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Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone ( P =0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.
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Objective:To analyze and summarize the clinical efficacy and safety of lymphocyte apheresis combined with plasma exchange in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage.Methods:A observational study was conducted. A total of 69 hepatitis B virus-related liver failure at the ascending stage patients who were hospitalized at Affiliated Guangzhou Eighth People's Hospital of Guangzhou Medical University from January 2016 to December 2020 were enrolled in this study. The patients were grouped according to their condition and wishes, including 38 patients treated with conservative medical treatment (control group) and 31 patients treated with lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment (study group). Clinical data were compared between the two groups 1-4 weeks after treatment, including dynamic changes of total bilirubin (TBil), international normalized ratio (INR), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, and the rate of clinical improvement at 4 weeks after treatment. In addition, the adverse effects and dynamic changes of white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), and hemoglobin (Hb) within 4 weeks after treatment were compared between the two groups.Results:Both groups showed significant improvement in clinical parameters after 1-4 weeks of initiation of therapy. The improvement of TBil, INR and MELD score at 1-4 weeks after treatment were significantly better in the treatment group than those in the control group [TBil (μmol/L): 248 (117, 335) vs. 398 (328, 464) at 1 week, 173 (116, 278) vs. 326 (184, 476) at 2 weeks, 107 (84, 235) vs. 355 (129, 467) at 3 weeks, 70 (61, 172) vs. 290 (82, 534) at 4 weeks; INR: 1.72±0.70 vs. 2.13±0.69 at 1 week, 1.67±0.61 vs. 2.28±1.35 at 2 weeks, 1.65±0.75 vs. 2.15±0.92 at 3 weeks, 1.61±0.93 vs. 2.19±1.17 at 4 weeks; MELD score: 18.35±5.32 vs. 23.38±4.56 at 1 week, 16.47±5.16 vs. 23.71±7.94 at 2 weeks, 16.30±5.75 vs. 22.64±6.99 at 3 weeks, 14.63±6.76 vs. 20.97±8.19 at 4 weeks], with significant differences (all P < 0.05). In addition, ALT levels at 1 week and 2 weeks after treatment in the study group were significantly lower than those in the control group [U/L: 128 (93, 206) vs. 240 (167, 436) at 1 week, 64 (42, 110) vs. 85 (69, 143) at 2 weeks, both P < 0.05]. The rate of clinical improvement at 4 weeks after treatment in the study group was 54.84% (17/31), which was significantly higher than that in the control group [28.95% (11/38)], with statistically significant difference ( P < 0.05). There was no significant difference in the rate of new infection between the study group and the control group [22.58% (7/31) vs. 34.21% (13/38), P > 0.05]. Additionally, expect that the PLT level at 1 week after treatment in the study group was significantly lower than that in the control group (×10 9/L: 101±42 vs. 128±59, P < 0.01), there was no significant difference in WBC, LYM or Hb at different time points after treatment between the two groups. Conclusion:Clinical efficacy of lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage is superior to conservative medical treatment alone, which can improve clinical improvement rate and recovery rate of liver function with high safety.
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Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods In this study, an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS-CoV-2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital, Guangzhou Medical University, since May 21, 2021, and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS-CoV-2 were enrolled, among whom there were 32 (37.6%) pediatric patients infected with Delta variant and 53 (62.4%) pediatric patients infected with Omicron variant, and there were no significant differences between the two groups in age, sex, body height, body weight, and comorbidities (all P > 0.05). There were no significant differences between the two groups in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase, total bilirubin, albumin, and cholinesterase (all P > 0.05), and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA) than those infected with Delta variant ( Z =-2.336, P =0.020). However, the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups ( P > 0.05). Among the 85 pediatric patients, 10 (11.8%) had a mild increase in liver function parameters, among whom 7 had an increase in TBA, 1 had an increase in ALT, 1 had increases in ALT and AST, and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6.3% vs 15.1%, χ 2 =0.691, P =0.406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS-CoV-2, but further studies are needed to evaluate the long-term influence of such infection on liver function.
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Objective To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China. Methods The patients with SARS-CoV-2 Delta variant infection who belonged to the same chain of transmission in Guangdong Province (Guangzhou and Foshan) and were admitted to Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 21 to June 18, 2021 were enrolled in this study, and the judgment criteria for liver function were alanine aminotransferase (male/female) > 50/40 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 μmol/L, gamma-glutamyl transpeptidase > 60 U/L, and alkaline phosphatase (ALK) > 125 U/L. Abnormality in any one item of the above criteria was defined as abnormal liver function, and such patients were included in analysis (the patients, aged < 18 years, who had a mild or moderate increase in ALP alone were not included in analysis). Clinical data were compared between the patients with normal liver function and those with abnormal liver function, and the etiology and prognosis of abnormal liver function were analyzed. The Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Among the 166 patients with SARS-CoV-2 Delta variant infection, 32 (19.3%) had abnormal liver function with mild-to-moderate increases in liver function parameters, and compared with the normal liver function group, the abnormal liver function group had a significantly higher proportion of critical patients ( χ 2 =38.689, P < 0.001) and significantly higher age and inflammatory cytokines [C-reactive protein type, serum amyloid A, and interleukin-6 (IL-6)](all P < 0.05). Among the 32 patients with abnormal liver function, 13 patients had abnormal liver function on admission (defined as primary group), while 19 patients had normal liver function on admission but were found to have abnormal liver function by reexamination after treatment (defined as secondary group). For the primary group, the evidence of abnormal liver function was not found for 3 patients (3/13, 23.1%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. Among the 19 patients in the secondary group, 9 (47.4%) had mild/common type and 10 (52.6%) had critical type, and all critical patients had the evidence of liver injury indirectly caused by the significant increases in C-reactive protein type, serum amyloid A, and IL-6 and hypoxemia; the evidence of abnormal liver function was not found for only 1 patient (1/19, 5.3%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. All 32 patients with abnormal liver function had [JP2]significant reductions in liver function parameters after treatment including liver protection. Conclusion As for the patients with SARS-CoV-2 Delta variant infection who belong to the same chain of transmission in Guangdong Province, the critical patients show a significantly higher proportion of patients with abnormal liver function than the patients with other clinical types, and other factors except SARS-CoV-2 infection and indirect injury caused by SARS-CoV-2 infection are the main cause of liver injury.
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Objective To investigate and analyze the relationship between hepatitis B virus (HBV) S gene mutations and the occurrence of HBV-related acute on chronic liver failure (HBV-ACLF).Methods A total of 377 patients were enrolled in this study,including 51 inactive hepatitis B surface antigen (HBsAg)carriers,78 chronic hepatitis B (CHB) patients,101 HBV-ACLF patients,69 HBV-related liver cirrhosis (LC) patients and 78 HBV-related hepatocellular carcinoma (HCC) patients.Serum samples were collected from July 2012 to September 2017 in Guangzhou Eighth People's Hospital.Nested polyoneras chain reaction (PCR) was performed for all the samples,the HBV whole genome and HBV S gene were amplified.PCR products were sequenced by Sanger sequencing method.HBV genotypes were determined by the phylogenetic tree based on HBV S gene constructed by Mega 7.0 software with the neighbor-joining method.Geneious R10.0.5 software was used to analyze the mutations of the HBV genome.The data in different groups were compared by x2 test or Fisher's exact test.The correlation analysis was done by logistic regression.Results Among the 377 patients enrolled in this study,the HBV-ACLF,CHB,inactive HBsAg carriers,and HCC patients infected with HBV genotype B were 83,51,34,31,and 35 cases respectively,and the patients infected with HBV genotype C were 18,27,17,38,and 43 cases respectively.The results of this study showed that 11 mutations were significantly higher in HBV-ACLF patients than CHB patients who were infected with HBV genotype B,including T216C,G285A and A529G in HBV S gene,A1317G in HBV enchanter I,A1762T/G1764A in basal core promoter (BCP) gene,A1846T,C1913A,G1896A,T2045A,C2078G,C2304A in HBV preC/C gene.However,no significant difference mutations were found in HBV-ACLF patients and CHB patients who were infected with HBV genotype C.In the patients infected with HBV genotype B,the prevalence of T216C (sL21S) mutation in HBV-ACLF was significantly higher than those in inactive HBsAg carriers,CHB and HCC patients (x2 =14.474,10.982,and 5.440,respectively,all P ＜ 0.05),whereas T216C mutation did not differnce between HBV-ACLF and LC patients (x2 =2.641,P =0.106).The prevalence of G285A (sG44E) mutation in HBV-ACLF was significantly higher than those in inactive HBsAg carriers,CHB,LC and HCC patients (x2 =27.301,29.287,15.719,and 16.076,respectively,all P ＜0.01).However,in the patients infected with HBV genotype C,the mutations in HBV S gene did not differnce between HBV-ACLF,inactive HBsAg carriers,CHB,LC and HCC patients (P ＞ 0.05).Logistic regression analysis showed that male (OR =6.90,95％ CI:1.52-24.39,P =0.010),hepatitis B e antigen negative (OR=4.73,95％ CI:1.60-13.94,P=0.005),HBV genotypeB (OR=4.80,95％ CI:1.82-12.16,P =0.006) and G285A mutation (OR =7.72,95％ C1:5.64-16.37,P =0.006) were the independent risk factors associated with HBV-ACLF.Conclusions The HBV S gene mutation may be associated with HBV-ACLF.
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To analyze the clinical features and prognosis of fulminant Wilson's disease (FWD) in patients with hepatitis B virus (HBV) infection.Twenty-seven patients were enrolled in Guangzhou Eighth People's Hospital from 2005 to 2015,including 13 FWD patients with HBV infection and 14 FWD patients without HBV infection.Clinical efficacy and survival rate were evaluated.Baseline biochemical data in two groups were comparable(P ＞ 0.05),including total bilirubin,prothrombin activity,serum albumin,alpha fetal protein,alanine transaminase,ceruloplasmin and 24 hours urine copper.Treatment in FWD group with HBV infection was ineffective,including 9(9/13) deaths and 4(4/13) patients receiveing liver transplants.However,7 (7/14) cases in the other group did not response to the treatment,including 6 (6/14) deaths and 1 (1/14)patient receiving liver transplant.The prognosis in the two groups is significantly different(P =0.006),which is much worse in FWD patients with HBV infection.
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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.
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0.05).Contrast between the two groups after infusing PS,pH and PaO_2 gained obvious difference,which showed rectification of hypoxemia and acid-intoxication.Preventative group's incidence of HMD was 27.45% while the treat group's was 80%(?~2=16.26,P