Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB.

Objective: This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40, CD80, CD83, and CD86. Method: This was a cross-sectional study in which patients were divided into a natural history group (namely NH group), a long-term oral nucleoside analogs treatment group (namely NA group), and a plateau-arriving group (namely P group). The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results: In total, 143 patients were enrolled (NH group, n = 49; NA group, n = 47; P group, n = 47). The results demonstrated that CD141/CD1c double negative myeloid dendritic cell (DNmDC)/lymphocytes and monocytes (%) in P group (0.041 [0.024, 0.069]) was significantly lower than that in NH group (0.270 [0.135, 0.407]) and NA group (0.273 [0.150, 0.443]), and CD86 mean fluorescence intensity of DNmDCs in P group (1832.0 [1484.0, 2793.0]) was significantly lower than that in NH group (4316.0 [2958.0, 5169.0]) and NA group (3299.0 [2534.0, 4371.0]), Adjusted P all < 0.001. Conclusion: Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens.

BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS: Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS: 420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION: NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

The Ability to Dissipate Heat Is Likely to Be a More Important Limitation on Lactation in Striped Hamsters with Greater Reproductive Efforts under Warmer Conditions.

The limitations on energy availability and outputs have been implied to have a profound effect on the evolution of many morphological and behavioral traits. It has been suggested that the reproductive performance of mammals is frequently constrained by intrinsic physiological factors, such as the capacity of the mammary glands to produce milk (the peripheral limitation [PL] hypothesis) or that of the body to dissipate heat (the heat dissipation limitation [HDL] hypothesis). Research on a variety of small mammals, however, has so far failed to provide unequivocal support for one hypothesis over the other. We tested the PL and HDL hypotheses in female striped hamsters (Cricetulus barabensis) with artificially manipulated litter sizes of two (three or four pups removed from natural litter size), five, eight (two or three pups added to natural litter size), and 12 (five to seven pups added to natural litter size) pups at ambient temperatures of 21° and 30°C. Energy intake and milk output of mothers, litter size, and litter mass were measured throughout lactation. Several markers indicating digestive enzyme activity and the gene expression of hypothalamic neuropeptides related to food intake were also measured. Food consumption and milk output increased with increasing litter size but reached a ceiling at 12 pups, causing 12-pup litters to have significantly lower litter mass and pup body mass than litters composed of fewer pups. Litter mass and maternal metabolic rate, milk output, maltase, sucrase, and aminopeptidase activity in the small intestine, and gene expression of hypothalamic orexigenic peptides were significantly lower at 30°C than at 21°C, and these differences were considerably more pronounced in 12-pup litters. These results suggest that PL and HDL can operate simultaneously but that the HDL hypothesis is probably more valid at warmer temperatures. Our results suggest that increased environmental temperatures in future climates may limit reproductive output through heat dissipation limits.

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.

Intensive care unit-acquired complicated necrotizing pneumonia caused by Enterobacter cloacae: A case report.

A 58-year-old man with a history of diabetes mellitus and end-stage renal disease acquired pneumonia with acute respiratory failure during his stay in an intensive care unit (ICU). Empirical antimicrobial therapy with ceftazidime and vancomycin was initiated, and imipenem replaced ceftazidime 2 days later due to the patients pulmonary condition failed to improve. However, within 5 days, pulmonary consolidation rapidly progressed to necrotizing pneumonia complicated by lung abscess, empyema, pyopneumothorax, and tension pneumothorax, leading to the patient's death. After the patient had died, all bacterial isolates from cultures of pleural effusion, blood, and tracheal aspirate were identified as Enterobacter cloacae (E. cloacae), which was susceptible to imipenem but resistant to ceftazidime. E. cloacae should be considered in the differential diagnosis of complicated necrotizing pneumonia with lung abscess, empyema, pyopneumothorax, and tension pneumothorax. Carbapenem therapy should be immediately initiated until the pathogen in such rapidly progressive ICU-acquired pneumonia is confirmed. Increased awareness among physicians regarding E. cloacae-induced complicated necrotizing pneumonia acquired in ICUs could enable earlier detection and appropriate antimicrobial therapy for this invasive disease.

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B.

BACKGROUND: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). METHODS: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-ß1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-ß1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. RESULTS: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ2 = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-ß1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ2 = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (ß= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (ß = -0.358, t = -2.308, P = 0.024), HBsAg (ß = -0.359, t = -2.288, P = 0.025), and HBeAg contents (ß = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (ß = -0.459, t = -4.225, P = 0.000; ß = -0.616, t = -6.334, P = 0.000; and ß = -0.290, t = -2.433, P = 0.018; respectively). CONCLUSIONS: IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

Quantitation of Plasmacytoid Dendritic Cells in Chronic Hepatitis B Patients with HBeAg Positivity During PEG-IFN and Entecavir Therapy.

Plasmacytoid dendritic cells (pDCs) are crucial for control of chronic hepatitis B (CHB) virus infection. In this study, we evaluated the frequencies of pDCs and expression of functional molecules on pDCs in patients treated with PEG-IFN-α-2a or entecavir (ETV) and investigated changes during treatment. The mean fluorescence intensity of CD86 (CD86MFI) on the surface of pDCs and frequencies of pDCs and CD86+ pDCs in peripheral blood were measured. Compared with baseline, CD86+ pDC% and CD86MFI increased obviously after PEG-IFN-α-2a treatment for 12 and 24 weeks. For patients treated with ETV, only pDC% increased observably after treatment weeks 12 and 24 (P < 0.001) compared with baseline. Hepatitis B surface antigen (HBsAg) decline was significantly associated with elevated CD86+ pDC% (r = 0.348, P = 0.015) during PEG-IFN-α-2a treatment. In the HBsAg response group, CD86+ pDC% and CD86MFI (P < 0.001) increased observably after PEG-IFN-α-2a therapy, whereas only CD86MFI had a statistically significant difference after therapy compared with baseline (12 weeks versus 0 weeks, P = 0.022; 24 weeks versus 0 weeks, P = 0.015) in the HBsAg nonresponse group. CD86+ pDC% between the 2 groups had statistically significant differences at baseline (P = 0.001) and at the treatment time points of 12 and 24 weeks (P < 0.001), respectively. For patients receiving ETV therapy, pDC% increased observably, but CD86+ pDC% decreased significantly (P < 0.001) in the HBV DNA nonresponse group during early treatment with ETV. In CHB patients, HBsAg response in PEG-IFN-α-2a therapy correlated with the increase of CD86+ pDC% and HBV DNA nonresponse in ETV treatment correlated with the decrease of CD86+ pDC%.

Antioxidant Activity of Water Extract from Fermented Mycelia of Cordyceps sobolifera (Ascomycetes) in Caenorhabditis elegans.

This research aimed to evaluate the potential of Cordyceps sobolifera in mycelial biomass production via liquid culture and to assay the safety and determine the antioxidative and antiaging activities of Caenorhabditis elegans. A C. sobolifera isolate was cultured using the one-factor-at-a-time method to illustrate its carbon and nitrogen requirements. To assess safety, we determined the lethality, locomotion behavior, and reproduction of C. elegans cultured on a mycelial water extract (MWE) containing nematode growth medium (NGM). To investigate antiaging activity, C. elegans treated with MWE was incubated on NGM plates. The lethality was recorded throughout the whole life cycle. To identify antioxidant activity, C. elegans treated with MWE was exposed to paraquat, causing superoxide conditions. The results showed that C. sobolifera was favored by glucose and peptone as carbon and nitrogen sources, respectively. MWE was considered to be safe, as no abnormal behaviors were observed in C. elegans. Compared with nematodes pretreated with no MWE but with water instead, MWE at 1.0 mg/mL significantly prolonged the mean lifespan of C. elegans by 24%. We observed an obvious dose-effect relation between concentration and mean lifespan. The effective antioxidant activity was recorded at the high concentration of MWE. These findings demonstrate the potential antiaging and antioxidant properties of C. sobolifera as functional food and dietary supplement.

Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection. METHODS: The healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-ß1 and TGF-ß2, were performed using Luminex multiplex technology. RESULTS: In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-ß1, and TGF-ß2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05). CONCLUSIONS: This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-ß.

Negative Correlation of Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Levels with the Severity of Liver Inflammation in Treatment-naïve Patients with Chronic Hepatitis B Virus Infection.

BACKGROUND: Estimating the grades of liver inflammation is critical in the determination of antiviral therapy in patients chronically infected with hepatitis B virus (HBV). The aim of this study was to investigate the correlation of serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) with the liver inflammation grades in treatment-naïve patients with chronic HBV infection. METHODS: We retrospectively enrolled 584 treatment-naïve HBeAg-positive patients who underwent liver biopsy in Ditan Hospital from January 2008 to January 2016. Based on the severity of liver inflammation, the patients were divided into minimal, mild, and moderate groups. SPSS software was used for statistical analysis of all relevant data. RESULTS: The liver histological examinations showed that 324, 194, and 66 patients had minimal, mild, and moderate liver inflammation, respectively. The median age of the three groups was 30, 33, and 38 years, respectively (Χ2 = 26.00, P < 0.001). The median HBsAg levels in minimal, mild, and moderate inflammation groups were 4.40, 4.16, and 3.67 log U/ml, respectively, and the median HBeAg levels in the three groups were 3.12, 2.99, and 1.86 log sample/cutoff, respectively; both antigens tended to decrease as the grade of inflammation increased (Χ2 = 99.68 and Χ2 = 99.23, respectively; both P < 0.001). The cutoff values of receiver operating characteristic curve in the age, HBsAg and HBeAg levels were 36 years, 4.31 log U/ml, and 2.86 log S/CO, respectively, l to distinguish minimal grade and other grades of treatment-naïve HBeAg-positive patients with chronic HBV infection. CONCLUSIONS: Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values might help us to distinguish minimal grades and other grades and detect those who do not need antiviral therapy in treatment-naïve HBeAg-positive patients with chronic HBV infection.

Ratios of T-helper 2 Cells to T-helper 1 Cells and Cytokine Levels in Patients with Hepatitis B.

BACKGROUND: Hepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases. METHODS: Thirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study. Th cell proportions in peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen were detected. RESULTS: The Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including IT, IC, and AHB groups) were significantly different from those in HI group (24.10% ± 8.66% and 1.72 ± 0.61 vs. 15.16% ± 4.34% and 2.40 ± 0.74, respectively; all P < 0.001). However, there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-γ, and interleukin (IL)-17A were significantly lower than those in HI group (29.26 pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96 pg/ml, respectively; all P < 0.05). IFN-α2, IL-10, and transforming growth factor (TGF)-ß2 median levels in hepatitis group (including patients in AHB and IC groups) were significantly higher than those in IT group (40.14 pg/ml, 13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml, respectively; all P < 0.05), while patients in hepatitis group had significant lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared with IC group, patients in AHB group had significant higher median levels of IL-10, TGF-ß1, and TGF-ß2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs. 8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05). CONCLUSIONS: Compared with chronic HBV-infected patients in immune-tolerance phase, chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th1 ratios, significantly higher levels of IFN-α2, IL-10, and TGF-ß. AHB patients had significantly higher IL-10 and TGF-ß levels than chronic HBV-infected patients in immune-active phase.

The Predictive Value of Baseline HBsAg Level and Early Response for HBsAg Loss in Patients with HBeAg-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment.

OBJECTIVE: To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. METHODS: A total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 µg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment. RESULTS: The median treatment time for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). CONCLUSION: Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment.

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. METHODS: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 µg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. RESULTS: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. CONCLUSIONS: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes.

OBJECTIVES:: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS:: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS:: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS:: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential.

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes

OBJECTIVES: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential.

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a.

AIM: To examine the association between interferon (IFN) therapy and loss of hepatitis B surface antigen (HBsAg) in inactive HBsAg carriers. METHODS: This was a retrospective cohort study in inactive HBsAg carriers, who were treatment-naive, with a serum HBsAg level < 100 IU/mL and an undetectable hepatitis B virus (HBV) DNA level (< 100 IU/mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 µg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBsAg, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen (65.0%) of 20 treated patients achieved HBsAg loss, 12 of whom achieved HBsAg seroconversion. Mean HBsAg level in treated patients decreased to 6.69 ± 13.04 IU/mL after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/mL. Serum HBV DNA level remained undetectable (< 100 IU/mL) in all treated patients during the study. HBsAg level of the control group decreased from 25.72 ± 25.58 IU/mL at baseline to 17.11 ± 21.62 IU/mL at week 96 (P = 0.108). In the control group, no patient experienced HBsAg loss/seroconversion, and two (5.0%) developed HBV reactivation. CONCLUSION: IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations.

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses.

OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%), nodules with or without cavities (79%), pleural effusions (71%), peripheral wedge-shaped opacities (64%), patchy ground-glass opacities (50%), air bronchograms within a nodule (36%), consolidations (21%), halo signs (14%), and lung abscesses (14%). Nine (64%) of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14%) patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis.