across the van der Waals barrier of the graphene wrinkle. The graphene wrinkle in combination with nano-bubble engineering constitutes an innovative and agile platform to design graphene and other more general two-dimensional (2D) thermoelectrics and opens the possibility for realizing active on-chip cooling for 2D nanoelectronics with van der Waals junctions.

Association of cytokines with hepatitis B virus and its antigen.

To investigate the characteristics of cytokines in patients with different HBV infection status and their correlation with HBV DNA, HBsAg, and HBeAg levels. Peripheral blood samples were collected from patients with chronic HBV infection in immune tolerance phase (IT), HBeAg-positive chronic hepatitis B (CHB), and acute hepatitis B (AHB) groups, and levels of cytokines were detected by Luminex technique, and analyzed by FLEXMAP 3D analyzer. The correlation between cytokines and HBV DNA load, HBsAg, HBeAg, and alanine aminotransferase (ALT) level in patients with chronic HBV infection was analyzed. In total 312 subjects (184 males and 128 females) were enrolled in the study. There were significant differences among IT, CHB, and AHB groups in Flt-3L value (P = .003; H = 12.312), IFN-γ (P = .001; H = 11.723), IL-10 (P = .001; H = 18.736), IL-17A ((P = .001; H = 12.735), and TGF-ß1 (P = .001; Z = 48.571). IFN-α2 levels in CHB group were significantly higher than those in IT and AHB groups (15.24 vs 35.78 pg/mL, P = .000; Z = 3.727; 13.88 vs 35.78 pg/mL, P = .024; Z = -2.258. In CHB group, the levels of HBsAg and ALT were positively correlated with the levels of IL-10 (r = .173; P = .006; r = 0.176; P = .006, respectively), while HBeAg level was positively correlated with the IFN-α2 level (r = .153; P = .016). In AHB group, the HBsAg level was positively correlated with Flt-3L, IFN-α2, IL-10, and IL-6 (r = .402; P = .023; r = .436; P = .016; r = .524, P = .002; r = .405; P = .022, respectively). HBeAg level was positively correlated with IFN-γ and IL-17A levels (r = .400; P = .023; r = .373; P = .036, respectively), and ALT level was positively correlated with IL-6 levels (r = .367; P = .039). In either AHB or CHB group, HBV DNA load was only related to TGF-ß level (r = .493; P = .004; r = -.218, P = 0.009 respectively). The correlation between Flt-3L and HBsAg (F = 7.422; P = .007); IL-17, IL-6, and HBeAg (F = 5.757; P = .017; F = 6.156; P = .014) were statistically significant. There was significant correlation between TGF-ß2 and HBV DNA (F = 11.795; P = .001), and between ALT and HBsAg, HBV DNA (F = 26.089; P = .000; F = 4.724; P = .031). HBsAg, HBeAg, and HBV DNA were correlated with cytokines and ALT in patients with HBV infection. The level of IFN-α2 was significantly higher in patients with CHB. HBV DNA load was only correlated with the level of TGF-ß in acute or CHB.

Exploiting black phosphorus based-Tamm plasmons in the terahertz region.

Polarization-sensitive Tamm plasmons are investigated in a multi-layer photonic configuration where a monolayer black phosphorus (BP) is coated on a Bragg mirror separated by a dielectric. Owing to the in-plane anisotropy of BP, the Tamm plasmon can be excited selectively by tuning the BP carrier density. Cross-polarization conversion occurs when the armchair direction of BP makes an angle with the incident plan, i.e., ϕ≠0 or 90°. The BP-based Tamm device can be used as an intensity modulator with a modulation depth up to ∼100% and an insertion loss smaller than -0.55 dB. By analyzing the polarization evolution carefully, a multichannel polarization division multiplexing scheme is proposed and discussed. These findings open a new avenue for exploiting versatile tunable THz devices based on the monolayer of BP.

Ultrafast freestanding microfiber humidity sensor based on three-dimensional graphene network cladding.

An all-fiber humidity sensor is proposed and fabricated by depositing three-dimensional graphene network (3DGN) around the surface of a freestanding microfiber (MF). The high specific surface area and porosity of 3DGN enhances its interaction with water molecules, allowing high performance of the humidity sensor. The sensor can operate in a wide relative humidity (RH) range of 11.6%RH-90.9%RH with a high sensitivity of -2.841 dB/%RH in the RH range (80.3%RH - 90.9%RH). The response and recovery times of this type of microfiber sensor are measured respectively to be 57 ms and 55 ms, which are one order magnitude faster than those of other fiber RH sensors activated by two-dimensional materials coating. Such an all-fiber RH sensor with high sensitivity and fast response property possesses great potential of application in widespread fields, such as biology, chemical processing and food processing.

Residual thickness enhanced core-removed D-shaped single-mode fiber and its application for VOC evaporation monitoring.

A core-removed D-shaped structure with different residual thickness (RT) was manufactured on a single mode silica fiber (SMF) to enhance the sensitivity by using of ultra-precise polishing technology. With six different RTs ranging from ∼55 µm to ∼28 µm, the RT enhancement effect in a D-shaped SMF was researched in detail. The influence of the RT on its transmission spectra was investigated both theoretically and experimentally. Considering a compromise between the multimode interference efficiency and optical power loss, an optimum RT value of 34.09 µm was achieved. The obtained refractive index (RI) sensitivity was 10243 nm/RIU in the RI range of 1.430-1.444, corresponding to a RI resolution of 1.9×10-6 RIU. A high-performance all-fiber sensor was developed to monitor the evaporation process volatile organic compounds (VOCs) based on the RT-enhanced D-shaped SMF. As proof of concept, a 2-hour continuous monitoring was carried to monitor the chloroform and alcohol mixture. As a result, the evaporation of alcohol and chloroform were clearly identified and monitored. The developed RT-enhanced D-shaped fiber sensor provides an alternative way for chemical process monitoring and industrial applications.

Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy.

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)-negative CHB patients. In this prospective study, 176 HBeAg-negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3-6 months during the 48-week follow-up. The sustained functional cure was evaluated. After the 48-week follow-up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135-127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824-37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.

Evaluation of a logistic regression model for predicting liver necroinflammation in hepatitis B e antigen-negative chronic hepatitis B patients with normal and minimally increased alanine aminotransferase levels.

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non-invasive index for diagnosing liver necroinflammation. This study aimed to create a non-invasive index to predict liver necroinflammation in patients who lack clear-cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)-negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609-0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723-0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg-negative patients with CHB who have normal or minimally elevated ALT levels.