Objective:To investigate the long-term characteristic changes of virus, immune status, and liver fibrosis markers in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients after receiving direct-antiviral agents (DAAs).Methods:HIV/HCV co-infected patients who visited the Guangzhou Eighth People’s Hospital, Guangzhou Medical University from May 2014 to December 2019 were selected as the research subjects. The changes of virological response rate, peripheral blood CD4 +T lymphocyte level and serological markers of liver fibrosis (APRI score and FIB-4 index) were observed during 144 weeks of follow-up course after the end of DAAs treatment. Kruskal-Wallis test was used for statistical approach. Results:A total of 103 cases were included in the study. There were 87 males (87.5%), with a median age of 44 years. Sustained virological response rate at 12 weeks (SVR12) after DAAs treatment was 97.6%, and the SVR during the entire follow-up period was at least 95.9%. Compared with baseline, CD4 +T lymphocyte count were significantly increased equally at 12 weeks ( Z = -2.283, P = 0.022), 24 weeks (Z = -3.538, P < 0.001), 48 weeks ( Z = -3.297, P = 0.001), 96 weeks ( Z = -3.562, P < 0.001), and 144 weeks ( Z = -2.842, P = 0.004). APRI score ( Z = -6.394, P < 0.001) and FIB-4 index ( Z = -2.528, P = 0.011) were significantly lower than baseline at week 4 of DAAs treatment, and thereafter remained at a low level, without further declination. Conclusion:HIV/HCV co-infected patients can maintain high SVR for a long time, acquire good immune reconstitution, and significantly improve liver fibrosis after DAAs treatment.

Objective:To investigate the immunological features of 135 patients with corona virus disease 2019 (COVID-19), and to provide reference for the pathogenesis of the disease.Methods:The clinical and laboratory data of 135 confirmed COVID-19 patients in Guangzhou Eighth People′s Hospital from January 23 to February 29, 2020 were collected. The features of lymphocytes (CD4 + and CD8 + T lymphocytes, B lymphocytes, natural killer cells and natural killer T cells), and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) of patients at a median of 19 (14, 27) days of admission were analyzed. Kruskal-Wallis test, Mann-Whitney U test, chi-square test and Spearman rank correlation were used for statistical analysis. Results:Patients were divided into three groups according to the relevant diagnostic criteria, including mild group (14 cases), ordinary group (92 cases) and severe group (29 cases). Decreased CD4 + T lymphocytes were found in 44.4% (60/135) patients, while decreased CD8 + T lymphocytes were found in 42.2%(57/135) patients. Compared to mild group and ordinary group, level of CD4 + T lymphocytes in severe group was significant lower ( Z=4.379 and 3.799, respectively, both P<0.01), and level of CD8 + T lymphocytes was also significant lower ( Z=2.684 and 3.306, respectively, P=0.022 and 0.003, respectively). Decreased B lymphocytes were found in 25.3% (24/95) patients and significant different among the three groups, with the lowest levels ((88(56, 189)/μL; Z=6.199, P=0.045) and most frequency of decreased levels ((52.2%(12/23); χ2=11.723, P=0.003) in the severe group. Compared to the mild group and the ordinary group, IL-6 level in severe group was significant higher ( Z=-4.022 and -4.108, respectively, both P<0.01) and IL-10 level was also significant higher ( Z=-3.261 and -4.006, respectively, both P<0.01). Similar levels of IL-2, IL-4, TNF-α and IFN-γ were found among three groups (all P>0.05). The IL-6 level was positively correlated with the persistence of viral shedding ( r=0.301, P=0.007). Conclusion:The immune-mediated inflammation may be the important cause of disease deterioration of COVID-19, which might be the key target of the treatment of severe cases.

Objective: To analyze the characteristic mutations of epitopes in HBV Pre-S/S region in HIV/HBV co-infected patients’ peripheral blood to provide basic data for studying the pathogenesis of HIV/HBV co-infection. Methods: The chronic hepatitis B infected patients admitted to the Infectious Disease Center of the Eighth People′s Hospital of Guangzhou from January 2009 to December 2011 were enrolled into HIV/HBV co-infected group and HBV mono-infected group according to the result of HIV antibody detection respectively before treatment. HBV DNA in serum was extracted and Pre-S/S region of HBV DNA was amplified by nested-PCR. After sequencing of the obtained PCR products (direct sequencing), ContigExpress software was used for sequence splicing and BioEdit software was used for sequence alignment. With reference to the standard sequence of the matched genotype HBV, mutants of HBV Pre-S/S region in HIV/HBV co-infected group and HBV mono-infected group were analyzed respectively. Statistical analysis was performed by chi-square test with SPSS19.0 statistical analysis software. Results: HBV Pre-S/S fragments were successfully amplified from 150 patients, including 90 cases of HIV/HBV co-infected group and 60 cases of HBV mono-infected group, with matched gender, age, genotype, HBeAg status, alanine aminotransferase (ALT), aspartate aminotransferase (AST). The result of analyzing mutants of HBV Pre-S/S region indicated that the incidence of mutation in all epitopes for cytotoxic T cells (CTL cells) was higher in the HIV/HBV co-infected group, and Pre-S2 aa1-15 epitope was significantly higher (χ²=6.964, P=0.008). The incidence of deletions in PreS2 aa1-15 epitope in HIV/HBV co-infected group (11.1%) was higher than HBV mono-infected group (3.3%) (χ²=2.959, P=0.085). In the B cell epitopes, the incidence of mutations in Pre-S2 aa1-26 in the HIV/HBV co-infected group was significantly higher than HBV mono-infected group (χ²=6.924, P=0.010), and there was no statistical significance between two groups in other B cell epitopes. No differences in helper T cell (Th cell) epitopes were found between the two groups. Conclusions Co-infection with HIV increased the CTL cell epitopes’ mutations in the HBV Pre-S/S region, especially the 5′ end epitope mutations in Pre-S2 region, which indicated that HBV mutation is related to the host immune status, and showed guiding information for further study on the pathogenesis of HIV/HBV co-infection

Objective: To investigate the clinical, immunological and virological characteristics of HIV-1 infected patients in the acute phase, for the sake of improving the diagnosis of acute infection with HIV-1. Methods: We retrospectively analyzed the clinical manifestation and laboratory data of patients with acute HIV-1 infection who were admitted to the Center of Infectious Diseases, Guangzhou Eighth People’s Hospital from January 2012 to June 2017. Results: Forty-four patients were enrolled into the study, 86.4% of them were male. 59.1% patients were homosexually transmitted. Clinical symptoms and signs mostly consisted of fever (84.1%), lymphadenopathy (56.8%) and so on, while 15.9% patients had central nervous system symptoms. Most common opportunistic infection included lung infection (50.0%) and oropharyngeal candidiasis (22.7%). Leucopenia (10 patients, 22.7%), and decreased CD4⁺ T cell count (267.5 cells/μl), inverted CD4⁺ /CD8⁺ ratio (86.4%) was mostly seen. Compared to patients who had HIV RNA load less than 6 lg copies/ml, the group of patients who had HIV RNA load more than 6 lg copies/ml had lower levels of CD4⁺ T cells (t=-3.724, P=0.001). Conclusions Patients with acute HIV infection have many different kinds of clinical symptoms and can be accompanied by opportunistic infection, and with high viremia.

Objective To investigate the relationship between HBV mutations in the precore (PC)/core promoter region and the liver histological changes in HBeAg negative CHB patients. Method A total of 71 HBeAg negative CHB patients with liver biopsy from April 2012 to Dec 2013 were enrolled. DNA was extracted from blood serum, then the HBV S gene and PC/core promoter region were amplified by semi-nested PCR and sequenced. The relationship between significant liver histological changes and viral factors were analyzed by Logistic regression analysis. Results The incidence of significant necroinflammation (15.8% vs. 27.3%, χ2 =1.398, P = 0.237) and significant fibrosis (71.1% vs. 84.4%, χ2= 1.926, P = 0.165) were found to be similar between patients infected with HBV genotype B and genotype C . By Logistic regression analysis including risk factors of age, sex, HBV genotype and mutations (T1753V,A1762T/G1764A,A1846T and G1896A), the A1762T/G1764A mutation in HBV associated with significant necroinflammation (OR = 4.296, P = 0.037), while factors of age, sex, genotype and other mutation were not associated with significant liver histological changes. (all P > 0.05). Conclusion Mutation in PC/core promoter region of HBV may act as a marker to evaluate the liver histological changes.

Objective To investigate the prevalence and patterns of lamivudine (3TC) resistance mutations in acquired immune deficiency syndrome (AIDS)/chronic hepatitis B (CHB) co-infected patients receiving 3TC as a part of antiretroviral therapy.Methods Data of patients with AIDS/CHB co-infection from 2005 to 2010 were collected.HBV DNA was tested at the time of highly active antiretroviral therapy (HAART) and after 12,24,36,48 and 60 months therapy.HBV reverse transcriptase (RT) was amplified in detectable samples.3TC resistance mutations were identified.Results 185 co-infected patients were enrolled.3TC resistance mutations were negative at the time of HAART.3TC resistance mutations occurred in 29 co-infected patients after treatment,of these,7 patients were detected resistance mutations in two different points.9 patients were HBV non-viraemia at the time of antiviral therapy.Resistance mutations were detected after 12 months therapy in 3 patients.Patients with 3TC resistance mutations were more frequently HBeAg positive (65.5％ vs.33.3％,P =0.001),had higher HBV viral load (7.49 copies/ml vs.6.59 copies/ml,P =0.017) and longer duration of 3TC (40 months vs.26.5 months,P ＜ 0.001) than patients without 3TC resistance mutations.Four patterns of 3TC resistance mutations were detected:rtM204I (n=7),rtL180M (n=2),rtL180M + rtM204V/I (n =23) and rtL80V +rtM204I (n=4).Conclusions The prevalence of 3TC resistance mutations is low among AIDS/CHB co-infected patients in Guangzhou.Patients with HBV DNA negative before HAART are likely to develop resistance early during therapy.

Objective To investigate the diagnosis value of spleen stiffness measurement by transient elastography (FibroScan, FS) for esophageal-gastric varices (EV) in patients with HBV-related liver cirrhosis receiving anti-viral treatment. Method Total of 41 patients from Jan 2014 to Dec 2014 diagnosed with HBV-related liver cirrhosis receiving anti-viral treatment were enrolled. All patients were evaluated for spleen and liver stiffness measurement by FS and checked by gastroscopy for diagnosis of EV. Using gastroscopy as the gold standard, the area under receiver operating characteristic curve (AUROC) were used to evaluate the value of the spleen stiffness and liver stiffness in diagnosis of EV and its degree. Results The spleen and liver FS values in patients were (40.64 ± 25.45) kPa and (20.76 ± 13.21) kPa respectively, and they showed a positive correlation (r = 0.402, P < 0.001). The spleen FS values in patients without EV were significantly lower than those in patients with mild EV and moderate-severe EV (all P < 0.05). Furthermore, they showed significantly lower in patients with mild EV than those in patients with moderate-severe EV too (P < 0.05). The AUROC of spleen FS in patients with EV was 0.863, with sensitivity of 79.4% and specificity of 83.2%. Moreover, the AUROC of spleen FS in patients with moderate-severe EV was 0.924, with sensitivity of 87.9% and specificity of 91.3%. Both of them were much higher than those of liver FS. Conclusion Spleen FS may act as a non-invasive marker to predict EV and its degree in patients with HBV-related liver cirrhosis receiving anti-viral treatment.

Objective To investigate the epidemiologic and clinical features of human immunodeficiency virus (HIV)/hepatitis B virus (HBV)co-infected patients.Methods Patients who confirmed with HIV infection and received highly active anti-retroviral therapy (HAART)at Guangzhou Eighth People′s Hospital were enrolled.HIV/HBV co-infected patients and HIV mono-infected patients were screened and their epidemiological and clinical features were analyzed before HAART.Comparison of the levels of alanine transaminase (ALT),aspartate transaminase (AST),CD4 + T lymphocyte and HIV RNA between the two groups were conducted.The data were statistically analyzed by chi-square test and nonparametric test.Results One hundred and sixty-five out of 1 218 (13.5 %)patients were hepatitis B surface antigen positive.The median ALT and AST levels of HIV mono-infected patients were 29 U/L and 34 U/L respectively,which were both higher than HIV/HBV co-infected patients (22 U/L and 25 U/L, respectively)(Z = - 4.270 and Z = - 5 .780,respectively,both P = 0.000 ).The median CD4 + T lymphocyte count of HIV/HBV co-infected patients was significantly lower than that of HIV mono-infected patients (Z = -2.980,P =0.003 ).The CD4 + T lymphocyte count was lower in hepatitis B e antigen (HBeAg)positive patients than HBeAg negative patients (Z =-2.660,P =0.008).The median CD4 + T lymphocyte count in patients with HBV DNA≥5 lg copy/mL was significantly lower than those with HBV DNA<5 lg copy/mL (Z = -2.311 ,P =0.021 ).The proportions of positive HBV DNA, HBV DNA≥5 lg copy/mL,abnormal ALT and AST in 54 patiens with CD4 + T lymphocyte counts <50/μL were 81 .5 %,66.7%,44.4% and 53.7%,respectively.All were significantly higher than patients with CD4 + T lymphocyte count≥50/μL(χ2 =6.159,P =0.046 ;χ2 =6.618,P =0.037 ;χ2 =7.144,P =0.028 andχ2 =9.586,P =0.008,respectively).Conclusions The prevalence of HBV/HIV co-infection is high in this study.The CD4 + T lymphocyte counts in HIV/HBV co-infected patients are lower,especially in patients with HBeAg positive and high HBV DNA level.The CD4 + T lymphocyte counts are associated with HBV DNA replication levels.

Coinfection ; Hepatitis B, Chronic ; pathology ; Hepatitis E ; pathology ; Hepatitis E virus ; Humans

Objective To investigate the liver histological characteristics of children with chronic hepatitis B (CHB).Methods We recruited data of children with CHB and liver biopsy,then analyzed their liver histopathological characteristics and their associations with laboratory parameters.Results One hundred and twenty-four children with CHB were included in the present study,including 114 (91.9％) HBeAg-positive CHB children and 10 (8.1％) HBeAg-negative CHB children.In HBeAg-positive CHB children,the frequency of significant necroinflammation stratified by ALT levels was 32.1％ (9/28) in ALT ≤ULN,60.7％ (17/28) in ALT(1-2) ×ULN and 81.0％ (47/58) in ALT＞2 ×ULN group,while significant fibrosis was 46.4％ (13/28) in ALT ≤ ULN,71.4％ (20/28) in ALT (1-2) × ULN and 74.1％ (43/58) in ALT ＞ 2 × ULN group,respectively.Significant liver histological abnormalities were much higher in the ALT ＞ 2 × ULN and ALT (1-2) × ULN groups than the ALT ≤ ULN group.Logistic analysis indicated only AST levels associated with significant inflammation (OR =1.032,P =0.008) and significant fibrosis (OR =1.026,P =0.007).Conclusion Frequencies of significant liver histological abnormalities in children with CHB are high,and AST levels are associated with them.