Publications by authors named "Chao-Shuang Lin"

32 Publications

The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients.

Gastroenterol Rep (Oxf) 2021 Aug 10;9(4):313-322. Epub 2021 Apr 10.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.

Background: Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs.

Methods: This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed.

Results: After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse.

Conclusions: There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.
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http://dx.doi.org/10.1093/gastro/goab013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460097PMC
August 2021

Factors associated with non-compliance with breastfeeding recommendation: a retrospective survey in hepatitis B virus-infected mothers who had taken Nucleos(t)ide analogs during pregnancy.

BMC Pregnancy Childbirth 2021 Aug 12;21(1):551. Epub 2021 Aug 12.

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China.

Background: We encourage Hepatitis B virus-infected mothers to breastfeed postpartum, even when continuing pregnancy category B nucleos(t)ide analogs (NAs) treatment. However, a large proportion of the Hepatitis B virus-infected mothers were noncompliant with this breastfeeding recommendation. This study aimed to investigate the factors associated with noncompliance with breastfeeding recommendation in Hepatitis B virus-infected mothers who had received NAs treatment during pregnancy.

Methods: A total of 155 mothers with chronic hepatitis B receiving NAs treatment for preventing mother-to-child transmission during the late gestation period were included and divided into exclusive breastfeeding (n = 63), mixed feeding (n = 34), and artificial feeding (n = 58) groups according to the postpartum feeding methods. Independent variables associated with feeding methods were analyzed using logistic regression analysis.

Results: Compared to the breastfeeding and mixed feeding groups, the artificial feeding group had significantly more multiparity, later postpartum timing of stopping NAs treatment, and a lower proportion of having knowledge of NAs medications (all P < 0.05). In addition, multivariable logistic regression analysis confirmed that multiparity, later postpartum timing of stopping NAs treatment, and lacking knowledge of medication were independent factors associated with noncompliance with breastfeeding recommendation.

Conclusions: Hepatitis B virus-infected mothers who stopped NAs treatment at late postpartum period or had less knowledge of medication were more likely to be noncompliant with breastfeeding recommendation. Strengthening health education for participants taking NAs may be an important method to improve compliance with breastfeeding recommendation.
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http://dx.doi.org/10.1186/s12884-021-04020-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359301PMC
August 2021

The safety of antiviral therapy and drug withdrawal for the prevention of mother-to-child transmission of HBV during pregnancy.

J Med Virol 2020 May 15. Epub 2020 May 15.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune-tolerant phase with HBV DNA levels >6 log  IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum-elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% [27/53] vs 58.3% [14/24] vs 40.7% [11/27], respectively; P  = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.
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http://dx.doi.org/10.1002/jmv.26011DOI Listing
May 2020

Transient Elastography and Ultrasonography: Optimal Evaluation of Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis B Concurrent with Nonalcoholic Fatty Liver Disease.

Biomed Res Int 2019 23;2019:3951574. Epub 2019 Jan 23.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun-Yat-sen University, Guangzhou, China.

Background And Aims: Concordance between transient elastography (TE) and ultrasonography (US) in assessing liver fibrosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD) has been rarely studied. This study aimed to evaluate the individual and combined performances of TE and US in assessing liver fibrosis and cirrhosis.

Patients And Methods: Consecutive CHB patients with NAFLD were prospectively enrolled. TE and US examinations were performed, with liver biopsy as a reference standard. Receiver operating characteristic (ROC) curves were obtained to evaluate the diagnostic performance. Differences between the areas under the ROC curves (AUCs) were compared using DeLong's test.

Results: TE and US scores correlated significantly with the histological fibrosis staging scores. TE was significantly superior to US in the diagnosis of significant fibrosis (AUC, 0.84 vs 0.73; P=0.02), advanced fibrosis (AUC, 0.95 vs 0.76; P<0.001), and cirrhosis (AUC, 0.96 vs 0.71; P<0.001). Combining TE with US did not increase the accuracy of detecting significant fibrosis, advanced cirrhosis, or cirrhosis (P=0.62, P=0.69, and P=0.38, respectively) compared to TE alone. However, TE combined with US significantly increased the positive predictive value for significant fibrosis when compared to TE alone. The optimal cut-off values of TE for predicting advanced fibrosis and cirrhosis were 8.7 kPa and 10.9 kPa, with negative predictive values of 92.4% and 98.7%, respectively.

Conclusions: TE is useful for predicting hepatic fibrosis and excluding cirrhosis in CHB patients with NAFLD. A combination of TE and US does not improve the accuracy in assessing liver fibrosis or cirrhosis.
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http://dx.doi.org/10.1155/2019/3951574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364122PMC
June 2019

Increased IL-17-producing CD8 T cell frequency predicts short-term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Ther Clin Risk Manag 2018 30;14:2127-2136. Epub 2018 Oct 30.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,

Background: IL-17-producing CD8 T (Tc17) cells promote inflammation and have been identified in chronic hepatitis. However, the role of Tc17 cells in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) remains unclear.

Methods: The frequency of Tc17 cells in blood samples from 66 patients with HBV-ACLF was determined by flow cytometry. The levels of Tc17 cell-related cytokines were measured by FlowCytomix assays. The prognostic prediction accuracy was evaluated by the receiver operating characteristic (ROC) curve analysis. Survival was analyzed using Kaplan-Meier curves. Mortality predictors were determined by the Cox regression analysis.

Results: The frequency of Tc17 cells was markedly higher in patients with HBV-ACLF than in those with chronic hepatitis B and normal control subjects. Increased frequencies of Tc17 cells may indicate liver injury and were positively correlated with disease severity. The Tc17 cell frequency was significantly higher in non-surviving patients with HBV-ACLF than in surviving patients. The ROC curve analysis showed that Tc17 cell frequency accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na, and Chronic Liver Failure Consortium ACLF scores. Kaplan-Meier analysis showed an association between the increase in circulating Tc17 cells and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that Tc17 cell frequency was an independent predictor of overall survival in patients with HBV-ACLF.

Conclusion: Tc17 cells may play a proinflammatory role in HBV-ACLF pathogenesis. Furthermore, the increased frequency of circulating Tc17 cells could be an independent prognostic biomarker in patients with HBV-ACLF.
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http://dx.doi.org/10.2147/TCRM.S184809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214596PMC
October 2018

Th17 cells over 5.9% at admission indicate poor prognosis in patients with HBV-related acute-on-chronic liver failure.

Medicine (Baltimore) 2018 Oct;97(40):e12656

Department of Infectious Diseases.

Our previous study demonstrated that Th17 cells increased significantly in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty-eight consecutive HBV-ACLF patients were enrolled in this cohort study. Th17 cells were examined using flow cytometry. Disease severity scores were assessed. ROC curves were used to evaluate the value in predicting prognosis. Survival was analyzed using Kaplan-Meier curves. Predictors of mortality were determined by regression analysis.Th17 cells were significantly higher in HBV-ACLF patients compared to patients with chronic hepatitis B and normal controls (both P < .001). Also, Th17 cells were higher in nonsurviving HBV-ACLF patients than in surviving patients (P = .014). Th17 cells were positively correlated with CLIF-Consortium ACLF (CLIF-C ACLF) score (r = 0.240, P = .048). ROC curves showed that the frequency of Th17 cells had accuracy in predicting 90-day prognosis equivalent to MELD, MELD-Na and CLIF-C ACLF scores in HBV-ACLF (P = .34, P = .26, and P = .15, respectively). More importantly, the area under the ROC curve (AUROC) increased when Th17 cells were combined with MELD, MELD-Na or CLIF-C ACLF score than using Th17 cells alone (P = .021, P = .006, and P = .023, respectively). Kaplan-Meier analysis revealed that higher Th17 cells (≥5.9%) were closely associated with poor overall survival in HBV-ACLF (P = .0086). Additionally, multivariate regression analysis showed that the frequency of Th17 cells over 5.9% was an independent predictor of mortality (OR = 0.154, P = .025).Circulating Th17 cells positively correlated with disease severity in HBV-ACLF. The frequency of Th17 cells over 5.9% could serve as a prognostic biomarker for HBV-ACLF patients.
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http://dx.doi.org/10.1097/MD.0000000000012656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200497PMC
October 2018

The effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells and natural killer cells in patients with chronic hepatitis C.

J Med Virol 2019 02 24;91(2):278-286. Epub 2018 Sep 24.

Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Currently, hepatitis C antiviral therapy is entering a new era with the use of direct-acting antiviral (DAA) agents. However, the precise immunological influences of DAA therapy in patients with chronic hepatitis C (CHC) are insufficiently understood. This study aimed to investigate the effects of DAA therapy on the frequency of myeloid-derived suppressor cells (MDSCs), T lymphocytes, and natural killer (NK) cells in patients with CHC. Thirty-two treatment-naive CHC patients were treated with DAA therapy, and the frequency of immune cells was analyzed by flow cytometry at various time points during and after therapy. Sixteen healthy donors were recruited for comparison. DAA therapy decreased the frequency of MDSCs and monocytic MDSCs in patients with CHC to a normal level. DAA therapy also increased the CD8 T and NK cell levels in patients with CHC. In addition, activation (NKp30 and NKp46) and inhibitory (NKG2A) receptors on NK cells were downregulated to yield an NK cell phenotype resembling that observed in the healthy controls. This study provides insight into the normalization of immune cell levels under DAA therapy and indicates that restoration of the immune system in patients with CHC strongly supports long-term curative hepatitis C virus eradication.
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http://dx.doi.org/10.1002/jmv.25302DOI Listing
February 2019

48-Week Outcome after Cessation of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patient and the Associated Factors with Relapse.

Can J Gastroenterol Hepatol 2018 10;2018:1817680. Epub 2018 May 10.

Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.

Background And Aims: We aimed to ascertain the feasibility and safety of NA cessation, the status of patients after cessation, and the predictive factors for relapse and subsequent retreatment.

Methods: A total of 92 patients were enrolled in this prospective study. Patients were monitored every month for the first 3 months after cessation and every 3 months thereafter.

Results: Sixty-two patients finished 48 weeks of follow-up. None died or developed liver failure, cirrhosis, or HCC. The 62 patients could be divided into 4 categories according to the 48-week clinical development of relapse. Virologic relapses occurred in 39 (62.9%) patients, with 72.7% occurring in the first 24 weeks in origin HBeAg positive patients and 82.4% in the first 12 weeks in origin HBeAg negative patients. Age (OR = 1.06, 95% CI = 1.02-1.10; = 0.003), the HBsAg level (OR = 2.21, 95% CI = 1.47-3.32; < 0.001), and positive origin HBeAg status (OR = 0.32, 95% CI = 0.14-0.74; = 0.008) were predictive factors to virologic relapse. HBV DNA level (OR = 1.34, 95% CI = 1.13-1.58; < 0.001) was predictive factor to retreatment.

Conclusions: NA cessation is safe under supervision. Age, HBsAg level, and origin HBeAg status can be predictive factors for virologic relapse. The study was submitted to ClinicalTrials.gov Protocol Registration and Results System with the assigned NCT ID NCT02883647.
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http://dx.doi.org/10.1155/2018/1817680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971349PMC
April 2019

Dynamic Changes of the Frequency of Classic and Inflammatory Monocytes Subsets and Natural Killer Cells in Chronic Hepatitis C Patients Treated by Direct-Acting Antiviral Agents.

Can J Gastroenterol Hepatol 2017 8;2017:3612403. Epub 2017 May 8.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.

Objective: Up to now, little was known about the immunological changes of chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAAs); we try to explore the effect of DAAs on the frequency of monocytes, NK cells, and cytokines that promote their activation.

Methods: 15 treatment-naive CHC patients and 10 healthy controls were recruited. Patients were examined before DAAs therapy (0 w) and at week 4 (4 w) and week 12 (12 w) of therapy. Percentage of monocytes and NK cells of the peripheral blood was analyzed by flow cytometry. Serum cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 were measured by enzyme linked immunosorbent assay.

Results: The frequency of CD3CD16CD56 NK cells and classic CD14CD16 monocytes decreased, while CD14CD16 monocytes and cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 increased at 0 w compared to healthy controls. During DAAs treatment, the decreased NK cells and classic monocytes gradually increased to normal levels; the increased inflammatory monocytes and cytokines IL-12 and CXCL11 decreased to normal levels, but the increased cytokines IL-18, CXCL10, sCD14, and sCD163 still remained at high levels at 12 w though they decreased rapidly from 0 w.

Conclusion: Our results showed that DAAs treatment attenuated the activation of monocytes and NK cells in CHC patients. Trial registration number is NCT03063723.
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http://dx.doi.org/10.1155/2017/3612403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439071PMC
April 2018

Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment.

Biomed Res Int 2017 23;2017:8061091. Epub 2017 Jan 23.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou, China.

Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, -1.33 versus 0.86, < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored.
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http://dx.doi.org/10.1155/2017/8061091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292367PMC
March 2017

Health care workers in Pearl River Delta Area of China are not vaccinated adequately against hepatitis B: a retrospective cohort study.

BMC Infect Dis 2015 Nov 22;15:542. Epub 2015 Nov 22.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Backgrounds: Health-care workers' (HCWs) exposure to bodily fluids puts them at risk of hepatitis B virus HBV infection. This study investigated HBV vaccination practices and outcomes in HCWs and assessed postvaccination seroprotection across HCWs in different departments.

Methods: A survey of HCWs in a Chinese public general hospital was carried out with a retrospective cohort of 1420 hospital HCWs (458 males and 962 females). HBV vaccination status (10-μg/dose used) was investigated in the cohort from vaccination records from the period of 1988 to 2008. Blood samples were collected and tested for hepatitis B surface antigen (HBsAg) and HBV antibodies (anti-HBs).

Results: The overall vaccination (complete course) and HBsAg carrier rates among HCWs were 40.42 % (574/1420) and 6.13 % (87/1420), respectively. Vaccination rates differed by department, with HCWs in internal medicine (39.5 %) and emergency (42.0 %) departments having particularly low rates. The natural infection rate was 7.53 % (107/1420) among HCWs. HCWs in the department of infectious diseases (vaccination rate, 57.8 %) had the highest rate of antibody produced by natural infection (88.2 %).

Conclusion: The vaccination rate was a disappointingly low among HCWs in Pearl River Delta Area of China. HCWs working in infectious diseases departments and technicians were at particularly likely to have been infected with HBV. A concerted effort is needed to bring vaccination rates up among Chinese HCWs in Pearl River Delta Area of southern China.
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http://dx.doi.org/10.1186/s12879-015-1278-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655081PMC
November 2015

Expansion of myeloid-derived suppressor cells from peripheral blood decreases after 4-week antiviral treatment in patients with chronic hepatitis C.

Int J Clin Exp Med 2014 15;7(4):998-1004. Epub 2014 Apr 15.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.

Myeloid-derived suppressor cells (MDSCs) are one of the most important regulators of anti-tumor T-cell responses in cancers. This study aimed to investigate MDSCs in the peripheral blood of patients with chronic hepatitis C (CHC) before and after 4-week treatment with pegylated interferon (PEG-IFN) and ribavirin, and to evaluate their correlation with CD4(+)CD25(high) regulatory T cells (Tregs) and clinical parameters. A total of 80 patients with CHC were enrolled into this study, 37 of whom were treated with PEG-IFN and ribavirin. Compared with healthy controls (0.462% [range 0.257%-0.634%]), the proportion of MDSCs in the peripheral blood of 80 CHC patients (0.601% [range 0.333%-1.027%]) increased significantly before therapy (P=0.011). For 37 HCV patients, the proportion of circulating MDSCs (0 w: 0.597% [range 0.296%-1.021%], 4 w: 0.126% [0.066%-0.239%], P<0.01) and Tregs (0 w: 2.467±0.927%, 4 w: 2.074±0.840%, P=0.047) decreased significantly after 4-week antiviral treatment. No significant correlation was found between MDSCs and Tregs. These findings suggest that MDSCs expand in the peripheral blood of CHC patients, but decrease after 4-week antiviral treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057852PMC
June 2014

Expression and clinical significance of myeloid derived suppressor cells in chronic hepatitis B patients.

Asian Pac J Cancer Prev 2014 ;15(10):4367-72

Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Shaoguan, Guangdong, China E-mail :

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/ PBMC median (X(2)=11.877, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/ PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference (X(2)=17.198, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.
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http://dx.doi.org/10.7314/apjcp.2014.15.10.4367DOI Listing
May 2015

Pretreatment HBsAg level and an early decrease in MELD score predict prognosis to lamivudine treatment for HBeAg-negative acute-on-chronic liver failure.

Clin Res Hepatol Gastroenterol 2014 Jun 30;38(3):331-6. Epub 2013 Dec 30.

Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, No 600# Tianhe Road, Guangzhou 510630, P.R. China.

Background And Objective: Few data are available about the predictability of HBsAg quantification to nucleos(t)ide analogues treatment in acute-on-chronic liver failure (ACLF). The aim of this study was to investigate HBsAg level combined with the model for end-stage liver disease (MELD) score for predicting prognosis to lamivudine monotherapy in HBeAg-negative ACLF.

Methods: Fifty-seven nucleoside-naïve patients with HBeAg-negative ACLF were treated with 100mg of lamivudine daily. Serum levels of HBsAg, HBV DNA and biochemical items were detected at baseline, before death (patients died within 3months) or month 3 meanwhile MELD score was calculated. Dynamic of these items and 3-month mortality were analyzed.

Results: HBV DNA level significantly decreased while HBsAg level did not after treatment. Twenty-six patients died within 3months and the others survived. Regardless pre- or post-treatment, HBsAg level of survival group was significantly higher than that of dead group meanwhile MELD scores of the former were significantly lower than those of the latter (all P<0.05). Post-treatment MELD scores of 32 patients with pretreatment HBsAg levels above 4000 COI were significantly lower than those of 25 patients below to it (t=-2.116, P=0.044) and the 3-month mortality of the formers was significantly lower than that of the latter (34.3% [11/32] vs 64.0% [16/25], χ(2)=4.941, P=0.026).

Conclusions: In HBeAg-negative ACLF, patient with higher pretreatment HBsAg levels and early decrease in MELD score has lower 3-month mortality than one without it during lamivudine monotherapy.
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http://dx.doi.org/10.1016/j.clinre.2013.10.012DOI Listing
June 2014

Dynamic changes of clinical features that predict the prognosis of acute-on-chronic hepatitis B liver failure: a retrospective cohort study.

Int J Med Sci 2013 23;10(12):1658-64. Epub 2013 Sep 23.

1. Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University; ; 2. Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangdong, China. No 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China.

Objective: The natural history of acute-on-chronic hepatitis B liver failure (ACHBLF) is complex and highly variable. However, the global clinical characteristics of this entity remain ill-defined. We aimed to investigate the dynamic patterns of the natural progression as well as their impact on the outcomes of ACHBLF.

Methods: The clinical features and disease states were retrospectively investigated in 54 patients with ACHBLF at the China South Hepatology Center. The clinical and laboratory profiles including hepatic encephalopathy (HE), hepatorenal syndrome (HRS), and spontaneous bacterial peritonitis (SBP) were evaluated. The disease state estimated by the model for end-stage liver disease (MELD) score and the dynamic patterns during the clinical course of ACHBLF were extrapolated.

Results: Twenty-two patients died during the 3-month follow-up period (40.74%). The patients were predominantly male (88.89%). Baseline characteristics showed that there were significant differences in only hepatitis B virus (HBV) DNA levels and platelet count between the deceased and surviving patients (P=0.014 and P=0.012, respectively). Other baseline characteristics were similar in both groups. The dynamic state of the MELD score gradually increased from an initial hepatic flare until week 4 of ACHBLF progression. There were notable changes of the dynamic state of the MELD score at two time points (week 2 and week 4) during ACHBLF progression. The MELD scores were significantly greater in the death group (24.80 ± 2.99) than in the survival group (19.49±1.96, P<0.05) during the clinical course of ACHBLF; the MELD scores of the survival group began to decrease from week 4, while they continued to rise and eventually decreased as more patients died. The gradients of the ascent and descent stages could predict exactly the severity and prognosis of ACHBLF.

Conclusions: The natural progression of ACHBLF could be divided approximately into four stages including ascent, plateau, descent, and convalescence stages according to different trends of liver failure progression, respectively. Thus, the special patterns of the natural progression of ACHBLF may be regarded as a significant predictor of the 3-month mortality of ACHBLF.
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http://dx.doi.org/10.7150/ijms.6415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804791PMC
May 2014

Prevalence of IL-28B and ITPA genotypes in Chinese Han population infected persistently with hepatitis C virus genotype 6 or HCV-1.

J Med Virol 2013 Jul;85(7):1163-9

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

The geographic distribution, demographics, epidemiology, host factors, and clinical characteristics of persistent HCV-6 infection in China need further characterization. This multicenter study enrolled 63 patients with persistent HCV-6 infection and 63 patients with persistent HCV-1 infection as controls. Blood biochemistry, quantitation of HCV RNA levels, and identification of host IL-28B genotypes (rs12979860, rs8099917, and rs12980275) and ITPA genotype (rs1127354) were performed to estimate potential variability in host factors that may affect response to treatment. The mean HCV-6 RNA level (3.8E6 IU/ml) was significantly higher than that in patients infected with HCV-1 (1.7E6 IU/ml; P < 0.001). Patients persistently infected with HCV-6 had a high prevalence of IL-28B rs12979860 CC genotype (92.1%), rs8099917 TT genotype (93.7%), and rs12980275 AA genotype (90.5%). Their prevalence in patients infected with HCV-1 was only modestly lower (82.5%, 84.1%, and 82.5%, respectively; P > 0.05). The inosine triphosphate pyrophosphatase (ITPA) SNP rs1127354 CC genotype was present in 66.7% of patients infected with HCV-6, comparable to that of patients infected with HCV-1 (65.1%; P > 0.05). There were no differences in the liver function, proportion of hepatic cirrhosis patients or patients with increased serum glucose between these two groups. Persistent HCV-6 infection in Chinese Han is found mainly in the southern China. Chinese Han with chronic HCV-1 or HCV-6 infection have IL-28B genotypes, suggesting responsiveness to interferon-based pharmacotherapy. Most patients (67%) possess the ITPA genotype associated with susceptibility to ribavirin-induced hemolysis. The routes of transmission for HCV-6 genotype were more diversified than HCV-1 genotype. The outbreak of HCV-6 infection through blood transfusion progressed faster than HCV-1.
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http://dx.doi.org/10.1002/jmv.23561DOI Listing
July 2013

High level of IL-27 positively correlated with Th17 cells may indicate liver injury in patients infected with HBV.

Liver Int 2014 Feb 25;34(2):266-73. Epub 2013 Jul 25.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun-Yat-Sen University, GuangZhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.

Background: Interleukin-6/IL-12 family cytokines play a key role in inflammatory diseases via their effects on the differentiation or regulation of T helper cells.

Aims: The aim of this study was to determine the role of interleukin-27 (IL-27) and its association with helper T cells in hepatitis B virus (HBV)-infected patients.

Methods: Samples were assessed from 51 HBV-infected patients [28 chronic hepatitis B (CHB) subjects and 23 acute-on-chronic liver failure (ACLF) subjects] and 18 normal controls (NC). Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Circulating helper T cells were determined using flow cytometry and associations between IL-27 expression and helper T cells were analysed.

Results: Serum IL-27 levels rose in HBV-infected patients (502.88 ± 23.35 pg/ml) compared to (NC, 277.14 ± 23.96 pg/ml, P < 0.0001). Furthermore, it significantly increased in patients with ACLF (587.90 ± 33.08 pg/ml) when compared with CHB (433.04 ± 26.57 pg/ml, P = 0.001). However, no statistically significant differences were observed between IL-27 and the presence of HBeAg. High levels of IL-27 then positively correlated with Tbil levels (r = 0.401, P = 0.004), but negatively associated with prothrombin time activity levels (r = -0.496, P < 0.001), and a slightly negative correlation trend with HBV-DNA loads (r = -0.228, P = 0.107) existed in these HBV-infected subjects. Additionally, frequency of circulating interleukin-17-producing CD4(+) T cells (Th17 cells) increased in HBV-infected patients (ACLF, mean, 5.39%; CHB, median, 3.12%) as compared to NC subjects (median, 2.22%, P < 0.0001). Moreover, correlation analysis showed that serum IL-27 level was positively associated with circulating Th17 cells (r = 0.342, P = 0.036).

Conclusion: These results provided evidence that IL-27 was positively correlated with Th17 cells commitment, and may exerted a proinflammatory effect in the development of liver injury in HBV-infected patients.
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http://dx.doi.org/10.1111/liv.12268DOI Listing
February 2014

A Novel prognostic scoring system to predict 3-month mortality risk in patients with acute-on-chronic liver failure in hepatitis B: a retrospective cohort study.

Hepatol Int 2012 Oct 29;6(4):727-34. Epub 2012 Jan 29.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Tianhe Road 600# Gangding, Guangzhou City, 510630, People's Republic of China.

Purpose: The present study was done to establish an objective, sensitive prognostic scoring system and to determine the applicability of this model in predicting the 3-month mortality of patients with acute-on-chronic liver failure in hepatitis B (ACLFB).

Methods: We developed a novel prognostic scoring system, calculated from six clinical indices including serum total bilirubin, prothrombin activity, serum creatinine, hepatic encephalopathy, infections, and the depth of ascites from 499 patients with ACLFB. Differences in the sensitivity, specificity, and practicality of a Novel prognostic scoring system and the model of end-stage liver disease (MELD) were analyzed.

Results: The areas under the receiver operating characteristic curve (ROC) for the Novel scoring systems and MELD scoring systems were 0.967 (95% CI, 0.956-0.977) and 0.900 (95% CI, 0.878-0.922), respectively. The analysis of the ROC curve indicated that the Novel scoring systems were an exact, pertinent, and objective prognostic model with greater accuracy than the MELD. In the Novel scoring systems, the survival rate of these patients whose scores ranged from 2 to 6 was 98.80%, while for those whose scores point at 7 and 15, the mortality rates were 8.70% (2/23) and 95.45% (21/22), respectively, and the mortality rate of these patients whose scores were 16 and above was 100.00%. However, in the MELD prognostic scoring systems, there were no score ranges with 100.00% survival rate.

Conclusions: We developed an objective, pertinent, and sensitive prognostic scoring system that predicted the 3-month mortality of patients with ACLFB with greater accuracy than the MELD.
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http://dx.doi.org/10.1007/s12072-011-9335-2DOI Listing
October 2012

Effect of healthcare insurance policy on the quality of life of chronic hepatitis C patients receiving interferon α-2a plus ribavirin therapy.

Exp Ther Med 2012 Jun 16;3(6):1062-1066. Epub 2012 Mar 16.

Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, P.R. China.

The aim of this study was to evaluate the effect of pegylated interferon α-2a plus ribavirin therapy on the quality of life (QOL) of chronic hepatitis C patients when this treatment was paid for by healthcare insurance. The QOL questionnaire (GQOLI-74) was used to assess patient QOL. A total of 42 cases received 1-year pegylated interferon α-2a plus ribavirin treatment paid for by Guangzhou Medical Insurance (group A), and 30 cases received treatment self-subsidized by the patients themselves (group B). Another 30 patients did not receive interferon therapy (group C). All groups completed the evaluation twice; prior to interferon treatment (T0) and at the end of treatment (T1). There was no statistically significant difference among the three groups (P>0.05). At T1, patients in group A had higher scores for each questionnaire dimension and a higher total score than those of group C (P<0.05). Patients in group B also had higher scores than those of group C (P<0.05), except for material well-being (P=0.305). Compared with group B, patients in group A had higher scores for mental function, material well-being and a higher total score (P<0.05). Patients in group A had higher scores for each dimension and a higher total score at T1 than at T0 (P=0.05), while patients in group B had higher scores for physical function, social function and a higher total score at T1 than at T0 (P=0.05). Pegylated interferon α-2a plus ribavirin treatment is able to improve the QOL of chronic hepatitis C patients. Patients whose treatment was financed by medical insurance exhibited increased improvement in QOL compared to those who paid for their own treatment.
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http://dx.doi.org/10.3892/etm.2012.519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438712PMC
June 2012

Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure.

PLoS One 2012 23;7(7):e41392. Epub 2012 Jul 23.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou City, People's Republic of China.

Uncontrolled hepatic immunoactivation is regarded as the primary pathological mechanism of fulminant hepatic failure (FHF). The major acute-phase mediators associated with FHF, including IL-1β, IL-6, and TNF-α, impair the regeneration of liver cells and stem cell grafts. Amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) have the capacity, under specific conditions, to differentiate into hepatocytes. Interleukin-1-receptor antagonist (IL-1Ra) plays an anti-inflammatory and anti-apoptotic role in acute and chronic inflammation, and has been used in many experimental and clinical applications. In the present study, we implanted IL-1Ra-expressing AF-MSCs into injured liver via the portal vein, using D-galactosamine-induced FHF in a rat model. IL-1Ra expression, hepatic injury, liver regeneration, cytokines (IL-1β, IL-6), and animal survival were assessed after cell transplantation. Our results showed that AF-MSCs over-expressing IL-1Ra prevented liver failure and reduced mortality in rats with FHF. These animals also exhibited improved liver function and increased survival rates after injection with these cells. Using green fluorescent protein as a marker, we demonstrated that the engrafted cells and their progeny were incorporated into injured livers and produced albumin. This study suggests that AF-MSCs genetically modified to over-express IL-1Ra can be implanted into the injured liver to provide a novel therapeutic approach to the treatment of FHF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041392PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402415PMC
November 2012

[Quality of life in patients with chronic hepatitis C after PEG-Interferon a-2a therapy].

Zhonghua Gan Zang Bing Za Zhi 2011 Dec;19(12):890-3

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Objective: To evaluate the quality of life (QOL) in the patients with chronic hepatitis C (CHC) after PEG-Interferon a-2a therapy.

Methods: A study based on 102 CHC patients (group A, before PEG- Interferon a-2a therapy, T0) and 44 healthy persons (group B) was carried out using the general quality of life inventory (GQOLI-74) questionnaire, and QOL were compared between the two groups. Patients in group A were divided into subgroup A1 (72 patients ) which was given PEG-Interferon a-2a plus Ribavirin for one year and subgroup A2 (30 patients) without any antivirus therapy. QOL of patients in these two subgroups was investigated using GQOLI-74 questionnaire on the end of PEG-Interferon a-2a plus Ribavirin therapy (T1) and half one year after the end of PEG-Interferon a-2a plus Ribavirin therapy (T2). QOL of CHC patients (group A1 and A2) were compared at T0, T1 and T2, respectively.

Results: Compared with group B, patients in group A had lower QOL (P < 0.05) on other scales and total scores of the GQOLI-74 questionnaire except psychological function(P > 0.05). Both on T1 and T2, patients in subgroup A1 had higher QOL on physical function, psychological function, social function and total scores than patients in subgroup A2 at the same time (P < 0.05). Patients in subgroup A1 at T1 had higher QOL on physical function, psychological function, social function and total scores than at T0 (P < 0.05). Patients in subgroup A1 at T2 had higher QOL on social function than that at T1 (P < 0.05).

Conclusions: QOL of CHC patients is more impaired than healthy persons. PEG-Interferon a-2a therapy will improve the QOL.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2011.12.003DOI Listing
December 2011

[A five-year follow-up of one hundred and thirty-six patients of hepatitis C].

Zhonghua Gan Zang Bing Za Zhi 2011 Nov;19(11):823-7

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Objective: To investigate the clinical outcome and effect of interferon treatment on patients with chronic hepatitis C.

Methods: 136 cases of patients with chronic hepatitis C were followed up by methods of retrospective survey combined with prospective study. SPSS16. 0 was used to perform chi-square test and multiple logistic regression.

Results: 136 cases of patients were infected with HCV virus mainly through blood and blood products transfusion. They were diagnosed mainly between 2000 and 2005. 98 cases of them had anti-viral treatment with interferon and ribavirin, while the rest did not; 12 new cases developed HCV-related cirrhosis or liver carcinoma in five years, which accounted for 8.8% of the total. Among 76 cases once treated with interferon, 46 cases (60.5%) relapsed in five years. For patients with age < 40, the rates of cirrhosis and liver cancer were 0, and patients with age ≥ 40 but < 60 years, the rates of cirrhosis and liver cancer were 12.5% (7/56 cases), while for those ≥ 60 years old the rates were 35.7% (10/28 cases). The difference was significant ( B = 0.111, Wald = 4.324, P = 0.038) as analysed by logistic regression. The rates of cirrhosis and liver cancer were zero for those with normal or within twice the upper normal AST limit in five years, 43.5% (10/23 cases) for those with AST ranging from 2 to 4 fold the upper normal limit, and 58.3% (7/12 cases) for those with AST higher than four times the upper normal limit. The difference was also significant ( B = 2.184, Wald = 5.443, P = 0.02) by logistic regression analysis. The rate of relapse was 29.7% (11/37 cases) for those using pegylated interferon and 89.7% (35/39 cases) for those using interferon. The difference was significant ( Result of logistic regression showed-B = -2.077, Wald = 4.352, P = 0.037). The rate of relapse was 100% (15/15 cases) for those with treatment less than 24 weeks, 76.2% (16/21 cases) for those with treatment more than 24 weeks but less than 48 weeks, and 37.5% (14/40 cases) for those with treatment more than 48 weeks. The difference was significant (Result of logistic regression showed-B = -1.632, Wald = 6.651, P = 0.01). 42 cases of the relapsed (91.3%) were administrated with interferon once again with ideal effect.

Conclusion: Hepatitis C virus infection increases the risk of liver cirrhosis and liver cancer. Interferon combined with ribavirin therapy could effectively control the virus and improve outcomes. We can reduce the incidence of relapse by choosing the treatment of pegylated interferon instead of interferon and by completing the full treatment.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2011.11.008DOI Listing
November 2011

Diethylene glycol poisoning and liver function following accidental diethylene glycol injection.

EXCLI J 2012 20;11:98-107. Epub 2012 Mar 20.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China. 510630.

The aim of the present study was to investigate the hepatotoxic effects of accidental intravenous diethylene glycol (DEG) poisoning in patients with liver disease. Clinical manifestations were recorded and liver function tests were carried out for 64 patients with liver disease who had been accidentally treated intravenously with DEG. Comparisons were made between the poisoned and non-poisoned groups. Of the 64 cases with preexisting liver disease, 15 cases (23.4 %) developed toxic presentations after exposure to DEG. All cases were men. Twelve of the 15 poisoned patients (80 %) died within seven days. The intravenous administration of DEG resulted in only mild liver function impairment. Gender (p = 0.039) and the severity of jaundice prior to DEG administration were risk factors related to the occurrence of toxin-induced renal failure (p < 0.006). The results suggest that DEG may worsen liver damage in patients with preexisting liver disease. However, our study demonstrated only mild, transient alterations in patients' baseline liver functions. Severe liver damage secondary to DEG was only occasionally seen in patients with concomitant renal failure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920036PMC
June 2016

Collagen proportionate area of liver tissue determined by digital image analysis in patients with HBV-related decompensated cirrhosis.

Hepatobiliary Pancreat Dis Int 2011 Oct;10(5):497-501

Department of Infectious Disease, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.

Background: The accurate assessment of the degree of hepatic fibrosis plays a critical role in guiding the diagnosis, treatment and prognostic assessment of chronic liver diseases. Liver biopsy is currently the most reliable method to evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive procedure associated with morbidity and mortality, and has several limitations in patients with decompensated cirrhosis. There is no report on the collagen proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis. This study aimed to determine the CPA of resected liver tissue samples from patients with HBV-related decompensated cirrhosis using digital image analysis, and to analyze the relationship between the CPA and liver functional reserve.

Methods: Fifty-three resected liver tissue samples from liver transplant patients with chronic hepatitis B-induced decompensated cirrhosis were stained with Masson's trichrome, and the CPA in these samples was quantitatively determined using digital image analysis. The values of relevant liver function just before liver transplantation, the CPA in liver tissue, and their correlation were analyzed.

Results: The mean CPA at the decompensated stage of cirrhosis was 35.93+/-14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a model for end-stage liver disease score, serum total bilirubin and international standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively (P<0.001). With increasing CPA values, the three indices reflecting liver functional reserve also changed significantly.

Conclusions: The degree of fibrosis may be correlated with the functional reserve. With the advancement of fibrosis, the liver functional reserve is attenuated accordingly.
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http://dx.doi.org/10.1016/s1499-3872(11)60084-2DOI Listing
October 2011

[Antiviral treatment of kidney transplant patients with hepatitis C recurrence: a case report].

Zhonghua Gan Zang Bing Za Zhi 2010 Sep;18(9):720

Department of Infectious Disease, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2010.09.022DOI Listing
September 2010

Effect of revaccination using different schemes among adults with low or undetectable anti-HBs titers after hepatitis B virus vaccination.

Clin Vaccine Immunol 2010 Oct 18;17(10):1548-51. Epub 2010 Aug 18.

Department of Infectious Disease, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Our objective was to investigate the effect of various reimmunization schemes for hepatitis B in adults with low or undetectable anti-HBs titers. Over 2 years, 10 μg of Saccharomyces cerevisiae-recombinant hepatitis B virus (HBV) vaccine (synthesized in China) was used in at least one standardized scheme to immunize 2,310 healthy male and nonpregnant female adults. Of these, 240 subjects tested negative for hepatitis B markers. These 240 subjects were equally divided into 4 groups. The first group, designated Engerix-40, was revaccinated with 40 μg Engerix-B; the second, Engerix-20, was revaccinated with 20 μg Engerix-B; the third, Chinese-20, was revaccinated with 20 μg Chinese-made yeast-recombinant vaccine; and the last group, Chinese-10, was revaccinated with 10 μg Chinese-made yeast-recombinant vaccine. Blood samples were collected before and 1, 2, 8, and 12 months after the first injection. The anti-HBs-positive conversion rates of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than that of the Chinese-10 group (P < 0.01). Over time, the anti-HBs conversion rate increased in all groups, but values were significantly different from those for the other groups only in the Chinese-10 group (P < 0.001). The anti-HBs geometric mean titers (GMTs) of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than in the Chinese-10 group (P < 0.05). Increased doses raise and maintain anti-HBs titers in subjects with low or undetectable titers after HBV vaccination.
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http://dx.doi.org/10.1128/CVI.00064-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952995PMC
October 2010

[The effects of diethylene glycol on liver function].

Zhonghua Gan Zang Bing Za Zhi 2010 Mar;18(3):217-21

Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

Objective: To investigate the hepatotoxic effects of accidental intravenous diethylene glycol (DEG.) poisoning in patients with liver disease.

Methods: Clinical data and liver function results were obtained from 64 patients with liver diseases who had been accidentally treated with diethyl glycol-contaminated agent and 45 cases with hepatorenal failure. The hepatotoxic effects of diethylene glycol DEG on the patients with liver diseases were assessed by multivariable logistical regression analysis.

Results: Of the 64 cases with liver diseases, 15 cases (23.4%) developed toxic presentations following the accidental administration of DEG. All affected cases were male. Twelve of the 15 poisoned patients (80%), died within 7 days of exposure to DEG. The most common clinical manifestations included kidney damage, renal failure, metabolic acidosis, and nerve system disturbances. The intravenous administration of DEG resulted in only mild liver function impairment. In terms of risk factors, both gender (r = 4.266, P less than 0.05) and the severity of jaundice prior to DEG administration were related to the occurrence of toxin-induced renal failure (r = 7.640, P less than 0.01).

Conclusions: DEG may worsen liver damage in patients with liver diseases.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2010.03.016DOI Listing
March 2010

[Status of hepatitis C in Guangzhou from 2005 to 2008].

Zhonghua Gan Zang Bing Za Zhi 2010 Jan;18(1):63-4

Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2010.01.016DOI Listing
January 2010

[Study on rhGM-CSF as adjuvant in revaccination among adults of non-and hyporesponders to hepatitis B vaccine].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 Jun;23(3):177-9

Guangdong International Travel Healthcare Center, Guangzhou 510635, China.

Objective: To investigate the effect of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) as adjuvant on immune response in adults of non-and hyporesponders to hepatitis B vaccine.

Methods: Those who were once immunized with recombined yeast gene hepatitis B vaccine more than one standard scheme in two years and negative for hepatitis B markers were randomly sorted as group A and group B. 33 adults of group A were given hepatitis B vaccine 10 microg each time. The immune procedure was 0, 1 and 6 month. 34 adults of group B were given rhGM-CSF 300 microg for the first day, then 10 microg each time for routine immune. The blood samples were collected before the first injection and in 1, 2 and 8 months (T1, T2, T8) following the first injection to test Anti-HBs.

Results: Anti-HBs positive conversion rates of group A and B at T8 was 39.39% and 64.71% respectively (P = 0.038). Anti-HBs levels of group B at T1, T2, T8 were (113.85 +/- 198.56) mIU/ml, (312.40 +/- 349.44) mIU/ml, (427.74 +/- 411.58) mIU/ml (P = 0.001). There was significant difference between group A and B in T8 Anti-HBs levels (P = 0.010).

Conclusion: Better immune response was found in the group of rhGM-CSF with hepatitis B vaccine. So rhGM-CSF can induce the immune respond to hepatitis B vaccine.
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June 2009

[Immune effects of three different programs for revaccination among adults of non- and hypo-responders to hepatitis B vaccine].

Zhonghua Yu Fang Yi Xue Za Zhi 2009 Jan;43(1):37-40

Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

Objective: To investigate the immune effects of three different programs for revaccination among adults of non- and hypo-responders to recombinant Hepatitis B vaccine.

Methods: Those who were once immunized with recombinant Hepatitis B vaccine more than one standard schedule (0, 1, and 6 months) in two years and negative for Hepatitis B markers were randomly given three-different projects for revaccination. 34 adults of A group were given GM-CSF 300 microg by subcutaneous injection for the first day, then 10 microg each time by intramuscular route for routine immune method. 33 adults of B group were given Hepatitis B vaccine 20 microg each time. 33 adults of C group were given Hepatitis B vaccine 10 microg each time. The blood samples were collected before the first injection and in 1, 2 and 8 months following the first injection to test Anti-HBs.

Results: At T1, the anti-HBs positive conversion rate of group A, B and C was 26.47%, 48.48% and 18.18% respectively (chi-2 = 7.20, P = 0.027). At T8, the anti-HBs positive conversion rate of group A (64.71%) and group B (75.76%) were higher than group C (39.39%), and there was significant difference (chi-2 = 9.07, P = 0.011). At T1, the anti-HBs level of group B (417.00 +/- 69.36) was higher than that of group A (203.74 +/- 79.56). At T2, the anti-HBs level of group B (458.17 +/- 64.09) was higher than that of group C (257.86 +/- 76.60). At T8, the anti-HBs level of group A (501.48 +/- 70.00) and group B (532.73 +/- 68.82) were higher than those of group C (256.12 +/- 75.39) (t =4.27, P = 0.0173).

Conclusion: Schemes of augmentation doses of Hepatitis B vaccine and being combined with GM-CSF should be in effect for non- and hypo-responders to Hepatitis B vaccine.
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January 2009
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