Stereotactic body radiation therapy in patients with centrally located hepatocellular carcinoma: A retrospective, single-arm, multi-center study.

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

New Staging Model for Radiation-based Hepatocellular Carcinoma Treatment: A National Multicenter Study.

Background and Aims: The study aimed to create a new staging model for radiotherapy-based treatment for prognostic hepatocellular carcinoma (HCC) classification. Methods: The training cohort comprised 658 patients receiving stereotactic body radiotherapy and external validation cohort comprised 533 patients receiving three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. We established a modified staging system as follows: stage I, solitary nodule without macrovascular invasion, or 2-3 nodules no more than 3.0 cm apart, and performance status (PS) 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with any one nodule more than 3.0-cm apart, or ≥4 nodules, and performance status 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion, regional lymph node metastasis or distant metastasis, and performance status 0-2 (IIIa: ALBI-1 grade; IIIb: ALBI-2 grade); stage IV: performance status 3-4, or performance status 0-2 with ALBI-3 grade. We analyzed long-term overall survival based on different stages. Results: The staging model showed an excellent ability to discriminate patients according to four stages and seven substages with notably different curves in the training and validation cohort. The median survival decreased from stages I to IV with 63.0 months in stage I (not reached in Ia, and 53.0 months in Ib), 24.0 months in stage II (28.0 months in IIa, and 22.0 months in IIb), 11.0 months in stage III (18.0 months in IIIa, and 9.0 months in IIIb), and less than 9.0 months in stage IV in the training cohort. Conclusions: The modified staging model may provide an alternative for clinical radiation oncologists.

Hepatic Resection Versus Stereotactic Body Radiation Therapy Plus Transhepatic Arterial Chemoembolization for Large Hepatocellular Carcinoma: A Propensity Score Analysis.

BACKGROUND AND AIMS: There are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus transhepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). Therefore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC. METHODS: A total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups. RESULTS: Thirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3%, 77.8% and 66.7% in the HR group and 80.6%, 72.2% and 52.8% in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6%, 57.3% and 42.3% in the HR group and 66.1%, 45.8% and 39.3% in the CK-SBRT+TACE group, respectively (OS: p=0.143; PFS: p=0.445). Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS. CONCLUSIONS: CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.

The effects of stereotactic body radiotherapy on peripheral natural killer and CD3+CD56+ NKT-like cells in patients with hepatocellular carcinoma.

BACKGROUND: Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. METHODS: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. RESULTS: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. CONCLUSIONS: SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.

Stereotactic body radiotherapy versus hepatic resection for hepatocellular carcinoma (≤ 5 cm): a propensity score analysis.

BACKGROUND: CyberKnife stereotactic body radiation therapy (CK-SBRT) has been applied to hepatocellular carcinoma (HCC) patients for several years. The study aim was to compare the efficacy of hepatic resection (HR) and CK-SBRT in naive small hepatocellular carcinoma (sHCC) patients with hepatitis virus-related cirrhosis using a 5-year follow-up study. MATERIALS AND METHODS: This retrospective cohort study included 317 naive sHCC patients (246 men and 71 women) with hepatitis B or C virus cirrhosis who were treated with HR (n = 195) or CK-SBRT (n = 122) from November 2011 to December 2015. Cumulative overall survival (OS) rates and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. RESULTS: After the propensity score-matched analysis, 104 patients were selected from each group for further analysis. The 1-, 2-, 3-, and 5-year OS rates were 96.2%, 89.4%, 85.5% and 70.7% in the HR group and 93.3%, 89.4%, 83.7% and 71.0% in the CK-SBRT group, respectively. The 1-, 2-, 3-, and 5-year PFS rates were 78.8%, 64.3%, 56.4% and 47.3% in the HR group and 84.5%, 67.8%, 58.9% and 49.0% in the CK-SBRT group, respectively. No significant difference was found between the two groups in the OS and PFS rates (OS, p = 0.673; PFS, p = 0.350). No death occurred due to the toxicity or complications of HR or CK-SBRT. CONCLUSION: CK-SBRT could be an effective alternative to HR for sHCC naive patients with hepatitis-related cirrhosis, especially if patients have higher CP scores and lower PLT counts. PLT counts should be factored into survival evaluation of HCC treatment.

Prevalence of psychological symptoms among Ebola survivors and healthcare workers during the 2014-2015 Ebola outbreak in Sierra Leone: a cross-sectional study.

The 2014-2015 Ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. The epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. We evaluated the psychological symptoms of 161 participants including Ebola survivors and healthcare workers in Sierra Leone, analyzed the impact of job classification, education level on psychological status. We found that the order of total general severity index (GSI) scores from high to low was EVD survivors, SL medical staff, SL logistic staff, SL medical students, and Chinese medical staff. There were 5 dimensions (obsession-compulsion, anxiety, hostility, phobic anxiety, and paranoid ideation) extremely high in EVD survivors. GSI were associated with university education negatively. We believed our information is necessary to develop the comprehensive emergency response plan for emerging infectious disease outbreak.

Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone.

BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥106 copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients' survival was less than 15 % when blood viral load was greater than 106 copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1-4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients.

The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation.

Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients.

BACKGROUND: A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease. METHODS: A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time. RESULTS: Among the 288 confirmed EVD patients (149 male and 139 female, median age 28 years, and median log viral load 6.68), 98 died, 36 recovered, and 154 were lost to follow-up. Common symptoms were fever (77.78%), fatigue (64.93%), abdominal pain (64.58%), headache (62.85%), and diarrhea (61.81%). Compared to patients aged<18 years, those who were older than 40 years had a higher probability of death (odds ratio 2.855, p=0.044). Patients with a viral load of >10(6) copies/ml had a higher case fatality rate than those with <10(6) copies/ml (odds ratio 3.095, p=0.004). Cox regression showed that age, viral load, and the presence of diarrhea correlated with mortality. CONCLUSION: Patients with a high viral load, of older age, and with diarrhea had a higher mortality and shorter survival time.

[Relation between serum levels of high mobility group box 1 and hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To evaluate the levels of high mobility group box 1 protein (HMGB1) in serum of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and investigate its potential relation to the clinical features of these patients. METHODS: Sixty patients with HBV-related ACLF, 30 patients with chronic hepatitis B (CHB), and 24 healthy individuals (controls) were enrolled in the study. Markers of liver function, such as aspartate aminotransferase (AST), were measured by routine biochemical methods. Imaging studies, such as abdominal computed tomography or magnetic resonance imaging, were used for disease staging. Serum levels of HMGB1 were measured by ELISA. Deaths within the 2-month follow-up after serum collection were used for the survival analysis. Patients who developed peritonitis, pneumonia, or other bacterial and fungal infections during the 2-month follow-up after serum collection were classified as the infected group. Pairwise comparisons were carried out by t-test, and multiple comparisons were carried out by analysis of variance. RESULTS: Patients with HBV-related ACLF had significantly higher serum levels of HMGB1 than CHB patients or controls (P = 0.003). Among the patients with HBV-related ACLF, those in the late stage (n = 20) had significantly higher levels of HMGB1 than those in the early stage (n = 20) (P = 0.005). The serum levels of HMGB1 correlated well with AST level in patients with HBV-related ACLF (P = 0.006). In addition, patients with HBV-related ACLF who developed infection or died during follow-up also had significantly higher levels of HMGB1 (P = 0.028 or P = 0.017, respectively). CONCLUSION: Enhanced serum level of HMGB1 is associated with development of HBV-related ACLF in CHB patients. The strong correlation between HMGB1 and AST levels suggest that HMGB1 may be useful as a prognostic marker for development of ACLF.

Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure.

AIM: To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF). METHODS: Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 µg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34(+) cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate. RESULTS: The peripheral neutrophil and CD34(+) cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P < 0.001) compared to that in controls. After 3 mo of follow-up observation, the survival rate in the treatment group (48.1%) was significantly higher than that in the control group (21.4%) (P = 0.0181). CONCLUSION: G-CSF therapy promoted CD34(+) cell mobilization in patients with HBV-associated ACLF, and improved the liver function and the survival rate of these patients.

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure.

AIM: To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis. RESULTS: A total of 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014]. The highest risk of death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001). CONCLUSION: Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances, and HE also affect patient survival.

[The study on frequency distribution of regulatory T cells and its functional markers in peripheral blood of chronic hepatitis B].

OBJECTIVE: To explore the role of treg cells and its functional markers in pathogenesis of chronic hepatitis B, and the correlation with disease progression. METHODS: 20 cases of healthy control people,53 cases of chronic hepatitis B patients and 24 cases of liver cirrhosis patients were enrolled into the groups. Detecting the frequencies of CD4+ CD25+ Fox3+ cells, CD4+ CD25+ CD127(low) cells, CD39+ treg cells and CTLA-4+ treg cells in treg cells by flow cytometry. Clinical parameters were investigated in the same time. RESULTS: The frequencies of treg cells, CD4+ CD25+ CD127(low) cells and CD39+ treg cells were significant different among healthy control group, CHB group and LC group (P < 0.01). The frequencies of treg cells, CD4+ CD25+ CD127(low) cells and CD39+ treg cells were significantly different in moderate-severe CHB group compared with mild CHB group (P < 0.05, P < 0.05, P < 0.01). In CHB group the frequencies of CD4+ CD25+ Foxp3+ cells were positively correlated with ALT (r = 0. 289, P < 0.05) and AST (r = 0.302, P < 0.05), the frequencies of CD4+ CD25+ Foxp3+ cells had a significant positive correlation with the frequencies of CD4+ CD25+ CD127(low) cells (r = 0.478, P < 0.01). CONCLUSION: The frequencies of treg cells and its functional markers probably had a dynamic tendency in the process of chronic hepatitis B and were closely related with the change of liver function parameters. CD39+ treg cells may be a group of functional treg cells, which indicated that CD39 be a sensitive marker to react treg cells function. In some sense, CD4+ CD25+ CD127(low) cells frequency could represent treg cell frequency.

[Association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients].

OBJECTIVE: To explore the association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients. METHODS: Serum samples were collected from 2922 patients with HBV infection. HBV genotyping was performed with type-specific primers polymerase chain reaction, and the virological and biochemical markers were detected, which differences in the genotypes between various clinical types of HBV infection and liver function and virological markers between various HBV genotyping were analyzed. RESULTS: The genotype B, C, BC combinations, D of 2922 patients with HBV infection accounted for 15.9%, 83.5%, 0.41%, 0.21% respectively. The ratio of genotype B in acute hepatitis group was higher (P = 0.003), which the ratio of genotype C in the cirrhosis group and the hepatocellular carcinoma group was higher (P = 0.000, 0.000). The difference in ratio of genotype C was not statistically significant between acute-on-chronic liver failure group and chronic hepatitis group. HBeAg-positive rate, viral load and liver function markers of B, C genotype group in acute hepatitis group and chronic hepatitis group were not significant different. HBeAg-positive rates of genotype C in acute-on-chronic liver failure group, cirrhosis group, hepatocellular carcinoma group were higher than that of genotype B (P = 0.000, 0.024, 0.003). Viral load of genotype C in hepatocellular carcinoma group was higher than that of genotype B (P = 0.025). Cholinesterase levels of genotype C in the acute-on-chronic liver failure group and the hepatocellular carcinoma group was lower than that of genotype B (P = 0.0004, 0.02). CONCLUSION: There were HBV genotype B, C, B/C combinations and D in Chinese patients with HBV infection, with genotype B and C being the major ones. Compared with HBV genotype B, genotype C in Chinese patients with HBV infection was more likely to chronic infection, evolved to cirrhosis and hepatocellular carcinoma, but genotype difference was not observed in occurrence of acute-on-chronic liver failure. Genotype was not significant effect in acute and chronic hepatitis B, but HBeAg-positive rate/viral load was higher and liver damage was more severe in severe and end-stage genotype C HBV infection patients.

[Lamivudine and entecavir significantly improved the prognosis of early-to-mid stage hepatitis B related acute on chronic liver failure].

OBJECTIVE: To clinically study the antiviral effects of lamivudine and entecavir on patients with early-to-mid stage Hepatitis B related acute on chronic liver failure (HBV-ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of nucleoside analogues on patients with early-to-mid stage HBV-ACLF. Three groups were set for controlled study, i. e. basic treatment group, lamivudine plus basic treatment group and entecavir plus basic treatment group. RESULTS: One month after treatment, the improvement rates of lamivudine group and entecavir group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of patients with the antiviral treatments, i.e., lamivudine, entecavir, were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in patients with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the patients with pretreatment HBV DNA > or = 10(7), the cumulative survival rate in patients with entecavir treatments group was higher than that of patients in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either lamivudine or entecavia could significantly increase the improvement rate of patients with early-to-mid stage HBV-ACLF. But severe complications, including hepatorenal syndrome, electrolyte imbalance and hepatic encephalopathy, medical history of liver cirrhosis, and pretreatment HBV DNA > or = 10(7) had significant impacts on prognosis of this group patients. CONCLUSIONS: Antiviral therapy by using either lamivudine or entecavia could significantly increase the survival rate of patients with early-to-mid stage HBV-ACLF.

[Rescue of dendritic cells malfunction and loading with HBV proteins in patients with chronic hepatitis B in vitro].

OBJECTIVE: To investigate dendritic cell (DC) malfunctions in patients with chronic hepatitis B (CHB) and try some means to restore the function in vitro. METHODS: Twelve CHB patients and 10 healthy people were enrolled in the study. Phenotype analysis and allogeneic mixed lymphocyte reaction (AMLR) assay of DC from these subjects were made. Enzyme-linked ELISpot method for detecting IFN-gamma-producing CD8 (+) T cells were used to evaluate the efficacy of DC loaded in vitro with HBsAg or HBcAg. RESULTS: DC from patients had a lower expression of co-stimulatory molecules and impaired AMLR capacity, but was restored partially by cytokine cocktail in vitro. Mature DC loaded with HBsAg or HBcAg showed a greater capacity for IFN-gamma-production than immature DC. CONCLUSION: Malfunction of DC from CHB patients may be rescued by a cocktail of cytokines, and therapeutic DC vaccines loaded with HBV protein might be helpful to treat CHB patients.

[A multicenter retrospective analysis of diagnosis and treatment of 72 hemophagocytic syndrome patients.].

OBJECTIVE: To explore early diagnosis of hemophagocytic syndrome (HPS) and effective treatment. METHODS: A multicenter retrospective study was carried out to analyze the causes, clinical features, laboratory findings, treatment and clinical outcomes of 72 patients with HPS. RESULTS: Among the 72 patients, EBV infection and T lymphoma were the most common initiating diseases. The most common clinical features were persistent fever (100%) and splenomegaly (83.3%). The diagnostic sensitivity was persistent fever (100%), peripheral cytopenia in two or more lineages (97.2%), high concentration of serum soluble CD25 (93.1%) and low NK cell activity (94.4%). The median percentage of serum glycosylated ferritin was significantly lower in patients in HPS group \[(17.4 +/- 16.0)%\] than in control group \[(53.6 +/- 13.3)%\] (P < 0.01). And the median level of serum TNF-alpha was significantly higher in patients group \[(143.2 +/- 64.8) microg/L\] than in controls \[(66.9 +/- 19.4) microg/L\] (P < 0.01). Hepatic dysfunction was seen in most patients (83.6%) mainly manifested as elevated liver enzymes and hypoalbuminemia. The 15-week total survival rate was 46.8% in 47 treated patients, and was 63% in 27 treated with fludarabine in combination with high dose methylprednisolone. The platelet count and fibrinogen level were significantly lower in death group than in survival group. CONCLUSIONS: The diagnostic sensitivities of presistent fever, peripheral cytopenia in two or more lineages, high concentration of serum soluble CD25 and low NK cell activity are relatively high and lacking hemophagocytosis does not exclude the diagnosis. Low percentage of glycosylated ferritin and high concentration of TNF-alpha would be helpful to the diagnosis. High dose methylprednisolone combined with fludarabine is an effective therapy. Platelet count and fibrinogen level are poor prognostic factors for HPS.

Correlation of hepatitis B virus (HBV) genotypes and mutations in basal core promoter/precore with clinical features of chronic HBV infection.

BACKGROUND/AIMS: To investigate the correlation of hepatitis B virus (HBV) genotypes and basal core promoter (BCP) and precore (PC) mutations in patients with chronic hepatitis B. METHODS: HBV genotyping, nucleotide mutation, serum HBV DNA level and serological markers were analyzed in 121 patients with chronic HBV infection using INNO-LiPA HBV genotyping, polymerase chain reaction (PCR) product-based sequencing, fluorescence quantitative PCR and enzyme-linked immunosorbent assays respectively. RESULTS: Forty (33.0%), 77 (63.6%), two (1.7%) and two (1.7%) patients had genotypes B, C, B/C and D infections respectively. Significant differences were found in serum HBV DNA levels (log10 copies/ml: 6.18 vs. 5.61, P=0.042) and mutations at nucleotide (nt) 1762/1764 (71.4% vs. 42.5%, P=0.002) between genotypes C- and B-infected patients. There were significant differences in the mean age, serum biochemical parameter levels and mutation rates in BCP/PC among hepatitis e antigen (HBeAg)-positive and -negative chronic hepatitis B (CHB) and liver cirrhosis (LC) groups. CONCLUSION: Genotypes C and B are predominant in China, and the frequent nt 1762/1764 mutation, which occurs commonly in HBeAg-negative CHB, especially in genotype C patients, may be associated with the progress of chronic HBV infection.