Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B.

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.

Exposure to bisphenol A and fiber-type microplastics induce oxidative stress and cell damage in disk abalone Haliotis discus hannai: Bioaccumulation and toxicity.

Along with environmental pollution caused by rapid economic development and industrialization, plastic waste is emerging as a global concern in relation to marine ecosystems and human health. Among the microplastics, fiber-type microfibers (MF) and bisphenol A (BPA), which are widely used as plasticizers, do not decompose well in the ocean, and tend to accumulate in organisms, generating an increased oxidative stress response. This study investigated the abalones' antioxidant and cell death responses following exposure to the environmental pollutants MF and BPA. Levels of malondialdehyde (MDA) and DNA damage increased over time, demonstrating the degree of lipid peroxidation and DNA damage in abalones exposed to individual and combined environmental conditions of MF and BPA. Compared to the single MF and BPA exposure groups, the combined exposure group showed a higher expression of antioxidant enzymes. A similar pattern was seen in the expression of the apoptosis enzyme caspase-3. Both MF and BPA caused oxidative stress and antioxidant enzymes were expressed to alleviate it, but it is believed that cell damage occurred because the stress level exceeded the allowed range.

Risk of hepatocellular carcinoma after curative treatment when switching from tenofovir disoproxil fumarate or entecavir to tenofovir alafenamide: A real-world multicenter cohort study.

AIM: Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high-quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence. METHODS: Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time-varying effect of NA use on HCC recurrence was analyzed using various statistical methods. RESULTS: Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68-1.47; p = 1.00) by time-varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67-1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51-2.33; p = 0.82 for ETV). Kaplan-Meier analysis showed comparable HCC recurrence-free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time-varying Cox analyses in various subgroups confirmed the primary findings. CONCLUSIONS: TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.

Effects of red-light irradiation and melatonininjection on the antioxidant capacity and occurrence of apoptosis in abalones (Haliotis discus hannai) subjected to thermal stress.

High ocean temperatures caused by global warming induce oxidative stress in aquatic organisms. Melatonin treatment and irradiation using red light-emitting diodes (LEDs) have been reported to reduce oxidative stress in a few aquatic organisms. However, the effects of red LED irradiation and melatonin injection on the antioxidant capacity and degree of apoptosis in abalones, which are nocturnal organisms, have not yet been reported. In this study, we compared the expression levels of antioxidant enzymes, total antioxidant capacity, and the degree of apoptosis in abalones subjected to red LED irradiation and melatonin treatment. The results revealed that at high water temperatures (25 °C), the mRNA expression levels of the superoxide dismutase (SOD) and glutathione peroxidase (GPx) genes and the antioxidant activity of SOD decreased in abalones in the red-LED irradiated and melatonin-treated groups compared with those in abalones in the control group. Although high water temperatures induced DNA damage in the abalone samples, the degree of apoptosis was lower in the red-LED irradiated and melatonin-treated groups than in the control group. Overall, the abalones in the melatonin-treated and red-LED irradiated groups showed reduced oxidative stress and increased antioxidant enzyme levels under thermal stress compared with those in the control group. Therefore, red LED irradiation is a promising alternative to melatonin treatment, which is difficult to administer continuously for a long time, for protecting abalones from oxidative stress.

Toxic effects of polystyrene microbeads and benzo[α]pyrene on bioaccumulation, antioxidant response, and cell damage in goldfish Carassius auratus.

Microplastics (MP) are harmful, causing stress in aquatic species and acting as carriers of hydrophobicity. In aquatic environments, benzo[α]pyrene (BaP) is an endocrine-disrupting chemical that accumulates in the body and causes toxic reactions in living organisms. We investigated the effects of single and combined microbead (MB) and BaP environments on goldfish antioxidant response and apoptosis. For 120 h, goldfish were exposed to single (MB10, MB100, and BaP5) and combined (MB10+BaP5 and MB100+BaP5) environments of 10 and 100 beads/L of 0.2 µm polystyrene MB and 5 µg/L BaP. We measured MB and BaP bioaccumulation as well as plasma parameters including ALT, AST, and glucose. The level of oxidative stress was determined by evaluating lipid peroxidation (LPO) and total antioxidant capacity (TAC) in plasma, as well as antioxidant-related genes for superoxide dismutase and catalase (SOD and CAT) and caspase-3 (Casp3) mRNA expression in liver tissue. The TUNEL assay was used to examine SOD in situ hybridization and apoptosis in goldfish livers. Except for the control group, plasma LPO levels increased at the end of the exposure period in all experimental groups. TAC increased up to 24 h of exposure and then maintained a similar level until the trial ended. SOD, CAT, and Casp3 mRNA expression increased substantially up to 120 h as the exposure concentration and time increased. The TUNEL assay revealed more signals and apoptotic signals in the combined exposure environments as a consequence of SOD in situ hybridization than in single exposure environments. These results suggest that combined exposure to toxic substances causes oxidative stress in organisms, which leads to apoptosis.

Toxicity response to benzo[α]pyrene exposure: Modulation of immune parameters of the bay scallop, Argopectenirradians.

Bay scallops were exposed to four BaP concentrations (0.5, 1.0, 10 and 50 µg/L) for 72 h to elucidate their immune response. Immune parameters were evaluated by measuring nitric oxide (NO) levels in hemolymph. Additionally, we measured peptidoglycan recognition proteins (PGRP), fibrinogen-domain-containing protein (FReDC1), metallothionein (MT), and heat shock protein (HSP) 70 mRNA expression in digestive diverticula. NO as well as FReDC1 and MT expression in each BaP group increased significantly over time except for the BaP 0.5 group. The PGRP and HSP70 mRNA expression in the BaP 50 group increased in the range 6-24 h and then decreased. In situ hybridization also confirmed that there was higher MT mRNA expression in the BaP 50 group than in the control group at 72 h. Our results suggest that higher levels of BaP dampened scallop immune responses, while simultaneously reducing their ability to cope with oxidative stress and DNA damage. BaP exposure can be considered a potential immune inducer in bay scallop.

Ocular blood flow by laser speckle flowgraphy to detect cerebral ischemia during carotid endarterectomy.

Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus contributed by the ophthalmic artery, the main first branch originating from the internal carotid artery (ICA). The aim of this study was to assess the feasibility of ocular blood flow measurement by LSFG to detect ischemic stress due to carotid clamping during carotid endarterectomy (CEA). Nineteen patients undergoing CEA with ocular blood flow measurement by LSFG and intraoperative monitoring (IOM) were prospectively enrolled between August 2016 and March 2019. The mean blur rate (MBR) of ocular blood flow by LSFG, representing relative blood flow of the branch of the retinal artery originating from the optic nerve head, was compared between before and after carotid clamping during CEA. The correlation between the reduction ratio of MBR and the regional saturation oxygen (rSO2) index by near infrared spectroscopy was investigated. Ocular blood flow measurement by LSFG could not be performed in one patient with a severe cataract. In the other 18 patients, LSFG could be performed in all 106 sessions during surgery. The MBR reduction ratio between before and after carotid clamping ranged from - 12 to 100%. The MBR reduction ratio was positively correlated with the rSO2 index (r = 0.694, 95% confidence interval: 0.336-0.877, p = 0.001). The MBR reduction ratio of ocular blood flow by LSFG after carotid clamping was significantly correlated with the rSO2 index. The ocular blood flow by LSFG could be considered an adjunct modality for evaluating cerebral ischemic tolerance during CEA.

Motor evoked potential monitoring can evaluate ischemic tolerance to carotid artery occlusion during surgery.

Balloon test occlusion (BTO) is a useful examination for evaluating ischemic tolerance to internal carotid artery (ICA) occlusion. The aim of this study was to investigate the relationships between intraoperative motor evoked potential (MEP) monitoring and the results of preoperative BTO. Between 2013 and 2017, 32 patients undergoing surgery under general anesthesia with intraoperative MEP monitoring, in whom preoperative BTO was performed, were identified. A receiver operator characteristic (ROC) analysis was performed to determine the appropriate cutoff value of MEP amplitude for BTO-positive. Furthermore, the accuracy of MEP monitoring for BTO-positive was compared with electroencephalogram (EEG) and somatosensory evoked potential (SEP) monitoring. Four of 32 (12.5%) patients were BTO-positive. The cutoff value of MEP amplitude for BTO-positive was a > 80% reduction from the baseline level, which showed sensitivity of 100% and specificity of 100%. Thus, the sensitivity and specificity for BTO-positive were significantly higher for MEP than for EEG (100% and 72.0%, p = 0.02) in 28 patients, but they were not significantly different compared with SEP (33.3% and 100%, p = 0.48) in 21 patients. MEP monitoring might be one of the alternatives for evaluating ischemic tolerance to ICA occlusion during surgery. The cutoff value of MEP amplitude was a > 80% reduction.

Exogenous cortisol and red light irradiation affect reproductive parameters in the goldfish Carassius auratus.

Reproductive hormones play essential roles in the control of reproduction and gonadal maturation in fish. The purpose of this study was to determine the effects of cortisol administration (10 µg/g or 50 µg/g) or red light irradiation at two intensities (0.5 W/m2 or 1.0 W/m2) on the reproductive hormones in goldfish (Carassius auratus). The effects of different treatments were analyzed by determining the mRNA expression levels of gonadotropin-inhibitory hormone receptor (GnIH-R), chicken gonadotropin-releasing hormone (cGnRH-II), salmon GnRH (sGnRH), FSHß, LHß, and plasma testosterone and the level of 17ß-estradiol for 48 h. Additionally, by double immunofluorescence staining, we detected the expression of both GnIH and GnRH in the diencephalons of goldfish brains. The mRNA expression of GnIH-R was significantly higher in the cortisol group and red light-irradiated group from 3 to 48 h than in the control group. Additionally, the mRNA levels of cGnRH-II, sGnRH, FSHß, LHß, testosterone, and 17ß-estradiol were significantly lower in the cortisol group than in the other groups from 3 to 48 h. These results indicated that both cortisol and red light-emitting diode (LED) light increased GnIH expression and inhibited GnRH expression. In particular, red light irradiation suppressed reproductive responses as much as the cortisol treatment at 48 h. Thus, it could be an alternative method for suppressing reproductive responses in future aquacultures.

C2 extradural schwannoma compressing the dominant internal jugular vein: a case report.

We describe a rare case of extradural schwannoma in the upper cervical spine compressing the dominant internal jugular vein (IJV) presenting with atypical headaches. A 50-year-old woman complained of a subcutaneous neck mass associated with atypical headaches. Radiological examinations revealed the right IJV was compressed anteriorly by C2 extradural mass and occluded with markedly dilated collateral cerebral venous drainage through deep cervical veins. Subtotal removal was performed via the posterolateral approach and the atypical headaches resolved immediately. This case demonstrates that extradural schwannoma in the upper cervical spine could compress the IJV and manifest as cerebral venous circulation disturbances.

Racial and Ethnic Differences in Mental Health among Asian Americans and Non-Hispanic Whites: Based on California Health Interview Survey.

While Asians are becoming the largest ethnic group in the United States, studies have focused on Asians as a single population. The purpose of this study was to explore the racial and ethnic mental health differences between non-Hispanic Whites and Asians, with an emphasis on understudied subgroups, from the California Health Interview Survey 2011/2012. In this dataset Asians had significantly lower adjusted odds ratios for both mental distress and serious mental illness. However, when Asians were divided into subgroups and compared to Whites, Vietnamese and Japanese subgroups were significantly lower than Whites for mental distress while Koreans were significantly higher. Vietnamese and Chinese were found to have significantly less serious mental illness than Whites in the subgroup analyses. Our results underscore the importance of recognizing that Asian subgroups should not be overlooked, and all Asians should not automatically be treated as a homogenous group.

Partial wrap-clipping of the entrance of the pseudolumen of a fusiform aneurysm in the posterior inferior cerebellar artery: a technical note.

BACKGROUND: Fusiform aneurysms in the posterior inferior cerebellar artery (PICA) are rare and challenging to treat. Surgical treatment options for a fusiform aneurysm in the PICA include trapping with/without bypass and wrap-clipping, when elimination of the pathological wall from the systemic circulation and prevention of perforator injury are important. In addition, lower cranial nerve impairment due to surgical manipulation should also be avoided. METHOD: A fusiform-shaped aneurysm was found in a proximal part of the PICA by magnetic resonance angiography undertaken for evaluation of repeated vertigo in a 36-year-old man. The patient underwent direct surgery via a lateral suboccipital transcondylar fossa approach. The entrance of the pseudolumen was the only part to be wrapped and obstructed by clip application, through the corridor between the acoustic and glossopharyngeal nerves to avoid lower cranial nerve injury. RESULTS: Indocyanine green (ICG) videoangiography demonstrated obliteration of pseudolumen and patency of peripheral PICA and perforator contributing to the medulla oblongata. The postoperative course was uneventful without periprocedural complications, including dysphagia and hoarseness. CONCLUSIONS: Partial wrap-clipping technique for obstruction of the entrance into a pseudolumen is one of alternatives for dissecting fusiform-shaped aneurysm in the PICA. ICG videoangiography was helpful to confirm the obliteration of the pseudolumen and patency of parent vessel and perforators.

Quantitative analysis of the trajectory of simulated basilar apex aneurysms through the internal carotid artery to assess the need for an orbitozygomatic approach.

BACKGROUND: The aim of this study was to identify the correlation between the location of the internal carotid artery (ICA) and the need for an orbitozygomatic approach (OZA) when approaching a basilar apex (BX) aneurysm. MATERIALS AND METHODS: By imaging the virtual trajectory to access the basilar artery (BA) through the ICA, the correlations among the height of the BX, the height and lateral breadth of the bifurcation of the ICA, and the need for removal of the orbital rim or zygomatic arch were investigated using three-dimensional computed tomography angiography (3DCTA) data of approximately 80 random samples not limited to BX aneurysms. Furthermore, the utility of 3D simulation to determine the need for the OZA was verified using data from five patients with BX aneurysms. RESULTS: The height of the bifurcation of the ICA was inversely correlated and the height of the BX was positively correlated with the need for the OZA (both p < 0.017). Among patients undergoing surgery, clipping was successfully performed without the OZA in two patients in whom the distance from the simulated skull point on the extended line from the BX through the bifurcation of the ICA was more than 4 cm from the zygoma and orbital rim. CONCLUSIONS: It is necessary to determine the spatial relationship between the basilar artery and the ICA to decide whether the OZA is needed for surgery. Correlations of the height of the ICA and BX with the need for the OZA were not very strong individually, though they were significant. Therefore, simulation using 3DCTA appears to be important for planning the surgical approach for the treatment of BX aneurysms.

Effectiveness of Telephone-Delivered Interventions Following Suicide Attempts: A Systematic Review.

AIM: To evaluate efficacy of telephone-delivered interventions following suicide attempts. METHODS: Systematic review, meta-analysis, and narrative synthesis. RESULTS: Five papers evaluating telephone interventions were included. Three studies provided suicide attempters with telephone contact intervention, and two studies provided deliberate self-harm patients with crisis cards to help after discharge. Meta-analyses showed that telephone contact intervention did not significantly reduce further suicide attempts and completed suicides, and the crisis card did not significantly reduce further deliberate self-harm. CONCLUSION: Telephone-delivered interventions have been suggested as an alternative to face-to-face psychotherapy, but their effectiveness in reducing the recurrence of suicide attempts is not supported.

Visualization of Regional Cerebral Blood Flow Dynamics during Cortical Venous Occlusion using Laser Speckle Contrast Imaging in a Rat Model.

BACKGROUND: Cerebral venous ischemia (CVI) is a rare but potentially significant complication of neurosurgical procedures. However, it is still unclear how cerebral venous occlusion (VO) affects regional cerebral blood flow (rCBF) dynamics. To elucidate its pathophysiology in detail, we examined the real-time perfusion dynamics during adjacent vein occlusions using laser speckle contrast imaging (LSCI) in a rat 2-vein occlusion model. METHODS: Two cortical veins were occluded photochemically using rose Bengal dye in 6 male Wistar rats; rCBF was measured in real time with an LSCI before and after VO. Regions of interest were defined between the 2 veins (A) and on the opposite side of the first occluded vein (B) on semi-quantitative pseudocolor images for off-line analysis. Histopathologic evaluation was performed 3 days after the procedure to assess the extent of infarction. RESULTS: LSCI revealed a stepwise reduction in CBF, with a sudden decrease just after the first vein occlusion (~20%) and a further decrease after the second (~30%). Significant differences were observed between rCBF dynamics within regions of interest A and B (P = .0004). All rats exhibited infarcts in the superficial cerebral cortex histopathologically. CONCLUSIONS: This is the first report of LSCI specifically applied to the study of CVI. The extensive real-time measurement with high temporal and spatial resolution revealed the stepwise reduction in rCBF during sequential VO and the ensuing infarcts.

[A case of intraventricular isolated neurosarcoidosis diagnosed by neuroendoscopic biopsy].

A 76-year-old woman was admitted to our hospital because of dementia, nausea, and speech disturbances. Computed tomography(CT)of her brain showed hydrocephalus and an intra-ventricular mass with a left temporo-parieto-occipital low density area. She underwent emergency ventricular drainage. Thereafter, she was referred to our department: neurosurgery. Gadolinium-enhanced magnetic resonance imaging of the brain showed homonymous enhancement in the left lateral, third, and fourth ventricles. CT of her chest and abdomen showed no abnormal findings. Initially, we performed a neuro-endoscopic biopsy and made a histopathological diagnosis of noncaseating granuloma. However, because we did not detect pulmonary or ocular lesions, we eventually made a diagnosis of isolated neurosarcoidosis. She received a ventricular-peritoneal shunt and steroid pulse therapy, and recovered from all her symptoms. Neurosurgeons should be aware of the possibility of hydrocephalus mimicking an intraventricular tumor and caused by isolated neurosarcoidosis. In this article, we provide a case description and review of the literature.

[A Case of Symptomatic Cyst Formation after BCNU Wafer Implantation for Glioblastoma].

We report a case of a 56-year-old woman admitted to our hospital for status epilepticus. Three months before hospitalization, the patient underwent gross total removal of a glioblastoma with BCNU wafer implantation in the left parietal lobe. The cavity was subsequently lined with five BCNU wafers. After admission, magnetic resonance imaging(MRI)showed cyst formation accompanied by strong edema, with no recurrence of glioblastoma. She was initially administered antiepileptic drugs and glycerol with betamethasone, after which her seizures stopped but recurred one month later due to a decrease in betamethasone. The BCNU wafers were removed four months after the initial surgery, after which the seizures completely stopped. Histopathological examination of the cavity indicated the presence of inflamed tissue and no recurrence of glioblastoma. Neurosurgeons should be aware of the possibility of cyst formation after BCNU wafer implantation for malignant gliomas. In this manuscript, we provide a case presentation and a review of the literature.

A case of cauda equina cavernous angioma coexisting with multiple cerebral cavernous angiomas.

The simultaneous presence of cavernous angiomas in both the brain and spinal cord is a very rare finding, as is the location of a cavernous angioma in the cauda equina. We reported a unique case of coexisting with multiple cerebral cavernous angiomas in the brain and cauda equina.

Melatonin injection and red light irradiation affect the antioxidant response and cell damage in disk abalone (Haliotis discus hannai) exposed to high water temperatures.

The effects of red light-emitting diode (LED) light irradiation (630 nm, 0.5 W/m2) and melatonin (10-8 and 10-7 M) on oxidative stress and physiological responses in abalones exposed to high temperatures (28°C) were investigated. Changes in messenger RNA (mRNA) expressions of melatonin receptor (MT-R), heat shock protein 70 (HSP70), and antioxidant enzymes, as well as alterations in H2O2 levels in the hemolymph, were examined. The results revealed that high-temperature-stressed abalones treated with melatonin injections or exposed to red LED light showed a significant increase in MT-R mRNA expression, while HSP70 mRNA expression decreased. Notably, HSP70 mRNA expression levels in the red LED light-irradiated group were similar to those in the group injected with 10-8 M melatonin after 24 h exposure. Abalones treated with melatonin at 20°C or irradiated with red LED light exhibited decreased H2O2 levels and reduced antioxidant enzyme mRNA expression compared with those of the control group. However, the high-temperature environment induced oxidative stress in abalones, leading to increased antioxidant enzyme mRNA expression compared with that under 20°C conditions. Moreover, abalones exposed to high-temperature stress exhibited hepatopancreatic DNA damage, which was attenuated by melatonin treatment or red LED light irradiation. Hence, red LED light reduces oxidative stress, boosts antioxidant enzymes, and alleviates DNA damage in high-temperature-stressed abalones, akin to 10-8 M melatonin treatment. Therefore, considering the practical challenges of continuous melatonin administration to abalones, utilizing red LED light emerges as a practical, effective alternative to protect abalones from oxidative stress compared to 10-8 M melatonin treatment.

Lack of association between early on-treatment HBeAg seroclearance and development of hepatocellular carcinoma or decompensated cirrhosis.

Background & Aims: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue (NA) treatment and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) remains unclear. Here, we aimed to investigate the association of HBeAg seroclearance during potent NA treatment with the development of HCC and decompensated cirrhosis. Methods: Using a multicenter historical cohort including 2,392 non-cirrhotic adult patients with HBeAg-positive CHB who initiated NA treatment with tenofovir or entecavir, the risk of HCC and decompensated cirrhosis was compared between patients who achieved HBeAg seroclearance within 36 months of NA treatment (the HBeAg-loss group) and those who did not (the HBeAg-maintained group), using inverse probability of treatment weighting. Results: Over a median of 6.6 years of NA treatment, 1,077 patients achieved HBeAg seroclearance (HBeAg loss rate = 6.0 per 100 person-years), 64 patients developed HCC (HCC incidence rate = 0.39 per 100 person-years), and 46 patients developed decompensated cirrhosis (decompensation incidence rate = 0.28 per 100 person-years). The HBeAg-loss and HBeAg-maintained groups had a similar risk of developing HCC (hazard ratio 0.89; 95% CI 0.47-1.68; p = 0.72) and decompensated cirrhosis (hazard ratio 0.98; 95% CI 0.48-1.81; p = 0.91). Compared with delayed HBeAg seroclearance beyond 10 years of NA treatment, the risk of HCC was comparable in those who achieved earlier HBeAg seroclearance at any time point within 10 years, regardless of baseline age and fibrotic burden. Conclusions: Early HBeAg seroclearance during NA treatment was not associated with a reduced risk of development of HCC or decompensated cirrhosis in non-cirrhotic HBeAg-positive patients with CHB. Impact and implications: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue treatment and the risk of hepatocellular carcinoma in patients with chronic hepatitis B remains unclear. Our findings indicate that early on-treatment HBeAg seroclearance within 3 years was not associated with the development of hepatocellular carcinoma or decompensated cirrhosis. Achieving HBeAg seroclearance may not be an appropriate surrogate endpoint for preventing the development of liver-related outcomes in non-cirrhotic patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.