Relationship of paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size to disease burden and risk of major vascular events in untreated patients: results from the International PNH Registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by acquired gene mutations resulting in deficiency of glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins on the surface of blood cells, leading to terminal complement-mediated intravascular hemolysis and increased risk of major adverse vascular events (MAVEs). Using data from the International PNH Registry, this study investigated the relationship between the proportion of GPI-deficient granulocytes at PNH onset and (1) the risk for MAVEs (including thrombotic events [TEs]) and (2) the following parameters at last follow-up: high disease activity (HDA); lactate dehydrogenase (LDH) ratio; fatigue; abdominal pain; and rates of overall MAVEs and TEs. A total of 2813 patients untreated at enrollment were included and stratified by clone size at PNH disease onset (baseline). At last follow-up, higher proportion of GPI-deficient granulocytes (≤ 5% vs. > 30% clone size) at baseline was associated with significantly increased HDA incidence (14% vs. 77%), mean LDH ratio (1.3 vs. 4.7 × upper limit of normal), and rates of MAVEs 1.5 vs. 2.9 per 100 person-years) and TEs (0.9 vs. 2.0 per 100 person-years). Fatigue was evident in 71 to 76% of patients regardless of clone size. Abdominal pain was more frequently reported with clone size > 30%. A larger clone size at baseline appears to indicate a greater disease burden and risk of TEs and MAVEs and may inform decision making among physicians managing PNH patients at risk of experiencing TEs or other MAVEs. ClinicalTrials.gov ID: NCT01374360.

Risk factors for thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): a nested case-control study in the International PNH Registry.

The objective of this analysis was to identify risk factors for thromboembolic events (TE) in patients with paroxysmal nocturnal hemoglobinuria (PNH) who were not treated with C5 inhibitors. Patients with PNH and a history of ≥ 1 TE at enrollment in the International PNH Registry (NCT01374360; registration date, January 2011) were each matched with up to 5 patients without TE. Multivariable analysis was performed with the following variables: percentage glycosylphosphatidylinositol (GPI)-negative cells, high disease activity (HDA), non-TE major adverse vascular event history, and recent anticoagulation. Of 2541 eligible patients, 57 with TE and 189 matched controls were analyzed. Multivariable analysis (odds ratio [95% CI]) identified the following factors as being associated with increased thrombotic risk: patients with no history of TE (with recent anticoagulation, 9.30 [1.20-72.27]), patients with history of TE (with recent anticoagulation, 8.91 [0.86-92.62]; without recent anticoagulation, 5.33 [0.26-109.57]), patients with ≥ 30% GPI-negative granulocytes (≥ 30% to < 50%, 4.94 [0.54-45.32]; ≥ 50%, 1.97 [0.45-8.55]), or patients with lactate dehydrogenase (LDH) ratio ≥ 1.5 × upper limit of normal (ULN) plus ≥ 2 HDA criteria (2-3 criteria, 3.18 [0.44-23.20]; ≥ 4 criteria, 3.60 [0.38-33.95]). History of TE, ≥ 30% GPI-negative granulocytes, and LDH ratio ≥ 1.5 × ULN with ≥ 2 HDA criteria are TE risk factors for patients with PNH. These findings will aid physicians by providing important clinical and laboratory risk factors that can be used to identify and manage patients with PNH who are at risk of developing TE.

Heat shock protein B8 promotes proliferation and migration in lung adenocarcinoma A549 cells by maintaining mitochondrial function.

Heat shock protein B8 (HSPB8) impacts on tumor proliferation and migration of malignancy. However, the role of HSPB8 in lung adenocarcinoma (LUAC) remains unclear. The aim of this study, therefore, was to clarify whether HSPB8 could bring benefits to proliferation and migration of LUAC and its underlying mechanisms. The expression of HSPB8 was first evaluated by immunohistochemistry in 35 LUAC samples. Then, A549 lung adenocarcinoma cells were transfected with pcDNA-HSPB8 or si-HSPB8 to induce HSPB8 overexpression and silence. Cellular activity was evaluated with a Cell Counting Kit-8 (CCK-8) assay. Cell proliferation and migration were observed by EdU assay and scratch assay. Mitochondria-specific reactive oxygen species (mtROS) and membrane potential were measured using MitoSOX Red probe and JC-1 staining. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) level were measured using commercial kits, respectively. HSPB8 protein, mitochondrial fusion protein MFN2 and mitochondrial fission protein p-Drp1/Drp1 were measured using western blot. Compared with the normal tissues, the expression of HSPB8 protein was higher in LUAC tissues and upregulation of HSPB8 protein was related to tumor size and tumor location. Furthermore, HSPB8 overexpression aggravated cell proliferation and migration of A549 cells. Mechanistically, HSPB8 suppressed mitochondrial impairment, leading to promoting the progress of A549 lung adenocarcinoma cells. These data demonstrate that HSPB8 plays an important role in progression of LUAC and may be a new target to treat LUAC.

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is "equipoise and above."

Critical review of long-term ozone exposure and asthma development.

Asthma, a chronic respiratory disorder with complex etiology and various phenotypes, is a considerable public health concern in the USA and worldwide. While there is evidence suggesting ambient ozone exposure may exacerbate asthma, information regarding the potential role of ozone in asthma development is more limited. Thus, we conducted a critical review of observational epidemiology studies to determine whether long-term ambient ozone exposure is a risk factor for asthma development. We identified 14 relevant studies; 11 evaluated asthma development in children, while three studies, based on a single cohort, assessed this outcome in adults. Studies of childhood asthma and long-term ozone exposure - including exposure in utero, during the first year of life and during early childhood - reported inconsistent findings, which were further weakened by critical methodological limitations in statistical analyses and in exposure and outcome assessments, such as exposure measurement error and a lack of adjustment for key confounders. For adult-onset asthma, long-term ozone exposure was associated with an increased risk in men but not women. In addition to considerable uncertainties due to potential exposure measurement error and a lack of adjustment for key confounders, this study has limited generalizability to the US general population. While experimental evidence indicates that it may be biologically plausible that long-term ozone exposure could contribute to asthma development, it does not provide insight regarding an established mode of action. Future research is needed to address the uncertainties regarding the role of long-term ambient ozone exposure in asthma development.

Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade.

BACKGROUND: Higher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading. METHODS: We characterized vessel morphology (area and irregularity) among 511 patients diagnosed with prostate cancer during 1986 to 2000, re-reviewed Gleason grade, and followed men through 2012. Men were grouped according to integrated vessel lumen irregularity and vessel area across Gleason grade. The more angiogenic group was identified as those with more irregular vessel lumen and smaller vessel area. Crude rates (95 % confidence intervals) and survival probability were estimated across Gleason grade and vessel morphology. RESULTS: During a median 14-year follow-up, 62 men developed bone metastases or died of prostate cancer. Lethality rates were uniformly low within Gleason grade categories 6 and 7(3 + 4), regardless of vessel morphology. However, among men with Gleason grades of 7(4 + 3) or 8-10, the more angiogenic group was associated with fourfold higher risk of lethal outcomes compared to those with less angiogenic potential. Ten-year survival probability ranged from 95 to 74 % according to the extent of vessel morphology (p < 0.0001, log-rank test). CONCLUSIONS: Vessel morphology may aid Gleason grading in predicting prostate cancer mortality risks among men diagnosed with high-grade Gleason cancers.

Pleural plaques and lung function in the Marysville worker cohort: a re-analysis.

BACKGROUND: In the 2014 Integrated Risk Information System (IRIS) assessment for Libby amphibole asbestos (LAA), US EPA calculated a reference concentration (RfC) based on the prevalence of pleural plaques in a group of vermiculite workers in Marysville, Ohio. This RfC is based on the assumption that pleural plaques are associated with adverse lung function. In this study, we evaluated the association between pleural plaques and lung function in the Marysville worker cohort to determine whether they are associated with adverse effects or, rather, are more likely a biomarker of cumulative exposure to LAA. METHODS: We obtained the dataset on the Marysville worker cohort from University of Cincinnati, which included information on demographics, occupational exposures and results of chest high-resolution computed tomography (HRCT)/computed tomography (CT) scans and pulmonary function tests (PFTs). We used multivariate linear regression to estimate mean differences in several lung function parameters, and logistic regression to evaluate the odds of abnormal ventilatory patterns, among men with different pulmonary findings on HRCT/CT scans. RESULTS: No statistically significant differences in FEV1, FVC, FEV1/FVC, TLC, RV or DLCO were observed between workers with normal scans and those with pleural plaques but no other abnormalities. In contrast, workers with other abnormal findings had statistically significant lower FEV1, FVC, TLC and DLCO, compared with those with normal scans. CONCLUSIONS: This study does not indicate that pleural plaques have a significant effect on lung function when past asbestos exposure is accounted for.

Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse cardiovascular health impacts.

The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb). Epidemiology findings were mixed for all biomarker categories, with only a few studies reporting statistically significant changes and with no consistency in the direction of the reported effects. Controlled human exposure studies of 2 to 5 hours conducted at ozone concentrations above 75 ppb reported small elevations in biomarkers for inflammation and oxidative stress that were of uncertain clinical relevance. Experimental animal studies reported more consistent results among certain biomarkers, although these were also conducted at ozone exposures well above 75 ppb and provided limited information on ozone exposure-response relationships. Overall, the current WoE does not provide a convincing case for a causal relationship between short-term ozone exposure below the NAAQS and adverse changes in levels of biomarkers within and across categories, but, because of study limitations, they cannot not provide definitive evidence of a lack of causation.

Systematic review of pleural plaques and lung function.

CONTEXT: US EPA proposed a Reference Concentration for Libby amphibole asbestos based on the premise that pleural plaques are adverse and cause lung function deficits. OBJECTIVE: We conducted a systematic review to evaluate whether there is an association between pleural plaques and lung function and ascertain whether results were dependent on the method used to identify plaques. METHODS: Using the PubMed database, we identified studies that evaluated pleural plaques and lung function. We assessed each study for quality, then integrated evidence and assessed associations based on the Bradford Hill guidelines. We also compared the results of HRCT studies to those of X-ray studies. RESULTS: We identified 16 HRCT and 36 X-ray studies. We rated six HRCT and 16 X-ray studies as higher quality based on a risk-of-bias analysis. Half of the higher quality studies reported small but statistically significant mean lung function decrements associated with plaques. None of the differences were clinically significant. Many studies had limitations, such as inappropriate controls and/or insufficient adjustment for confounders. There was little consistency in the direction of effect for the most commonly reported measurements. X-ray results were more variable than HRCT results. Pleural plaques were not associated with changes in lung function over time in longitudinal studies. CONCLUSION: The weight of evidence indicates that pleural plaques do not impact lung function. Observed associations are most likely due to unidentified abnormalities or other factors.

Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects.

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans. We found that the risks of CV effects are largely null across human and experimental animal studies. The few positive associations reported in studies of CV morbidity and mortality are very small in magnitude, mainly reported in single-pollutant models, and likely attributable to bias, chance, or confounding. The few positive effects in experimental animal studies were observed mainly in ex vivo studies at high exposures, and even the in vivo findings are not likely relevant to humans. The available data also do not support a biologically plausible mechanism for the effects of ozone on the CV system. Overall, the current WoE provides no convincing case for a causal relationship between long-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation; thus, we categorize the strength of evidence for a causal relationship between long-term exposure to ozone and CV effects as "below equipoise."

Weight-of-evidence evaluation of short-term ozone exposure and cardiovascular effects.

There is a relatively large body of research on the potential cardiovascular (CV) effects associated with short-term ozone exposure (defined by EPA as less than 30 days in duration). We conducted a weight-of-evidence (WoE) analysis to assess whether it supports a causal relationship using a novel WoE framework adapted from the US EPA's National Ambient Air Quality Standards causality framework. Specifically, we synthesized and critically evaluated the relevant epidemiology, controlled human exposure, and experimental animal data and made a causal determination using the same categories proposed by the Institute of Medicine report Improving the Presumptive Disability Decision-making Process for Veterans ( IOM 2008). We found that the totality of the data indicates that the results for CV effects are largely null across human and experimental animal studies. The few statistically significant associations reported in epidemiology studies of CV morbidity and mortality are very small in magnitude and likely attributable to confounding, bias, or chance. In experimental animal studies, the reported statistically significant effects at high exposures are not observed at lower exposures and thus not likely relevant to current ambient ozone exposures in humans. The available data also do not support a biologically plausible mechanism for CV effects of ozone. Overall, the current WoE provides no convincing case for a causal relationship between short-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation. Thus, we categorize the strength of evidence for a causal relationship between short-term exposure to ozone and CV effects as "below equipoise."

Deep Blue CsPbBr3 Quantum Wires with Tailored Shapes.

Low-dimension metal halide perovskites are attractive for bandgap tunable optoelectronic materials. Among them, 1-D CsPbBr3 quantum wires (QWs) are emerging as promising deep-blue luminescent material. However, the growth dynamics of 1-D perovskite QWs are intricate, making the study and control of 1-D QWs highly challenging. In this study, a strategy for controlling both the length and width of the CsPbBr3 QWs was realized. The temperature-dependent isotropic growth mechanism was revealed and employed as the main tool for the oriented growth of 1-D CsPbBr3 QWs for various aspect ratios. Our results pave the way for the controlled synthesis of ultrasmall perovskite nanocrystals.

Real-world utilization of immune checkpoint inhibitors in extensive stage small-cell lung cancer in community settings.

Aim: This study examined real-world treatment patterns for extensive-stage small-cell lung cancer (ES-SCLC) after immune checkpoint inhibitors (ICIs) became available for frontline use. Methods: Adult patients with ES-SCLC initiating 1L systemic treatment were identified from electronic health records. Results: Among patients with recurrent/progressive ES-SCLC, the most common treatment classes were platinum-based chemotherapy (81.1% of 228) and ICI monotherapy (35.1% of 191) in 1L and 2L, respectively. Among patients with de novo ES-SCLC, the most common treatment classes were ICI + platinum-based chemotherapy (64.4% of 1268) and other chemotherapy (44.9% of 512) in 1L and 2L, respectively. Among patients who received no ICI in 1L, 62.6%-70.3% received it in 2L and 62.6-68.5% in 3L. Some who received 1L ICI were re-treated with ICI in subsequent lines (14.5-18.8% in 2L, 18.2-50.0% in 3L). Conclusion: Real-world ICI utilization in ES-SCLC, particularly ICI re-challenge, demonstrates high unmet needs in this patient population.

Small-cell lung cancer (SCLC) is a type of lung cancer that is highly lethal. About 70% of patients have advanced SCLC when they first get their diagnosis and most die within 5 years. This study focused on immune checkpoint inhibitors (ICIs), a type of treatments that can help the immune system to fight cancer and has only been approved to treat SCLC in the past 4­5 years. We studied 1496 patients with advanced SCLC treated at community cancer practices in USA between October 2018 and February 2020. Patients averaged about 68 years old when they started treatment. By looking at the types and sequences of treatments, we found that although ICI are often used to treat SCLC, patients with this aggressive cancer still need other effective treatment choices.

Real-World Treatment Patterns and Outcomes of First-Line Immunotherapy Among Patients With Advanced Nonsquamous NSCLC Harboring BRAF, MET, or HER2 Alterations.

Introduction: Data on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited. Methods: This retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021. Results: Of the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti-PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti-PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar. Conclusions: Substantial use of anti-PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.

Molecular epidemiology study of programmed death ligand 1 and ligand 2 protein expression assessed by immunohistochemistry in extensive-stage small-cell lung cancer.

Objectives: Prevalence of tumor PD-L1 expression in extensive-stage small-cell lung cancer (ES-SCLC) is variable, and data on PD-L2 expression are limited. The prognostic values of these biomarkers are not well understood. The current study was conducted to address these data gaps. Methods: A retrospective cohort study of Danish patients with histologically confirmed ES-SCLC and evaluable tumor samples who were receiving usual care before the introduction of immunotherapy was conducted. Protein expression of PD-L1 and PD-L2 was determined by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx assay and a PD-L2 IHC assay using a propriety mouse monoclonal antibody. A combined positive score (CPS) of ≥1 was used to define biomarker positivity. Kaplan-Meier plots and Cox proportional hazard models were employed to assess the relationship between PD-L1 and PD-L2 protein expression and OS. Results: Among 80 patients, 31% (n=25) and 36% (n=29) had disease positive for PD-L1 and PD-L2, respectively. Overall, 85% (n=68) of patients had concordant PD-L1/PD-L2 status; 26% (n=21) had double positive disease (both PD-L1 and PD-L2 CPS ≥1) and 59% (n=47) had double negative disease (both PD-L1 and PD-L2 CPS <1). PD-L1 and PD-L2 positivity were each associated with longer OS (unadjusted hazard ratios [HRs], 0.35 [95% CI, 0.21-0.61] and 0.50 [95% CI, 0.31-0.82]); the associations persisted after adjustment for several known prognostic factors (HRs, 0.41 [95% CI, 0.22-0.75] and 0.44 [95% CI, 0.25-0.79] for PD-L1 and PD-L2 positivity, respectively). When evaluating OS in patients with double positive disease, unadjusted and adjusted HRs for double positive compared with double negative were similar to those with only PD-L1 or PD-L2 positivity (unadjusted HR, 0.36 [95% CI, 0.20-0.64]; adjusted HR, 0.36 [0.18-0.73]). Conclusion: PD-L1 and PD-L2 positivity were observed in approximately one-third of assessed ES-SCLC tumor samples and were highly congruent. Patients with PD-L1 and PD-L2 positivity, alone or combined, were associated with longer OS, independent of other prognostic factors.

Incidence of Pneumonitis Among Limited Stage Small Cell Lung Cancer Patients Exposed to Concurrent Chemoradiation: A Systematic Literature Review and Meta-Analysis.

Severe pneumonitis (≥ grade 3 by Common Terminology Criteria for Adverse Events [CTCAE]) is a toxicity associated with concurrent chemoradiation therapy (CCRT), which is the standard first-line treatment for patients with limited-stage small cell lung cancer (LS-SCLC). We summarize and quantify the risk of pneumonitis in LS-SCLC patients receiving first-line CCRT. A systematic literature review (SLR) and meta-analysis were performed in accordance with Cochrane and PRISMA guidelines. Electronic databases were searched to identify relevant randomized controlled trials (RCTs), observational studies, and non-randomized trials between 2014 to July 16, 2020. The primary outcome was incidence of pneumonitis. Thirteen studies were included in the SLR and 1539 pooled patients from 10 studies were included in the base-case meta-analysis. The pooled incidence of ≥ grade 3 pneumonitis was 3.28% (95% confidence interval [CI]: 1.52%-5.04%) in RCTs, and 6.34% (95% CI: 3.64%-9.04%) in non-RCTs. The pooled incidence risk of grade 5 (fatal) pneumonitis was 0.29% (95% CI: 0.00%-0.62%) in RCTs and 0.88% (95% CI: 0.02%-1.74%) in non-RCT. Results from sensitivity analyses were consistent with the base-case analysis. The results from this analysis show that the incidence of ≥ grade 3 pneumonitis in patients with LS-SCLC was 3.28% to 6.34%. The incidence of pneumonitis was higher in studies conducted in non-RCTs compared to RCTs. These results can be used to understand the safety, with regard to pneumonitis, of novel therapeutic agents when administered with CCRT to treat patients with LS-SCLC. To summarize and quantify the risk of pneumonitis in LS-SCLC patients receiving first-line CCRT, a systematic literature review (SLR) and meta-analysis were performed in accordance with Cochrane and PRISMA guidelines.

[A retrospective study of clinical and pathological spectrum in 91 patients with chronic severe hepatitis B].

OBJECTIVE: In China, liver failure is also termed as severe hepatitis in whom chronic severe hepatitis B (CSHB) is most common. The aim of this study was to assess whether CSHB based on different liver injury extent can meet the international definition of acute-on-chronic liver failure(ACLF)criteria, according by their clinical and pathological feature. METHODS: A total of 91 patients with CSHB were involved in the study. The clinical findings, laboratory data and liver pathology features were retrospectively analyzed and grouped by hepatitis virus B carrier state (HBC), chronic hepatitis B (CHB) or liver cirrhosis (LC) before they started liver failure. RESULTS: 74 out of the 91 patients were male and 17 were female, the mean age was 40.6+/-11.2 years. 9.9%, 7.7% and 82.4% of the patients were based on HBC, CHB and LC respectively. The ages of HBC group were youngest. The mean age of HBC group (years) (25.8+/-6.6) was significantly lower than that of CHB group (36.9+/-9.0) and LC group (42.0+/-10.5)with P values of 0.032 and 0.001 respectively. Most cases presented with sub-acute liver failure characterized by high icterus and ascites. Predisposing factors included exertion, superinfection, virus variation, drugs or alcoholic injury. No difference found between PTA (F = 0.906, P = 0.408) and TBil (F = 0.839, P = 0.436) among the above three groups. The Alb and CHE levels in LC group were (30.3+/-5.1) g/L and (2926.8+/-1471.1) U/L respectively, which were lower than both HBC group [Alb (35.6+/-5.1) g/L, CHE (4363.5+/-2063.2) U/L] and CHB group [Alb (37.4+/-5.0) g/L, CHE (5167.1+/-1522.1) U/L] (F = 9.450; F = 9.297; P value less than 0.01).The level of CHO (1.8+/-1.0) mmol/L in LC group was lower than that of HBC group (2.9+/-1.0mmol/L, P = 0.034), while serum HBV DNA level of HBC group [(6.8+/-1.7) log10copies/ml] was higher than that of LC group [(4.2+/-2.6) log10copies/ml]. The liver tissue in HBC and CHB group showed massive or submassive necrosis which distribute evenly in different parts of liver and similarly in slides, most like acute/subacute severe hepatitis. The chronic lesion was easily covered by extensive necrosis in CSHB based on CHB, with portal fibrosis can be seen by masson stain. Characteristic picture of LC group were massive or submassive necrosis with some nodules were intact or only patchy necrosis of the parenchyma, disparity of extent and stage of necrosis existed in slides, which were the major difference in histopathological change in HBC and CHB group. CONCLUSION: Most of CSHB cases were based on liver cirrhosis, which match with the international definition of ACLF, while small part of CSHB cases based on HBC and CHB are identical to acute/subacute liver failure.